DOI: 10.1002/chem.201405558
Communication
& Organic Synthesis
Biaryl Synthesis by Ring-Opening Friedel–Crafts Arylation of 1,4Epoxy-1,4-dihydronaphthalenes Catalyzed by Iron Trichloride Yoshinari Sawama,* Shota Asai, Takahiro Kawajiri, Yasunari Monguchi, and Hironao Sajiki*[a] catalyzed C H activation of arenes bearing pyridine moieties at the ortho-positions as the directing groups,[10] the variety (substituent diversity at the aromatic rings) of the obtained products is relatively limited. Meanwhile, we have recently reported a Lewis acid catalyzed ring-opening functionalization method of the 1,4-epoxy moiety of 1 using allyl, azido, and cyano nucleophiles.[11] In this reaction, the substitutions (R1, R2 ; Scheme 1) at the bridge-head positions of 1 play a key role in
Abstract: Biaryl and heterobiaryl compounds are important frameworks across a range of fields including pharmaceutical and functional material chemistries. We have accomplished the efficient synthesis of various naphthalene-linked arenes and heteroarenes as biaryls and heterobiaryls by the FeCl3-catalyzed Friedel-Crafts reactions accompanied by the ring-opening of the 1,4-epoxy moiety of 1,4-epoxy-1,4-dihydronaphthalenes. Especially, it is noteworthy that 1-silylated substrates were regioselectively transformed to the 3-aryl-1-silylnaphthalenes and the double Friedel–Crafts reactions using thiophene derivatives could directly produce the corresponding bisnaphthlated thiophene derivatives.
Introduction Biaryls and heterobiaryls possessing naphthalene-linked arenes[1] and heteroarenes, such as benzofurans[2] or indoles,[3] are important in the pharmaceutical sciences, and p-conjugated polyarenes composed of a continuous arene and thiophene sequence, such as bis-arylated thiophenes, are also attractive for use in the field of pharmaceuticals[4g] as well as the materials[4a–f,h] sciences. 1,4-Epoxy-1,4-dihydronaphthalenes (1), which are easily prepared from various benzynes and furanes, are widely utilized to construct the corresponding naphthalene derivatives by various functionalizations accompanied by the ring-opening of the 1,4-epoxy moieties.[5] Although many nucleophilic arene-introduction methods into 1 by using a stoichiometric aryl Grignard[6a–d] or aluminum[6e] reagent and the transition-metal (Pd, Ni and Rh)-catalyzed coupling reactions using aryl halides[7] and indole[8] have been developed to produce 1-hydroxy-2-aryl-1,2-dihydronaphthalenes, the production of sludges (e.g., metals and acids) and the use of scarce and precious transition metals are still problematic issues. Although the direct biaryl (2-aryl-naphthalene derivatives) syntheses were also accomplished by the Pd-catalyzed dimerization of 1,[9a] Ni-catalyzed coupling with 1 and aryl iodides,[9b,c] and Rh-
Scheme 1. Ring-opening Friedel–Crafts arylation of 1,4-disubstituted 1,4epoxy-1,4-dihydronaphthalenes.
stabilizing the cation intermediate (A)[12] generated by the acid-induced ring-opening of 1. Furthermore, we demonstrated that an inexpensive and safe FeCl3 effectively catalyzed the cleavage of various benzylic C O bonds[13] and Friedel–Craftstype reaction using arenes as green aromatic sources without harmful byproducts.[13d, 14] We now report an efficient biaryl and heterobiaryl synthetic method by the FeCl3-catalyzed ringopening Friedel–Crafts arylation of 1,4-disubstituted 1,4-epoxy1,4-dihydronaphthalenes (1) accompanied by the production of only water as a byproduct, and a novel regioselective cleavage method of the 1,4-epoxy moiety of unsymmetrical substrates (1) possessing a silyl substituent as R1 and the subsequent arene introduction (Scheme 1).
Results and Discussion As expected, the FeCl3-catalyzed (5 mol %) reaction of 1,4-dimethyl-1,4-epoxy-1,4-dihydronaphthalene (1 a) as a simple substrate with 1,3,5-trimethoxybenzene (2 a: 2 equiv) smoothly proceeded in CH2Cl2 at room temperature for 10 min to give the desired biaryl product (3 a) in quantitative yield, and 2,4-dimethyl-1-naphthanol (4 a) resulting from the rearrangement[12e]
[a] Dr. Y. Sawama, S. Asai, T. Kawajiri, Dr. Y. Monguchi, Prof. Dr. H. Sajiki Laboratory of Organic Chemistry, Gifu Pharmaceutical University 1-25-4 Daigakunishi, Gifu 501-1196 (Japan) E-mail: [email protected] [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201405558. Chem. Eur. J. 2014, 20, 1 – 9
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Communication of the methyl group was never obtained [Equation (1)].[15–17] Furthermore, the site-selective cleavage of the 1,4-epoxy moiety of unsymmetrical 1-silyl-4-methyl substrates (1 b–d) was next investigated due to the potential of the subsequent functionalization of the aromatic silyl group. Consequently, the 1-silylated 3-arylnaphthalene derivatives (3 b–d) were regioselectively obtained by the use of the trimethylsilyl (TMS), triethylsilyl (TES), or tert-butyldimethylsilyl (TBS)-substituted substrate.
Table 1. Optimization for the Friedel–Crafts arylation of 1-triethylsilyl-4methyl-1,4-epoxy-1,4-dihydronaphthalene (1 c) and trimethoxybenzene (2 a).
Entry
Acid
Solvent
t
Yield [%] 3c 6
1 2[a] 3 4 5 6 7 8 9 10 11 12
FeCl3 FeCl3 FeBr3 AuCl3 BF3·Et2O TMSOTf FeCl2·4 H2O TFA FeCl3 FeCl3 FeCl3 FeCl3
CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CHCl3 toluene 1,4-dioxane THF
10 min 10 min 10 min 10 min 10 min 10 min 24 h 24 h 8h 24 h 24 h 24 h
76 92 60 77 33 0 no no 39 25 no no
0 0 26 0 0 16 reaction reaction 0 0 reaction reaction
[a] 3 equiv of 2 a were used.
biaryl (6) was also obtained as a byproduct by the cleavage of the aromatic silyl bond due to the strong acidity of FeBr3 or HBr generated in association with the reaction progress (entry 3). Other Lewis acids (e.g., BF3·Et2O, TMSOTf, and FeCl2·4 H2O) and trifluoroacetic acid (TFA) as a Brønsted acid were inappropriate catalysts for the present reaction (entries 5–8). The reaction in solvents, such as CHCl3, toluene, 1,4dioxane, and THF, resulted in poor yields (entries 9–12). We chose the easily accessible and inexpensive FeCl3 as the suitable catalyst in CH2Cl2 and the further increment of the usage of 2 a (3 equiv) could improve the reaction efficiency to provide 3 c in 92 % isolated yield (entry 2).[18] The present biaryl synthesis could be applied to various 1,4disubstituted 1,4-epoxy-1,4-dihydronaphthalenes (1; 1,4-dialkyl, 1-phenyl-4-alkyl, 1-silyl-4-alkyl substituents, etc.) and relatively electron-sufficient arenes including heteroarenes at room temperature in a short time (Scheme 3).[19, 20] The 1,4-dimethyl substrates bearing methoxy groups (1 e and f) as an electron-donating group and bromo group (1 g) on the aromatic ring were smoothly reacted with 2 a to give the corresponding biaryls (3 e–g) in excellent yields, respectively. The unsymmetrical substrates possessing methoxy groups (1 h) on the aromatic ring and a phenyl group (1 i) at one of the bridge-head positions were also effectively transformed into the biaryls (3 h and i) with good yields and perfect regioselectivities.[21] 1-Bromo3,5-dimethoxybenzene (2 b), 1,3-dimethoxybenzene (2 c), 1,3dihydroxybenzene (2 d), and 1- or 2-naphthol (2 e, 2 f) also played the role of efficient nucleophiles to form the corresponding biaryls (3 j–o) with moderate to high yields and good regioselectivities. Benzofuran (2 g), pyrrole (2 h), N-methyl pyrrole (2 i), indole (2 j), and N-phenyl indole (2 k) as heteroarenes efficiently promoted the desired reactions to afford the various heterobiaryls (3 p–t), respectively. 1-Triethylsilyl-4-alkyl substituents as 1-silylated substrates (1 c, j–m) underwent the FeCl3-
The Lewis acid induced ring-opening of the 1,4-epoxy moiety of the 1-TES substrate (1 c) can be transformed into two possible cation intermediates (B and C) (Scheme 2). Inter-
Scheme 2. Proposed mechanism.
mediate B is more favorable due to the sterical repulsion between the TES group and Lewis acid coordinated oxygen atom of C. Therefore, the nucleophilic addition of 1,3,5-trimethoxybenzene can proceed at the 3-position of B to generate the biaryl (3 c) accompanied by the subsequent dehydration. The regioisomer (5 c) by the sterically hindered intermediate (C) was never obtained, while a small amount of 4 c was produced as a byproduct by rearrangement of the methyl group to the 3-position of B and the following aromatization of D during the reaction process. As the result of the optimization using 1 c and 2 a (2 equiv), FeCl3 and AuCl3 were found to be efficient catalysts (Table 1, entries 1 and 4). Meanwhile, the use of FeBr3 also gave the desired biaryl (3 c) in moderate yield, although the desilylated &
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Scheme 3. Scope of substrates and arenes. [a] 2 equiv of the arene were used in the reaction of 1 a and 1 e–i, and 3 equiv of the arene were used in the reaction of 1c and 1 j–m unless otherwise noted. [b] Yields of minor regioisomers are depicted in Supporting Information. [c] 5 equiv of arene were used. [d] 10 equiv of arene were used.
catalyzed ring-opening Friedel–Crafts arylation with perfect regioselectivities as shown in Scheme 2 to give the corresponding 1-silyl-3-aryl-naphthalenes (3 u–ae) as highly functionalized biaryls in moderate to high yields. The further chemical modification of the obtained silylated products (3 c and 3 u) were next investigated (Scheme 4). Monobromination of 3 c by using 1.1 equivalents of N-bromosuccinimde (NBS) selectively proceeded at the electron-rich 2,4,6-trimethoxyphenyl ring in preference to the transformation of Ar-TES into Ar-Br to give the monobrominated biaryl
(7) in good yield. Thus, 2.2 equivalents of NBS were necessary to achieve the double bromination of 3 c to provide the desired dibromo biaryls (8).[22] Additionally, the TES functionality of 7 could be converted into Ar H by the use of BBr3 without demethylation of the trimethoxybenzene moiety.[23] A similar monobromination of 3 u could also be accomplished using 1.1 equivalents of NBS to form the monobrominated biaryl (10) in excellent yield, and 1,3-dibromo-5,5-dimethyl hydantoin (DBH, 2.2 equiv) was the more effective reagent for the double bromination of 3 u into 11.[24] Materially useful bis-arylated thiophene derivatives are generally prepared by the stepwise coupling reactions using the modified arene and thiophene derivatives.[4] To the best of our knowledge, there seems to be no direct synthetic procedure between the thiophene and naphthalene derivatives/precursors. Furan, pyrrole, and thiophene are known to react with electrophiles at their 2- and/or 5-positions, which are known to be the more nucleophilc positions of these heterocycles. The FeCl3-catalyzed ring-opening Friedel–Crafts arylation between the 1,4-disubstituted 1,4-epoxy-1,4-dihydronaphthalenes (1) and pyrroles (2 h and i) selectively provided the 2-monoarylated pyrroles (3 q, r, x, and y) as shown in Scheme 3. The reaction using furan derivatives could not be controlled and pro-
Scheme 4. Modification of silylated products (3 c and 3 u). Chem. Eur. J. 2014, 20, 1 – 9
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Communication Experimental Section Typical procedure for Equations 1 and 2, Table 1, Schemes 3, and 4, and the synthesis of 13 h and 13 i (Scheme 5) An arene (2: 0.4, 0.6, or 1.0 mmol) and FeCl3 (0.01 mmol: 5 mol % of the substrate) were added to a solution of the 1,4-disubstituted 1,4-epoxy-1,4-dihydronaphthalene (1: 0.2 mmol) in CH2Cl2 (1 mL) and the mixture was stirred at room temperature under argon. After an adequate reaction time, the mixture was quenched with water and extracted with additional CH2Cl2. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel-column chromatography to give the biaryl (3).
Typical procedure for the synthesis of 13 b–f (Scheme 5) Thiophene (12: 0.2 mmol) and FeCl3 (0.01 mmol: 5 mol % of the substrate) were added to a solution of a 1,4-disubstituted 1,4epoxy-1,4-dihydronaphthalene (1: 0.6 mmol) in CH2Cl2 (1 mL) and the mixture was stirred at room temperature under argon. After an adequate reaction time, the mixture was quenched with water and diluted with cold hexane. The resulting precipitate was filtrated and washed with cold hexane to give the arylated thiophene product (13) (13 a and g were purified by silica-gel column chromatography). 1,4-Dimethyl-2-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 a): Colorless solid; m.p. 135–139 8C; IR (ATR): n˜ = 3066, 2997, 2936, 2836, 2176, 1607, 1584, 1502, 1463, 1412, 1385, 1333, 1223, 1203, 1183, 1156, 1123, 1058, 1037 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.10– 8.08 (m, 1 H), 8.00–7.99 (m, 1 H), 7.51–7.49 (m, 2 H), 7.12 (s, 1 H), 6.26 (s, 2 H), 3.89 (s, 3 H), 3.69 (s, 6 H), 2.66 (s, 3 H), 2.39 ppm (s, 3 H); 13 C NMR (100 MHz, CDCl3): d = 160.6, 158.5, 133.0, 132.1, 131.4, 130.9, 130.7, 130.4, 125.1, 125.0, 124.8, 124.6, 90.8, 55.8, 55.4, 19.4, 15.8 ppm; ESI-HRMS: m/z: calcd for C20H23O3 : 323.1642; found 323.1638 [M+H] + .
Scheme 5. Double Friedel–Crafts reaction of thiophene derivatives. [a] 5 equiv of thiophene derivative were used for 1.
duced a complex mixture. On the other hand, thiophene (12 a) effectively reacted with 1 a at both the 2- and 5-positions of 12 a to directly give the 2,5-bisnaphthly thiophene derivative (13 a) by the use of an excess amount of 1 a (3 equiv) (Scheme 5). Intriguingly, various thiophene derivatives, such as 2,2’-bithiophene (12 b), 2,2’:5,2”-terthiophene (12 c), 3,4-ethylenedioxythiophene (12 d), and thieno[3,2-b]thiophene (12 e), also underwent the efficient bis-arylation with 1 a and 1 g to give the corresponding polyarenes (13 b–f) in good yields. The reaction of 1-triethylsilyl-4-methyl-1,4-epoxy-1,4-dihydronaphthalenes (1 c) with thiophene (12 a) regioselectively gave the mononaphthylated thiophene (13 g), although the reason why the second naphthylation at the 5-position of 13 g did not take place is unclear. The Friedel-Crafts reaction is generally hampered by the use of halogenated arenes. Nevertheless, the 2-bromo and iodo thiophenes (12 f and g) could be effectively converted into the corresponding 2-naphthyl-5-halo thiophenes (13 h and i) as heterobiaryl products, respectively. The aromatic halogens of 13 f, h and i can be useful for further chemical transformation into various polyarene derivatives.
4-Methyl-3-(2’,4’,6’-trimethoxyphenyl)-1-trimethylsilylnaphthalene (3 b): Pale-yellow oil; IR (ATR): n˜ = 2953, 2836, 1605, 1582, 1499, 1454, 1436, 1411, 1359, 1333, 1249, 1222, 1183, 1152, 1123, 1061, 1037 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.13–8.09 (m, 2 H), 7.49–7.46 (m, 3 H), 6.27 (s, 2 H), 3.88 (s, 3 H), 3.69 (s, 6 H), 2.43 (s, 3 H), 0.43 ppm (s, 9 H); 13C NMR (125 MHz, CDCl3): d = 160.7, 158.5, 137.5, 136.2, 134.9, 134.1, 133.0, 130.3, 128.6, 125.3, 124.8, 124.7, 112.6, 90.8, 55.7, 55.4, 16.2, 0.4 ppm; ESI-HRMS: m/z: calcd for C23H29O3Si: 381.1880; found: 381.1894 [M+H] + . 4-Methyl-1-triethylsilyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 c): Pale-yellow oil; IR (ATR): n˜ = 2951, 2873, 1605, 1583, 1498, 1454, 1412, 1333, 1222, 1202, 1152, 1124, 1061, 1038 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.11 (d, J = 8.0 Hz, 1 H), 8.08 (d, J = 6.4 Hz, 1 H), 7.47–7.44 (m, 2 H), 7.46 (s, 1 H), 6.27 (s, 2 H), 3.88 (s, 3 H), 3.67 (s, 6 H), 2.44 (s, 3 H), 0.98 ppm (s, 15 H); 13C NMR (100 MHz, CDCl3): d = 160.7, 158.6, 139.1, 136.9, 134.7, 133.0, 130.9, 130.2, 128.5, 125.3, 124.8, 124.6, 112.8, 90.9, 55.7, 55.4, 16.3, 7.7, 4.7 ppm; ESIHRMS: m/z: calcd for C26H34O3SiNa: 445.2169; found: 445.2170 [M+Na] + .
Conclusion We have achieved the efficient synthesis of biaryl (naphthalene-benzene/naphthalene types), heterobiaryl (naphthalenepyrrole/thiophene/benzofuran/indole types) and polyarenes (the continuous naphthalene-thiophene sequence) by the ironcatalyzed Friedel–Crafts reaction accompanied by the ringopening of 1,4-epoxy moieties in various 1,4-disubstituted 1,4epoxy-1,4-dihydronaphthalenes. The present method requires inexpensive and safe FeCl3 and only water is generated as a byproduct. Additionally, the ring-opening site of the 1,4-epoxy moiety could be controlled by the silyl substitution at the bridge-head position to provide the highly-functionalized biaryl derivatives. &
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1-tert-Butyldimethylsilyl-4-methyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 d): Pale-yellow oil; IR (ATR): n˜ = 2952, 2927, 2853, 1605, 1583, 1498, 1462, 1436, 1411, 1359, 1333, 1252, 1222, 1202, 1183, 1152, 1125, 1061, 1038 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.13 (d, J = 7.5 Hz,1 H), 8.11 (d, J = 7.0 Hz, 1 H),7.49–7.44 (m, 3 H), 6.28 (s, 2 H), 3.90 (s, 3 H), 3.69 (s, 6 H), 2.45 (s, 3 H), 0,95 (s, 9 H), 0.47 ppm (s, 6 H); 13C NMR (125 MHz, CDCl3): d = 160.7, 158.6, 139.9, 137.1, 134.9, 133.0, 132.0, 130.0, 129.8, 125.1, 124.7, 124.5, 112.7,
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Communication 90.8, 55.7, 55.4, 27.2, 18.1, 16.3, 2.7 ppm; ESI-HRMS: m/z: calcd for C26H35O3Si: 423.2350; found: 423.2350 [M+H] + .
2-(2’,4’-Dimethoxyphenyl)-1,4-dimethylnaphthalene (3 k): Colorless solid; m.p. 120–126 8C; IR (ATR): n˜ = 3067, 2997, 2934, 2833, 1608, 1579, 1505, 1462, 1437, 1414, 1384, 1300, 1280, 1258, 1228, 1205, 1156, 1118, 1032 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.10 (dd, J = 6.8, 2.0 Hz, 1 H), 8.01 (dd, J = 6.8, 2.0 Hz, 1 H), 7.54–7.51 (m, 2 H), 7.19 (s, 1 H), 7.12 (d, J = 9.2 Hz, 1 H), 6.60–6.58 (m, 2 H), 3.88 (s, 3 H), 3.74 (s, 3 H), 2.67 (s, 3 H), 2.45 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 160.2, 157.7, 134.7, 132.9, 132.0, 131.7, 131.3, 130.5, 129.7, 125.5, 125.0, 124.5, 124.3, 104.2, 104.1, 98.6, 55.5, 55.4, 19.3, 16.0 ppm; ESI-HRMS m/z: calcd for C20H21O2 : 293.1536; found: 293.1527 [M+H] + .
5,8-Dimethoxy-1,4-dimethyl-2-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 e): Colorless solid; m.p. 161–163 8C; IR (ATR): n˜ = 2933, 2834, 1606, 1583, 1501, 1453, 1411, 1380, 1334, 1255, 1224, 1203, 1154, 1122, 1056, 1033 cm 1; 1H NMR (500 MHz, CDCl3): d = 6.98 (s, 1 H), 6.75–6.70 (m, 2 H), 6.24 (s, 2 H), 3.87 (s, 3 H), 3.86 (s, 3 H), 3.84 (s, 3 H), 3.68 (s, 6 H), 2.81 (s, 3 H), 2.53 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 160.4, 158.4, 153.0, 152.8, 133.1, 132.4, 131.8, 131.2, 128.0, 127.1, 113.2, 106.1, 105.4, 90.7, 56.3, 56.1, 55.9, 55.3, 25.5, 20.4 ppm; ESI-HRMS m/z: calcd for C23H26O5Na: 405.1672; found: 405.1664 [M+Na] + .
5,8-Dimethoxy-2-(2’,4’-dimethoxyphenyl)-1,4-dimethylnaphthalene (3 l): Colorless solid; m.p. 144–146 8C; IR (ATR): n˜ = 2934, 2833, 1609, 1577, 1507, 1455, 1380, 1301, 1256, 1232, 1207, 1158, 1139, 1113, 1034 cm 1; 1H NMR (500 MHz, CDCl3): d = 7.10 (d, J = 8.5 Hz, 1 H), 7.05 (s, 1 H), 6.78 (d, J = 8.8 Hz, 1 H), 6.73 (d, J = 8.8 Hz, 1 H), 6.58–6.56 (m, 2 H), 3.87 (s, 3 H), 3.86 (s, 3 H), 3.85 (s, 3 H), 3.74 (s, 3 H), 2.82 (s, 3 H), 2.56 ppm (s, 3 H); 13C NMR (125 MHz, CD2Cl2): d = 160.4, 157.9, 152.9, 152.6, 136.8, 132.5, 131.6, 131.5, 131.1, 128.0, 126.9, 124.8, 106.3, 105.5, 104.4, 98.4, 56.1, 56.0, 55.6, 55.5, 25.3, 20.8 ppm; ESI-HRMS: m/z: Calcd for C22H25O4 : 353.1747; found: 353.1736 [M+H] + .
6,7-Dimethoxy-1,4-dimethyl-2-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 f): Light-red solid; m.p. 216–219 8C; IR (ATR): n˜ = 2936, 2834, 1605, 1584, 1506, 1456, 1414, 1333, 1257, 1224, 1202, 1159, 1144, 1122, 1051, 1036 cm 1; 1H NMR (400 MHz, CDCl3): d = 7.32 (s, 1 H), 7.22 (s, 1 H), 7.01 (s, 1 H), 6.25 (s, 2 H), 4.02 (s, 3 H), 4.01 (s,3 H), 3.88 (s, 3 H), 3.68 (s, 6 H), 2.60 (s, 3 H), 2.33 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 160.5, 158.5, 148.5, 148.5, 130.0, 129.5, 129.1, 128.9, 128.5, 127.7, 112.7, 104.3, 103.7, 90.7, 55.8, 55.8, 55.7, 55.4, 19.7, 16.1 ppm; ESI-HRMS m/z: calcd for C23H26O5Na: 405.1672; found: 405.1663 [M+Na] + .
5-(1’,4’-Dimethyl-2’-naphthyl)-1,3-benzenediol (3 m): Colorless solid; m.p. 174–177 8C; IR (ATR): n˜ = 3353, 2921, 1619, 1596, 1509, 1458, 1384, 1301, 1236, 1153, 1100, 1029 cm 1; 1H NMR (500 MHz, CD3OD): d = 8.13–8.11 (m, 1 H), 8.05–8.03 (m, 1 H), 7.56–7.52 (m, 2 H), 7.18 (s, 1 H), 6.93 (d, J = 8.0, 1 H), 6.45–6.42 (m, 2 H), 2.68 (s, 3 H), 2.48 ppm (s, 3 H); 13C NMR (125 MHz, [D6]DMSO): d = 157.6, 155.3, 135.6, 132.5, 131.4, 131.3, 130.5, 130.0, 129.6, 125.6, 125.0, 124.8, 124.3, 120.0, 106.3, 102.5, 18.9, 15.9 ppm; ESI-HRMS m/z: calcd for C18H16O2Na: 287.1043; found: 287.1045 [M+Na] + .
6,7-Dibromo-1,4-dimethyl-2-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 g): Colorless solid; m.p. 176–180 8C; IR (ATR): n˜ = 2936, 2835, 1605, 1583, 1499, 1462, 1412, 1381, 1333, 1224, 1202, 1158, 1142, 1123, 1065, 1038 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.36 (s, 1 H), 8.25 (s, 1 H), 7.15 (s, 1 H), 6.25 (s, 2 H), 3.89 (s, 3 H), 3.70 (s, 6 H), 2.61 (s, 3 H), 2.34 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 161.2, 158.5, 133.4, 132.6, 132.5, 132.2, 131.6, 130.5, 130.2, 129.5, 121.5, 121.2, 111.7, 90.9, 56.0, 55.6, 19.5, 16.0 ppm; ESI-HRMS: m/z: calcd for C21H19O3Br2 : 476.9706; found: 476.9705 [M H] .
1-(1’,4’-Dimethyl-2’-naphthyl)-2-naphthol (3 n): Pale-orange solid; m.p. 176–178 8C; IR (ATR): n˜ = 3519, 3062, 2919, 1619, 1597, 1512, 1462, 1400, 1380, 1342, 1262, 1215, 1187, 1150, 1133, 1028 cm 1; 1 H NMR (500 MHz, CD2Cl2): d = 8.16–8.14 (m, 1 H), 8.12–8.10 (m, 1 H), 7.85–7.83 (m, 2 H), 7.65–7.60 (m, 2 H), 7.33–7.26 (m, 3 H), 7.20– 7.18 (m, 2 H), 5.01 (br s, 1 H), 2.69 (s, 3 H), 2.35 ppm (s, 3 H); 13C NMR (125 MHz, [D6]DMSO): d = 152.0, 133.5, 132.9, 132.8, 131.9,131.3, 130.8, 130.0, 128.7, 128.1, 127.9, 126.3, 125.8, 125.5, 124.9, 124.6, 124.2, 122.6, 121.0, 118.4, 19.0, 15.6 ppm; ESI-HRMS m/z: calcd for C22H19O: 297.1285; found: 297.1289 [M H] .
5,7-Dimethoxy-1,4-dimethyl-2-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 h): Light-red solid; m.p. 164–167 8C; IR (ATR): n˜ = 2934, 1606, 1583, 1510, 1454, 1407, 1333, 1261, 1223, 1204, 1179, 1149, 1122, 1083, 1058, 1036 cm 1; 1H NMR (400 MHz, CDCl3): d = 6.90 (d, J = 2.2 Hz, 1 H), 6.87 (s, 1 H), 6.49 (d, J = 2.2 Hz, 1 H), 6.25 (s, 2 H), 3.92 (s, 3 H), 3.88 (s, 3 H), 3.88 (s, 3 H), 3.68 (s, 6 H), 2.80 (s, 3 H), 2.29 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 160.5, 159.9, 158.4, 157.2, 135.9, 132.0, 131.8, 129.8, 129.6, 120.6, 112.7, 97.5, 96.1, 90.7, 55.8, 55.4, 55.3, 55.1, 25.2, 16.7 ppm; ESI-HRMS: m/z: calcd for C23H26O5Na: 405.1672; found: 405.1676 [M+Na] + .
2-(1’,4’-Dimethyl-2’-naphthyl)-1-naphthol (3 o): Dark-yellow solid; m.p. 145–147 8C; IR (ATR): n˜ = 3524, 3055, 2941, 1598, 1570, 1505, 1438, 1382, 1279, 1237, 1196, 1141, 1082, 1025 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.30–8.29 (m, 1 H), 8.17–8.15 (m, 1 H), 8.10– 8.09 (m, 1 H), 7.88–7.86 (m, 1 H), 7.64–7.62 (m, 2 H), 7.54–7.51 (m, 3 H), 7.32–7.25 (m, 2 H), 2.72 (s, 3 H), 2.54 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 147.9, 134.2, 133.4, 133.1, 132.5, 132.3, 131.6, 129.0, 127.9, 127.5, 126.3, 126.2, 126.0, 125.5, 125.1, 124.7, 124.0, 122.3, 121.6, 119.8, 19.3, 15.8 ppm; ESI-HRMS m/z: calcd for C22H18ONa: 321.1250; found: 321.1260 [M+Na] + .
4-Methyl-1-phenyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 i): Colorless solid; m.p. 129–132 8C; IR (ATR): n˜ = 2937, 1607, 1581, 1498, 1454, 1411, 1331, 1222, 1204, 1181, 1154, 1121, 1059, 1033 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.14 (d, J = 8.8 Hz, 1 H), 7.95 (d, J = 8.4 Hz, 1 H), 7.55–7.38 (m, 8 H), 6.26 (s, 2 H), 3.89 (s, 3 H), 3.71 (s, 6 H), 2.45 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 160.7, 158.5, 141.2, 137.2, 133.1, 133.0, 131.0, 130.9, 130.7, 130.4, 128.0, 126.8, 126.4, 125.3, 125.1, 124.8, 112.1, 90.6, 55.8, 55.4, 16.1 ppm; ESI-HRMS: m/z: calcd for C26H24O3Na: 407.1618; found: 407.1599 [M+Na] + .
2-(1’,4’-Dimethyl-2’-naphthyl)benzofuran (3 p): Colorless solid; m.p. 86–88 8C; IR (ATR): n˜ = 3067, 2921, 1572, 1510, 1452, 1386, 1302, 1258, 1207, 1166, 1010 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.20–8.17 (m, 1 H), 8.05–8.02 (m, 1 H), 7.68–7.57 (m, 5 H), 7.34–7.27 (m, 2 H), 6.90 (s, 1 H), 2.87 (s, 3 H), 2.73 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 156.4, 154.7, 133.2, 132.7, 132.3, 130.8, 129.1, 127.0, 126.8, 126.1, 126.0, 125.4, 124.6, 124.1, 122.8, 120.9, 111.2, 106.2, 19.4, 16.3 ppm; ESI-HRMS m/z: calcd for C20H17O: 273.1274; found: 273.1273 [M+H] + .
2-(2’-Bromo-4’,6’-dimethoxyphenyl)-1,4-dimethylnaphthalene (3 j): Colorless solid; m.p. 156–158 8C; IR (ATR): n˜ = 2936, 1600, 1560, 1490, 1457, 1434, 1405, 1301, 1266, 1210, 1153, 1129, 1034 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.11–8.10 (m, 1 H), 8.04– 8.02 (m, 1 H), 7.54–7.53 (m, 2 H), 7.05 (s, 1 H), 6.86 (s, 1 H), 6.53 (s, 1 H), 3.86 (s, 3 H), 3.67 (s, 3 H), 2.68 (s, 3 H), 2.37 ppm (s, 3 H); 13 C NMR (125 MHz, CDCl3): d = 160.0, 158.6, 133.8, 132.8, 132.3, 131.5, 131.0, 129.2, 125.4, 125.2, 125.2, 125.1, 125.0, 124.7, 108.5, 98.2, 55.9, 55.6, 19.4, 15.5 ppm; ESI-HRMS: m/z: calcd for C20H19O2BrNa: 393.0461; found: 393.0463 [M+Na] + . Chem. Eur. J. 2014, 20, 1 – 9
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2-(1’,4’-Dimethyl-2’-naphthyl)-1H-pyrrole (3 q): Pale-purple solid; m.p. 125–128 8C; IR (ATR) cm 1: n˜ = 3424, 3069, 2943, 1604, 1510,
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Communication 1452, 1411, 1382, 1116, 1095, 1029; 1H NMR (500 MHz, CDCl3): d = 8.31 (br s, 1 H), 8.13–8.10 (m, 1 H), 8.02–8.00 (m, 1 H), 7.59–7.51 (m, 2 H), 7.35 (s, 1 H), 6.94–6.92 (m, 1 H), 6.37–6.36 (m, 1 H), 2.75 (s, 3 H), 2.68 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 133.3, 132.2, 132.1, 131.8, 129.7, 129.1, 128.0, 125.9, 125.3, 125.1, 124.5, 118.0, 109.4, 109.1, 19.3, 16.7 ppm; ESI-HRMS m/z: calcd for C16H16N: 222.1277; found: 222.1289 [M+H] + .
CDCl3): d = 148.0, 137.3, 136.8, 134.9, 134.6, 134.1, 132.9, 131.9, 128.6, 128.0, 127.5, 126.4, 126.0, 125.8, 125.5, 125.3, 123.9, 122.3, 121.7, 119.9, 16.2, 7.7, 4.5 ppm; ESI-HRMS m/z: calcd for C27H29OSi: 397.1993; found: 397.1987 [M H] . 2-(4’-Methyl-1’-triethysilyl-3’-naphthyl)-1H-pyrrole (3 x): Colorless solid; m.p. 76–78 8C; IR (ATR): n˜ = 3433, 2951, 2872, 1505, 1456, 1415, 1357, 1235, 1113, 1091, 1002 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.29 (br s, 1 H), 8.13 (d, J = 8.0 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 1 H), 7.65 (s, 1 H), 7.56–7.46 (m, 2 H), 6.96–6.94 (m, 1 H), 6.39–6.37 (m, 2 H), 2.76 (s, 3 H), 1.02–0.94 ppm (m, 15 H); 13C NMR (125 MHz, CDCl3): d = 136.5, 136.0, 133.1, 133.1, 132.5, 132.4, 129.5, 128.4, 125.7, 125.4, 125.2, 118.0, 109.4, 109.2, 16.5, 7.7, 4.5 ppm; ESI-HRMS m/z: calcd for C21H26NSi: 320.1840; found: 320.1842 [M H] .
N-Methyl-2-(1’,4’-dimethyl-2’-naphthyl)pyrrole (3 r): Colorless oil; IR (ATR): n˜ = 2919, 1601, 1483, 1442, 1406, 1382, 1295, 1265, 1231, 1086, 1028 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.10–8.08 (m, 1 H), 8.04–8.02 (m, 1 H), 7.57–7.55 (m, 2 H), 7.24 (s, 1 H), 6.74 (s, 1 H), 6.26–6.25 (m, 1 H), 6.13–6.12 (m, 1 H), 3.40 (s, 3 H), 2.67 (s, 3 H), 2.51 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 134.1, 132.9, 132.3, 132.1, 131.6, 129.8, 129.7, 125.6, 125.1, 124.6, 121.6, 108.7, 107.3, 34.2, 19.2, 16.1 ppm; ESI-HRMS m/z: calcd for C17H18N: 236.1434; found: 236.1428 [M+H] + .
N-Methyl-2-(4’-methyl-1’-triethysilyl-3’-naphthyl)pyrrole (3 y): Colorless oil; IR (ATR): n˜ = 2951, 2909, 2873, 1504, 1455, 1416, 1234, 1005 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.12–8.11 (m, 2 H), 7.56– 7.52 (m, 3 H), 6.77 (br s, 1 H), 6.27 (br s, 1 H), 6.15 (br s, 1 H), 3.42 (s, 3 H), 2.55 (s, 3 H), 1.00–0.96 ppm (m, 15 H); 13C NMR (125 MHz, CDCl3): d = 137.6, 137.0, 135.4, 134.3, 132.8, 132.4, 129.4, 128.5, 125.6, 125.4, 125.4, 121.7, 109.0, 107.3, 34.3, 16.5, 7.7, 4.5 ppm; ESIHRMS m/z: calcd for C22H30NSi: 336.2142; found: 336.2156 [M+H] + .
3-(1’,4’-Dimethyl-2’-naphthyl)-1H-indole (3 s): Colorless solid; m.p. 58–61 8C; IR (ATR): n˜ = 3411, 3059, 2921, 1602, 1508, 1454, 1417, 1385, 1336, 1241, 1124, 1093, 1009 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.23 (br s, 1 H), 8.15–8.13 (m, 1 H), 8.06–8.04 (m, 1 H), 7.59–7.53 (m, 2 H), 7.51 (d, J = 8.0 Hz, 1 H), 7.45 (d, J = 8.0 Hz, 1 H), 7.27–7.22 (m, 2 H), 7.15 (t, J = 8.0 Hz, 1 H), 2.70 (s, 1 H), 2.64 ppm (s, 1 H); 13 C NMR (125 MHz, CDCl3): d = 135.8, 133.3, 131.8, 131.6, 131.1, 130.3, 130.2, 127.5, 125.6, 125.1, 125.0, 124.5, 123.2, 122.2, 120.2, 120.0, 118.4, 111.2, 19.3, 16.4 ppm; ESI-HRMS m/z: calcd for C20H16N: 270.1288; found: 270.1289 [M H] .
N-Phenyl-3-(4’-methyl-1’-triethysilyl-2’-naphthyl)indole (3 z): Colorless solid; m.p. 101–103 8C; IR (ATR): n˜ = 2952, 2871, 1595, 1500, 1454, 1378, 1299, 1222, 1115, 1074, 1003 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.19 (d, J = 8.0 Hz, 1 H), 8.15 (d, J = 8.0 Hz, 1 H), 7.79 (s, 1 H), 7.69–7.51 (m, 8 H), 7.41–7.38 (m, 2 H), 7.30 (t, J = 7.0 Hz, 1 H), 7.21 (t, J = 7.0 Hz, 1 H), 2.74 (s, 3 H), 1.04–0.96 ppm (m, 15 H); 13 C NMR (125 MHz, CDCl3): d = 139.7, 138.2, 137.8, 136.7, 135.8, 133.6, 130.2, 129.7, 129.7, 128.5, 127.0, 126.5, 125.4, 125.4, 124.9, 124.4, 124.2, 122.6, 120.8, 120.6, 110.7, 108.5, 16.9, 7.8, 4.6 ppm; ESI-HRMS m/z: calcd for C31H34NSi: 448.2455; found: 448.2463 [M+H] + .
N-Phenyl-3-(1’,4’-dimethyl-2’-naphthyl)indole (3 t): Colorless solid; m.p. 75–78 8C; IR (ATR): 3063, 2920, 1595, 1545, 1499, 1454, 1361, 1315, 1298, 1221, 1134, 1074, 1028 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.18–8.16 (m, 1 H), 8.08–8.06 (m, 1 H), 7.68–7.66 (m, 1 H), 7.62– 7.54 (m, 7 H), 7.48 (s, 1 H), 7.40–7.37 (m, 2 H), 7.31–7.27 (m, 1 H), 7.22–7.18 (m, 1 H), 2.72 (s, 3 H), 2.71 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 139.7, 135.8, 133.4, 132.0, 131.7, 130.7, 130.4, 130.1, 129.7, 129.0, 126.9, 126.4, 125.7, 125.3, 125.1, 124.6, 124.3, 122.6, 120.6, 120.6, 119.3, 110.6, 19.3, 16.6 ppm; ESI-HRMS m/z: calcd for C26H22N: 348.1747; found: 348.1742 [M+H] + .
4-Ethyl-1-triethylsilyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 aa): Pale-yellow oil; IR (ATR): n˜ = 2952, 2873, 1606, 1584, 1500, 1456, 1412, 1334, 1223, 1203, 1153, 1125, 1056, 1039, 1014 cm 1; 1 H NMR (500 MHz, CDCl3): d = 8.15 (d, J = 8.0 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 1 H), 7.47–7.43 (m, 2 H), 7.35 (s, 1 H), 6.26 (s, 2 H), 3.90 (s, 3 H), 3.65 (s, 6 H), 2.86 (q, J = 7.5 Hz, 2 H), 1.13 (t, J = 7.5 Hz, 3 H), 0.97 ppm (s, 15 H); 13C NMR (125 MHz, CDCl3): d = 160.5, 158.6, 140.4, 139.0, 137.5, 132.0, 131.5, 130.1, 128.8, 125.3, 124.7, 124.4, 112.9, 90.7, 55.6, 55.3, 23.2, 14.6, 7.7, 4.6 ppm; ESI-HRMS m/z: calcd for C27H36O3SiNa: 459.2326; found: 459.2322 [M+Na] + .
3-(2’,4’-Dimethoxyphenyl)-4-methyl-1-triethylsilylnaphthalene (3 u): Colorless oil; IR (ATR): n˜ = 2951, 2872, 1609, 1578, 1504, 1454, 1414, 1300, 1280, 1257, 1236, 1205, 1156, 1135, 1108, 1034 cm 1; 1 H NMR (500 MHz, CDCl3): d = 8.13 (d, J = 8.5 Hz, 1 H), 8.10 (d, J = 8.0 Hz, 1 H), 7.53–7.46 (m, 3 H), 7.15–7.13 (m, 1 H), 6.60–6.59 (m, 2 H), 3.87 (s, 3 H), 3.73 (s, 3 H), 2.50 (s, 3 H), 0.98 ppm (s, 15 H); 13 C NMR (125 MHz, CDCl3): d = 160.2, 157.8, 137.9, 136.7, 134.3, 133.7, 132.9, 132.0, 131.8, 128.4, 125.3, 125.2, 124.8, 124.3, 104.1, 98.7, 55.4, 55.4, 16.5, 7.7, 4.6 ppm; ESI-HRMS m/z: calcd for C25H32O2SiNa: 415.2064; found: 415.2060 [M+Na] + .
6,7-Dimethoxy-4-methyl-1-triethylsilyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 ab): Colorless solid; m.p. 121–123 8C; IR (ATR): n˜ = 2951, 1605, 1583, 1509, 1464, 1413, 1333, 1258, 1221, 1201, 1155, 1121, 1061, 1038, 1010 cm 1; 1H NMR (500 MHz, CDCl3): d = 7.43 (s, 1 H), 7.35 (s, 1 H), 7.34 (s, 1 H), 6.27 (s, 2 H), 4.02 (s, 3 H), 4.01 (s, 3 H), 3.89 (s, 3 H), 3.69 (s, 6 H), 2.39 (s, 3 H), 1.02–0.95 ppm (m, 15 H); 13C NMR (125 MHz, CDCl3): d = 160.5, 158.5, 148. 1, 133.3, 132.6, 129.0, 128.7, 128.4, 112.8, 107.8, 104.4, 104.3, 90.8, 90.7, 55.7, 55.7, 55.4, 55.3, 16.6, 7.7, 4.7 ppm; ESI-HRMS m/z: calcd for C28H38O5SiNa: 505.2381; found: 505.2373 [M+Na] + .
1-(4’-Methyl-1’-triethysilyl-3’-naphthyl)-2-naphthol (3 v): Paleyellow oil; IR (ATR): n˜ = 3533, 2952, 2873, 1619, 1596, 1504, 1463, 1378, 1345, 1260, 1214, 1179, 1145, 1127, 1004 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.24–8.19 (m, 2 H), 7.88–7,85 (m, 2 H), 7.63– 7.60 (m, 2 H). 7.53 (s, 1 H), 7.36–7.29 (m, 3 H), 7.23 (d, J = 7.6 Hz, 1 H), 4.98 (s, 1 H), 2.43 (s, 3 H), 1.03–0.94 ppm (m, 15 H); 13C NMR (100 MHz, CDCl3): d = 150.4, 137.6, 137.5, 136.4, 134.7, 133.3, 133.1, 129.4, 129.1, 129.0, 128.7, 128.1, 126.5, 125.9,125.9, 125.4, 124.7, 123.3, 121.0, 117.2, 15.9, 7.7, 4.5 ppm; ESI-HRMS m/z: calcd for C27H29OSi: 397.1993; found: 397.2003 [M H] .
1-(6’,7’-Dimethoxy-4’-methy-1’-triethylsilyl-3’-naphthyl)-2-naphthol (3 ac): Colorless solid; m.p. 79–83 8C; IR (ATR): n˜ = 3529, 2951, 2872, 1620, 1596, 1509, 1465, 1429, 1390, 1345, 1258, 1226, 1166, 1131, 1061, 1006 cm 1; 1H NMR (500 MHz, CDCl3): d = 7.86 (s, 1 H), 7.85 (s, 1 H), 7.54 (s, 1 H), 7.39 (s, 1 H), 7.39 (s, 1 H), 7.34–7.20 (m, 3 H), 7.22 (d, J = 8.5 Hz, 1 H), 5.03 (s, 1 H), 4.08 (s, 3 H), 4.06 (s, 3 H), 2.37 (s, 3 H), 0.98 ppm (s, 15 H); 13C NMR (125 MHz, CDCl3): d = 150.4, 149.0, 148.9, 135.7, 134.8, 133.5, 133.4, 132.5, 129.3, 128.9, 128.7, 128.0, 127.5, 126.4, 124.8, 123.2, 121.3, 117.1, 107.8, 104.1,
2-(4’-Methyl-1’-triethysilyl-3’-naphthyl)-1-naphthol (3 w): Paleyellow oil; IR (ATR): n˜ = 3539, 3070, 2952, 2873, 1571, 1504, 1459, 1381, 1318, 1238, 1197, 1144, 1081, 1007 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.32–8.30 (m, 1 H), 8.19–8.17 (m, 2 H), 7.88–7.87 (m, 1 H), 7.61–7.57 (m, 3 H), 7.55–7.53 (m, 3 H), 7.33 (d, J = 8.5 Hz, 1 H), 5.33 (s, 1 H), 2.56 (m, 3 H), 1.03–0.95 ppm (m, 15 H); 13C NMR (125 MHz,
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Communication 55.8, 55.8, 16.2, 7.7, 4.5 ppm; ESI-HRMS m/z: calcd for C29H34O3SiNa: 481.2169; found: 481.2163 [M+Na] + .
[5] Review: a) M. Lautens, K. Fagnou, S. Hiebert, Acc. Chem. Res. 2003, 36, 48 – 58; b) K. Fagnou, M. Lautens, Chem. Rev. 2003, 103, 169 – 196; c) T. Hayashi, K. Yamasaki, Chem. Rev. 2003, 103, 2829 – 2844; d) M. Lautens, K. Fagnou, Proc. Natl. Acad. Sci. USA 2004, 101, 5455 – 5460. [6] a) M. Nakamura, K. Matsuo, T. Inoue, E. Nakamura, Org. Lett. 2003, 5, 1373 – 1375; b) R. Gmez Arrays, S. Cabrera, J. C. Carretero, Org. Lett. 2003, 5, 1333 – 1336; c) R. Gmez Arrays, S. Cabrera, J. C. Carretero, Synthesis 2006, 1205 – 1219; d) R. Millet, L. Gremaud, T. Bernardez, L. Palais, A. Alexakis, Synthesis 2009, 2101 – 2112; e) R. Millet, T. Bernardez, L. Palais, A. Alexakis, Tetrahedron Lett. 2009, 50, 3474 – 3477. [7] For seleted references, see: a) J.-P. Duan, C.-H. Cheng, Organometallics 1995, 14, 1608 – 1618; b) K. Fugami, S. Hagiwara, H. Oda, M. Kosugi, Synlett 1998, 477 – 478; c) C.-C. Feng, M. Nandi, T. Sambaiah, C.-H. Cheng, J. Org. Chem. 1999, 64, 3538 – 3543; d) M. Murakami, H. Igawa, Chem. Commun. 2002, 390 – 391; e) M. Lautens, C. Dockendorff, K. Fagnou, A. Malicki, Org. Lett. 2002, 4, 1311 – 1314; f) M. Lautens, C. Dockendorff, Org. Lett. 2003, 5, 3695 – 3698; g) C.-L. Chen, S. F. Martin, J. Org. Chem. 2006, 71, 4810 – 4817; h) T.-K. Zhang, D.-L. Mo, L.-X. Dai, X. -L, Hou, Org. Lett. 2008, 10, 5337 – 5340; i) G. C. Tsui, J. Tsoung, P. Dougan, M. Lautens, Org. Lett. 2012, 14, 5542 – 5545. [8] a) M. Lautens, K. Fagnou, J. Am. Chem. Soc. 2001, 123, 7170 – 7171; b) M. Lautens, K. Fagnou, D. Yang, J. Am. Chem. Soc. 2003, 125, 14884 – 14892; c) R. Webster, A. Boyer, M. J. Fleming, M. Lautens, Org. Lett. 2010, 12, 5418 – 5421; d) T. D. Nguyen, R. Webster, M. Lautens, Org. Lett. 2011, 13, 1370 – 1373. [9] a) H.-T. Shih, H.-H. Shih, C.-H. Cheng, Org. Lett. 2001, 3, 811 – 814; b) D. K. Rayabarapu, P. Shukla, C.-H. Cheng, Org. Lett. 2003, 5, 4903 – 4906; c) S. Madan, C.-H. Cheng, J. Org. Chem. 2006, 71, 8312 – 8315. [10] a) Z. Qi, X. Li, Angew. Chem. Int. Ed. 2013, 52, 8995 – 9000; Angew. Chem. 2013, 125, 9165 – 9170. [11] a) Y. Sawama, K. Kawamoto, H. Satake, N. Krause, Y. Kita, Synlett 2010, 14, 2151 – 2155; b) Y. Sawama, Y. Shishido, T. Yanase, K. Kawamoto, R. Goto, Y. Monguchi, H. Sajiki, Angew. Chem. Int. Ed. 2013, 52, 1515 – 1519; Angew. Chem. 2013, 125, 1555 – 1559; c) Y. Sawama, Y. Ogata, K. Kawamoto, H. Satake, K. Shibata, Y. Monguchi, H. Sajiki, Y. Kita, Adv. Synth. Catal. 2013, 355, 1529. [12] a) G. Wittig, L. Pohmer, Chem. Ber. 1956, 89, 1334 – 1351; b) E. Wolthuis, B. Bossenbroek, G. DeWall, E. Geels, A. Leegwater, J. Org. Chem. 1963, 28, 148 – 152; c) M. Fetizon, N. T. Anh, Bull. Soc. Chim. Fr. 1965, 3208 – 3210; d) M. D. Cooke, T. A. Dransfield, J. M. Vernon, J. Chem. Soc. Perkin Trans. 2 1984, 1377 – 1381; e) F. Peng, B. Fan, Z. Shao, X. Pu, P. Li, H. Zhang, Synthesis 2008, 3043 – 3046. [13] a) Y. Sawama, Y. Sawama, N. Krause, Org. Lett. 2009, 11, 5034 – 5037; b) Y. Sawama, S. Nagata, Y. Yabe, K. Morita, Y. Monguchi, H. Sajiki, Chem. Eur. J. 2012, 18, 16608 – 16611; c) Y. Sawama, K. Shibata, Y. Sawama, M. Takubo, Y. Monguchi, N. Krause, H. Sajiki, Org. Lett. 2013, 15, 5282 – 5285; d) Y. Sawama, Y. Shishido, T. Kawajiri, R. Goto, Y. Monguchi, H. Sajiki, Chem. Eur. J. 2014, 20, 510 – 516; e) Y. Sawama, R. Goto, S. Nagata, Y. Shishido, Y. Monguchi, H. Sajiki, Chem. Eur. J. 2014, 20, 2631 – 2636. [14] FeCl3 was used in Friedel–Crafts reactions toward various substrates. For examples, see: a) I. Iovel, K. Mertins, J. Kischel, A. Zapf, M. Beller, Angew. Chem. Int. Ed. 2005, 44, 3913 – 3917; Angew. Chem. 2005, 117, 3981 – 3985; b) B.-Q. Wang, S.-K. Xiang, Z.-P. Sun, B.-T. Guan, P. Hu, K.-Q. Zhao, Z.-J. Shi, Tetrahedron Lett. 2008, 49, 4310 – 4312; c) D. Stadler, T. Bach, Angew. Chem. Int. Ed. 2008, 47, 7557 – 7559; Angew. Chem. 2008, 120, 7668 – 7670. [15] Substrate bearing H atom on the bridge-head was transformed into the 1-naphthol derivative without the nucleophilic addition of 2 a by the rapid 1,2-hydride shift by the stable tert-carbocation intermediate.
6,7-Dimethoxy-4-pentyl-1-triethylsilyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 ad): Pale-yellow oil; IR (ATR): n˜ = 2951, 2872, 1605, 1584, 1510, 1464, 1411, 1333, 1256, 1221, 1202, 1155, 1122, 1062, 1033 cm 1; 1H NMR (500 MHz, CDCl3): d = 7.43 (s, 1 H), 7.39 (s, 1 H), 7.23 (s, 1 H), 6.25 (s, 2 H), 4.01 (s, 6 H), 3.90 (s, 3 H), 3.65 (s, 6 H), 2.77–2.73 (m, 2 H), 1.54 (br s, 2 H), 1.26–1.21 (m, 4 H), 1.02–0.95 (m, 15 H), 0.81 ppm (t, J = 6.5 Hz, 3 H); 13C NMR (125 MHz, CDCl3): d = 160.3, 158.5, 148.0, 147.9, 138.0, 137.3, 133.2, 129.5, 128.8, 127.6, 113.2, 108.0, 104.5, 90.6, 55.6, 55.6, 55.4, 55.3, 32.3, 30.4, 29.3, 22.4, 14.0, 7.8, 4.6 ppm; ESI-HRMS m/z: calcd for C32H46O5SiNa: 561.3007; found: 561.3008 [M+Na] + . 6,7-Dibromo-4-methyl-1-triethylsilyl-3-(2,4,6-trimethoxyphenyl)naphthalene (3 ae): Colorless solid; m.p. 57–61 8C; IR (ATR): n˜ = 2953, 1605, 1585, 1455, 1412, 1333, 1223, 1203, 1155, 1124, 1064, 1039 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.38 (s, 1 H), 8.34 (s, 1 H), 7.47 (s, 1 H), 6.26 (s, 2 H), 3.88 (s, 3 H), 3.69 (s, 6 H), 2.38 (s, 3 H), 0.99–0.94 ppm (m, 15 H); 13C NMR (125 MHz, CDCl3): d = 160.9, 158.3, 140.5, 136.7, 134.0, 133.3, 132.7, 131.7, 130.5, 130.0, 120.8, 120.7, 111.7, 90.7, 55.7, 55.4, 16.2, 7.6, 4.5 ppm; ESI-HRMS m/z: calcd for C26H31O3Br2Si: 577.0415; found: 577.0432 [M H] . Characteristic data of some products (7–11 and 13 a–13 i) were described in the Supporting Information.
Acknowledgements This work was partially supported by Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science (JSPS) and Takeda Science Foundation. Keywords: arenes · biaryls · Friedel–Crafts reaction · iron catalyst · ring-opening reaction [1] a) R. E. Mewshaw, R. J. Edsall, Jr., C. Yang, E. S. Manas, Z. B. Xu, R. A. Henderson, J. C. Keith, Jr., H. A. Harris, J. Med. Chem. 2005, 48, 3953 – 3979; b) S. Song, H. Lee, Y. Jin, Y. M. Ha, S. Bae, H. Y. Chung, H. Suh, Bioorg. Med. Chem. Lett. 2007, 17, 461 – 464; c) C. Maurin, C. Lion, F. Bailly, N. Touati, H. Vezin, G. Mbemba, J. F. Mouscadet, Z. Debyser, M. Witvrouw, P. Cotelle, Bioorg. Med. Chem. 2010, 18, 5194 – 5201; d) M. Wetzel, S. Marchais-Oberwinkler, E. Perspicace, G. Mçller, J. Admski, R. W. Hartmann, J. Med. Chem. 2011, 54, 7547 – 7557; e) A. S. Kumar, M. A. Reddy, N. Jain, C. Kishor, T. R. Murthy, D. Ramesh, B. Supriya, A. Addlagatta, S. V. Kalivendi, B. Sreedhar, Eur. J. Med. Chem. 2013, 60, 305 – 324. [2] S. Kumar, W. Namkung, A. S. Verkman, P. K. Sharma, Bioorg. Med. Chem. 2012, 20, 4237 – 4244. [3] a) T. Vasiljevik, L. N. Franks, B. M. Ford, J. T. Douglas, P. L. Prather, W. E. Fantegrossi, T. E. Prisinzano, J. Med. Chem. 2013, 56, 4537 – 4550; b) G. Pereira, E. M. S. Castanheira, P. M. T. Ferreira, M.-J. R. P. Queiroz, Eur. J. Org. Chem. 1997, 97, 464 – 475. [4] a) J. Roncali, Chem. Rev. 1997, 97, 173 – 206; b) H. Meng, Z. Bao, A. J. Lovinger, B.-C. Wang, A. M. Mujsce, J. Am. Chem. Soc. 2001, 123, 9214 – 9215; c) M. Mushrush, A. Facchetti, M. Lefenfeld, H. E. Katz, T. J. Marks, J. Am. Chem. Soc. 2003, 125, 9414 – 9423; d) M. M. M. Raposo, A. M. C. Fonseca, G. Kirsch, Tetrahedron 2004, 60, 4071 – 4078; e) J. A. Merlo, C. R. Newman, C. P. Gerlach, T. W. Kelley, D. V. Muyres, S. E. Fritz, M. F. Toney, C. D. Frisbie, J. Am. Chem. Soc. 2005, 127, 3997 – 4009; f) N. Hergu, P. Frre, Org. Biomol. Chem. 2007, 5, 3442 – 3449; g) H. Tian, J. Shi, B. He, N. Hu, S. Dong, D. Yan, J. Zhang, Y. Geng, F. Wang, Adv. Funct. Mater. 2007, 17, 1940 – 1951; h) E. Bey, S. Marchais-Oberwinker, R. Werth, M. Negri, Y. A. Al-Sound, P. Kruchten, A. Oster, M. Frotscher, B. Birk, R. W. Hartmann, J. Med. Chem. 2008, 51, 6725 – 6739; i) D. Urselmann, D. Antovic, T. J. J. Mller, Beilstein J. Org. Chem. 2011, 7, 1499 – 1503. Chem. Eur. J. 2014, 20, 1 – 9
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[16] 2,4-Dimethyl-1-naphthanol (4 a) could be obtained without the nucleophilic attack of 2 a as shown below. [17] Scale-up reaction using 1 a (5.2 mmol) with 2 a (2 equiv) provided 3 a in quantitative yield.
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Communication corresponding benzylic cation (F). Therefore, 3 h and 3 i were regioselectively obtained.
[18] Similar results were obtained by the optimization of the reaction conditions using 1 a. In the reaction of 1 a, 2 equiv of arene were sufficient to give the desired biaryl (3 k). See the Supporting Information. [19] The principal regioisomers are depicted in Scheme 3. When the formation of the corresponding regioisomer could be detected, the results are shown in the Supporting Information. [20] The reaction of 1 a with toluene or o-xylene gave only 4 a, which was produced by the rearrangement of the methyl group without the nucleophilic attack of arene. See ref. [16]. [21] The electron-donating methoxy group can stabilize the generated cation intermediate (E), and the phenyl group of 1 i also stabilizes the
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[22] Bromination of the aromatic silyl group by using NBS has been reported, see: T. Ozawa, T. Kurahashi, S. Matsubara, Org. Lett. 2011, 13, 5390 – 5393. [23] The reaction mechanism is unclear. [24] The reaction of 3 u by using 2.2 equivalents of NBS gave a mixture of 10 (22 %) and 11 (65 %). Received: October 7, 2014 Published online on && &&, 0000
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COMMUNICATION & Organic Synthesis Y. Sawama,* S. Asai, T. Kawajiri, Y. Monguchi, H. Sajiki* && – &&
Biaryl and heterobiaryl compounds are the important frameworks in the fields of pharmaceutical and materials chemistry. An efficient synthesis of various naphthalene-linked arenes and hetero-
Chem. Eur. J. 2014, 20, 1 – 9
arenes as biaryls and heterobiaryls has been accomplished by FeCl3-catalyzed Friedel–Crafts reactions accompanied by the ring-opening of 1,4-epoxy-1,4-dihydronaphthalenes (see scheme).
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Biaryl Synthesis by Ring-Opening Friedel–Crafts Arylation of 1,4-Epoxy1,4-dihydronaphthalenes Catalyzed by Iron Trichloride
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Biaryl Synthesis by Ring-Opening Friedel–Crafts Arylation of 1,4Epoxy-1,4-dihydronaphthalenes Catalyzed by Iron Trichloride Yoshinari Sawama,* Shota Asai, Takahiro Kawajiri, Yasunari Monguchi, and Hironao Sajiki*[a] catalyzed C H activation of arenes bearing pyridine moieties at the ortho-positions as the directing groups,[10] the variety (substituent diversity at the aromatic rings) of the obtained products is relatively limited. Meanwhile, we have recently reported a Lewis acid catalyzed ring-opening functionalization method of the 1,4-epoxy moiety of 1 using allyl, azido, and cyano nucleophiles.[11] In this reaction, the substitutions (R1, R2 ; Scheme 1) at the bridge-head positions of 1 play a key role in
Abstract: Biaryl and heterobiaryl compounds are important frameworks across a range of fields including pharmaceutical and functional material chemistries. We have accomplished the efficient synthesis of various naphthalene-linked arenes and heteroarenes as biaryls and heterobiaryls by the FeCl3-catalyzed Friedel-Crafts reactions accompanied by the ring-opening of the 1,4-epoxy moiety of 1,4-epoxy-1,4-dihydronaphthalenes. Especially, it is noteworthy that 1-silylated substrates were regioselectively transformed to the 3-aryl-1-silylnaphthalenes and the double Friedel–Crafts reactions using thiophene derivatives could directly produce the corresponding bisnaphthlated thiophene derivatives.
Introduction Biaryls and heterobiaryls possessing naphthalene-linked arenes[1] and heteroarenes, such as benzofurans[2] or indoles,[3] are important in the pharmaceutical sciences, and p-conjugated polyarenes composed of a continuous arene and thiophene sequence, such as bis-arylated thiophenes, are also attractive for use in the field of pharmaceuticals[4g] as well as the materials[4a–f,h] sciences. 1,4-Epoxy-1,4-dihydronaphthalenes (1), which are easily prepared from various benzynes and furanes, are widely utilized to construct the corresponding naphthalene derivatives by various functionalizations accompanied by the ring-opening of the 1,4-epoxy moieties.[5] Although many nucleophilic arene-introduction methods into 1 by using a stoichiometric aryl Grignard[6a–d] or aluminum[6e] reagent and the transition-metal (Pd, Ni and Rh)-catalyzed coupling reactions using aryl halides[7] and indole[8] have been developed to produce 1-hydroxy-2-aryl-1,2-dihydronaphthalenes, the production of sludges (e.g., metals and acids) and the use of scarce and precious transition metals are still problematic issues. Although the direct biaryl (2-aryl-naphthalene derivatives) syntheses were also accomplished by the Pd-catalyzed dimerization of 1,[9a] Ni-catalyzed coupling with 1 and aryl iodides,[9b,c] and Rh-
Scheme 1. Ring-opening Friedel–Crafts arylation of 1,4-disubstituted 1,4epoxy-1,4-dihydronaphthalenes.
stabilizing the cation intermediate (A)[12] generated by the acid-induced ring-opening of 1. Furthermore, we demonstrated that an inexpensive and safe FeCl3 effectively catalyzed the cleavage of various benzylic C O bonds[13] and Friedel–Craftstype reaction using arenes as green aromatic sources without harmful byproducts.[13d, 14] We now report an efficient biaryl and heterobiaryl synthetic method by the FeCl3-catalyzed ringopening Friedel–Crafts arylation of 1,4-disubstituted 1,4-epoxy1,4-dihydronaphthalenes (1) accompanied by the production of only water as a byproduct, and a novel regioselective cleavage method of the 1,4-epoxy moiety of unsymmetrical substrates (1) possessing a silyl substituent as R1 and the subsequent arene introduction (Scheme 1).
Results and Discussion As expected, the FeCl3-catalyzed (5 mol %) reaction of 1,4-dimethyl-1,4-epoxy-1,4-dihydronaphthalene (1 a) as a simple substrate with 1,3,5-trimethoxybenzene (2 a: 2 equiv) smoothly proceeded in CH2Cl2 at room temperature for 10 min to give the desired biaryl product (3 a) in quantitative yield, and 2,4-dimethyl-1-naphthanol (4 a) resulting from the rearrangement[12e]
[a] Dr. Y. Sawama, S. Asai, T. Kawajiri, Dr. Y. Monguchi, Prof. Dr. H. Sajiki Laboratory of Organic Chemistry, Gifu Pharmaceutical University 1-25-4 Daigakunishi, Gifu 501-1196 (Japan) E-mail: [email protected] [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201405558. Chem. Eur. J. 2014, 20, 1 – 9
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Communication of the methyl group was never obtained [Equation (1)].[15–17] Furthermore, the site-selective cleavage of the 1,4-epoxy moiety of unsymmetrical 1-silyl-4-methyl substrates (1 b–d) was next investigated due to the potential of the subsequent functionalization of the aromatic silyl group. Consequently, the 1-silylated 3-arylnaphthalene derivatives (3 b–d) were regioselectively obtained by the use of the trimethylsilyl (TMS), triethylsilyl (TES), or tert-butyldimethylsilyl (TBS)-substituted substrate.
Table 1. Optimization for the Friedel–Crafts arylation of 1-triethylsilyl-4methyl-1,4-epoxy-1,4-dihydronaphthalene (1 c) and trimethoxybenzene (2 a).
Entry
Acid
Solvent
t
Yield [%] 3c 6
1 2[a] 3 4 5 6 7 8 9 10 11 12
FeCl3 FeCl3 FeBr3 AuCl3 BF3·Et2O TMSOTf FeCl2·4 H2O TFA FeCl3 FeCl3 FeCl3 FeCl3
CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CHCl3 toluene 1,4-dioxane THF
10 min 10 min 10 min 10 min 10 min 10 min 24 h 24 h 8h 24 h 24 h 24 h
76 92 60 77 33 0 no no 39 25 no no
0 0 26 0 0 16 reaction reaction 0 0 reaction reaction
[a] 3 equiv of 2 a were used.
biaryl (6) was also obtained as a byproduct by the cleavage of the aromatic silyl bond due to the strong acidity of FeBr3 or HBr generated in association with the reaction progress (entry 3). Other Lewis acids (e.g., BF3·Et2O, TMSOTf, and FeCl2·4 H2O) and trifluoroacetic acid (TFA) as a Brønsted acid were inappropriate catalysts for the present reaction (entries 5–8). The reaction in solvents, such as CHCl3, toluene, 1,4dioxane, and THF, resulted in poor yields (entries 9–12). We chose the easily accessible and inexpensive FeCl3 as the suitable catalyst in CH2Cl2 and the further increment of the usage of 2 a (3 equiv) could improve the reaction efficiency to provide 3 c in 92 % isolated yield (entry 2).[18] The present biaryl synthesis could be applied to various 1,4disubstituted 1,4-epoxy-1,4-dihydronaphthalenes (1; 1,4-dialkyl, 1-phenyl-4-alkyl, 1-silyl-4-alkyl substituents, etc.) and relatively electron-sufficient arenes including heteroarenes at room temperature in a short time (Scheme 3).[19, 20] The 1,4-dimethyl substrates bearing methoxy groups (1 e and f) as an electron-donating group and bromo group (1 g) on the aromatic ring were smoothly reacted with 2 a to give the corresponding biaryls (3 e–g) in excellent yields, respectively. The unsymmetrical substrates possessing methoxy groups (1 h) on the aromatic ring and a phenyl group (1 i) at one of the bridge-head positions were also effectively transformed into the biaryls (3 h and i) with good yields and perfect regioselectivities.[21] 1-Bromo3,5-dimethoxybenzene (2 b), 1,3-dimethoxybenzene (2 c), 1,3dihydroxybenzene (2 d), and 1- or 2-naphthol (2 e, 2 f) also played the role of efficient nucleophiles to form the corresponding biaryls (3 j–o) with moderate to high yields and good regioselectivities. Benzofuran (2 g), pyrrole (2 h), N-methyl pyrrole (2 i), indole (2 j), and N-phenyl indole (2 k) as heteroarenes efficiently promoted the desired reactions to afford the various heterobiaryls (3 p–t), respectively. 1-Triethylsilyl-4-alkyl substituents as 1-silylated substrates (1 c, j–m) underwent the FeCl3-
The Lewis acid induced ring-opening of the 1,4-epoxy moiety of the 1-TES substrate (1 c) can be transformed into two possible cation intermediates (B and C) (Scheme 2). Inter-
Scheme 2. Proposed mechanism.
mediate B is more favorable due to the sterical repulsion between the TES group and Lewis acid coordinated oxygen atom of C. Therefore, the nucleophilic addition of 1,3,5-trimethoxybenzene can proceed at the 3-position of B to generate the biaryl (3 c) accompanied by the subsequent dehydration. The regioisomer (5 c) by the sterically hindered intermediate (C) was never obtained, while a small amount of 4 c was produced as a byproduct by rearrangement of the methyl group to the 3-position of B and the following aromatization of D during the reaction process. As the result of the optimization using 1 c and 2 a (2 equiv), FeCl3 and AuCl3 were found to be efficient catalysts (Table 1, entries 1 and 4). Meanwhile, the use of FeBr3 also gave the desired biaryl (3 c) in moderate yield, although the desilylated &
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Scheme 3. Scope of substrates and arenes. [a] 2 equiv of the arene were used in the reaction of 1 a and 1 e–i, and 3 equiv of the arene were used in the reaction of 1c and 1 j–m unless otherwise noted. [b] Yields of minor regioisomers are depicted in Supporting Information. [c] 5 equiv of arene were used. [d] 10 equiv of arene were used.
catalyzed ring-opening Friedel–Crafts arylation with perfect regioselectivities as shown in Scheme 2 to give the corresponding 1-silyl-3-aryl-naphthalenes (3 u–ae) as highly functionalized biaryls in moderate to high yields. The further chemical modification of the obtained silylated products (3 c and 3 u) were next investigated (Scheme 4). Monobromination of 3 c by using 1.1 equivalents of N-bromosuccinimde (NBS) selectively proceeded at the electron-rich 2,4,6-trimethoxyphenyl ring in preference to the transformation of Ar-TES into Ar-Br to give the monobrominated biaryl
(7) in good yield. Thus, 2.2 equivalents of NBS were necessary to achieve the double bromination of 3 c to provide the desired dibromo biaryls (8).[22] Additionally, the TES functionality of 7 could be converted into Ar H by the use of BBr3 without demethylation of the trimethoxybenzene moiety.[23] A similar monobromination of 3 u could also be accomplished using 1.1 equivalents of NBS to form the monobrominated biaryl (10) in excellent yield, and 1,3-dibromo-5,5-dimethyl hydantoin (DBH, 2.2 equiv) was the more effective reagent for the double bromination of 3 u into 11.[24] Materially useful bis-arylated thiophene derivatives are generally prepared by the stepwise coupling reactions using the modified arene and thiophene derivatives.[4] To the best of our knowledge, there seems to be no direct synthetic procedure between the thiophene and naphthalene derivatives/precursors. Furan, pyrrole, and thiophene are known to react with electrophiles at their 2- and/or 5-positions, which are known to be the more nucleophilc positions of these heterocycles. The FeCl3-catalyzed ring-opening Friedel–Crafts arylation between the 1,4-disubstituted 1,4-epoxy-1,4-dihydronaphthalenes (1) and pyrroles (2 h and i) selectively provided the 2-monoarylated pyrroles (3 q, r, x, and y) as shown in Scheme 3. The reaction using furan derivatives could not be controlled and pro-
Scheme 4. Modification of silylated products (3 c and 3 u). Chem. Eur. J. 2014, 20, 1 – 9
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Communication Experimental Section Typical procedure for Equations 1 and 2, Table 1, Schemes 3, and 4, and the synthesis of 13 h and 13 i (Scheme 5) An arene (2: 0.4, 0.6, or 1.0 mmol) and FeCl3 (0.01 mmol: 5 mol % of the substrate) were added to a solution of the 1,4-disubstituted 1,4-epoxy-1,4-dihydronaphthalene (1: 0.2 mmol) in CH2Cl2 (1 mL) and the mixture was stirred at room temperature under argon. After an adequate reaction time, the mixture was quenched with water and extracted with additional CH2Cl2. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel-column chromatography to give the biaryl (3).
Typical procedure for the synthesis of 13 b–f (Scheme 5) Thiophene (12: 0.2 mmol) and FeCl3 (0.01 mmol: 5 mol % of the substrate) were added to a solution of a 1,4-disubstituted 1,4epoxy-1,4-dihydronaphthalene (1: 0.6 mmol) in CH2Cl2 (1 mL) and the mixture was stirred at room temperature under argon. After an adequate reaction time, the mixture was quenched with water and diluted with cold hexane. The resulting precipitate was filtrated and washed with cold hexane to give the arylated thiophene product (13) (13 a and g were purified by silica-gel column chromatography). 1,4-Dimethyl-2-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 a): Colorless solid; m.p. 135–139 8C; IR (ATR): n˜ = 3066, 2997, 2936, 2836, 2176, 1607, 1584, 1502, 1463, 1412, 1385, 1333, 1223, 1203, 1183, 1156, 1123, 1058, 1037 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.10– 8.08 (m, 1 H), 8.00–7.99 (m, 1 H), 7.51–7.49 (m, 2 H), 7.12 (s, 1 H), 6.26 (s, 2 H), 3.89 (s, 3 H), 3.69 (s, 6 H), 2.66 (s, 3 H), 2.39 ppm (s, 3 H); 13 C NMR (100 MHz, CDCl3): d = 160.6, 158.5, 133.0, 132.1, 131.4, 130.9, 130.7, 130.4, 125.1, 125.0, 124.8, 124.6, 90.8, 55.8, 55.4, 19.4, 15.8 ppm; ESI-HRMS: m/z: calcd for C20H23O3 : 323.1642; found 323.1638 [M+H] + .
Scheme 5. Double Friedel–Crafts reaction of thiophene derivatives. [a] 5 equiv of thiophene derivative were used for 1.
duced a complex mixture. On the other hand, thiophene (12 a) effectively reacted with 1 a at both the 2- and 5-positions of 12 a to directly give the 2,5-bisnaphthly thiophene derivative (13 a) by the use of an excess amount of 1 a (3 equiv) (Scheme 5). Intriguingly, various thiophene derivatives, such as 2,2’-bithiophene (12 b), 2,2’:5,2”-terthiophene (12 c), 3,4-ethylenedioxythiophene (12 d), and thieno[3,2-b]thiophene (12 e), also underwent the efficient bis-arylation with 1 a and 1 g to give the corresponding polyarenes (13 b–f) in good yields. The reaction of 1-triethylsilyl-4-methyl-1,4-epoxy-1,4-dihydronaphthalenes (1 c) with thiophene (12 a) regioselectively gave the mononaphthylated thiophene (13 g), although the reason why the second naphthylation at the 5-position of 13 g did not take place is unclear. The Friedel-Crafts reaction is generally hampered by the use of halogenated arenes. Nevertheless, the 2-bromo and iodo thiophenes (12 f and g) could be effectively converted into the corresponding 2-naphthyl-5-halo thiophenes (13 h and i) as heterobiaryl products, respectively. The aromatic halogens of 13 f, h and i can be useful for further chemical transformation into various polyarene derivatives.
4-Methyl-3-(2’,4’,6’-trimethoxyphenyl)-1-trimethylsilylnaphthalene (3 b): Pale-yellow oil; IR (ATR): n˜ = 2953, 2836, 1605, 1582, 1499, 1454, 1436, 1411, 1359, 1333, 1249, 1222, 1183, 1152, 1123, 1061, 1037 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.13–8.09 (m, 2 H), 7.49–7.46 (m, 3 H), 6.27 (s, 2 H), 3.88 (s, 3 H), 3.69 (s, 6 H), 2.43 (s, 3 H), 0.43 ppm (s, 9 H); 13C NMR (125 MHz, CDCl3): d = 160.7, 158.5, 137.5, 136.2, 134.9, 134.1, 133.0, 130.3, 128.6, 125.3, 124.8, 124.7, 112.6, 90.8, 55.7, 55.4, 16.2, 0.4 ppm; ESI-HRMS: m/z: calcd for C23H29O3Si: 381.1880; found: 381.1894 [M+H] + . 4-Methyl-1-triethylsilyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 c): Pale-yellow oil; IR (ATR): n˜ = 2951, 2873, 1605, 1583, 1498, 1454, 1412, 1333, 1222, 1202, 1152, 1124, 1061, 1038 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.11 (d, J = 8.0 Hz, 1 H), 8.08 (d, J = 6.4 Hz, 1 H), 7.47–7.44 (m, 2 H), 7.46 (s, 1 H), 6.27 (s, 2 H), 3.88 (s, 3 H), 3.67 (s, 6 H), 2.44 (s, 3 H), 0.98 ppm (s, 15 H); 13C NMR (100 MHz, CDCl3): d = 160.7, 158.6, 139.1, 136.9, 134.7, 133.0, 130.9, 130.2, 128.5, 125.3, 124.8, 124.6, 112.8, 90.9, 55.7, 55.4, 16.3, 7.7, 4.7 ppm; ESIHRMS: m/z: calcd for C26H34O3SiNa: 445.2169; found: 445.2170 [M+Na] + .
Conclusion We have achieved the efficient synthesis of biaryl (naphthalene-benzene/naphthalene types), heterobiaryl (naphthalenepyrrole/thiophene/benzofuran/indole types) and polyarenes (the continuous naphthalene-thiophene sequence) by the ironcatalyzed Friedel–Crafts reaction accompanied by the ringopening of 1,4-epoxy moieties in various 1,4-disubstituted 1,4epoxy-1,4-dihydronaphthalenes. The present method requires inexpensive and safe FeCl3 and only water is generated as a byproduct. Additionally, the ring-opening site of the 1,4-epoxy moiety could be controlled by the silyl substitution at the bridge-head position to provide the highly-functionalized biaryl derivatives. &
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1-tert-Butyldimethylsilyl-4-methyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 d): Pale-yellow oil; IR (ATR): n˜ = 2952, 2927, 2853, 1605, 1583, 1498, 1462, 1436, 1411, 1359, 1333, 1252, 1222, 1202, 1183, 1152, 1125, 1061, 1038 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.13 (d, J = 7.5 Hz,1 H), 8.11 (d, J = 7.0 Hz, 1 H),7.49–7.44 (m, 3 H), 6.28 (s, 2 H), 3.90 (s, 3 H), 3.69 (s, 6 H), 2.45 (s, 3 H), 0,95 (s, 9 H), 0.47 ppm (s, 6 H); 13C NMR (125 MHz, CDCl3): d = 160.7, 158.6, 139.9, 137.1, 134.9, 133.0, 132.0, 130.0, 129.8, 125.1, 124.7, 124.5, 112.7,
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Communication 90.8, 55.7, 55.4, 27.2, 18.1, 16.3, 2.7 ppm; ESI-HRMS: m/z: calcd for C26H35O3Si: 423.2350; found: 423.2350 [M+H] + .
2-(2’,4’-Dimethoxyphenyl)-1,4-dimethylnaphthalene (3 k): Colorless solid; m.p. 120–126 8C; IR (ATR): n˜ = 3067, 2997, 2934, 2833, 1608, 1579, 1505, 1462, 1437, 1414, 1384, 1300, 1280, 1258, 1228, 1205, 1156, 1118, 1032 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.10 (dd, J = 6.8, 2.0 Hz, 1 H), 8.01 (dd, J = 6.8, 2.0 Hz, 1 H), 7.54–7.51 (m, 2 H), 7.19 (s, 1 H), 7.12 (d, J = 9.2 Hz, 1 H), 6.60–6.58 (m, 2 H), 3.88 (s, 3 H), 3.74 (s, 3 H), 2.67 (s, 3 H), 2.45 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 160.2, 157.7, 134.7, 132.9, 132.0, 131.7, 131.3, 130.5, 129.7, 125.5, 125.0, 124.5, 124.3, 104.2, 104.1, 98.6, 55.5, 55.4, 19.3, 16.0 ppm; ESI-HRMS m/z: calcd for C20H21O2 : 293.1536; found: 293.1527 [M+H] + .
5,8-Dimethoxy-1,4-dimethyl-2-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 e): Colorless solid; m.p. 161–163 8C; IR (ATR): n˜ = 2933, 2834, 1606, 1583, 1501, 1453, 1411, 1380, 1334, 1255, 1224, 1203, 1154, 1122, 1056, 1033 cm 1; 1H NMR (500 MHz, CDCl3): d = 6.98 (s, 1 H), 6.75–6.70 (m, 2 H), 6.24 (s, 2 H), 3.87 (s, 3 H), 3.86 (s, 3 H), 3.84 (s, 3 H), 3.68 (s, 6 H), 2.81 (s, 3 H), 2.53 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 160.4, 158.4, 153.0, 152.8, 133.1, 132.4, 131.8, 131.2, 128.0, 127.1, 113.2, 106.1, 105.4, 90.7, 56.3, 56.1, 55.9, 55.3, 25.5, 20.4 ppm; ESI-HRMS m/z: calcd for C23H26O5Na: 405.1672; found: 405.1664 [M+Na] + .
5,8-Dimethoxy-2-(2’,4’-dimethoxyphenyl)-1,4-dimethylnaphthalene (3 l): Colorless solid; m.p. 144–146 8C; IR (ATR): n˜ = 2934, 2833, 1609, 1577, 1507, 1455, 1380, 1301, 1256, 1232, 1207, 1158, 1139, 1113, 1034 cm 1; 1H NMR (500 MHz, CDCl3): d = 7.10 (d, J = 8.5 Hz, 1 H), 7.05 (s, 1 H), 6.78 (d, J = 8.8 Hz, 1 H), 6.73 (d, J = 8.8 Hz, 1 H), 6.58–6.56 (m, 2 H), 3.87 (s, 3 H), 3.86 (s, 3 H), 3.85 (s, 3 H), 3.74 (s, 3 H), 2.82 (s, 3 H), 2.56 ppm (s, 3 H); 13C NMR (125 MHz, CD2Cl2): d = 160.4, 157.9, 152.9, 152.6, 136.8, 132.5, 131.6, 131.5, 131.1, 128.0, 126.9, 124.8, 106.3, 105.5, 104.4, 98.4, 56.1, 56.0, 55.6, 55.5, 25.3, 20.8 ppm; ESI-HRMS: m/z: Calcd for C22H25O4 : 353.1747; found: 353.1736 [M+H] + .
6,7-Dimethoxy-1,4-dimethyl-2-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 f): Light-red solid; m.p. 216–219 8C; IR (ATR): n˜ = 2936, 2834, 1605, 1584, 1506, 1456, 1414, 1333, 1257, 1224, 1202, 1159, 1144, 1122, 1051, 1036 cm 1; 1H NMR (400 MHz, CDCl3): d = 7.32 (s, 1 H), 7.22 (s, 1 H), 7.01 (s, 1 H), 6.25 (s, 2 H), 4.02 (s, 3 H), 4.01 (s,3 H), 3.88 (s, 3 H), 3.68 (s, 6 H), 2.60 (s, 3 H), 2.33 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 160.5, 158.5, 148.5, 148.5, 130.0, 129.5, 129.1, 128.9, 128.5, 127.7, 112.7, 104.3, 103.7, 90.7, 55.8, 55.8, 55.7, 55.4, 19.7, 16.1 ppm; ESI-HRMS m/z: calcd for C23H26O5Na: 405.1672; found: 405.1663 [M+Na] + .
5-(1’,4’-Dimethyl-2’-naphthyl)-1,3-benzenediol (3 m): Colorless solid; m.p. 174–177 8C; IR (ATR): n˜ = 3353, 2921, 1619, 1596, 1509, 1458, 1384, 1301, 1236, 1153, 1100, 1029 cm 1; 1H NMR (500 MHz, CD3OD): d = 8.13–8.11 (m, 1 H), 8.05–8.03 (m, 1 H), 7.56–7.52 (m, 2 H), 7.18 (s, 1 H), 6.93 (d, J = 8.0, 1 H), 6.45–6.42 (m, 2 H), 2.68 (s, 3 H), 2.48 ppm (s, 3 H); 13C NMR (125 MHz, [D6]DMSO): d = 157.6, 155.3, 135.6, 132.5, 131.4, 131.3, 130.5, 130.0, 129.6, 125.6, 125.0, 124.8, 124.3, 120.0, 106.3, 102.5, 18.9, 15.9 ppm; ESI-HRMS m/z: calcd for C18H16O2Na: 287.1043; found: 287.1045 [M+Na] + .
6,7-Dibromo-1,4-dimethyl-2-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 g): Colorless solid; m.p. 176–180 8C; IR (ATR): n˜ = 2936, 2835, 1605, 1583, 1499, 1462, 1412, 1381, 1333, 1224, 1202, 1158, 1142, 1123, 1065, 1038 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.36 (s, 1 H), 8.25 (s, 1 H), 7.15 (s, 1 H), 6.25 (s, 2 H), 3.89 (s, 3 H), 3.70 (s, 6 H), 2.61 (s, 3 H), 2.34 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 161.2, 158.5, 133.4, 132.6, 132.5, 132.2, 131.6, 130.5, 130.2, 129.5, 121.5, 121.2, 111.7, 90.9, 56.0, 55.6, 19.5, 16.0 ppm; ESI-HRMS: m/z: calcd for C21H19O3Br2 : 476.9706; found: 476.9705 [M H] .
1-(1’,4’-Dimethyl-2’-naphthyl)-2-naphthol (3 n): Pale-orange solid; m.p. 176–178 8C; IR (ATR): n˜ = 3519, 3062, 2919, 1619, 1597, 1512, 1462, 1400, 1380, 1342, 1262, 1215, 1187, 1150, 1133, 1028 cm 1; 1 H NMR (500 MHz, CD2Cl2): d = 8.16–8.14 (m, 1 H), 8.12–8.10 (m, 1 H), 7.85–7.83 (m, 2 H), 7.65–7.60 (m, 2 H), 7.33–7.26 (m, 3 H), 7.20– 7.18 (m, 2 H), 5.01 (br s, 1 H), 2.69 (s, 3 H), 2.35 ppm (s, 3 H); 13C NMR (125 MHz, [D6]DMSO): d = 152.0, 133.5, 132.9, 132.8, 131.9,131.3, 130.8, 130.0, 128.7, 128.1, 127.9, 126.3, 125.8, 125.5, 124.9, 124.6, 124.2, 122.6, 121.0, 118.4, 19.0, 15.6 ppm; ESI-HRMS m/z: calcd for C22H19O: 297.1285; found: 297.1289 [M H] .
5,7-Dimethoxy-1,4-dimethyl-2-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 h): Light-red solid; m.p. 164–167 8C; IR (ATR): n˜ = 2934, 1606, 1583, 1510, 1454, 1407, 1333, 1261, 1223, 1204, 1179, 1149, 1122, 1083, 1058, 1036 cm 1; 1H NMR (400 MHz, CDCl3): d = 6.90 (d, J = 2.2 Hz, 1 H), 6.87 (s, 1 H), 6.49 (d, J = 2.2 Hz, 1 H), 6.25 (s, 2 H), 3.92 (s, 3 H), 3.88 (s, 3 H), 3.88 (s, 3 H), 3.68 (s, 6 H), 2.80 (s, 3 H), 2.29 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 160.5, 159.9, 158.4, 157.2, 135.9, 132.0, 131.8, 129.8, 129.6, 120.6, 112.7, 97.5, 96.1, 90.7, 55.8, 55.4, 55.3, 55.1, 25.2, 16.7 ppm; ESI-HRMS: m/z: calcd for C23H26O5Na: 405.1672; found: 405.1676 [M+Na] + .
2-(1’,4’-Dimethyl-2’-naphthyl)-1-naphthol (3 o): Dark-yellow solid; m.p. 145–147 8C; IR (ATR): n˜ = 3524, 3055, 2941, 1598, 1570, 1505, 1438, 1382, 1279, 1237, 1196, 1141, 1082, 1025 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.30–8.29 (m, 1 H), 8.17–8.15 (m, 1 H), 8.10– 8.09 (m, 1 H), 7.88–7.86 (m, 1 H), 7.64–7.62 (m, 2 H), 7.54–7.51 (m, 3 H), 7.32–7.25 (m, 2 H), 2.72 (s, 3 H), 2.54 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 147.9, 134.2, 133.4, 133.1, 132.5, 132.3, 131.6, 129.0, 127.9, 127.5, 126.3, 126.2, 126.0, 125.5, 125.1, 124.7, 124.0, 122.3, 121.6, 119.8, 19.3, 15.8 ppm; ESI-HRMS m/z: calcd for C22H18ONa: 321.1250; found: 321.1260 [M+Na] + .
4-Methyl-1-phenyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 i): Colorless solid; m.p. 129–132 8C; IR (ATR): n˜ = 2937, 1607, 1581, 1498, 1454, 1411, 1331, 1222, 1204, 1181, 1154, 1121, 1059, 1033 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.14 (d, J = 8.8 Hz, 1 H), 7.95 (d, J = 8.4 Hz, 1 H), 7.55–7.38 (m, 8 H), 6.26 (s, 2 H), 3.89 (s, 3 H), 3.71 (s, 6 H), 2.45 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 160.7, 158.5, 141.2, 137.2, 133.1, 133.0, 131.0, 130.9, 130.7, 130.4, 128.0, 126.8, 126.4, 125.3, 125.1, 124.8, 112.1, 90.6, 55.8, 55.4, 16.1 ppm; ESI-HRMS: m/z: calcd for C26H24O3Na: 407.1618; found: 407.1599 [M+Na] + .
2-(1’,4’-Dimethyl-2’-naphthyl)benzofuran (3 p): Colorless solid; m.p. 86–88 8C; IR (ATR): n˜ = 3067, 2921, 1572, 1510, 1452, 1386, 1302, 1258, 1207, 1166, 1010 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.20–8.17 (m, 1 H), 8.05–8.02 (m, 1 H), 7.68–7.57 (m, 5 H), 7.34–7.27 (m, 2 H), 6.90 (s, 1 H), 2.87 (s, 3 H), 2.73 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 156.4, 154.7, 133.2, 132.7, 132.3, 130.8, 129.1, 127.0, 126.8, 126.1, 126.0, 125.4, 124.6, 124.1, 122.8, 120.9, 111.2, 106.2, 19.4, 16.3 ppm; ESI-HRMS m/z: calcd for C20H17O: 273.1274; found: 273.1273 [M+H] + .
2-(2’-Bromo-4’,6’-dimethoxyphenyl)-1,4-dimethylnaphthalene (3 j): Colorless solid; m.p. 156–158 8C; IR (ATR): n˜ = 2936, 1600, 1560, 1490, 1457, 1434, 1405, 1301, 1266, 1210, 1153, 1129, 1034 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.11–8.10 (m, 1 H), 8.04– 8.02 (m, 1 H), 7.54–7.53 (m, 2 H), 7.05 (s, 1 H), 6.86 (s, 1 H), 6.53 (s, 1 H), 3.86 (s, 3 H), 3.67 (s, 3 H), 2.68 (s, 3 H), 2.37 ppm (s, 3 H); 13 C NMR (125 MHz, CDCl3): d = 160.0, 158.6, 133.8, 132.8, 132.3, 131.5, 131.0, 129.2, 125.4, 125.2, 125.2, 125.1, 125.0, 124.7, 108.5, 98.2, 55.9, 55.6, 19.4, 15.5 ppm; ESI-HRMS: m/z: calcd for C20H19O2BrNa: 393.0461; found: 393.0463 [M+Na] + . Chem. Eur. J. 2014, 20, 1 – 9
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2-(1’,4’-Dimethyl-2’-naphthyl)-1H-pyrrole (3 q): Pale-purple solid; m.p. 125–128 8C; IR (ATR) cm 1: n˜ = 3424, 3069, 2943, 1604, 1510,
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Communication 1452, 1411, 1382, 1116, 1095, 1029; 1H NMR (500 MHz, CDCl3): d = 8.31 (br s, 1 H), 8.13–8.10 (m, 1 H), 8.02–8.00 (m, 1 H), 7.59–7.51 (m, 2 H), 7.35 (s, 1 H), 6.94–6.92 (m, 1 H), 6.37–6.36 (m, 1 H), 2.75 (s, 3 H), 2.68 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 133.3, 132.2, 132.1, 131.8, 129.7, 129.1, 128.0, 125.9, 125.3, 125.1, 124.5, 118.0, 109.4, 109.1, 19.3, 16.7 ppm; ESI-HRMS m/z: calcd for C16H16N: 222.1277; found: 222.1289 [M+H] + .
CDCl3): d = 148.0, 137.3, 136.8, 134.9, 134.6, 134.1, 132.9, 131.9, 128.6, 128.0, 127.5, 126.4, 126.0, 125.8, 125.5, 125.3, 123.9, 122.3, 121.7, 119.9, 16.2, 7.7, 4.5 ppm; ESI-HRMS m/z: calcd for C27H29OSi: 397.1993; found: 397.1987 [M H] . 2-(4’-Methyl-1’-triethysilyl-3’-naphthyl)-1H-pyrrole (3 x): Colorless solid; m.p. 76–78 8C; IR (ATR): n˜ = 3433, 2951, 2872, 1505, 1456, 1415, 1357, 1235, 1113, 1091, 1002 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.29 (br s, 1 H), 8.13 (d, J = 8.0 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 1 H), 7.65 (s, 1 H), 7.56–7.46 (m, 2 H), 6.96–6.94 (m, 1 H), 6.39–6.37 (m, 2 H), 2.76 (s, 3 H), 1.02–0.94 ppm (m, 15 H); 13C NMR (125 MHz, CDCl3): d = 136.5, 136.0, 133.1, 133.1, 132.5, 132.4, 129.5, 128.4, 125.7, 125.4, 125.2, 118.0, 109.4, 109.2, 16.5, 7.7, 4.5 ppm; ESI-HRMS m/z: calcd for C21H26NSi: 320.1840; found: 320.1842 [M H] .
N-Methyl-2-(1’,4’-dimethyl-2’-naphthyl)pyrrole (3 r): Colorless oil; IR (ATR): n˜ = 2919, 1601, 1483, 1442, 1406, 1382, 1295, 1265, 1231, 1086, 1028 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.10–8.08 (m, 1 H), 8.04–8.02 (m, 1 H), 7.57–7.55 (m, 2 H), 7.24 (s, 1 H), 6.74 (s, 1 H), 6.26–6.25 (m, 1 H), 6.13–6.12 (m, 1 H), 3.40 (s, 3 H), 2.67 (s, 3 H), 2.51 ppm (s, 3 H); 13C NMR (125 MHz, CDCl3): d = 134.1, 132.9, 132.3, 132.1, 131.6, 129.8, 129.7, 125.6, 125.1, 124.6, 121.6, 108.7, 107.3, 34.2, 19.2, 16.1 ppm; ESI-HRMS m/z: calcd for C17H18N: 236.1434; found: 236.1428 [M+H] + .
N-Methyl-2-(4’-methyl-1’-triethysilyl-3’-naphthyl)pyrrole (3 y): Colorless oil; IR (ATR): n˜ = 2951, 2909, 2873, 1504, 1455, 1416, 1234, 1005 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.12–8.11 (m, 2 H), 7.56– 7.52 (m, 3 H), 6.77 (br s, 1 H), 6.27 (br s, 1 H), 6.15 (br s, 1 H), 3.42 (s, 3 H), 2.55 (s, 3 H), 1.00–0.96 ppm (m, 15 H); 13C NMR (125 MHz, CDCl3): d = 137.6, 137.0, 135.4, 134.3, 132.8, 132.4, 129.4, 128.5, 125.6, 125.4, 125.4, 121.7, 109.0, 107.3, 34.3, 16.5, 7.7, 4.5 ppm; ESIHRMS m/z: calcd for C22H30NSi: 336.2142; found: 336.2156 [M+H] + .
3-(1’,4’-Dimethyl-2’-naphthyl)-1H-indole (3 s): Colorless solid; m.p. 58–61 8C; IR (ATR): n˜ = 3411, 3059, 2921, 1602, 1508, 1454, 1417, 1385, 1336, 1241, 1124, 1093, 1009 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.23 (br s, 1 H), 8.15–8.13 (m, 1 H), 8.06–8.04 (m, 1 H), 7.59–7.53 (m, 2 H), 7.51 (d, J = 8.0 Hz, 1 H), 7.45 (d, J = 8.0 Hz, 1 H), 7.27–7.22 (m, 2 H), 7.15 (t, J = 8.0 Hz, 1 H), 2.70 (s, 1 H), 2.64 ppm (s, 1 H); 13 C NMR (125 MHz, CDCl3): d = 135.8, 133.3, 131.8, 131.6, 131.1, 130.3, 130.2, 127.5, 125.6, 125.1, 125.0, 124.5, 123.2, 122.2, 120.2, 120.0, 118.4, 111.2, 19.3, 16.4 ppm; ESI-HRMS m/z: calcd for C20H16N: 270.1288; found: 270.1289 [M H] .
N-Phenyl-3-(4’-methyl-1’-triethysilyl-2’-naphthyl)indole (3 z): Colorless solid; m.p. 101–103 8C; IR (ATR): n˜ = 2952, 2871, 1595, 1500, 1454, 1378, 1299, 1222, 1115, 1074, 1003 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.19 (d, J = 8.0 Hz, 1 H), 8.15 (d, J = 8.0 Hz, 1 H), 7.79 (s, 1 H), 7.69–7.51 (m, 8 H), 7.41–7.38 (m, 2 H), 7.30 (t, J = 7.0 Hz, 1 H), 7.21 (t, J = 7.0 Hz, 1 H), 2.74 (s, 3 H), 1.04–0.96 ppm (m, 15 H); 13 C NMR (125 MHz, CDCl3): d = 139.7, 138.2, 137.8, 136.7, 135.8, 133.6, 130.2, 129.7, 129.7, 128.5, 127.0, 126.5, 125.4, 125.4, 124.9, 124.4, 124.2, 122.6, 120.8, 120.6, 110.7, 108.5, 16.9, 7.8, 4.6 ppm; ESI-HRMS m/z: calcd for C31H34NSi: 448.2455; found: 448.2463 [M+H] + .
N-Phenyl-3-(1’,4’-dimethyl-2’-naphthyl)indole (3 t): Colorless solid; m.p. 75–78 8C; IR (ATR): 3063, 2920, 1595, 1545, 1499, 1454, 1361, 1315, 1298, 1221, 1134, 1074, 1028 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.18–8.16 (m, 1 H), 8.08–8.06 (m, 1 H), 7.68–7.66 (m, 1 H), 7.62– 7.54 (m, 7 H), 7.48 (s, 1 H), 7.40–7.37 (m, 2 H), 7.31–7.27 (m, 1 H), 7.22–7.18 (m, 1 H), 2.72 (s, 3 H), 2.71 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3): d = 139.7, 135.8, 133.4, 132.0, 131.7, 130.7, 130.4, 130.1, 129.7, 129.0, 126.9, 126.4, 125.7, 125.3, 125.1, 124.6, 124.3, 122.6, 120.6, 120.6, 119.3, 110.6, 19.3, 16.6 ppm; ESI-HRMS m/z: calcd for C26H22N: 348.1747; found: 348.1742 [M+H] + .
4-Ethyl-1-triethylsilyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 aa): Pale-yellow oil; IR (ATR): n˜ = 2952, 2873, 1606, 1584, 1500, 1456, 1412, 1334, 1223, 1203, 1153, 1125, 1056, 1039, 1014 cm 1; 1 H NMR (500 MHz, CDCl3): d = 8.15 (d, J = 8.0 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 1 H), 7.47–7.43 (m, 2 H), 7.35 (s, 1 H), 6.26 (s, 2 H), 3.90 (s, 3 H), 3.65 (s, 6 H), 2.86 (q, J = 7.5 Hz, 2 H), 1.13 (t, J = 7.5 Hz, 3 H), 0.97 ppm (s, 15 H); 13C NMR (125 MHz, CDCl3): d = 160.5, 158.6, 140.4, 139.0, 137.5, 132.0, 131.5, 130.1, 128.8, 125.3, 124.7, 124.4, 112.9, 90.7, 55.6, 55.3, 23.2, 14.6, 7.7, 4.6 ppm; ESI-HRMS m/z: calcd for C27H36O3SiNa: 459.2326; found: 459.2322 [M+Na] + .
3-(2’,4’-Dimethoxyphenyl)-4-methyl-1-triethylsilylnaphthalene (3 u): Colorless oil; IR (ATR): n˜ = 2951, 2872, 1609, 1578, 1504, 1454, 1414, 1300, 1280, 1257, 1236, 1205, 1156, 1135, 1108, 1034 cm 1; 1 H NMR (500 MHz, CDCl3): d = 8.13 (d, J = 8.5 Hz, 1 H), 8.10 (d, J = 8.0 Hz, 1 H), 7.53–7.46 (m, 3 H), 7.15–7.13 (m, 1 H), 6.60–6.59 (m, 2 H), 3.87 (s, 3 H), 3.73 (s, 3 H), 2.50 (s, 3 H), 0.98 ppm (s, 15 H); 13 C NMR (125 MHz, CDCl3): d = 160.2, 157.8, 137.9, 136.7, 134.3, 133.7, 132.9, 132.0, 131.8, 128.4, 125.3, 125.2, 124.8, 124.3, 104.1, 98.7, 55.4, 55.4, 16.5, 7.7, 4.6 ppm; ESI-HRMS m/z: calcd for C25H32O2SiNa: 415.2064; found: 415.2060 [M+Na] + .
6,7-Dimethoxy-4-methyl-1-triethylsilyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 ab): Colorless solid; m.p. 121–123 8C; IR (ATR): n˜ = 2951, 1605, 1583, 1509, 1464, 1413, 1333, 1258, 1221, 1201, 1155, 1121, 1061, 1038, 1010 cm 1; 1H NMR (500 MHz, CDCl3): d = 7.43 (s, 1 H), 7.35 (s, 1 H), 7.34 (s, 1 H), 6.27 (s, 2 H), 4.02 (s, 3 H), 4.01 (s, 3 H), 3.89 (s, 3 H), 3.69 (s, 6 H), 2.39 (s, 3 H), 1.02–0.95 ppm (m, 15 H); 13C NMR (125 MHz, CDCl3): d = 160.5, 158.5, 148. 1, 133.3, 132.6, 129.0, 128.7, 128.4, 112.8, 107.8, 104.4, 104.3, 90.8, 90.7, 55.7, 55.7, 55.4, 55.3, 16.6, 7.7, 4.7 ppm; ESI-HRMS m/z: calcd for C28H38O5SiNa: 505.2381; found: 505.2373 [M+Na] + .
1-(4’-Methyl-1’-triethysilyl-3’-naphthyl)-2-naphthol (3 v): Paleyellow oil; IR (ATR): n˜ = 3533, 2952, 2873, 1619, 1596, 1504, 1463, 1378, 1345, 1260, 1214, 1179, 1145, 1127, 1004 cm 1; 1H NMR (400 MHz, CDCl3): d = 8.24–8.19 (m, 2 H), 7.88–7,85 (m, 2 H), 7.63– 7.60 (m, 2 H). 7.53 (s, 1 H), 7.36–7.29 (m, 3 H), 7.23 (d, J = 7.6 Hz, 1 H), 4.98 (s, 1 H), 2.43 (s, 3 H), 1.03–0.94 ppm (m, 15 H); 13C NMR (100 MHz, CDCl3): d = 150.4, 137.6, 137.5, 136.4, 134.7, 133.3, 133.1, 129.4, 129.1, 129.0, 128.7, 128.1, 126.5, 125.9,125.9, 125.4, 124.7, 123.3, 121.0, 117.2, 15.9, 7.7, 4.5 ppm; ESI-HRMS m/z: calcd for C27H29OSi: 397.1993; found: 397.2003 [M H] .
1-(6’,7’-Dimethoxy-4’-methy-1’-triethylsilyl-3’-naphthyl)-2-naphthol (3 ac): Colorless solid; m.p. 79–83 8C; IR (ATR): n˜ = 3529, 2951, 2872, 1620, 1596, 1509, 1465, 1429, 1390, 1345, 1258, 1226, 1166, 1131, 1061, 1006 cm 1; 1H NMR (500 MHz, CDCl3): d = 7.86 (s, 1 H), 7.85 (s, 1 H), 7.54 (s, 1 H), 7.39 (s, 1 H), 7.39 (s, 1 H), 7.34–7.20 (m, 3 H), 7.22 (d, J = 8.5 Hz, 1 H), 5.03 (s, 1 H), 4.08 (s, 3 H), 4.06 (s, 3 H), 2.37 (s, 3 H), 0.98 ppm (s, 15 H); 13C NMR (125 MHz, CDCl3): d = 150.4, 149.0, 148.9, 135.7, 134.8, 133.5, 133.4, 132.5, 129.3, 128.9, 128.7, 128.0, 127.5, 126.4, 124.8, 123.2, 121.3, 117.1, 107.8, 104.1,
2-(4’-Methyl-1’-triethysilyl-3’-naphthyl)-1-naphthol (3 w): Paleyellow oil; IR (ATR): n˜ = 3539, 3070, 2952, 2873, 1571, 1504, 1459, 1381, 1318, 1238, 1197, 1144, 1081, 1007 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.32–8.30 (m, 1 H), 8.19–8.17 (m, 2 H), 7.88–7.87 (m, 1 H), 7.61–7.57 (m, 3 H), 7.55–7.53 (m, 3 H), 7.33 (d, J = 8.5 Hz, 1 H), 5.33 (s, 1 H), 2.56 (m, 3 H), 1.03–0.95 ppm (m, 15 H); 13C NMR (125 MHz,
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[5] Review: a) M. Lautens, K. Fagnou, S. Hiebert, Acc. Chem. Res. 2003, 36, 48 – 58; b) K. Fagnou, M. Lautens, Chem. Rev. 2003, 103, 169 – 196; c) T. Hayashi, K. Yamasaki, Chem. Rev. 2003, 103, 2829 – 2844; d) M. Lautens, K. Fagnou, Proc. Natl. Acad. Sci. USA 2004, 101, 5455 – 5460. [6] a) M. Nakamura, K. Matsuo, T. Inoue, E. Nakamura, Org. Lett. 2003, 5, 1373 – 1375; b) R. Gmez Arrays, S. Cabrera, J. C. Carretero, Org. Lett. 2003, 5, 1333 – 1336; c) R. Gmez Arrays, S. Cabrera, J. C. Carretero, Synthesis 2006, 1205 – 1219; d) R. Millet, L. Gremaud, T. Bernardez, L. Palais, A. Alexakis, Synthesis 2009, 2101 – 2112; e) R. Millet, T. Bernardez, L. Palais, A. Alexakis, Tetrahedron Lett. 2009, 50, 3474 – 3477. [7] For seleted references, see: a) J.-P. Duan, C.-H. Cheng, Organometallics 1995, 14, 1608 – 1618; b) K. Fugami, S. Hagiwara, H. Oda, M. Kosugi, Synlett 1998, 477 – 478; c) C.-C. Feng, M. Nandi, T. Sambaiah, C.-H. Cheng, J. Org. Chem. 1999, 64, 3538 – 3543; d) M. Murakami, H. Igawa, Chem. Commun. 2002, 390 – 391; e) M. Lautens, C. Dockendorff, K. Fagnou, A. Malicki, Org. Lett. 2002, 4, 1311 – 1314; f) M. Lautens, C. Dockendorff, Org. Lett. 2003, 5, 3695 – 3698; g) C.-L. Chen, S. F. Martin, J. Org. Chem. 2006, 71, 4810 – 4817; h) T.-K. Zhang, D.-L. Mo, L.-X. Dai, X. -L, Hou, Org. Lett. 2008, 10, 5337 – 5340; i) G. C. Tsui, J. Tsoung, P. Dougan, M. Lautens, Org. Lett. 2012, 14, 5542 – 5545. [8] a) M. Lautens, K. Fagnou, J. Am. Chem. Soc. 2001, 123, 7170 – 7171; b) M. Lautens, K. Fagnou, D. Yang, J. Am. Chem. Soc. 2003, 125, 14884 – 14892; c) R. Webster, A. Boyer, M. J. Fleming, M. Lautens, Org. Lett. 2010, 12, 5418 – 5421; d) T. D. Nguyen, R. Webster, M. Lautens, Org. Lett. 2011, 13, 1370 – 1373. [9] a) H.-T. Shih, H.-H. Shih, C.-H. Cheng, Org. Lett. 2001, 3, 811 – 814; b) D. K. Rayabarapu, P. Shukla, C.-H. Cheng, Org. Lett. 2003, 5, 4903 – 4906; c) S. Madan, C.-H. Cheng, J. Org. Chem. 2006, 71, 8312 – 8315. [10] a) Z. Qi, X. Li, Angew. Chem. Int. Ed. 2013, 52, 8995 – 9000; Angew. Chem. 2013, 125, 9165 – 9170. [11] a) Y. Sawama, K. Kawamoto, H. Satake, N. Krause, Y. Kita, Synlett 2010, 14, 2151 – 2155; b) Y. Sawama, Y. Shishido, T. Yanase, K. Kawamoto, R. Goto, Y. Monguchi, H. Sajiki, Angew. Chem. Int. Ed. 2013, 52, 1515 – 1519; Angew. Chem. 2013, 125, 1555 – 1559; c) Y. Sawama, Y. Ogata, K. Kawamoto, H. Satake, K. Shibata, Y. Monguchi, H. Sajiki, Y. Kita, Adv. Synth. Catal. 2013, 355, 1529. [12] a) G. Wittig, L. Pohmer, Chem. Ber. 1956, 89, 1334 – 1351; b) E. Wolthuis, B. Bossenbroek, G. DeWall, E. Geels, A. Leegwater, J. Org. Chem. 1963, 28, 148 – 152; c) M. Fetizon, N. T. Anh, Bull. Soc. Chim. Fr. 1965, 3208 – 3210; d) M. D. Cooke, T. A. Dransfield, J. M. Vernon, J. Chem. Soc. Perkin Trans. 2 1984, 1377 – 1381; e) F. Peng, B. Fan, Z. Shao, X. Pu, P. Li, H. Zhang, Synthesis 2008, 3043 – 3046. [13] a) Y. Sawama, Y. Sawama, N. Krause, Org. Lett. 2009, 11, 5034 – 5037; b) Y. Sawama, S. Nagata, Y. Yabe, K. Morita, Y. Monguchi, H. Sajiki, Chem. Eur. J. 2012, 18, 16608 – 16611; c) Y. Sawama, K. Shibata, Y. Sawama, M. Takubo, Y. Monguchi, N. Krause, H. Sajiki, Org. Lett. 2013, 15, 5282 – 5285; d) Y. Sawama, Y. Shishido, T. Kawajiri, R. Goto, Y. Monguchi, H. Sajiki, Chem. Eur. J. 2014, 20, 510 – 516; e) Y. Sawama, R. Goto, S. Nagata, Y. Shishido, Y. Monguchi, H. Sajiki, Chem. Eur. J. 2014, 20, 2631 – 2636. [14] FeCl3 was used in Friedel–Crafts reactions toward various substrates. For examples, see: a) I. Iovel, K. Mertins, J. Kischel, A. Zapf, M. Beller, Angew. Chem. Int. Ed. 2005, 44, 3913 – 3917; Angew. Chem. 2005, 117, 3981 – 3985; b) B.-Q. Wang, S.-K. Xiang, Z.-P. Sun, B.-T. Guan, P. Hu, K.-Q. Zhao, Z.-J. Shi, Tetrahedron Lett. 2008, 49, 4310 – 4312; c) D. Stadler, T. Bach, Angew. Chem. Int. Ed. 2008, 47, 7557 – 7559; Angew. Chem. 2008, 120, 7668 – 7670. [15] Substrate bearing H atom on the bridge-head was transformed into the 1-naphthol derivative without the nucleophilic addition of 2 a by the rapid 1,2-hydride shift by the stable tert-carbocation intermediate.
6,7-Dimethoxy-4-pentyl-1-triethylsilyl-3-(2’,4’,6’-trimethoxyphenyl)naphthalene (3 ad): Pale-yellow oil; IR (ATR): n˜ = 2951, 2872, 1605, 1584, 1510, 1464, 1411, 1333, 1256, 1221, 1202, 1155, 1122, 1062, 1033 cm 1; 1H NMR (500 MHz, CDCl3): d = 7.43 (s, 1 H), 7.39 (s, 1 H), 7.23 (s, 1 H), 6.25 (s, 2 H), 4.01 (s, 6 H), 3.90 (s, 3 H), 3.65 (s, 6 H), 2.77–2.73 (m, 2 H), 1.54 (br s, 2 H), 1.26–1.21 (m, 4 H), 1.02–0.95 (m, 15 H), 0.81 ppm (t, J = 6.5 Hz, 3 H); 13C NMR (125 MHz, CDCl3): d = 160.3, 158.5, 148.0, 147.9, 138.0, 137.3, 133.2, 129.5, 128.8, 127.6, 113.2, 108.0, 104.5, 90.6, 55.6, 55.6, 55.4, 55.3, 32.3, 30.4, 29.3, 22.4, 14.0, 7.8, 4.6 ppm; ESI-HRMS m/z: calcd for C32H46O5SiNa: 561.3007; found: 561.3008 [M+Na] + . 6,7-Dibromo-4-methyl-1-triethylsilyl-3-(2,4,6-trimethoxyphenyl)naphthalene (3 ae): Colorless solid; m.p. 57–61 8C; IR (ATR): n˜ = 2953, 1605, 1585, 1455, 1412, 1333, 1223, 1203, 1155, 1124, 1064, 1039 cm 1; 1H NMR (500 MHz, CDCl3): d = 8.38 (s, 1 H), 8.34 (s, 1 H), 7.47 (s, 1 H), 6.26 (s, 2 H), 3.88 (s, 3 H), 3.69 (s, 6 H), 2.38 (s, 3 H), 0.99–0.94 ppm (m, 15 H); 13C NMR (125 MHz, CDCl3): d = 160.9, 158.3, 140.5, 136.7, 134.0, 133.3, 132.7, 131.7, 130.5, 130.0, 120.8, 120.7, 111.7, 90.7, 55.7, 55.4, 16.2, 7.6, 4.5 ppm; ESI-HRMS m/z: calcd for C26H31O3Br2Si: 577.0415; found: 577.0432 [M H] . Characteristic data of some products (7–11 and 13 a–13 i) were described in the Supporting Information.
Acknowledgements This work was partially supported by Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science (JSPS) and Takeda Science Foundation. Keywords: arenes · biaryls · Friedel–Crafts reaction · iron catalyst · ring-opening reaction [1] a) R. E. Mewshaw, R. J. Edsall, Jr., C. Yang, E. S. Manas, Z. B. Xu, R. A. Henderson, J. C. Keith, Jr., H. A. Harris, J. Med. Chem. 2005, 48, 3953 – 3979; b) S. Song, H. Lee, Y. Jin, Y. M. Ha, S. Bae, H. Y. Chung, H. Suh, Bioorg. Med. Chem. Lett. 2007, 17, 461 – 464; c) C. Maurin, C. Lion, F. Bailly, N. Touati, H. Vezin, G. Mbemba, J. F. Mouscadet, Z. Debyser, M. Witvrouw, P. Cotelle, Bioorg. Med. Chem. 2010, 18, 5194 – 5201; d) M. Wetzel, S. Marchais-Oberwinkler, E. Perspicace, G. Mçller, J. Admski, R. W. Hartmann, J. Med. Chem. 2011, 54, 7547 – 7557; e) A. S. Kumar, M. A. Reddy, N. Jain, C. Kishor, T. R. Murthy, D. Ramesh, B. Supriya, A. Addlagatta, S. V. Kalivendi, B. Sreedhar, Eur. J. Med. Chem. 2013, 60, 305 – 324. [2] S. Kumar, W. Namkung, A. S. Verkman, P. K. Sharma, Bioorg. Med. Chem. 2012, 20, 4237 – 4244. [3] a) T. Vasiljevik, L. N. Franks, B. M. Ford, J. T. Douglas, P. L. Prather, W. E. Fantegrossi, T. E. Prisinzano, J. Med. Chem. 2013, 56, 4537 – 4550; b) G. Pereira, E. M. S. Castanheira, P. M. T. Ferreira, M.-J. R. P. Queiroz, Eur. J. Org. Chem. 1997, 97, 464 – 475. [4] a) J. Roncali, Chem. Rev. 1997, 97, 173 – 206; b) H. Meng, Z. Bao, A. J. Lovinger, B.-C. Wang, A. M. Mujsce, J. Am. Chem. Soc. 2001, 123, 9214 – 9215; c) M. Mushrush, A. Facchetti, M. Lefenfeld, H. E. Katz, T. J. Marks, J. Am. Chem. Soc. 2003, 125, 9414 – 9423; d) M. M. M. Raposo, A. M. C. Fonseca, G. Kirsch, Tetrahedron 2004, 60, 4071 – 4078; e) J. A. Merlo, C. R. Newman, C. P. Gerlach, T. W. Kelley, D. V. Muyres, S. E. Fritz, M. F. Toney, C. D. Frisbie, J. Am. Chem. Soc. 2005, 127, 3997 – 4009; f) N. Hergu, P. Frre, Org. Biomol. Chem. 2007, 5, 3442 – 3449; g) H. Tian, J. Shi, B. He, N. Hu, S. Dong, D. Yan, J. Zhang, Y. Geng, F. Wang, Adv. Funct. Mater. 2007, 17, 1940 – 1951; h) E. Bey, S. Marchais-Oberwinker, R. Werth, M. Negri, Y. A. Al-Sound, P. Kruchten, A. Oster, M. Frotscher, B. Birk, R. W. Hartmann, J. Med. Chem. 2008, 51, 6725 – 6739; i) D. Urselmann, D. Antovic, T. J. J. Mller, Beilstein J. Org. Chem. 2011, 7, 1499 – 1503. Chem. Eur. J. 2014, 20, 1 – 9
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[16] 2,4-Dimethyl-1-naphthanol (4 a) could be obtained without the nucleophilic attack of 2 a as shown below. [17] Scale-up reaction using 1 a (5.2 mmol) with 2 a (2 equiv) provided 3 a in quantitative yield.
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Communication corresponding benzylic cation (F). Therefore, 3 h and 3 i were regioselectively obtained.
[18] Similar results were obtained by the optimization of the reaction conditions using 1 a. In the reaction of 1 a, 2 equiv of arene were sufficient to give the desired biaryl (3 k). See the Supporting Information. [19] The principal regioisomers are depicted in Scheme 3. When the formation of the corresponding regioisomer could be detected, the results are shown in the Supporting Information. [20] The reaction of 1 a with toluene or o-xylene gave only 4 a, which was produced by the rearrangement of the methyl group without the nucleophilic attack of arene. See ref. [16]. [21] The electron-donating methoxy group can stabilize the generated cation intermediate (E), and the phenyl group of 1 i also stabilizes the
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[22] Bromination of the aromatic silyl group by using NBS has been reported, see: T. Ozawa, T. Kurahashi, S. Matsubara, Org. Lett. 2011, 13, 5390 – 5393. [23] The reaction mechanism is unclear. [24] The reaction of 3 u by using 2.2 equivalents of NBS gave a mixture of 10 (22 %) and 11 (65 %). Received: October 7, 2014 Published online on && &&, 0000
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COMMUNICATION & Organic Synthesis Y. Sawama,* S. Asai, T. Kawajiri, Y. Monguchi, H. Sajiki* && – &&
Biaryl and heterobiaryl compounds are the important frameworks in the fields of pharmaceutical and materials chemistry. An efficient synthesis of various naphthalene-linked arenes and hetero-
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arenes as biaryls and heterobiaryls has been accomplished by FeCl3-catalyzed Friedel–Crafts reactions accompanied by the ring-opening of 1,4-epoxy-1,4-dihydronaphthalenes (see scheme).
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Biaryl Synthesis by Ring-Opening Friedel–Crafts Arylation of 1,4-Epoxy1,4-dihydronaphthalenes Catalyzed by Iron Trichloride
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