DOI: 10.1002/chem.201503969
Communication
& Bioinspired Synthesis
Construction of Bridged Polycyclic Systems by Polyene Cyclization Keisuke Suzuki, Hiroyuki Yamakoshi, and Seiichi Nakamura*[a] Abstract: A stereoselective construction of bridged triand tetracyclic systems embedded in some 3,5-dimethylorsellinic acid (DMOA)-derived meroterpenoids was achieved by exploiting a polyene cyclization of suitably functionalized epoxyallylsilanes. Both the olefinic substituent on the epoxide and allylic trimethylsilyl (TMS) group were found to play pivotal roles in the success of the present reaction. The fact that the cyclization of monocyclized byproducts did not proceed strongly suggests that the reaction could be a concerted transformation.
A number of meroterpenoids containing a bridged [7.3.1.02, 7] tricyclic system and their derivatives have been isolated and characterized as fungal metabolites since the discovery of neoaustin in 1994 (Figure 1).[1, 2] Although some of these natural products have been reported to display remarkable biological activities (e.g., inhibition of caspase-1), studies toward the synthesis of these meroterpenoids have not been reported to date. In contrast, their novel polycyclic architecture stimulated considerable interest in their biosynthesis, leading to elucidation of the biosynthetic pathway on the basis of intermediates and bioinformatics studies.[3] It has been proposed that the characteristic carbocyclic framework is formed by an acid-promoted polyene cyclization of the epoxide, generated by C-alkylation of DMOA with farnesyl pyrophosphate followed by regioselective epoxidation.[4] Polyene cyclization is a well-known reaction that was first reported in the 1920s[5] and has been extensively studied for 60 years.[6, 7] Utilizing this biomimetic reaction, multiple rings can be formed in a single operation and stereocenters are installed in a stereoselective manner in many cases. The synthetic utility of the reaction has been demonstrated by the total syntheses of many natural products containing a fused polycyclic ring system.[8] However, to our surprise, bridged polycyclic systems have never been created by this cascade reaction without combinational use of rearrangement reactions.[9] We, therefore, wondered whether we could take advantage of the polyene cyclization reaction for the synthesis of bridged polycyclic compounds.
[a] K. Suzuki, Dr. H. Yamakoshi, Prof. Dr. S. Nakamura Graduate School of Pharmaceutical Sciences, Nagoya City University 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603 (Japan) E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201503969. Chem. Eur. J. 2015, 21, 17605 – 17609
Figure 1. Structures of meroterpenoids containing a common bridged polycyclic system.
We envisioned epoxydiene 1 as a suitable precursor to bridged tricyclic compound 2 by way of generation of cationic intermediate 3 triggered by exposure to acid, 6-endo cyclization that provides cation 4, and elimination (Scheme 1). The major concern with this polycyclization was the competing 5exo closure of intermediate 3, giving rise to [6,5,6]-fused tricyclic compound 2’.[10] In this regard, we noticed an unexceptional substitution of a methoxycarbonyl group at a bridgehead carbon atom in natural products. It was anticipated that introduction of an ester functionality as the R1 substituent would suppress the generation of a positive charge a to the electronwithdrawing substituent, leading to the preferential formation of bridged compound 2. Since the ester group lowers the electron density of the p-bond, we decided to use substrate 1 with a TMS group at the allylic position (R2 = TMS) aiming not only to enhance the nucleophilicity of the p-bond, but also to stabilize the positive charge on the b-carbon atom in intermediate 4.[11, 12] However, it remains uncertain whether conformational constraints imposed by the six-membered ring would allow intermediate 3 to adopt a required conformation for cyclization to occur. Synthesis of cyclization precursors 1 commenced with enantiomerically pure alcohol 5 (> 99 % ee), obtained through biore-
17605
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication
Scheme 1. Biosynthesis-inspired approach to bridged tricyclic compounds.
Scheme 2. Synthesis of cyclization precursors 1 a–c: a) POCl3, pyridine, RT to 80 8C; b) OsO4 (1 mol %), NMO, aq THF, 64 % (2 steps); c) H2, 10 % Pd/C, EtOH; d) NaIO4, aq CH2Cl2 ; e) DBU, LiCl, (EtO)2P(O)CHMeCO2Et, MeCN; f) DIBALH, CH2Cl2, ¢78 8C, 90 % (4 steps); g) PhSSPh, Bu3P, THF, 99 %; h) [(NH4)6Mo7O24·4H2O] (20 mol %), H2O2, pyridine, EtOH, 99 %; i) BuLi, bromide 9, THF/HMPA, ¢78 8C, 99 %; j) LiEt3BH, [PdCl2(dppp)] (5 mol %), THF, 0 8C; k) aq HCl, THF, 65 8C; l) NH4F, EtOH/MeOH, 56 % (3 steps); m) DHP, PPTS, CH2Cl2, 98 %; n) LDA, EtOCOCN, THF/HMPA, ¢78 8C, 84 %; o) NaH, Tf2O, Et2O, 95 %; p) TMSCH2MgCl, [Pd(PPh3)4] (5 mol %), LiCl, dioxane, 60 8C, 96 %; q) PPTS (10 mol %), EtOH, 50 8C, 99 %; r) L-DIPT (13 mol %), Ti(OiPr)4 (10 mol %), tBuO2H, 4 æ MS, CH2Cl2, ¢20 8C, 92 %, d.r. = 97:3; s) TBSCl, imidazole, CH2Cl2, 91 %; t) Dess-Martin periodinane, CH2Cl2, 97 %; u) Ph3PMeBr, KHMDS, THF, 0 8C, 94 %. NMO = N-methylmorpholine-N-oxide; DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene; TBDPS = tert-butyldiphenylsilyl; dppp = 1,3-bis(diphenylphosphino)propane; DHP = 3,4-dihydro-2H-pyran; PPTS = pyridinium p-toluenesulfonate; LDA = lithium diisopropylamide; DIPT = diisopropyl tartrate; MS = molecular sieves; KHMDS = potassium hexamethyldisilazane.
duction using baker’s yeast (Scheme 2).[13] Dehydration of alcohol 5 with POCl3 was followed by selective dihydroxylation under catalytic conditions to afford diol 6 in 64 % yield. After Chem. Eur. J. 2015, 21, 17605 – 17609
www.chemeurj.org
hydrogenation of the resultant olefin with the aid of 10 % Pd/ C, oxidative cleavage of the vicinal diol with NaIO4, followed by Horner–Wadsworth–Emmons reaction under Masamune conditions,[14] and reduction with diisobutylaluminum hydride (DIBALH) provided (E)-allyl alcohol 7 in 90 % overall yield for the four-step sequence. The hydroxy group in 7 was transformed to phenyl sulfone in a two-step process involving treatment with phenyl disulfide/tributylphosphine in tetrahydrofuran (THF)[15] and MoVI-catalyzed oxidation with H2O2[16] in preparation for the homologation. While alkylation of sulfone 8 with bromide 9[17] in THF/hexamethylphosphoric triamide (HMPA) proceeded quantitatively at ¢78 8C, removal of the superfluous phenylsulfonyl group by PdII-catalyzed reduction with SuperHydride[19] was accompanied by olefin isomerization, affording a 6:1 mixture of inseparable isomers. The isomers could be separated after acid hydrolysis of 1,3-dioxolane and desilylation with NH4F[20] to give allyl alcohol 10 in 56 % overall yield for the three-step sequence. After interim protection of the hydroxyl group as a tetrahydropyran-2-yl (THP) ether (98 % yield), C-acylation with Mander’s reagent in THF/HMPA gave ester 12 in 84 % yield. Installation of a TMS methyl group was achieved using a two-step procedure involving enol triflate formation (95 % yield) and Kumada–Tamao–Corriu cross-coupling, which was rendered reproducible and high-yielding (96 %) by the addition of LiCl.[21] At this juncture, the THP ether was uneventfully deprotected under mild acidic conditions (99 % yield) to give allyl alcohol 15, which was then subjected to Sharpless epoxidation[22] to afford 1 a in 92 % yield. Protection of alcohol 1 a with tert-butyldimethylsilyl (TBS) chloride provided TBS ether 1 b in 91 % yield, whereas vinyl epoxide 1 c was obtained in 91 % yield by Dess–Martin oxidation[23] and subsequent Wittig olefination.[24] With the route to epoxyallysilanes secured, we then proceeded to investigate the polycyclization reaction. While some hydroxymethyl oxiranes underwent cyclization upon exposure to SnCl4 in CH2Cl2,[12b] the SnCl4-promoted reaction of epoxyalcohol 1 a did not proceed at ¢55 8C and raising the temperature to 0 8C led only to decomposition.[25] The reactivity of the epoxide was enhanced by protection of the hydroxy group as a TBS ether, but a complex mixture was obtained by treatment of 1 b with SnCl4 in CH2Cl2 at ¢55 8C. We were gratified to find that the desired polycyclization occurred even at ¢78 8C when vinyl epoxide 1 c was reacted with SnCl4 in CH2Cl2, affording tricyclic compound 2 c in 56 % yield, without any 5-exo cyclization products isolated (Table 1, entry 1).[26] Titanium Lewis acids also promoted the desired cyclization, albeit in comparable yield due to the formation of byproducts 16–18 (entry 2). Isolation of allyl chloride 18 resulting from SN2’-type substitution prompted us to investigate promoters devoid of chlorine atoms,[27] but all attempts proved unsuccessful (entries 3–5). Finally, we found that a higher yield (67 %) could be obtained with Et2AlCl, the utility of which in polyene cyclization was documented by Corey and Sodeoka,[28] whereas the use of more Lewis acidic EtAlCl2 afforded no discernible benefit (entries 6 and 7). The chemical yield was further improved to 72 % by a decrease in reaction temperature to ¢98 8C (entry 8). It is noteworthy that monocyclization product 16 a could not be
17606
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication Table 2. Effect of substituents R1 and R2.
Table 1. Polycyclization of epoxyallylsilane 1 c.
Entry
Lewis acid
T [8C]
Yield [%]
1 2 3[a] 4 5 6[a] 7[a] 8[a]
SnCl4 (iPrO)2TiCl2 BF3·OEt2 TMSOTf TfOH EtAlCl2 Et2AlCl Et2AlCl
¢78 ¢78 ¢78 ¢78 ¢78 ¢78 ¢78 ¢98
56 59 47 27 28 57 67 72
[a] Product 2 c was obtained after hydrolysis of the corresponding TMS ether with TsOH in THF/MeOH (3:1).
Chem. Eur. J. 2015, 21, 17605 – 17609
www.chemeurj.org
Substrate R1
R2
Lewis acid
Product Yield [%]
1[a] 2 3 4[a] 5[a] 6[a] 7
1c 1d 1e 1e 1f 1g 1h
TMS TMS TMS TMS TMS TMS H
Et2AlCl Et2AlCl Et2AlCl BF3·OEt2 Et2AlCl Et2AlCl Et2AlCl
2c 2d 2e 2e 2f 2g 2c
CH=CH2 Z-CH=CHPh E-CH=CHCO2Et E-CH=CHCO2Et E-CH=CHCOiPr CCH CH=CH2
67 0[b] NR 65 42 33 0
[a] Products were obtained after hydrolysis of the corresponding TMS ether with TsOH in THF/MeOH (3:1). [b] Ketone 21 resulting from semipinacol rearrangement was obtained in 92 % yield. NR = no reaction.
converted to tricyclic product 2 c upon exposure to TfOH in CH2Cl2 at ¢78 8C,[29, 30] which indicates that the polycyclization could be a concerted rather than stepwise transformation (Scheme 3). In contrast to epoxyallylsilane 1 c, the reaction of which is presumed to proceed through a chair–chair–chairlike transition state (TS) A, the use of its diastereomer 19 was disappointing because polycyclization product 20, derived from the chair–boat–chairlike TS B, was obtained in only 13 % yield.[31] At this juncture, we surmised that the p-bonding electron density could influence the outcome of the reaction (Table 2). It was found that incorporation of a phenyl group facilitated semipinacol rearrangement, leading to the high-yielding (92 %) conversion to ketone 21 (Table 2, entry 2).[32] While the reaction of a,b-unsaturated ester 1 e did not proceed under optimized conditions (entry 3), desired product 2 e could be obtained in
Scheme 3. Attempts at cyclizations of byproduct 16 a and diastereomer 19.
Entry
comparable yield (65 %) when treated with BF3·OEt2 (entry 4). Conjugate enone 1 f and alkyne 1 g were completely consumed with the aid of Et2AlCl; however, the yields were less than satisfactory due to the formation of monocyclized byproducts (entries 5 and 6). The fact that the desired polycyclization of vinyl epoxide 1 h did not occur under optimized conditions revealed that the TMS group was critical to the success of this polycyclization reaction (entry 7). With a [7.3.1.02, 7] tricyclic framework successfully constructed, we next undertook an investigation into the extension of the protocol to construction of a tetracyclic system. As expected, treatment of vinyl epoxide 22[33] with Et2AlCl in CH2Cl2 at ¢78 8C resulted in the simultaneous creation of three six-membered rings, providing tetracyclo[11.3.1.02, 11.05, 10]heptadecane derivative 23 in 37 % yield (Scheme 4). While there is considerable room for improvement in the chemical yield of 23, the average yield of approximately 72 % per ring formed would be acceptable considering the suggestion by Corey and Shenvi that the chemical polycyclizations proceed at best with an efficiency of 70–80 % per ring formed.[7a] In conclusion, we have demonstrated that Et2AlCl-promoted polycyclization of epoxyallylsilanes in CH2Cl2 gave bridged triand tetracyclic compounds in acceptable yields with perfect stereoselectivity. This protocol represents the first example of
Scheme 4. Et2AlCl-promoted polycyclization with vinyl epoxide 22.
17607
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication employing polyene cyclization reactions in the construction of bridged polycyclic compounds. Further efforts toward the total syntheses of DMOA-derived meroterpenoids are currently underway in our laboratory and will be reported in due course.
Acknowledgements
[8]
This research was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, the Platform Project for Supporting in Drug Discovery and Life Science Research from Japan Agency for Medical Research and Development (AMED), and the Sasakawa Scientific Research Grant from The Japan Science Society. Keywords: bioinspired synthesis · bridged cyclization · Lewis acids · meroterpenoids
polycycles
·
[1] For a review, see: R. Geris, T. J. Simpson, Nat. Prod. Rep. 2009, 26, 1063 – 1094. [2] For representative reports, see: a) H. Hayashi, M. Mukaihara, S. Murao, M. Arai, A. Y. Lee, J. Clardy, Biosci. Biotechnol. Biochem. 1994, 58, 334 – 338; b) R. M. Geris dos Santos, E. Rodrigues-Fo, Phytochemistry 2002, 61, 907 – 912; c) R. M. G. Santos, E. Rodrigues-Fo, Z. Naturforsch. C 2003, 58, 663 – 669; d) D. B. Stierle, A. A. Stierle, J. D. Hobbs, J. Stokken, J. Clardy, Org. Lett. 2004, 6, 1049 – 1052; e) T. P. Fill, G. K. Pereira, R. M. G. Santos, E. Rodrigues-Fo, Z. Naturforsch. B 2007, 62, 1035 – 1044; f) D. B. Stierle, A. A. Stierle, B. Patacini, K. McIntyre, T. Girtsman, E. Bolstad, J. Nat. Prod. 2011, 74, 2273 – 2277. [3] a) H.-C. Lo, R. Entwistle, C.-J. Guo, M. Ahuja, E. Szewczyk, J.-H. Hung, Y.M. Chiang, B. R. Oakley, C. C. C. Wang, J. Am. Chem. Soc. 2012, 134, 4709 – 4720; b) Y. Matsuda, T. Awakawa, T. Wakimoto, I. Abe, J. Am. Chem. Soc. 2013, 135, 10962 – 10965. [4] Polyprenylated acylphloroglucinols (PPAPs) constitute a well-known family of meroterpenoids containing a bridged [3.3.1] bicyclic system, which is also biosynthesized through a dearomatization–cyclization sequence. For bioinspired total syntheses of PPAPs, see: a) D. R. Siegel, S. J. Danishefsky, J. Am. Chem. Soc. 2006, 128, 1048 – 1049; b) J. Qi, J. A. Porco Jr., J. Am. Chem. Soc. 2007, 129, 12682 – 12683; c) Q. Zhang, B. Mitasev, J. Qi, J. A. Porco Jr., J. Am. Chem. Soc. 2010, 132, 14212 – 14215; d) J. H. George, M. D. Hesse, J. E. Baldwin, R. M. Adlington, Org. Lett. 2010, 12, 3532 – 3535; e) N. S. Simpkins, M. D. Weller, Tetrahedron Lett. 2010, 51, 4823 – 4826; f) Q. Zhang, J. A. Porco, Jr., Org. Lett. 2012, 14, 1796 – 1799; g) B. A. Sparling, D. C. Moebius, M. D. Shair, J. Am. Chem. Soc. 2013, 135, 644 – 647; h) H. P. Pepper, J. H. George, Angew. Chem. Int. Ed. 2013, 52, 12170 – 12173; Angew. Chem. 2013, 125, 12392 – 12395; i) J. H. Boyce, J. A. Porco, Jr., Angew. Chem. Int. Ed. 2014, 53, 7832 – 7837; Angew. Chem. 2014, 126, 7966 – 7971; for reviews, see: j) R. Ciochina, R. B. Grossman, Chem. Rev. 2006, 106, 3963 – 3986; k) J.-A. Richard, R. H. Pouwer, D. Y.-K. Chen, Angew. Chem. Int. Ed. 2012, 51, 4536 – 4561; Angew. Chem. 2012, 124, 4612 – 4638. [5] a) L. Ruzicka, E. Capato, Helv. Chim. Acta 1925, 8, 259 – 274; for landmark studies that had a decisive influence on the following research, see: b) G. Stork, A. W. Burgstahler, J. Am. Chem. Soc. 1955, 77, 5068 – 5077; c) A. Eschenmoser, L. Ruzicka, O. Jeger, D. Arigoni, Helv. Chim. Acta 1955, 38, 1890 – 1904. [6] For reviews, see: a) K. U. Wendt, G. E. Schulz, E. J. Corey, D. R. Liu, Angew. Chem. Int. Ed. 2000, 39, 2812 – 2833; Angew. Chem. 2000, 112, 2930 – 2952; b) R. A. Yoder, J. N. Johnston, Chem. Rev. 2005, 105, 4730 – 4756. [7] For recent examples, see: a) R. A. Shenvi, E. J. Corey, Org. Lett. 2010, 12, 3548 – 3551; b) S. Rendler, D. W. C. MacMillan, J. Am. Chem. Soc. 2010, 132, 5027 – 5029; c) R. R. Knowles, S. Lin, E. N. Jacobsen, J. Am. Chem. Soc. 2010, 132, 5030 – 5032; d) S. G. Sethofer, T. Mayer, F. D. Toste, J. Am. Chem. Soc. 2010, 132, 8276 – 8277; e) S. A. Snyder, D. S. Treitler, A. P. Brucks, J. Am. Chem. Soc. 2010, 132, 14303 – 14314; f) A. Sakakura, M. Sakuma, K. Ishihara, Org. Lett. 2011, 13, 3130 – 3133; g) J. G. Sokol, C. S. Chem. Eur. J. 2015, 21, 17605 – 17609
www.chemeurj.org
[9]
[10]
[11]
[12]
[13] [14] [15]
17608
Korapala, P. S. White, J. J. Becker, M. R. Gagn¦, Angew. Chem. Int. Ed. 2011, 50, 5658 – 5661; Angew. Chem. 2011, 123, 5776 – 5779; h) K. Surendra, W. Qiu, E. J. Corey, J. Am. Chem. Soc. 2011, 133, 9724 – 9726; i) K. Surendra, E. J. Corey, J. Am. Chem. Soc. 2012, 134, 11992 – 11994; j) S. P. Morcillo, D. Miguel, S. Resa, A. Martn-Lasanta, A. Milln, D. ChoquesilloLazarte, J. M. Garca-Ruiz, A. J. Mota, J. Justicia, J. M. Cuerva, J. Am. Chem. Soc. 2014, 136, 6943 – 6951; k) G. Rajendar, E. J. Corey, J. Am. Chem. Soc. 2015, 137, 5837 – 5844. a) E. J. Corey, M. A. Tius, J. Das, J. Am. Chem. Soc. 1980, 102, 1742 – 1744; b) S. P. Tanis, Y.-H. Chuang, D. B. Head, Tetrahedron Lett. 1985, 26, 6147 – 6150; c) W. S. Johnson, M. S. Plummer, S. P. Reddy, W. R. Bartlett, J. Am. Chem. Soc. 1993, 115, 515 – 521; d) E. J. Corey, J. Lee, J. Am. Chem. Soc. 1993, 115, 8873 – 8874; e) A. B. Smith, III, T. Kinsho, T. Sunazuka, S. O¯mura, Tetrahedron Lett. 1996, 37, 6461 – 6464; f) E. J. Corey, G. Luo, L. S. Lin, J. Am. Chem. Soc. 1997, 119, 9927 – 9928; g) W. S. Johnson, W. R. Bartlett, B. A. Czeskis, A. Gautier, C. H. Lee, R. Lemoine, E. J. Leopold, G. R. Luedtke, K. J. Bancroft, J. Org. Chem. 1999, 64, 9587 – 9595; h) A. X. Huang, Z. Xiong, E. J. Corey, J. Am. Chem. Soc. 1999, 121, 9999 – 10003; i) M. Bogensttter, A. Limberg, L. E. Overman, A. L. Tomasi, J. Am. Chem. Soc. 1999, 121, 12206 – 12207; j) J. D. Rainier, A. B. Smith III, Tetrahedron Lett. 2000, 41, 9419 – 9423; k) D. Yang, M. Xu, Org. Lett. 2001, 3, 1785 – 1788; l) H. Ishibashi, K. Ishihara, H. Yamamoto, J. Am. Chem. Soc. 2004, 126, 11122 – 11123; m) Y.-J. Zhao, T.-P. Loh, Org. Lett. 2008, 10, 2143 – 2145; n) D. C. Behenna, E. J. Corey, J. Am. Chem. Soc. 2008, 130, 6720 – 6721; o) R. Tong, F. E. McDonald, Angew. Chem. Int. Ed. 2008, 47, 4377 – 4379; Angew. Chem. 2008, 120, 4449 – 4451; p) M. B. Kim, J. T. Shaw, Org. Lett. 2010, 12, 3324 – 3327; q) S. A. Snyder, D. S. Treitler, A. Schall, Tetrahedron 2010, 66, 4796 – 4804; r) E. C. Cherney, J. C. Green, P. S. Baran, Angew. Chem. Int. Ed. 2013, 52, 9019 – 9022; Angew. Chem. 2013, 125, 9189 – 9192; s) O. F. Jeker, A. G. Kravina, E. M. Carreira, Angew. Chem. Int. Ed. 2013, 52, 12166 – 12169; Angew. Chem. 2013, 125, 12388 – 12391; t) B. R. Rosen, E. W. Werner, A. G. O’Brien, P. S. Baran, J. Am. Chem. Soc. 2014, 136, 5571 – 5574; u) T. N. Barrett, A. G. M. Barrett, J. Am. Chem. Soc. 2014, 136, 17013 – 17015. The cedrene/funebrene and kaurane carbon frameworks were constructed, albeit in low yield, by a tandem reaction, wherein cationic polycyclization was combined with a hydride shift and pinacol rearrangement, respectively; a) S. V. Pronin, R. A. Shenvi, Nat. Chem. 2012, 4, 915 – 920; b) S. Desjardins, G. Maertens, S. Canesi, Org. Lett. 2014, 16, 4928 – 4931. Corey and Myers groups reported that 5-exo cyclizations occurred exclusively to afford [6,6,5,5]-fused tetracyclic compounds in the system capable of either 5-exo or 6-endo closure; a) E. J. Corey, H. B. Wood Jr., J. Am. Chem. Soc. 1996, 118, 11982 – 11983; b) A. G. Myers, M. Siu, Tetrahedron 2002, 58, 6397 – 6404. Conjugate esters are known to be poor terminating groups for polyene cyclization reactions. E. E. Van Tamelan, Acc. Chem. Res. 1968, 1, 111 – 120. For the use of epoxyallylsilanes/epoxypropargylsilanes to construct fused polycyclic ring systems, see: a) R. J. Armstrong, L. Weiler, Can. J. Chem. 1986, 64, 584; b) S. Hatakeyama, H. Numata, K. Osanai, S. Takano, J. Chem. Soc. Chem. Commun. 1989, 1893 – 1895; c) N. K. N. Yee, R. M. Coates, J. Org. Chem. 1992, 57, 4598 – 4608; d) M. Taton, P. Benveniste, A. Rahier, Biochemistry 1992, 31, 7892 – 7898; e) K. Mori, S. Aki, M. Kido, Liebigs Ann. Chem. 1994, 319 – 324; f) P. V. Fish, W. S. Johnson, J. Org. Chem. 1994, 59, 2324 – 2335; g) P. V. Fish, Tetrahedron Lett. 1994, 35, 7181 – 7184; h) E. J. Corey, J. Lee, D. R. Liu, Tetrahedron Lett. 1994, 35, 9149 – 9152; i) S. E. Sen, S. L. Roach, S. M. Smith, Y. z. Zhang, Tetrahedron Lett. 1998, 39, 3969 – 3972; k) V. K. Aggarwal, P. A. Bethel, R. Giles, J. Chem. Soc. Perkin Trans. 1 1999, 3315 – 3321; l) Y. Mi, J. V. Schreiber, E. J. Corey, J. Am. Chem. Soc. 2002, 124, 11290 – 11291; m) W.-D. Z. Li, J.-H. Yang, Org. Lett. 2004, 6, 1849 – 1852; n) N. Ribeiro, S. Streiff, D. Heissler, M. Elhabiri, A. M. Albrecht-Gary, M. Atsumi, M. Gotoh, L. D¦saubry, Y. Nakatani, G. Ourisson, Tetrahedron 2007, 63, 3395 – 3407; o) R. Tong, J. C. Valentine, F. E. McDonald, R. Cao, X. Fang, K. I. Hardcastle, J. Am. Chem. Soc. 2007, 129, 1050 – 1051. a) D. W. Brooks, H. Mazdiyasni, P. G. Grothaus, J. Org. Chem. 1987, 52, 3223 – 3232; b) Z.-L. Wei, Z.-Y. Li, G.-Q. Lin, Synthesis 2000, 1673 – 1676. M. A. Blanchette, W. Choy, J. T. Davis, A. P. Essenfeld, S. Masamune, W. R. Roush, T. Sakai, Tetrahedron Lett. 1984, 25, 2183 – 2186. I. Nakagawa, T. Hata, Tetrahedron Lett. 1975, 16, 1409 – 1412. Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication [16] a) H. S. Schultz, H. B. Freyermuth, S. R. Buc, J. Org. Chem. 1963, 28, 1140 – 1142; b) K. Jeyakumar, R. D. Chakravarthy, D. K. Chand, Catal. Commun. 2009, 10, 1948 – 1951. [17] Bromide 9 was prepared in 82 % yield by the reaction of (E)-4-(tert-butyldiphenylsilyl)oxy-3-methylbut-2-en-1-ol[18] with PBr3 in Et2O at 0 8C. [18] S. Ikeda, M. Shibuya, Y. Iwabuchi, Chem. Commun. 2007, 504 – 506. [19] M. Mohri, H. Kinoshita, K. Inomata, H. Kotake, Chem. Lett. 1985, 451 – 454. [20] W. Zhang, M. J. Robins, Tetrahedron Lett. 1992, 33, 1177 – 1180. [21] The effectiveness of LiCl in Kumada – Tamao – Corriu coupling reaction has been reported. V. S. Enev, H. Kaehlig, J. Mulzer, J. Am. Chem. Soc. 2001, 123, 10764 – 10765. [22] a) Y. Gao, R. M. Hanson, J. M. Klunder, S. Y. Ko, H. Masamune, K. B. Sharpless, J. Am. Chem. Soc. 1987, 109, 5765 – 5780; b) T. Katsuki, V. S. Martin, Org. React. 1996, 48, 1 – 299. [23] a) D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155 – 4156; b) D. B. Dess, J. C. Martin, J. Am. Chem. Soc. 1991, 113, 7277 – 7287; c) R. K. Boeckman, Jr., P. Shao, J. J. Mullins, Org. Synth. 2000, 77, 141 – 152. [24] See the Supporting Information for the preparation of substrates 1 d–h. [25] Very recently, Corey and Rajendar reported that conversion of epoxyalcohols to the corresponding alkoxy-SnCl3 complexes could induce cyclization through an intramolecular mode of action. See reference [7k]. [26] For the use of a vinyl group as a cation-stabilizing auxiliary, see: a) E. J. Corey, K. Liu, J. Am. Chem. Soc. 1997, 119, 9929 – 9930; b) J. Stephen Clark, J. Myatt, C. Wilson, L. Roberts, N. Walshe, Chem. Commun. 2003, 1546 – 1547. [27] Shenvi and Pronin suggested that a chloride anion could be generated by dissociation of either Lewis acid or its metallate anion, and alumi-
Chem. Eur. J. 2015, 21, 17605 – 17609
www.chemeurj.org
[28] [29]
[30] [31]
[32]
[33]
[34]
num Lewis acids are superior because the anions are most effectively sequestered away from the cation. See reference [9a]. E. J. Corey, M. Sodeoka, Tetrahedron Lett. 1991, 32, 7005 – 7008. Olefin isomers 16 ab and a trace amount of 17 were obtained upon treatment of trisubstituted olefin isomer 16 a with TfOH in CH2Cl2 at ¢78 8C. This result clearly revealed the generation of the corresponding cation intermediate from 16 a, which did not react with the allylsilane moiety. The use of Et2AlCl or BF3·OEt2 instead of TfOH resulted in complete recovery of 16 a. Tricyclo[7.3.1.02, 7]tridecane derivatives could be obtained by a 5-exo cyclization followed by rearrangement (i.e. 4’!2 in Scheme 1); however, it is unlikely that the 5-exo cyclization proceeds to form an unstabilized cation intermediate like 4’. For the use of a styryl group as a cation-stabilizing auxiliary, see: H. Matsukura, M. Morimoto, H. Koshino, T. Nakata, Tetrahedron Lett. 1997, 38, 5545 – 5548. Vinyl epoxide 22 was prepared following the same reaction sequence as that for 1 c except for the use of bromide i[34] instead of bromide 9.. J. D. Neighbors, M. S. Salnikova, J. A. Beutler, D. F. Wiemer, Bioorg. Med. Chem. 2006, 14, 1771 – 1784.
Received: October 5, 2015 Published online on October 22, 2015
17609
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication
& Bioinspired Synthesis
Construction of Bridged Polycyclic Systems by Polyene Cyclization Keisuke Suzuki, Hiroyuki Yamakoshi, and Seiichi Nakamura*[a] Abstract: A stereoselective construction of bridged triand tetracyclic systems embedded in some 3,5-dimethylorsellinic acid (DMOA)-derived meroterpenoids was achieved by exploiting a polyene cyclization of suitably functionalized epoxyallylsilanes. Both the olefinic substituent on the epoxide and allylic trimethylsilyl (TMS) group were found to play pivotal roles in the success of the present reaction. The fact that the cyclization of monocyclized byproducts did not proceed strongly suggests that the reaction could be a concerted transformation.
A number of meroterpenoids containing a bridged [7.3.1.02, 7] tricyclic system and their derivatives have been isolated and characterized as fungal metabolites since the discovery of neoaustin in 1994 (Figure 1).[1, 2] Although some of these natural products have been reported to display remarkable biological activities (e.g., inhibition of caspase-1), studies toward the synthesis of these meroterpenoids have not been reported to date. In contrast, their novel polycyclic architecture stimulated considerable interest in their biosynthesis, leading to elucidation of the biosynthetic pathway on the basis of intermediates and bioinformatics studies.[3] It has been proposed that the characteristic carbocyclic framework is formed by an acid-promoted polyene cyclization of the epoxide, generated by C-alkylation of DMOA with farnesyl pyrophosphate followed by regioselective epoxidation.[4] Polyene cyclization is a well-known reaction that was first reported in the 1920s[5] and has been extensively studied for 60 years.[6, 7] Utilizing this biomimetic reaction, multiple rings can be formed in a single operation and stereocenters are installed in a stereoselective manner in many cases. The synthetic utility of the reaction has been demonstrated by the total syntheses of many natural products containing a fused polycyclic ring system.[8] However, to our surprise, bridged polycyclic systems have never been created by this cascade reaction without combinational use of rearrangement reactions.[9] We, therefore, wondered whether we could take advantage of the polyene cyclization reaction for the synthesis of bridged polycyclic compounds.
[a] K. Suzuki, Dr. H. Yamakoshi, Prof. Dr. S. Nakamura Graduate School of Pharmaceutical Sciences, Nagoya City University 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603 (Japan) E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201503969. Chem. Eur. J. 2015, 21, 17605 – 17609
Figure 1. Structures of meroterpenoids containing a common bridged polycyclic system.
We envisioned epoxydiene 1 as a suitable precursor to bridged tricyclic compound 2 by way of generation of cationic intermediate 3 triggered by exposure to acid, 6-endo cyclization that provides cation 4, and elimination (Scheme 1). The major concern with this polycyclization was the competing 5exo closure of intermediate 3, giving rise to [6,5,6]-fused tricyclic compound 2’.[10] In this regard, we noticed an unexceptional substitution of a methoxycarbonyl group at a bridgehead carbon atom in natural products. It was anticipated that introduction of an ester functionality as the R1 substituent would suppress the generation of a positive charge a to the electronwithdrawing substituent, leading to the preferential formation of bridged compound 2. Since the ester group lowers the electron density of the p-bond, we decided to use substrate 1 with a TMS group at the allylic position (R2 = TMS) aiming not only to enhance the nucleophilicity of the p-bond, but also to stabilize the positive charge on the b-carbon atom in intermediate 4.[11, 12] However, it remains uncertain whether conformational constraints imposed by the six-membered ring would allow intermediate 3 to adopt a required conformation for cyclization to occur. Synthesis of cyclization precursors 1 commenced with enantiomerically pure alcohol 5 (> 99 % ee), obtained through biore-
17605
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication
Scheme 1. Biosynthesis-inspired approach to bridged tricyclic compounds.
Scheme 2. Synthesis of cyclization precursors 1 a–c: a) POCl3, pyridine, RT to 80 8C; b) OsO4 (1 mol %), NMO, aq THF, 64 % (2 steps); c) H2, 10 % Pd/C, EtOH; d) NaIO4, aq CH2Cl2 ; e) DBU, LiCl, (EtO)2P(O)CHMeCO2Et, MeCN; f) DIBALH, CH2Cl2, ¢78 8C, 90 % (4 steps); g) PhSSPh, Bu3P, THF, 99 %; h) [(NH4)6Mo7O24·4H2O] (20 mol %), H2O2, pyridine, EtOH, 99 %; i) BuLi, bromide 9, THF/HMPA, ¢78 8C, 99 %; j) LiEt3BH, [PdCl2(dppp)] (5 mol %), THF, 0 8C; k) aq HCl, THF, 65 8C; l) NH4F, EtOH/MeOH, 56 % (3 steps); m) DHP, PPTS, CH2Cl2, 98 %; n) LDA, EtOCOCN, THF/HMPA, ¢78 8C, 84 %; o) NaH, Tf2O, Et2O, 95 %; p) TMSCH2MgCl, [Pd(PPh3)4] (5 mol %), LiCl, dioxane, 60 8C, 96 %; q) PPTS (10 mol %), EtOH, 50 8C, 99 %; r) L-DIPT (13 mol %), Ti(OiPr)4 (10 mol %), tBuO2H, 4 æ MS, CH2Cl2, ¢20 8C, 92 %, d.r. = 97:3; s) TBSCl, imidazole, CH2Cl2, 91 %; t) Dess-Martin periodinane, CH2Cl2, 97 %; u) Ph3PMeBr, KHMDS, THF, 0 8C, 94 %. NMO = N-methylmorpholine-N-oxide; DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene; TBDPS = tert-butyldiphenylsilyl; dppp = 1,3-bis(diphenylphosphino)propane; DHP = 3,4-dihydro-2H-pyran; PPTS = pyridinium p-toluenesulfonate; LDA = lithium diisopropylamide; DIPT = diisopropyl tartrate; MS = molecular sieves; KHMDS = potassium hexamethyldisilazane.
duction using baker’s yeast (Scheme 2).[13] Dehydration of alcohol 5 with POCl3 was followed by selective dihydroxylation under catalytic conditions to afford diol 6 in 64 % yield. After Chem. Eur. J. 2015, 21, 17605 – 17609
www.chemeurj.org
hydrogenation of the resultant olefin with the aid of 10 % Pd/ C, oxidative cleavage of the vicinal diol with NaIO4, followed by Horner–Wadsworth–Emmons reaction under Masamune conditions,[14] and reduction with diisobutylaluminum hydride (DIBALH) provided (E)-allyl alcohol 7 in 90 % overall yield for the four-step sequence. The hydroxy group in 7 was transformed to phenyl sulfone in a two-step process involving treatment with phenyl disulfide/tributylphosphine in tetrahydrofuran (THF)[15] and MoVI-catalyzed oxidation with H2O2[16] in preparation for the homologation. While alkylation of sulfone 8 with bromide 9[17] in THF/hexamethylphosphoric triamide (HMPA) proceeded quantitatively at ¢78 8C, removal of the superfluous phenylsulfonyl group by PdII-catalyzed reduction with SuperHydride[19] was accompanied by olefin isomerization, affording a 6:1 mixture of inseparable isomers. The isomers could be separated after acid hydrolysis of 1,3-dioxolane and desilylation with NH4F[20] to give allyl alcohol 10 in 56 % overall yield for the three-step sequence. After interim protection of the hydroxyl group as a tetrahydropyran-2-yl (THP) ether (98 % yield), C-acylation with Mander’s reagent in THF/HMPA gave ester 12 in 84 % yield. Installation of a TMS methyl group was achieved using a two-step procedure involving enol triflate formation (95 % yield) and Kumada–Tamao–Corriu cross-coupling, which was rendered reproducible and high-yielding (96 %) by the addition of LiCl.[21] At this juncture, the THP ether was uneventfully deprotected under mild acidic conditions (99 % yield) to give allyl alcohol 15, which was then subjected to Sharpless epoxidation[22] to afford 1 a in 92 % yield. Protection of alcohol 1 a with tert-butyldimethylsilyl (TBS) chloride provided TBS ether 1 b in 91 % yield, whereas vinyl epoxide 1 c was obtained in 91 % yield by Dess–Martin oxidation[23] and subsequent Wittig olefination.[24] With the route to epoxyallysilanes secured, we then proceeded to investigate the polycyclization reaction. While some hydroxymethyl oxiranes underwent cyclization upon exposure to SnCl4 in CH2Cl2,[12b] the SnCl4-promoted reaction of epoxyalcohol 1 a did not proceed at ¢55 8C and raising the temperature to 0 8C led only to decomposition.[25] The reactivity of the epoxide was enhanced by protection of the hydroxy group as a TBS ether, but a complex mixture was obtained by treatment of 1 b with SnCl4 in CH2Cl2 at ¢55 8C. We were gratified to find that the desired polycyclization occurred even at ¢78 8C when vinyl epoxide 1 c was reacted with SnCl4 in CH2Cl2, affording tricyclic compound 2 c in 56 % yield, without any 5-exo cyclization products isolated (Table 1, entry 1).[26] Titanium Lewis acids also promoted the desired cyclization, albeit in comparable yield due to the formation of byproducts 16–18 (entry 2). Isolation of allyl chloride 18 resulting from SN2’-type substitution prompted us to investigate promoters devoid of chlorine atoms,[27] but all attempts proved unsuccessful (entries 3–5). Finally, we found that a higher yield (67 %) could be obtained with Et2AlCl, the utility of which in polyene cyclization was documented by Corey and Sodeoka,[28] whereas the use of more Lewis acidic EtAlCl2 afforded no discernible benefit (entries 6 and 7). The chemical yield was further improved to 72 % by a decrease in reaction temperature to ¢98 8C (entry 8). It is noteworthy that monocyclization product 16 a could not be
17606
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication Table 2. Effect of substituents R1 and R2.
Table 1. Polycyclization of epoxyallylsilane 1 c.
Entry
Lewis acid
T [8C]
Yield [%]
1 2 3[a] 4 5 6[a] 7[a] 8[a]
SnCl4 (iPrO)2TiCl2 BF3·OEt2 TMSOTf TfOH EtAlCl2 Et2AlCl Et2AlCl
¢78 ¢78 ¢78 ¢78 ¢78 ¢78 ¢78 ¢98
56 59 47 27 28 57 67 72
[a] Product 2 c was obtained after hydrolysis of the corresponding TMS ether with TsOH in THF/MeOH (3:1).
Chem. Eur. J. 2015, 21, 17605 – 17609
www.chemeurj.org
Substrate R1
R2
Lewis acid
Product Yield [%]
1[a] 2 3 4[a] 5[a] 6[a] 7
1c 1d 1e 1e 1f 1g 1h
TMS TMS TMS TMS TMS TMS H
Et2AlCl Et2AlCl Et2AlCl BF3·OEt2 Et2AlCl Et2AlCl Et2AlCl
2c 2d 2e 2e 2f 2g 2c
CH=CH2 Z-CH=CHPh E-CH=CHCO2Et E-CH=CHCO2Et E-CH=CHCOiPr CCH CH=CH2
67 0[b] NR 65 42 33 0
[a] Products were obtained after hydrolysis of the corresponding TMS ether with TsOH in THF/MeOH (3:1). [b] Ketone 21 resulting from semipinacol rearrangement was obtained in 92 % yield. NR = no reaction.
converted to tricyclic product 2 c upon exposure to TfOH in CH2Cl2 at ¢78 8C,[29, 30] which indicates that the polycyclization could be a concerted rather than stepwise transformation (Scheme 3). In contrast to epoxyallylsilane 1 c, the reaction of which is presumed to proceed through a chair–chair–chairlike transition state (TS) A, the use of its diastereomer 19 was disappointing because polycyclization product 20, derived from the chair–boat–chairlike TS B, was obtained in only 13 % yield.[31] At this juncture, we surmised that the p-bonding electron density could influence the outcome of the reaction (Table 2). It was found that incorporation of a phenyl group facilitated semipinacol rearrangement, leading to the high-yielding (92 %) conversion to ketone 21 (Table 2, entry 2).[32] While the reaction of a,b-unsaturated ester 1 e did not proceed under optimized conditions (entry 3), desired product 2 e could be obtained in
Scheme 3. Attempts at cyclizations of byproduct 16 a and diastereomer 19.
Entry
comparable yield (65 %) when treated with BF3·OEt2 (entry 4). Conjugate enone 1 f and alkyne 1 g were completely consumed with the aid of Et2AlCl; however, the yields were less than satisfactory due to the formation of monocyclized byproducts (entries 5 and 6). The fact that the desired polycyclization of vinyl epoxide 1 h did not occur under optimized conditions revealed that the TMS group was critical to the success of this polycyclization reaction (entry 7). With a [7.3.1.02, 7] tricyclic framework successfully constructed, we next undertook an investigation into the extension of the protocol to construction of a tetracyclic system. As expected, treatment of vinyl epoxide 22[33] with Et2AlCl in CH2Cl2 at ¢78 8C resulted in the simultaneous creation of three six-membered rings, providing tetracyclo[11.3.1.02, 11.05, 10]heptadecane derivative 23 in 37 % yield (Scheme 4). While there is considerable room for improvement in the chemical yield of 23, the average yield of approximately 72 % per ring formed would be acceptable considering the suggestion by Corey and Shenvi that the chemical polycyclizations proceed at best with an efficiency of 70–80 % per ring formed.[7a] In conclusion, we have demonstrated that Et2AlCl-promoted polycyclization of epoxyallylsilanes in CH2Cl2 gave bridged triand tetracyclic compounds in acceptable yields with perfect stereoselectivity. This protocol represents the first example of
Scheme 4. Et2AlCl-promoted polycyclization with vinyl epoxide 22.
17607
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication employing polyene cyclization reactions in the construction of bridged polycyclic compounds. Further efforts toward the total syntheses of DMOA-derived meroterpenoids are currently underway in our laboratory and will be reported in due course.
Acknowledgements
[8]
This research was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, the Platform Project for Supporting in Drug Discovery and Life Science Research from Japan Agency for Medical Research and Development (AMED), and the Sasakawa Scientific Research Grant from The Japan Science Society. Keywords: bioinspired synthesis · bridged cyclization · Lewis acids · meroterpenoids
polycycles
·
[1] For a review, see: R. Geris, T. J. Simpson, Nat. Prod. Rep. 2009, 26, 1063 – 1094. [2] For representative reports, see: a) H. Hayashi, M. Mukaihara, S. Murao, M. Arai, A. Y. Lee, J. Clardy, Biosci. Biotechnol. Biochem. 1994, 58, 334 – 338; b) R. M. Geris dos Santos, E. Rodrigues-Fo, Phytochemistry 2002, 61, 907 – 912; c) R. M. G. Santos, E. Rodrigues-Fo, Z. Naturforsch. C 2003, 58, 663 – 669; d) D. B. Stierle, A. A. Stierle, J. D. Hobbs, J. Stokken, J. Clardy, Org. Lett. 2004, 6, 1049 – 1052; e) T. P. Fill, G. K. Pereira, R. M. G. Santos, E. Rodrigues-Fo, Z. Naturforsch. B 2007, 62, 1035 – 1044; f) D. B. Stierle, A. A. Stierle, B. Patacini, K. McIntyre, T. Girtsman, E. Bolstad, J. Nat. Prod. 2011, 74, 2273 – 2277. [3] a) H.-C. Lo, R. Entwistle, C.-J. Guo, M. Ahuja, E. Szewczyk, J.-H. Hung, Y.M. Chiang, B. R. Oakley, C. C. C. Wang, J. Am. Chem. Soc. 2012, 134, 4709 – 4720; b) Y. Matsuda, T. Awakawa, T. Wakimoto, I. Abe, J. Am. Chem. Soc. 2013, 135, 10962 – 10965. [4] Polyprenylated acylphloroglucinols (PPAPs) constitute a well-known family of meroterpenoids containing a bridged [3.3.1] bicyclic system, which is also biosynthesized through a dearomatization–cyclization sequence. For bioinspired total syntheses of PPAPs, see: a) D. R. Siegel, S. J. Danishefsky, J. Am. Chem. Soc. 2006, 128, 1048 – 1049; b) J. Qi, J. A. Porco Jr., J. Am. Chem. Soc. 2007, 129, 12682 – 12683; c) Q. Zhang, B. Mitasev, J. Qi, J. A. Porco Jr., J. Am. Chem. Soc. 2010, 132, 14212 – 14215; d) J. H. George, M. D. Hesse, J. E. Baldwin, R. M. Adlington, Org. Lett. 2010, 12, 3532 – 3535; e) N. S. Simpkins, M. D. Weller, Tetrahedron Lett. 2010, 51, 4823 – 4826; f) Q. Zhang, J. A. Porco, Jr., Org. Lett. 2012, 14, 1796 – 1799; g) B. A. Sparling, D. C. Moebius, M. D. Shair, J. Am. Chem. Soc. 2013, 135, 644 – 647; h) H. P. Pepper, J. H. George, Angew. Chem. Int. Ed. 2013, 52, 12170 – 12173; Angew. Chem. 2013, 125, 12392 – 12395; i) J. H. Boyce, J. A. Porco, Jr., Angew. Chem. Int. Ed. 2014, 53, 7832 – 7837; Angew. Chem. 2014, 126, 7966 – 7971; for reviews, see: j) R. Ciochina, R. B. Grossman, Chem. Rev. 2006, 106, 3963 – 3986; k) J.-A. Richard, R. H. Pouwer, D. Y.-K. Chen, Angew. Chem. Int. Ed. 2012, 51, 4536 – 4561; Angew. Chem. 2012, 124, 4612 – 4638. [5] a) L. Ruzicka, E. Capato, Helv. Chim. Acta 1925, 8, 259 – 274; for landmark studies that had a decisive influence on the following research, see: b) G. Stork, A. W. Burgstahler, J. Am. Chem. Soc. 1955, 77, 5068 – 5077; c) A. Eschenmoser, L. Ruzicka, O. Jeger, D. Arigoni, Helv. Chim. Acta 1955, 38, 1890 – 1904. [6] For reviews, see: a) K. U. Wendt, G. E. Schulz, E. J. Corey, D. R. Liu, Angew. Chem. Int. Ed. 2000, 39, 2812 – 2833; Angew. Chem. 2000, 112, 2930 – 2952; b) R. A. Yoder, J. N. Johnston, Chem. Rev. 2005, 105, 4730 – 4756. [7] For recent examples, see: a) R. A. Shenvi, E. J. Corey, Org. Lett. 2010, 12, 3548 – 3551; b) S. Rendler, D. W. C. MacMillan, J. Am. Chem. Soc. 2010, 132, 5027 – 5029; c) R. R. Knowles, S. Lin, E. N. Jacobsen, J. Am. Chem. Soc. 2010, 132, 5030 – 5032; d) S. G. Sethofer, T. Mayer, F. D. Toste, J. Am. Chem. Soc. 2010, 132, 8276 – 8277; e) S. A. Snyder, D. S. Treitler, A. P. Brucks, J. Am. Chem. Soc. 2010, 132, 14303 – 14314; f) A. Sakakura, M. Sakuma, K. Ishihara, Org. Lett. 2011, 13, 3130 – 3133; g) J. G. Sokol, C. S. Chem. Eur. J. 2015, 21, 17605 – 17609
www.chemeurj.org
[9]
[10]
[11]
[12]
[13] [14] [15]
17608
Korapala, P. S. White, J. J. Becker, M. R. Gagn¦, Angew. Chem. Int. Ed. 2011, 50, 5658 – 5661; Angew. Chem. 2011, 123, 5776 – 5779; h) K. Surendra, W. Qiu, E. J. Corey, J. Am. Chem. Soc. 2011, 133, 9724 – 9726; i) K. Surendra, E. J. Corey, J. Am. Chem. Soc. 2012, 134, 11992 – 11994; j) S. P. Morcillo, D. Miguel, S. Resa, A. Martn-Lasanta, A. Milln, D. ChoquesilloLazarte, J. M. Garca-Ruiz, A. J. Mota, J. Justicia, J. M. Cuerva, J. Am. Chem. Soc. 2014, 136, 6943 – 6951; k) G. Rajendar, E. J. Corey, J. Am. Chem. Soc. 2015, 137, 5837 – 5844. a) E. J. Corey, M. A. Tius, J. Das, J. Am. Chem. Soc. 1980, 102, 1742 – 1744; b) S. P. Tanis, Y.-H. Chuang, D. B. Head, Tetrahedron Lett. 1985, 26, 6147 – 6150; c) W. S. Johnson, M. S. Plummer, S. P. Reddy, W. R. Bartlett, J. Am. Chem. Soc. 1993, 115, 515 – 521; d) E. J. Corey, J. Lee, J. Am. Chem. Soc. 1993, 115, 8873 – 8874; e) A. B. Smith, III, T. Kinsho, T. Sunazuka, S. O¯mura, Tetrahedron Lett. 1996, 37, 6461 – 6464; f) E. J. Corey, G. Luo, L. S. Lin, J. Am. Chem. Soc. 1997, 119, 9927 – 9928; g) W. S. Johnson, W. R. Bartlett, B. A. Czeskis, A. Gautier, C. H. Lee, R. Lemoine, E. J. Leopold, G. R. Luedtke, K. J. Bancroft, J. Org. Chem. 1999, 64, 9587 – 9595; h) A. X. Huang, Z. Xiong, E. J. Corey, J. Am. Chem. Soc. 1999, 121, 9999 – 10003; i) M. Bogensttter, A. Limberg, L. E. Overman, A. L. Tomasi, J. Am. Chem. Soc. 1999, 121, 12206 – 12207; j) J. D. Rainier, A. B. Smith III, Tetrahedron Lett. 2000, 41, 9419 – 9423; k) D. Yang, M. Xu, Org. Lett. 2001, 3, 1785 – 1788; l) H. Ishibashi, K. Ishihara, H. Yamamoto, J. Am. Chem. Soc. 2004, 126, 11122 – 11123; m) Y.-J. Zhao, T.-P. Loh, Org. Lett. 2008, 10, 2143 – 2145; n) D. C. Behenna, E. J. Corey, J. Am. Chem. Soc. 2008, 130, 6720 – 6721; o) R. Tong, F. E. McDonald, Angew. Chem. Int. Ed. 2008, 47, 4377 – 4379; Angew. Chem. 2008, 120, 4449 – 4451; p) M. B. Kim, J. T. Shaw, Org. Lett. 2010, 12, 3324 – 3327; q) S. A. Snyder, D. S. Treitler, A. Schall, Tetrahedron 2010, 66, 4796 – 4804; r) E. C. Cherney, J. C. Green, P. S. Baran, Angew. Chem. Int. Ed. 2013, 52, 9019 – 9022; Angew. Chem. 2013, 125, 9189 – 9192; s) O. F. Jeker, A. G. Kravina, E. M. Carreira, Angew. Chem. Int. Ed. 2013, 52, 12166 – 12169; Angew. Chem. 2013, 125, 12388 – 12391; t) B. R. Rosen, E. W. Werner, A. G. O’Brien, P. S. Baran, J. Am. Chem. Soc. 2014, 136, 5571 – 5574; u) T. N. Barrett, A. G. M. Barrett, J. Am. Chem. Soc. 2014, 136, 17013 – 17015. The cedrene/funebrene and kaurane carbon frameworks were constructed, albeit in low yield, by a tandem reaction, wherein cationic polycyclization was combined with a hydride shift and pinacol rearrangement, respectively; a) S. V. Pronin, R. A. Shenvi, Nat. Chem. 2012, 4, 915 – 920; b) S. Desjardins, G. Maertens, S. Canesi, Org. Lett. 2014, 16, 4928 – 4931. Corey and Myers groups reported that 5-exo cyclizations occurred exclusively to afford [6,6,5,5]-fused tetracyclic compounds in the system capable of either 5-exo or 6-endo closure; a) E. J. Corey, H. B. Wood Jr., J. Am. Chem. Soc. 1996, 118, 11982 – 11983; b) A. G. Myers, M. Siu, Tetrahedron 2002, 58, 6397 – 6404. Conjugate esters are known to be poor terminating groups for polyene cyclization reactions. E. E. Van Tamelan, Acc. Chem. Res. 1968, 1, 111 – 120. For the use of epoxyallylsilanes/epoxypropargylsilanes to construct fused polycyclic ring systems, see: a) R. J. Armstrong, L. Weiler, Can. J. Chem. 1986, 64, 584; b) S. Hatakeyama, H. Numata, K. Osanai, S. Takano, J. Chem. Soc. Chem. Commun. 1989, 1893 – 1895; c) N. K. N. Yee, R. M. Coates, J. Org. Chem. 1992, 57, 4598 – 4608; d) M. Taton, P. Benveniste, A. Rahier, Biochemistry 1992, 31, 7892 – 7898; e) K. Mori, S. Aki, M. Kido, Liebigs Ann. Chem. 1994, 319 – 324; f) P. V. Fish, W. S. Johnson, J. Org. Chem. 1994, 59, 2324 – 2335; g) P. V. Fish, Tetrahedron Lett. 1994, 35, 7181 – 7184; h) E. J. Corey, J. Lee, D. R. Liu, Tetrahedron Lett. 1994, 35, 9149 – 9152; i) S. E. Sen, S. L. Roach, S. M. Smith, Y. z. Zhang, Tetrahedron Lett. 1998, 39, 3969 – 3972; k) V. K. Aggarwal, P. A. Bethel, R. Giles, J. Chem. Soc. Perkin Trans. 1 1999, 3315 – 3321; l) Y. Mi, J. V. Schreiber, E. J. Corey, J. Am. Chem. Soc. 2002, 124, 11290 – 11291; m) W.-D. Z. Li, J.-H. Yang, Org. Lett. 2004, 6, 1849 – 1852; n) N. Ribeiro, S. Streiff, D. Heissler, M. Elhabiri, A. M. Albrecht-Gary, M. Atsumi, M. Gotoh, L. D¦saubry, Y. Nakatani, G. Ourisson, Tetrahedron 2007, 63, 3395 – 3407; o) R. Tong, J. C. Valentine, F. E. McDonald, R. Cao, X. Fang, K. I. Hardcastle, J. Am. Chem. Soc. 2007, 129, 1050 – 1051. a) D. W. Brooks, H. Mazdiyasni, P. G. Grothaus, J. Org. Chem. 1987, 52, 3223 – 3232; b) Z.-L. Wei, Z.-Y. Li, G.-Q. Lin, Synthesis 2000, 1673 – 1676. M. A. Blanchette, W. Choy, J. T. Davis, A. P. Essenfeld, S. Masamune, W. R. Roush, T. Sakai, Tetrahedron Lett. 1984, 25, 2183 – 2186. I. Nakagawa, T. Hata, Tetrahedron Lett. 1975, 16, 1409 – 1412. Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication [16] a) H. S. Schultz, H. B. Freyermuth, S. R. Buc, J. Org. Chem. 1963, 28, 1140 – 1142; b) K. Jeyakumar, R. D. Chakravarthy, D. K. Chand, Catal. Commun. 2009, 10, 1948 – 1951. [17] Bromide 9 was prepared in 82 % yield by the reaction of (E)-4-(tert-butyldiphenylsilyl)oxy-3-methylbut-2-en-1-ol[18] with PBr3 in Et2O at 0 8C. [18] S. Ikeda, M. Shibuya, Y. Iwabuchi, Chem. Commun. 2007, 504 – 506. [19] M. Mohri, H. Kinoshita, K. Inomata, H. Kotake, Chem. Lett. 1985, 451 – 454. [20] W. Zhang, M. J. Robins, Tetrahedron Lett. 1992, 33, 1177 – 1180. [21] The effectiveness of LiCl in Kumada – Tamao – Corriu coupling reaction has been reported. V. S. Enev, H. Kaehlig, J. Mulzer, J. Am. Chem. Soc. 2001, 123, 10764 – 10765. [22] a) Y. Gao, R. M. Hanson, J. M. Klunder, S. Y. Ko, H. Masamune, K. B. Sharpless, J. Am. Chem. Soc. 1987, 109, 5765 – 5780; b) T. Katsuki, V. S. Martin, Org. React. 1996, 48, 1 – 299. [23] a) D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155 – 4156; b) D. B. Dess, J. C. Martin, J. Am. Chem. Soc. 1991, 113, 7277 – 7287; c) R. K. Boeckman, Jr., P. Shao, J. J. Mullins, Org. Synth. 2000, 77, 141 – 152. [24] See the Supporting Information for the preparation of substrates 1 d–h. [25] Very recently, Corey and Rajendar reported that conversion of epoxyalcohols to the corresponding alkoxy-SnCl3 complexes could induce cyclization through an intramolecular mode of action. See reference [7k]. [26] For the use of a vinyl group as a cation-stabilizing auxiliary, see: a) E. J. Corey, K. Liu, J. Am. Chem. Soc. 1997, 119, 9929 – 9930; b) J. Stephen Clark, J. Myatt, C. Wilson, L. Roberts, N. Walshe, Chem. Commun. 2003, 1546 – 1547. [27] Shenvi and Pronin suggested that a chloride anion could be generated by dissociation of either Lewis acid or its metallate anion, and alumi-
Chem. Eur. J. 2015, 21, 17605 – 17609
www.chemeurj.org
[28] [29]
[30] [31]
[32]
[33]
[34]
num Lewis acids are superior because the anions are most effectively sequestered away from the cation. See reference [9a]. E. J. Corey, M. Sodeoka, Tetrahedron Lett. 1991, 32, 7005 – 7008. Olefin isomers 16 ab and a trace amount of 17 were obtained upon treatment of trisubstituted olefin isomer 16 a with TfOH in CH2Cl2 at ¢78 8C. This result clearly revealed the generation of the corresponding cation intermediate from 16 a, which did not react with the allylsilane moiety. The use of Et2AlCl or BF3·OEt2 instead of TfOH resulted in complete recovery of 16 a. Tricyclo[7.3.1.02, 7]tridecane derivatives could be obtained by a 5-exo cyclization followed by rearrangement (i.e. 4’!2 in Scheme 1); however, it is unlikely that the 5-exo cyclization proceeds to form an unstabilized cation intermediate like 4’. For the use of a styryl group as a cation-stabilizing auxiliary, see: H. Matsukura, M. Morimoto, H. Koshino, T. Nakata, Tetrahedron Lett. 1997, 38, 5545 – 5548. Vinyl epoxide 22 was prepared following the same reaction sequence as that for 1 c except for the use of bromide i[34] instead of bromide 9.. J. D. Neighbors, M. S. Salnikova, J. A. Beutler, D. F. Wiemer, Bioorg. Med. Chem. 2006, 14, 1771 – 1784.
Received: October 5, 2015 Published online on October 22, 2015
17609
Ó 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
