DOI: 10.1002/chem.201304798
Communication
& Carbonylation
Palladium-Catalyzed Alkoxycarbonylation of Terminal Alkenes To Produce a,b-Unsaturated Esters: The Key Role of Acetonitrile as a Ligand Andrei V. Malkov,*[a] Nolwenn Derrien,[a] Maciej Barłg,[b] and Pavel Kocˇovsky´*[c, d] Dedicated to Professor Bjçrn kermark on the occasion of his 80th birthday
Abstract: A mild protocol has been developed for the PdII-catalyzed alkoxycarbonylation of terminal olefins to produce a,b-unsaturated esters with a wide range of substrates. Key features are the use of MeCN as solvent (and/ or ligand) to control the reactivity of the intermediate Pd complexes and the combination of CO with O2, which facilitates the CuII-mediated reoxidation of the Pd0 complex to PdII and prevents double carbonylation.
Scheme 1. Oxidative alkoxycarbonylation of alkenes.
Carbon monoxide is an essential building block, allowing the transformation of readily available starting materials into more functionalized products, such as dyes, pharmaceuticals, and agrochemicals.[1] Oxidative alkoxycarbonylation of terminal alkenes 1 with CO in the presence of alcohols, catalyzed by PdII, is an important synthetic method because it allows the introduction of up to two functional groups into the molecule (Scheme 1).[2] Depending on the conditions, the reaction can result in three types of products: b-alkoxy esters 2 (route a), succinate derivatives 3 (route b), and a,b-unsaturated esters 4 (route c).[3] The first two routes have been extensively investigated, including mechanistic analysis and the development of enantioselective pathways.[4] By contrast, no adequate and
[a] Prof. Dr. A. V. Malkov, N. Derrien Chemistry Department Loughborough University Leicestershire, LE11 3TU (UK) Fax: (+ 44) 1509 22 3925 E-mail: [email protected] [b] Dr. M. Barłg Department of Chemistry, Texas A&M University at Qatar, P.O. Box 23874 Doha (Qatar) [c] Prof. Dr. P. Kocˇovsky´ Department of Organic Chemistry, Arrhenius Laboratory Stockholm University Stockholm SE 10691 (Sweden) E-mail: [email protected] [d] Prof. Dr. P. Kocˇovsky´ On leave from Department of Chemistry, WestChem University of Glasgow Glasgow, G12 8QQ (UK) E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201304798. Chem. Eur. J. 2014, 20, 4542 – 4547
practical method currently exists for directing the reaction selectively towards a,b-unsaturated esters 4. Previous reports on the synthesis of cinnamic esters by the carbonylation of styrene employed polymetallic systems, such as PdCl2/CuCl2/MgCl2/NaOAc[5] or PdCl2/CuCl2/Mn(OAc)2,[6] but the product yields and catalyst turnovers were low. Bianchini[7] reported on a selective formation of methyl cinnamate by using a Pd–diphosphine system. Depending on the conditions, and the nature of the phosphine ligand, either methyl cinnamate (selectivity 99 % at 75 % conversion) or the respective dimethyl succinate derivative (selectivity 88 %), was produced; however, the reaction required high CO pressure (800 psi) and elevated temperatures (80 8C). Oxidative methoxycarbonylation of styrene, catalyzed by PdII complexes with 1,1’(diphenylphosphino)-metallocene ligands, was shown to occur at lower CO pressures (43 psi),[8] although at the expense of the conversion and chemoselectivity of the reaction. Recently, a Pd-catalyzed oxidative carbonylation of terminal alkenes, to afford b,g-unsaturated esters, has been reported[9] and the reaction is believed to proceed by means of p-allyl Pd complexes generated by CH insertion.[10] However, the scope of this reaction appears to be limited to allylarenes with reactive CH bonds in the benzylic position (e.g., PhCH2CH=CH2). Herein, we present a mild protocol for the oxidative methoxycarbonylation of terminal alkenes 1!4, under an atmospheric pressure of CO, with a wide substrate range and good functional-group tolerance, resulting in a,b-unsaturated esters. In the course of our work on PdII-catalyzed carbonylative cyclization of olefinic carbamates,[11] we noticed that when the reaction was carried out in MeCN, an a,b-unsaturated ester of type 4 was formed; this outcome was found to be specific to the use of MeCN. We then set out to investigate this transformation in detail, with the aim to develop a new protocol for the carbonylation of alkenes and to obtain products that
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Communication Table 1. Optimization of chemoselectivity in the oxidative carbonylation of homoallylic carbonate 5 a catalyzed by Pd species.[a]
Entry
Catalyst [10 mol %]
Oxidant [3 equiv]
Conversion [%][b]
Ratio 6 a/7 a[c]
1 2 3 4 5 6
Pd(OAc)2 Pd(TFA)2 PdCl2 PdCl2 PdCl2 PdCl2
p-BQ p-BQ p-BQ CuCl2 FeCl3·6H2O Cu(OAc)2·2H2O
SM 50 70 SM SM 12
– 14:86 17:83 – – > 99:1
Table 2. Further optimization of the reaction conditions for the oxidative carbonylation of 5 a.[a]
[a] The reactions were carried out on a 0.50 mmol scale. A solution of the substrate in MeOH (4 mL) was added to a mixture of PdII catalyst (10 mol %) and oxidant (3 equiv) in MeCN (8 mL), under a CO atmosphere (balloon). The reaction mixture was then stirred at 60 8C for 24 h. [b] The conversion was calculated from the 1H NMR spectra by using naphthalene as an internal standard; SM = starting material. [c] Calculated from the 1H NMR spectra of the crude mixtures.
would normally be prepared by Wittig-type chemistry or olefin metathesis. To this end, the homoallylic carbonate, 5 a, with a terminal C=C bond, was chosen as a functionalized model substrate. The initial reactions were carried out under 1 atm of CO in the presence of a PdII catalyst and various oxidants, with MeCN as a solvent (Table 1). Initially, p-benzoquinone (p-BQ)[12] was evaluated as an oxidant with various palladium sources. Pd(OAc)2 proved to be inefficient (Table 1, entry 1), whereas moderate conversions were attained with Pd(TFA)2 (TFA = CF3CO2 ; 50 %, entry 2) and PdCl2 (70 %, entry 3). However, in both cases succinate 7 a, resulting from a double carbonylation, was identified as the major product, whereas the desired unsaturated ester, 6 a, was formed in minor quantities. Metal oxidants, CuCl2 or FeCl3·6 H2O, failed to show any conversion (entries 4 and 5). By contrast, the use of Cu(OAc)2·2 H2O gave exclusively the unsaturated ester 6 a, although with only 12 % conversion (entry 6). In the latter instance, rapid precipitation of palladium black was observed, blocking further reaction progress. To improve the conversion, we had to ensure a facile reoxidation of the Pd0 species to PdII, preventing agglomeration of the reduced Pd species and the subsequent precipitation of Pd black. After some experimentation, and following successful examples of Wacker-type oxidation chemistry,[13] we found that the use of an extra balloon of oxygen dramatically enhanced the regeneration of our palladium system. Thus, employing a 1:1 CO/O2 atmosphere, the a,b-unsaturated ester, 6 a, was obtained in 78 % yield (Table 2, entry 1). Notably, this protocol also allowed a decrease in the PdCl2 loading to 5 mol % and Cu(OAc)2·2 H2O to 1.2 equivalents. Tetrabutylammonium bromide, used to prevent the formation of colloidal Pd0species,[14] proved to be another important component of the reaction mixture and poor yields were obtained in its absence. On the other hand, the use of iodide Bu4N + I resulted in the formation of succinate 7 a as a major product. We also found that Chem. Eur. J. 2014, 20, 4542 – 4547
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Entry
Catalyst [5 mol %]
Additive
Solvent
Yield [%][b]
1 2 3 4 5 6 7 8 9 10 11 12
PdCl2 Pd(OAc)2 Pd(OAc)2 Pd(TFA)2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 [PdCl2(MeCN)2] [PdCl2(MeCN)2] [PdCl2(MeCN)2]
– – – – – DMSO [10 mol %] pyridine [10 mol %] CH(OEt)3 [10 mL] – – – –
MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN[g] THF MeCN MeCN THF
78[c] 62 20[d] 52 SM[e] 37[f] SM 42[f] SM 82 48[d] 72
[a] The reactions were carried out on a 0.50 mmol scale. Firstly, a mixture of the PdII catalyst (5 mol %), Cu(OAc)2·2 H2O (1.2 equiv), and Bu4N + Br (10 mol %) in a solvent (8 mL) was stirred under a CO atmosphere (balloon), at 40 8C for 2 h, followed by addition of a solution of the substrate in MeOH (4 mL) and then by introduction of O2 (second balloon). The reaction mixture was then stirred at 60 8C for 48 h. [b] Isolated yield; SM = starting material. [c] See entry 1 in Table 3. [d] Carried out in the absence of Bu4N + Br . [e] Carried out in the absence of Cu(OAc)2·2 H2O. [f] Succinate 7 a was formed as a major product (6 a/7 a 1:9). [g] Anhydrous Cu(OAc)2 was used.
the reaction mixture required vigorous stirring to prevent precipitation of Pd; any deposit appearing on the walls of the flask was easily redissolved by swirling. Replacing PdCl2 with Pd(OAc)2 or Pd(TFA)2[15] resulted in slightly reduced yields (62 and 52 %, respectively; Table 2, entries 2 and 4). In the absence of a halide ion the reaction stopped at low conversion (20 %), owing to the premature precipitation of Pd black (entry 3). As expected, no reaction was observed when molecular oxygen was used as the sole oxidant (entry 5), demonstrating that both oxygen and CuII are prerequisites for efficient reoxidation. Addition of 10 % DMSO to the reaction mixture (entry 6), known to accelerate reoxidation and prevent the precipitation of Pd black,[16] resulted in the formation of a complex mixture, with succinate 7 a being the main component. Pyridine, which is also known to facilitate the reoxidation of Pd0 species to PdII,[17] completely inhibited the reaction (entry 7); however, precipitation of the catalyst was not observed in this instance, suggesting that pyridine can compete with the substrate for coordination at the metal center. Acids, such as HCl and p-TsOH (TsOH = toluene sulfonic acid) were also found to inhibit the reaction, by eliciting a rapid precipitation of Pd black. Under anhydrous conditions, using Cu(OAc)2 and triethyl orthoformate,[18] the reaction switched to double carbonylation (entry 8). In THF, no conversion was observed (entry 9). These experiments allowed us to formulate a protocol with the following reaction conditions: the PdII and CuII salts should be dissolved in MeCN and the mixture should be heated at
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Communication 40 8C for 2 h under an atmosphere of CO, prior to the addition of a solution of the substrate in methanol.[19] This optimized protocol appears to indicate that MeCN plays an important role in the formation of the catalytically active species. The next experiments were, therefore, carried out with [(MeCN)2PdCl2] as a catalyst. In MeCN, 6 a was obtained in high yield (82 %, entry 10), and the reaction was found to proceed even in THF, previously identified as an unsuitable solvent (72 %, entry 12; compare with entry 9). In the absence of Bu4N + Br , the reaction afforded 6 a in lower yield (48 %, entry 11), reflecting the premature precipitation of Pd black (see also entry 3). After establishing the optimal conditions, the reaction scope was investigated by employing various terminal alkenes. The first group consisted of an extended range of homoallylic carbonates 5 a–h (Table 3, entries 1–9). The tert-butoxycarbonyl
Table 3. Oxidative alkoxycarbonylation of homoallylic carbonates and amides catalyzed by Pd.[a]
Entry
5
R1, R2, X
6 or 8
R3
Yield [%][b]
1
5a
H, H, OCO2Me
Me
78
2 3 4 5 6 7 8 9 10
5b 5c 5c 5d 5e 5f 5g 5h 5i
H, H, OCO2tBu Ph, H, OCO2Me Ph, H, OCO2Me 4-NO2C6H4, H, OCO2Me 3,4-(MeO)2C6H3, H, OCO2Me 2-thienyl, H, OCO2Me nC5H11, H, OCO2Me Ph, Me, OCO2Me[c] H, H, phthalimide
Me Me tBu Me Me Me Me Me Me
52 86 63 72 66 63 65 62 72
11
5j
Ph, H, phthalimide
Me
40[d]
12 13
5k 5l
Ph, H, NHCbz nC5H11, H, phthalimide
Me Me
60 12[d]
14
5m
nC5H11, H, NHCbz
Me
58
15
5n
nC5H11, H, NHTs
6 a/8 a (7:1) 6b 6c 6 c’ 6d 6e 6f 6g 6h 6 i/8 i (2.5:1) 6 j/8 j (6:1) 6k 6 l/8 l (3:1) 6 m/8 m (2.5:1) 6 n/8 n (3:1)
Me
53
tert-butanol, the respective tert-butyl ester, 6 c’, was isolated in 63 % yield (entry 4). The presence of an alkyl substituent in the a-position of the C=C bond[20] did not affect the reactivity (6 h, 62 %; entry 9). Related homoallylic amine derivatives 5 i–n were then investigated (Table 3, entries 10–15). Primary phthalimide 5 i reacted uneventfully (72 %), but secondary phthalimides 5 j and 5 l exhibited poor conversion, resulting in low isolated yields (40 % and 12 %, respectively). Carbonylation of carbamates 5 k and 5 m and tosylamide 5 n proceeded in acceptable yields (entries 12, 14, and 15). A general feature in all of these carbonylations was the formation of minor quantities of b,g-isomers 8, along with the expected a,b-unsaturated esters 6 in all but one case (6 k). It is noteworthy that the latter shift of the double bond (entries 10, 11, and 13–15) was not commonly observed in the carbonate series (entries 2–9), except for 5 a (entry 1), and, thus, seems to be characteristic of amides and imides, possibly originating from the enhanced propensity of these groups to coordinate Pd[11a] and other species,[21] affecting the reactivity of the intermediate complex. The reaction scope was further elucidated by using terminal alkenes 9 a–j (Table 4). Thus, the methoxycarbonylation of styrene afforded methyl cinnamate 10 a (87 %), but when the re-
Table 4. Oxidative methoxycarbonylation of alkenes.[a]
[a] The reactions were carried out on a 0.25–0.67 mmol scale. A mixture of PdCl2 (5 mol %), Cu(OAc)2·2 H2O (1.2 equiv), MeCN (8 mL) was stirred under a CO atmosphere (balloon), at 40 8C for 2 h, prior to the addition of a solution of the substrate ( 0.1 g) in R3OH (4 mL) and the introduction of an O2 balloon. The reaction mixture was then stirred at 60 8C for 24 h. Cbz = carbobenzyloxy, Ts = tosyl. [b] Isolated yield. [c] The syn-isomer of 5 h was employed. [d] Poor conversion.
[a] For conditions see Table 3.
(Boc) group turned out to be less suitable than methoxycarbonyl, as reflected in the reduced yield of 6 b (52 %, entry 2; compare with entry 1). Secondary carbonates with aryl (6 c–e), heteroaryl (6 f), and alkyl substituents (6 g) were obtained in good yields (63–86 %, entries 3–8). By replacing methanol with Chem. Eur. J. 2014, 20, 4542 – 4547
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action was carried out in tert-butanol instead of methanol, the yield (of 10 a’) dropped to 63 %, presumably owing to the increased steric bulk. Electron-rich and electron-poor styrenes (9 b and 9 c) readily produced the respective cinnamic esters 10 b and 10 c in good yields (70 and 62 %, respectively). Car-
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Communication bonylation of p-divinylbenzene 9 d afforded diester 10 d (82 %), with only traces of the monocarbonylated product detected. The cyclohexyl analogue, 10 e, isoxazolidine 10 f, and bromo derivative 10 g were obtained in practical yields (58–62 %). Carbonylation of the allyl silyl ether 9 h was accompanied by removal of the TMS group and a change in the position of the double bond, resulting in the formation of g-keto ester 10 h (65 %).[22] Two products were obtained from allyl benzene 9 i, namely the expected a,b-unsaturated ester, 10 i, and its b,g-isomer, 11, in a 1:3 ratio. Conjugation with the aromatic ring thus appears to be preferred over conjugation with the ester group. In a similar way, a-methylstyrene (9 j) furnished 10 j, presumably arising from the corresponding p-allyl Pd-complex. However, the reaction was sluggish, apparently owing to the steric hindrance; the product was formed in mere 20 % yield. According to the widely accepted mechanism,[4] PdCl2 and CO react with an olefin (in the absence of MeCN) to generate the corresponding h2-complex, which can react with MeOH either at the C O or C=C ligand, eventually giving rise to 2 or 3, depending on the actual conditions.[4] To account for the key role of MeCN, which promotes the formation of a,b-unsaturated esters 4 at the expense of 2 and 3 (Scheme 2), it can be reasoned that MeCN, as a ligand com-
The latter assumption is in line with the hypothesis that CO would not displace the remaining MeCN (as in A) under atmospheric pressure. However, the actual mechanism could be more complex, as Cu(OAc)2 is likely to play an additional role, by interacting with the Pd complex.[25] An alternative mechanism, involving chloropalladation[26] followed by HCl elimination, can be ruled out, since the reaction was found to proceed in the absence of halide ions (Table 2, entries 3 and 11), though less efficiently because of the premature precipitation of Pd black.[27] In order to illustrate the practical use of this new method, we resolved to synthesize the vanilloid receptor-1 antagonist TRPV-1 (16)[28] on a gram scale (Scheme 3). Under our standard
Scheme 3. Synthesis of the potent vanilloid receptor antagonist 16.
Scheme 2. Proposed mechanism for carbonylation (L = MeCN).
peting with CO, affects the reactivity of the Pd complex.[23] Thus, [(MeCN)2PdCl2], either used as such or generated in situ, when mixed with CO, can undergo a ligand exchange. It can be conjectured, however, that only one molecule of MeCN is replaced with CO in the equilibrium to generate the reactive complex A (L = MeCN), otherwise, if both molecules of MeCN were replaced, the reaction would follow the scenario discussed in the previous paragraph, giving rise to 2 or 3. Notably, the optimized reaction conditions require that the catalyst and CO (in MeCN) are allowed to “mature” before the olefin is added, indicating that an equilibrium needs to be reached prior to the reaction with the olefin. Complex A can then react with MeOH (added as a solvent of the substrate) to produce B,[24] which would then coordinate the olefin upon replacement of one of the MeCN molecules. The resulting complex, C, would then undergo olefin insertion to generate D. The latter complex, with MeCN in the coordination sphere of the Pd center, can then be assumed to react differently, compared with its counterpart lacking the MeCN ligand, and prefer b-H elimination over the second carbonylation, thus producing 4. Chem. Eur. J. 2014, 20, 4542 – 4547
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conditions, methoxycarbonylation of 4-tert-butylstyrene (12) afforded ester 13 (85 %), which was then hydrolyzed to furnish acid 14. The synthesis was completed by the conversion of 14 into the corresponding acid chloride, the reaction of which (in situ), with the aniline derivative 15, afforded the target amide 16 in 62 % yield over two steps (not optimized). The synthesis of 16 (920 mg) was, therefore, accomplished in three simple operations in 44 % overall yield. In conclusion, a mild protocol has been developed for the Pd-catalyzed alkoxycarbonylation of terminal alkenes to produce a,b-unsaturated esters (1!4) with a wide range of substrates. The reaction conditions, including PdCl2 (5 mol %), Cu(OAc)2 (1.2 equivalents), CO/O2 (1 atm), MeOH, and MeCN as a solvent, were optimized to attain good yields (60–87 % in most cases) and high chemoselectivity. Significantly, the reaction proceeds under an atmospheric pressure of CO and O2 (from two individual balloons), preventing the double carbonylation pathway and Pd-black precipitation. The use of oxygen as the second gas, which facilitates the reoxidation of the Pd0 species to PdII, mediated by CuII, and the key role of MeCN as a solvent (and Pd ligand) is particularly noteworthy. This new protocol can serve as an attractive alternative to the existing methods for the synthesis of a,b-unsaturated esters, such as Wittig-type alkenylation, cross-metathesis, Heck addition, and Suzuki–Miyaura coupling.[29] Of these methods, the new protocol is the most atom economical and sustainable because only two protons are lost from the reactants (one from the substrate olefin and one from MeOH).
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Communication Experimental Section General Procedure A 50 mL round-bottomed flask was charged with PdCl2 (5 mol %) and Cu(OAc)2·2 H2O (1.1 equivalents) and flushed first with N2, followed by CO. A CO balloon (diameter 15 cm) was then applied, MeCN (8 mL) was introduced by a syringe, and the reaction mixture was left to stir at 40 8C for 2 h. A solution of the substrate (0.5 mmol) in MeOH (4 mL) was added by a syringe, and an O2 balloon (diameter 7 cm) was applied. The reaction mixture was stirred at 60 8C for 24 h and then cooled. Ether (15 mL) was added and the mixture was washed with aqueous saturated NaHCO3 and brine and then dried over MgSO4. The solvent was evaporated under vacuum and the residue was purified by flash chromatography on silica gel (petroleum ether/Et2O 90:10) to afford a pure product. Note: a palladium deposit may occur during the reaction, but this can be easily re-dissolved by gentle shaking or swirling.[30] Experimental procedures, analytical and spectral data, and copies of the NMR spectra for the key compounds are available in the Supporting Information.
Acknowledgements We thank the EPSRC for grant EP/E011179/1 and Loughborough University for a fellowship to N. D. and other support. The Axel Wenner–Gren sabbatical scholarship awarded to P. K. and the additional support from COST through the ORCA action are also appreciated. Keywords: carbonylation · homogeneous catalysis · oxygen · palladium · solvent effects [1] B. Cornils, W. A. Herrmann, Applied Homogeneous Catalysis with Organometallic Compounds; Vol. 5: Applications, 2nd ed., Wiley-VCH, Weinheim, 2002, pp. 31 – 194. [2] a) P. P. Chiusoli, M. Costa in Handbook on Organopalladium Chemistry for Organic Synthesis Vol. 2, (Eds.: E. Negishi, A. de Meijere), Wiley, New York, 2002, pp. 2593 – 2623; b) J. Tsuji, Palladium Reagents and catalysts, Wiley-VCH, Weinheim, 2004, pp. 45 – 50; c) B. Gabriele, G. Salerno, M. Costa, Top. Organomet. Chem. 2006, 18, 239 – 272. [3] X.-F. Wu, H. Neumann, M. Beller, ChemSusChem 2013, 6, 229. [4] a) R. F. Heck, J. Am. Chem. Soc. 1969, 91, 6707 – 6714; b) R. F. Heck, J. Am. Chem. Soc. 1971, 93, 6896 – 6901; c) R. F. Heck, J. Am. Chem. Soc. 1972, 94, 2712 – 2716; d) D. M. Fenton, P. J. Steinwand, J. Org. Chem. 1972, 37, 2034 – 2035; e) D. E. James, L. F. Hines, J. K. Stille, J. Am. Chem. Soc. 1976, 98, 1806; f) D. E. James, J. K. Stille, J. Am. Chem. Soc. 1976, 98, 1810 – 1823; g) D. Zargarian, H. Alper, Organometallics 1991, 10, 2914 – 2921; h) S. C. A. Nefkens, M. Sperrle, G. Consiglio, Angew. Chem. 1993, 105, 1837 – 1838; Angew. Chem. Int. Ed. 1993, 32, 1719 – 1720; i) H. Zhou, J. Hou, J. Cheng, S. Lu, H. Fu, H. Wang, J. Organomet. Chem. 1997, 543, 227 – 228. [5] G. Cometti, G. P. Chiusoli, J. Organomet. Chem. 1979, 181, C14 – C16. [6] A. R. El’man, O. V. Boldyreva, E. V. Slivinskii, S. M. Loktev, Russ. Chem. Bull. 1992, 41, 435 – 438. [7] C. Bianchini, G. Mantovani, A. Meli, W. Oberhauser, P. Brggeller, T. Stampfl, J. Chem. Soc. Dalton Trans. 2001, 690 – 698. [8] C. Bianchini, A. Meli, W. Oberhauser, S. Parisel, O. V. Gusev, A. M. Kal’sin, N. V. Vologdin, F. M. Dolgushin, J. Mol. Catal. A 2004, 224, 35. [9] a) H. Chen, C. Cai, X. Liu, X. Li, H. Jiang, Chem. Commun. 2011, 47, 12224 – 12226. For the synthesis of b,g-unsaturated esters by carbonylation of allylic alcohols, see: b) B. Gabriele, G. Salerno, M. Costa, G. P. Chiusoli, J. Mol. Catal. A 1996, 111, 43 – 48; c) Q. Liu, L. Wu, H. Jiao, X. Fang, R. Jackstell, M. Beller, Angew. Chem. 2013, 125, 8222 – 8226; Angew. Chem. Int. Ed. 2013, 52, 8064 – 8068. Chem. Eur. J. 2014, 20, 4542 – 4547
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[10] a) D. Milstein, Organometallics 1982, 1, 888 – 890; b) B. C. Sçderberg, B. kermark, S. S. Hall, J. Org. Chem. 1988, 53, 2925 – 2937. [11] a) A. V. Malkov, M. Barłg, L. Miller-Potuck, M. A. Kabeshov, L. J. Farrugia, P. Kocˇovsky´, Chem. Eur. J. 2012, 18, 6873 – 6884. For our earlier work, see: b) P. Kocˇovsky´, M. Pour, J. Org. Chem. 1990, 55, 5580 – 5589. [12] For reviews on the use of p-BQ, CuII, and other oxidants of Pd intermediates, see: a) J.-E. Bckvall, Acc. Chem. Res. 1983, 16, 335 – 342; b) P. G. Andersson, J.-E. Bckvall, in Handbook of Organopalladium Chemistry for Organic Synthesis (Eds.: E. Negishi, A. de Meijere), Wiley, New York, 2002, Vol. 2, pp. 1859 – 1874; For interception of the p-BQ-Pd complex as intermediate, see: c) H. Grennberg, A. Gogoll, J.-E. Bckvall, Organometallics 1993, 12, 1790 – 1793. For another use of p-BQ in the transmetalation of organomercurials with PdII, followed by carbonylation, see: d) P. Kocˇovsky´, J. M. Grech, W. L. Mitchell, Tetrahedron Lett. 1996, 37, 1125 – 1128; e) P. Kocˇovsky´, V. Dunn, J. M. Grech, J. Sˇrogl, W. L. Mitchell, Tetrahedron Lett. 1996, 37, 5585 – 5588. [13] a) J. Tsuji, I. Shimizu, K. Yamamoto, Tetrahedron Lett. 1976, 17, 2975 – 2976; b) T. Hosokawa, T. Uno, S. Inui, S. I. Murahashi, J. Am. Chem. Soc. 1981, 103, 2318 – 2323; c) T. Nishimura, N. Kakiuchi, T. Onoue, K. Ohe, S. Uemura, J. Chem. Soc. Perkin Trans. 1 2000, 1915 – 1918; d) B. Weiner, A. Baeza, T. Jerphagnon, B. L. Feringa, J. Am. Chem. Soc. 2009, 131, 9473 – 9474. [14] a) M. H. G. Prechtl, J. D. Scholten, J. Dupont, Molecules 2010, 15, 3441 – 3461; b) D. Zim, A. L. Monteiro, J. Dupont, Tetrahedron Lett. 2000, 41, 8199 – 8202; c) V. Cal, P. Giannocaro, A. Nacci, A. Monopoli, J. Mol. Catal. A 2004, 214, 45 – 56. For other effects of halide ions (in particular Cl) on the Pd-catalyzed reactions, see, e.g., ref. [12 a,b] and the following: d) P. Kocˇovsky´, Sˇ. Vyskocˇil, I. C sarˇov, J. Sejbal, I. Tisˇlerov, M. Smrcˇina, G. C. Lloyd-Jones, S. C. Stephen, C. P. Butts, M. Murray, V. Langer, J. Am. Chem. Soc. 1999, 121, 7714 – 7715; e) P. Kocˇovsky´, A. V. Malkov, Sˇ Vyskocˇil, G. C. Lloyd-Jones, Pure Appl. Chem. 1999, 71, 1425 – 1433; f) G. C. Lloyd-Jones, S. C. Stephen, M. Murray, C P. Butts, Sˇ. Vyskocˇil, P. Kocˇovsky´, Chem. Eur. J. 2000, 6, 4348 – 4357; g) I. J. S. Fairlamb, G. C. Lloyd-Jones, Sˇ. Vyskocˇil, P. Kocˇovsky´, Chem. Eur. J. 2002, 8, 4443 – 4453; h) L. Gouriou, G. C. Lloyd-Jones, Sˇ. Vyskocˇil, P. Kocˇovsky´, J. Organomet. Chem. 2003, 687, 525 – 537. [15] For an early use of Pd(TFA)2 in PdII-catalyzed reactions, see: a) J. E. McMurry, P. Kocˇovsky´, Tetrahedron Lett. 1984, 25, 4187 – 4190; b) J. E. McMurry, P. Kocˇovsky´, Tetrahedron Lett. 1985, 26, 2171 – 2172. [16] a) B. A. Steinhoff, S. R. Fix, S. S. Stahl, J. Am. Chem. Soc. 2002, 124, 766 – 767; b) T. Diao, P. White, I. Guzei, S. S. Stahl, Inorg. Chem. 2012, 51, 11898 – 11909. [17] B. V. Popp, S. S. Stahl, Chem. Eur. J. 2009, 15, 2915 – 2922. [18] For the use of MeC(OR)3 or HC(OR)3 in PdII-catalyzed reactions, see ref. [11a] and the following: a) H. Harayama, A. Abe, T. Sakado, M. Kimura, K. Fugami, S. Tanaka, Y. Tamaru, J. Org. Chem. 1997, 62, 2113 – 2122; b) B. Gabriele, L. Veltri, V. Maltese, R. Spina, R. Mancuso, G. Salerno, Eur. J. Org. Chem. 2011, 5626 – 5635; c) B. Gabriele, R. Mancuso, G. Salerno, L. Veltri, M. Costa, A. Dibenedeto, ChemSusChem 2011, 4, 1778 – 1786. [19] The protocol was modified from ref. [11a]. [20] For the stereocontrolled synthesis of the parent alcohols, see: a) A. V. Malkov, M. Orsini, D. Pernazza, K. W. Muir, V. Langer, P. Meghani, P. Kocˇovsky´, Org. Lett. 2002, 4, 1047 – 1049; b) A. V. Malkov, M. Bell, M. Orsini, D. Pernazza, A. Massa, P. Herrmann, P. Meghani, P. Kocˇovsky´, J. Org. Chem. 2003, 68, 9659 – 9668; c) A. V. Malkov, M. Bell, M. Vassieu, V. Bugatti, P. Kocˇovsky´, J. Mol. Catal. A 2003, 196, 179 – 186; d) A. V. Malkov, L. Dufkov, L. Farrugia, P. Kocˇovsky´, Angew. Chem. 2003, 115, 3802 – 3805; Angew. Chem. Int. Ed. 2003, 42, 3674 – 3677; e) A. V. Malkov, M. Bell, F. Castelluzzo, P. Kocˇovsky´, Org. Lett. 2005, 7, 3219 – 3222; f) A. V. Malkov, M.-M. Westwater, A. Gutnov, P. Ram rez-Lpez. F. Friscourt, A. Kadlcˇ kov, J. Hodacˇov, Z. Rankovic, M. Kotora, P. Kocˇovsky´, Tetrahedron 2008, 64, 11335 – 11348; g) A. V. Malkov, M. Bell, P. Ram rez-Lpez, L. Biedermannov, L. Rul sˇek, L. Dufkov, M. Kotora, F. Zhu, P. Kocˇovsky´, J. Am. Chem. Soc. 2008, 130, 5341 – 5348; h) P. Kocˇovsky´, A. V. Malkov, Pure Appl. Chem. 2008, 80, 953 – 966; i) A. V. Malkov, S. Stoncˇius, M. Bell, F. Castelluzzo, P. Ram rez-Lpez, L. Biedermannov, L. Rul sˇek, V. Langer, P. Kocˇovsky´, Chem. Eur. J. 2013, 19, 9167 – 9185. [21] a) P. Kocˇovsky´, Tetrahedron Lett. 1988, 29, 2475 – 2478; b) P. Kocˇovsky´, I. Stary´, J. Org. Chem. 1990, 55, 3236 – 3243. For an overview of the related coordination of Rh species to amide groups in catalytic hydrogenation
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[22]
[23]
[24]
[25]
[26] [27]
affording amino acids, see: C. Njera, J. M. Sansano, Chem. Rev. 2007, 107, 4584 – 4671. Allyl silanes R3SiCH2CH=CH2 (R = Me or Ph), subjected to methoxycarbonylation, afforded complex mixtures of products with a loss of the silicon group. This behavior shows that Pd can readily insert into the OSi or CSi bond, complicating the reaction. For dramatic ligand effects on the reactivity of Pd complexes, see: ref. [12d], ref. [12e] and the following: a) R. M. Trend, Y. K. Ramtohul, B. M. Stoltz, J. Am. Chem. Soc. 2005, 127, 17778 – 17788; b) T. Hayashi, K. Yamasaki, M. Mimura, Y. Uozumi, J. Am. Chem. Soc. 2004, 126, 3036 – 3037; c) J. S. Nakhla, J. W. Kampf, J. P. Wolfe, J. Am. Chem. Soc. 2006, 128, 2893 – 2901. Complexes of the type Ln(X)PdCO2Me have been prepared independently and characterized, see: ref. [4a] and the following: a) F. Rivetti, U. Romano, J. Organomet. Chem. 1978, 154, 323 – 326; b) D. Milstein, Acc. Chem. Res. 1988, 21, 428 – 434. For discussion of the interaction of PdX2 species with MYn salts, see, e.g.: ref. [11b] and the following: a) K. Takehira, T. Hayakawa, H. Orita, M. Shimidzu, J. Mol. Catal. 1989, 53, 15 – 21; b) T. Hosokawa, S. Murahashi, Acc. Chem. Res. 1990, 23, 49 – 54; c) M. F. Semmelhack, C. Kim, N. Zhang, C. Budurow, M. Sanner, W. Dobler, M. Meier, Pure Appl. Chem. 1990, 62, 2035 – 2040; d) P. Kocˇovsky´, Organometallics 1993, 12, 1969 – 1971. J. Tsuji, M. Morikawa, J. Kiji, J. Am. Chem. Soc. 1964, 86, 4851 – 4853. A CH activation of the vinylic group could also be suggested, but this scenario seems less likely in view of the behavior of 9 j and in light of the current work in progress. For recent examples of the true C=CH activation, see: N. Gigant, J.-E. Bckvall, Chem. Eur. J. 2013, 19, 10799 – 10803 and references therein.
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[28] E. M. Doherty, C. Fotsch, Y. Bo, P. P. Chakrabarti, N. Chen, N. Gavva, N. Han, M. G. Kelly, J. Kincaid, L. Klionsky, Q. Liu, V. I. Ognyanov, R. Tamir, X. Wang, J. Zhu, M. H. Norman, J. J. S. Treanor, J. Med. Chem. 2005, 48, 71 – 90. [29] For comparison of the efficiency of these methods in the synthesis of allylic alcohols, see: J. Sˇtambasky´, A. V. Malkov, P. Kocˇovsky´, Collect. Czech. Chem. Commun. 2008, 73, 705 – 732. [30] Although the use of a CO balloon at atmospheric pressure represents an intrinsic risk, this is a procedure that has been repeatedly used in the literature as a standard technique. We have not experienced any problem using balloons of CO and O2. Nevertheless, considering that they can create highly flammable mixtures, the reactions were carried out in a well-ventilated fumehood, free from any source of ignition. Note that the two gasses are mixed in the reaction vessel, whereas the back-leaking and mixing in the balloons is minimal due to the small gauge of the needle that connects the balloon with the reaction vessel through a septum. Furthermore, although the reaction temperature is kept at 60 oC, the balloons experience room temperature, which further reduces the risk of explosion. To alleviate the hazards of toxicity and flammability of CO, the reaction can be performed in an autoclave under the same conditions. In fact, the model reaction (Table 2, entry 1) was also carried out in a stainless steel autoclave with 0.5 atm of each of CO and O2 to give a full conversion of 5 a into 6 a, with 70 % isolated yield.
Received: December 6, 2013 Published online on March 11, 2014
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& Carbonylation
Palladium-Catalyzed Alkoxycarbonylation of Terminal Alkenes To Produce a,b-Unsaturated Esters: The Key Role of Acetonitrile as a Ligand Andrei V. Malkov,*[a] Nolwenn Derrien,[a] Maciej Barłg,[b] and Pavel Kocˇovsky´*[c, d] Dedicated to Professor Bjçrn kermark on the occasion of his 80th birthday
Abstract: A mild protocol has been developed for the PdII-catalyzed alkoxycarbonylation of terminal olefins to produce a,b-unsaturated esters with a wide range of substrates. Key features are the use of MeCN as solvent (and/ or ligand) to control the reactivity of the intermediate Pd complexes and the combination of CO with O2, which facilitates the CuII-mediated reoxidation of the Pd0 complex to PdII and prevents double carbonylation.
Scheme 1. Oxidative alkoxycarbonylation of alkenes.
Carbon monoxide is an essential building block, allowing the transformation of readily available starting materials into more functionalized products, such as dyes, pharmaceuticals, and agrochemicals.[1] Oxidative alkoxycarbonylation of terminal alkenes 1 with CO in the presence of alcohols, catalyzed by PdII, is an important synthetic method because it allows the introduction of up to two functional groups into the molecule (Scheme 1).[2] Depending on the conditions, the reaction can result in three types of products: b-alkoxy esters 2 (route a), succinate derivatives 3 (route b), and a,b-unsaturated esters 4 (route c).[3] The first two routes have been extensively investigated, including mechanistic analysis and the development of enantioselective pathways.[4] By contrast, no adequate and
[a] Prof. Dr. A. V. Malkov, N. Derrien Chemistry Department Loughborough University Leicestershire, LE11 3TU (UK) Fax: (+ 44) 1509 22 3925 E-mail: [email protected] [b] Dr. M. Barłg Department of Chemistry, Texas A&M University at Qatar, P.O. Box 23874 Doha (Qatar) [c] Prof. Dr. P. Kocˇovsky´ Department of Organic Chemistry, Arrhenius Laboratory Stockholm University Stockholm SE 10691 (Sweden) E-mail: [email protected] [d] Prof. Dr. P. Kocˇovsky´ On leave from Department of Chemistry, WestChem University of Glasgow Glasgow, G12 8QQ (UK) E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201304798. Chem. Eur. J. 2014, 20, 4542 – 4547
practical method currently exists for directing the reaction selectively towards a,b-unsaturated esters 4. Previous reports on the synthesis of cinnamic esters by the carbonylation of styrene employed polymetallic systems, such as PdCl2/CuCl2/MgCl2/NaOAc[5] or PdCl2/CuCl2/Mn(OAc)2,[6] but the product yields and catalyst turnovers were low. Bianchini[7] reported on a selective formation of methyl cinnamate by using a Pd–diphosphine system. Depending on the conditions, and the nature of the phosphine ligand, either methyl cinnamate (selectivity 99 % at 75 % conversion) or the respective dimethyl succinate derivative (selectivity 88 %), was produced; however, the reaction required high CO pressure (800 psi) and elevated temperatures (80 8C). Oxidative methoxycarbonylation of styrene, catalyzed by PdII complexes with 1,1’(diphenylphosphino)-metallocene ligands, was shown to occur at lower CO pressures (43 psi),[8] although at the expense of the conversion and chemoselectivity of the reaction. Recently, a Pd-catalyzed oxidative carbonylation of terminal alkenes, to afford b,g-unsaturated esters, has been reported[9] and the reaction is believed to proceed by means of p-allyl Pd complexes generated by CH insertion.[10] However, the scope of this reaction appears to be limited to allylarenes with reactive CH bonds in the benzylic position (e.g., PhCH2CH=CH2). Herein, we present a mild protocol for the oxidative methoxycarbonylation of terminal alkenes 1!4, under an atmospheric pressure of CO, with a wide substrate range and good functional-group tolerance, resulting in a,b-unsaturated esters. In the course of our work on PdII-catalyzed carbonylative cyclization of olefinic carbamates,[11] we noticed that when the reaction was carried out in MeCN, an a,b-unsaturated ester of type 4 was formed; this outcome was found to be specific to the use of MeCN. We then set out to investigate this transformation in detail, with the aim to develop a new protocol for the carbonylation of alkenes and to obtain products that
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Communication Table 1. Optimization of chemoselectivity in the oxidative carbonylation of homoallylic carbonate 5 a catalyzed by Pd species.[a]
Entry
Catalyst [10 mol %]
Oxidant [3 equiv]
Conversion [%][b]
Ratio 6 a/7 a[c]
1 2 3 4 5 6
Pd(OAc)2 Pd(TFA)2 PdCl2 PdCl2 PdCl2 PdCl2
p-BQ p-BQ p-BQ CuCl2 FeCl3·6H2O Cu(OAc)2·2H2O
SM 50 70 SM SM 12
– 14:86 17:83 – – > 99:1
Table 2. Further optimization of the reaction conditions for the oxidative carbonylation of 5 a.[a]
[a] The reactions were carried out on a 0.50 mmol scale. A solution of the substrate in MeOH (4 mL) was added to a mixture of PdII catalyst (10 mol %) and oxidant (3 equiv) in MeCN (8 mL), under a CO atmosphere (balloon). The reaction mixture was then stirred at 60 8C for 24 h. [b] The conversion was calculated from the 1H NMR spectra by using naphthalene as an internal standard; SM = starting material. [c] Calculated from the 1H NMR spectra of the crude mixtures.
would normally be prepared by Wittig-type chemistry or olefin metathesis. To this end, the homoallylic carbonate, 5 a, with a terminal C=C bond, was chosen as a functionalized model substrate. The initial reactions were carried out under 1 atm of CO in the presence of a PdII catalyst and various oxidants, with MeCN as a solvent (Table 1). Initially, p-benzoquinone (p-BQ)[12] was evaluated as an oxidant with various palladium sources. Pd(OAc)2 proved to be inefficient (Table 1, entry 1), whereas moderate conversions were attained with Pd(TFA)2 (TFA = CF3CO2 ; 50 %, entry 2) and PdCl2 (70 %, entry 3). However, in both cases succinate 7 a, resulting from a double carbonylation, was identified as the major product, whereas the desired unsaturated ester, 6 a, was formed in minor quantities. Metal oxidants, CuCl2 or FeCl3·6 H2O, failed to show any conversion (entries 4 and 5). By contrast, the use of Cu(OAc)2·2 H2O gave exclusively the unsaturated ester 6 a, although with only 12 % conversion (entry 6). In the latter instance, rapid precipitation of palladium black was observed, blocking further reaction progress. To improve the conversion, we had to ensure a facile reoxidation of the Pd0 species to PdII, preventing agglomeration of the reduced Pd species and the subsequent precipitation of Pd black. After some experimentation, and following successful examples of Wacker-type oxidation chemistry,[13] we found that the use of an extra balloon of oxygen dramatically enhanced the regeneration of our palladium system. Thus, employing a 1:1 CO/O2 atmosphere, the a,b-unsaturated ester, 6 a, was obtained in 78 % yield (Table 2, entry 1). Notably, this protocol also allowed a decrease in the PdCl2 loading to 5 mol % and Cu(OAc)2·2 H2O to 1.2 equivalents. Tetrabutylammonium bromide, used to prevent the formation of colloidal Pd0species,[14] proved to be another important component of the reaction mixture and poor yields were obtained in its absence. On the other hand, the use of iodide Bu4N + I resulted in the formation of succinate 7 a as a major product. We also found that Chem. Eur. J. 2014, 20, 4542 – 4547
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Entry
Catalyst [5 mol %]
Additive
Solvent
Yield [%][b]
1 2 3 4 5 6 7 8 9 10 11 12
PdCl2 Pd(OAc)2 Pd(OAc)2 Pd(TFA)2 PdCl2 PdCl2 PdCl2 PdCl2 PdCl2 [PdCl2(MeCN)2] [PdCl2(MeCN)2] [PdCl2(MeCN)2]
– – – – – DMSO [10 mol %] pyridine [10 mol %] CH(OEt)3 [10 mL] – – – –
MeCN MeCN MeCN MeCN MeCN MeCN MeCN MeCN[g] THF MeCN MeCN THF
78[c] 62 20[d] 52 SM[e] 37[f] SM 42[f] SM 82 48[d] 72
[a] The reactions were carried out on a 0.50 mmol scale. Firstly, a mixture of the PdII catalyst (5 mol %), Cu(OAc)2·2 H2O (1.2 equiv), and Bu4N + Br (10 mol %) in a solvent (8 mL) was stirred under a CO atmosphere (balloon), at 40 8C for 2 h, followed by addition of a solution of the substrate in MeOH (4 mL) and then by introduction of O2 (second balloon). The reaction mixture was then stirred at 60 8C for 48 h. [b] Isolated yield; SM = starting material. [c] See entry 1 in Table 3. [d] Carried out in the absence of Bu4N + Br . [e] Carried out in the absence of Cu(OAc)2·2 H2O. [f] Succinate 7 a was formed as a major product (6 a/7 a 1:9). [g] Anhydrous Cu(OAc)2 was used.
the reaction mixture required vigorous stirring to prevent precipitation of Pd; any deposit appearing on the walls of the flask was easily redissolved by swirling. Replacing PdCl2 with Pd(OAc)2 or Pd(TFA)2[15] resulted in slightly reduced yields (62 and 52 %, respectively; Table 2, entries 2 and 4). In the absence of a halide ion the reaction stopped at low conversion (20 %), owing to the premature precipitation of Pd black (entry 3). As expected, no reaction was observed when molecular oxygen was used as the sole oxidant (entry 5), demonstrating that both oxygen and CuII are prerequisites for efficient reoxidation. Addition of 10 % DMSO to the reaction mixture (entry 6), known to accelerate reoxidation and prevent the precipitation of Pd black,[16] resulted in the formation of a complex mixture, with succinate 7 a being the main component. Pyridine, which is also known to facilitate the reoxidation of Pd0 species to PdII,[17] completely inhibited the reaction (entry 7); however, precipitation of the catalyst was not observed in this instance, suggesting that pyridine can compete with the substrate for coordination at the metal center. Acids, such as HCl and p-TsOH (TsOH = toluene sulfonic acid) were also found to inhibit the reaction, by eliciting a rapid precipitation of Pd black. Under anhydrous conditions, using Cu(OAc)2 and triethyl orthoformate,[18] the reaction switched to double carbonylation (entry 8). In THF, no conversion was observed (entry 9). These experiments allowed us to formulate a protocol with the following reaction conditions: the PdII and CuII salts should be dissolved in MeCN and the mixture should be heated at
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Communication 40 8C for 2 h under an atmosphere of CO, prior to the addition of a solution of the substrate in methanol.[19] This optimized protocol appears to indicate that MeCN plays an important role in the formation of the catalytically active species. The next experiments were, therefore, carried out with [(MeCN)2PdCl2] as a catalyst. In MeCN, 6 a was obtained in high yield (82 %, entry 10), and the reaction was found to proceed even in THF, previously identified as an unsuitable solvent (72 %, entry 12; compare with entry 9). In the absence of Bu4N + Br , the reaction afforded 6 a in lower yield (48 %, entry 11), reflecting the premature precipitation of Pd black (see also entry 3). After establishing the optimal conditions, the reaction scope was investigated by employing various terminal alkenes. The first group consisted of an extended range of homoallylic carbonates 5 a–h (Table 3, entries 1–9). The tert-butoxycarbonyl
Table 3. Oxidative alkoxycarbonylation of homoallylic carbonates and amides catalyzed by Pd.[a]
Entry
5
R1, R2, X
6 or 8
R3
Yield [%][b]
1
5a
H, H, OCO2Me
Me
78
2 3 4 5 6 7 8 9 10
5b 5c 5c 5d 5e 5f 5g 5h 5i
H, H, OCO2tBu Ph, H, OCO2Me Ph, H, OCO2Me 4-NO2C6H4, H, OCO2Me 3,4-(MeO)2C6H3, H, OCO2Me 2-thienyl, H, OCO2Me nC5H11, H, OCO2Me Ph, Me, OCO2Me[c] H, H, phthalimide
Me Me tBu Me Me Me Me Me Me
52 86 63 72 66 63 65 62 72
11
5j
Ph, H, phthalimide
Me
40[d]
12 13
5k 5l
Ph, H, NHCbz nC5H11, H, phthalimide
Me Me
60 12[d]
14
5m
nC5H11, H, NHCbz
Me
58
15
5n
nC5H11, H, NHTs
6 a/8 a (7:1) 6b 6c 6 c’ 6d 6e 6f 6g 6h 6 i/8 i (2.5:1) 6 j/8 j (6:1) 6k 6 l/8 l (3:1) 6 m/8 m (2.5:1) 6 n/8 n (3:1)
Me
53
tert-butanol, the respective tert-butyl ester, 6 c’, was isolated in 63 % yield (entry 4). The presence of an alkyl substituent in the a-position of the C=C bond[20] did not affect the reactivity (6 h, 62 %; entry 9). Related homoallylic amine derivatives 5 i–n were then investigated (Table 3, entries 10–15). Primary phthalimide 5 i reacted uneventfully (72 %), but secondary phthalimides 5 j and 5 l exhibited poor conversion, resulting in low isolated yields (40 % and 12 %, respectively). Carbonylation of carbamates 5 k and 5 m and tosylamide 5 n proceeded in acceptable yields (entries 12, 14, and 15). A general feature in all of these carbonylations was the formation of minor quantities of b,g-isomers 8, along with the expected a,b-unsaturated esters 6 in all but one case (6 k). It is noteworthy that the latter shift of the double bond (entries 10, 11, and 13–15) was not commonly observed in the carbonate series (entries 2–9), except for 5 a (entry 1), and, thus, seems to be characteristic of amides and imides, possibly originating from the enhanced propensity of these groups to coordinate Pd[11a] and other species,[21] affecting the reactivity of the intermediate complex. The reaction scope was further elucidated by using terminal alkenes 9 a–j (Table 4). Thus, the methoxycarbonylation of styrene afforded methyl cinnamate 10 a (87 %), but when the re-
Table 4. Oxidative methoxycarbonylation of alkenes.[a]
[a] The reactions were carried out on a 0.25–0.67 mmol scale. A mixture of PdCl2 (5 mol %), Cu(OAc)2·2 H2O (1.2 equiv), MeCN (8 mL) was stirred under a CO atmosphere (balloon), at 40 8C for 2 h, prior to the addition of a solution of the substrate ( 0.1 g) in R3OH (4 mL) and the introduction of an O2 balloon. The reaction mixture was then stirred at 60 8C for 24 h. Cbz = carbobenzyloxy, Ts = tosyl. [b] Isolated yield. [c] The syn-isomer of 5 h was employed. [d] Poor conversion.
[a] For conditions see Table 3.
(Boc) group turned out to be less suitable than methoxycarbonyl, as reflected in the reduced yield of 6 b (52 %, entry 2; compare with entry 1). Secondary carbonates with aryl (6 c–e), heteroaryl (6 f), and alkyl substituents (6 g) were obtained in good yields (63–86 %, entries 3–8). By replacing methanol with Chem. Eur. J. 2014, 20, 4542 – 4547
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action was carried out in tert-butanol instead of methanol, the yield (of 10 a’) dropped to 63 %, presumably owing to the increased steric bulk. Electron-rich and electron-poor styrenes (9 b and 9 c) readily produced the respective cinnamic esters 10 b and 10 c in good yields (70 and 62 %, respectively). Car-
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Communication bonylation of p-divinylbenzene 9 d afforded diester 10 d (82 %), with only traces of the monocarbonylated product detected. The cyclohexyl analogue, 10 e, isoxazolidine 10 f, and bromo derivative 10 g were obtained in practical yields (58–62 %). Carbonylation of the allyl silyl ether 9 h was accompanied by removal of the TMS group and a change in the position of the double bond, resulting in the formation of g-keto ester 10 h (65 %).[22] Two products were obtained from allyl benzene 9 i, namely the expected a,b-unsaturated ester, 10 i, and its b,g-isomer, 11, in a 1:3 ratio. Conjugation with the aromatic ring thus appears to be preferred over conjugation with the ester group. In a similar way, a-methylstyrene (9 j) furnished 10 j, presumably arising from the corresponding p-allyl Pd-complex. However, the reaction was sluggish, apparently owing to the steric hindrance; the product was formed in mere 20 % yield. According to the widely accepted mechanism,[4] PdCl2 and CO react with an olefin (in the absence of MeCN) to generate the corresponding h2-complex, which can react with MeOH either at the C O or C=C ligand, eventually giving rise to 2 or 3, depending on the actual conditions.[4] To account for the key role of MeCN, which promotes the formation of a,b-unsaturated esters 4 at the expense of 2 and 3 (Scheme 2), it can be reasoned that MeCN, as a ligand com-
The latter assumption is in line with the hypothesis that CO would not displace the remaining MeCN (as in A) under atmospheric pressure. However, the actual mechanism could be more complex, as Cu(OAc)2 is likely to play an additional role, by interacting with the Pd complex.[25] An alternative mechanism, involving chloropalladation[26] followed by HCl elimination, can be ruled out, since the reaction was found to proceed in the absence of halide ions (Table 2, entries 3 and 11), though less efficiently because of the premature precipitation of Pd black.[27] In order to illustrate the practical use of this new method, we resolved to synthesize the vanilloid receptor-1 antagonist TRPV-1 (16)[28] on a gram scale (Scheme 3). Under our standard
Scheme 3. Synthesis of the potent vanilloid receptor antagonist 16.
Scheme 2. Proposed mechanism for carbonylation (L = MeCN).
peting with CO, affects the reactivity of the Pd complex.[23] Thus, [(MeCN)2PdCl2], either used as such or generated in situ, when mixed with CO, can undergo a ligand exchange. It can be conjectured, however, that only one molecule of MeCN is replaced with CO in the equilibrium to generate the reactive complex A (L = MeCN), otherwise, if both molecules of MeCN were replaced, the reaction would follow the scenario discussed in the previous paragraph, giving rise to 2 or 3. Notably, the optimized reaction conditions require that the catalyst and CO (in MeCN) are allowed to “mature” before the olefin is added, indicating that an equilibrium needs to be reached prior to the reaction with the olefin. Complex A can then react with MeOH (added as a solvent of the substrate) to produce B,[24] which would then coordinate the olefin upon replacement of one of the MeCN molecules. The resulting complex, C, would then undergo olefin insertion to generate D. The latter complex, with MeCN in the coordination sphere of the Pd center, can then be assumed to react differently, compared with its counterpart lacking the MeCN ligand, and prefer b-H elimination over the second carbonylation, thus producing 4. Chem. Eur. J. 2014, 20, 4542 – 4547
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conditions, methoxycarbonylation of 4-tert-butylstyrene (12) afforded ester 13 (85 %), which was then hydrolyzed to furnish acid 14. The synthesis was completed by the conversion of 14 into the corresponding acid chloride, the reaction of which (in situ), with the aniline derivative 15, afforded the target amide 16 in 62 % yield over two steps (not optimized). The synthesis of 16 (920 mg) was, therefore, accomplished in three simple operations in 44 % overall yield. In conclusion, a mild protocol has been developed for the Pd-catalyzed alkoxycarbonylation of terminal alkenes to produce a,b-unsaturated esters (1!4) with a wide range of substrates. The reaction conditions, including PdCl2 (5 mol %), Cu(OAc)2 (1.2 equivalents), CO/O2 (1 atm), MeOH, and MeCN as a solvent, were optimized to attain good yields (60–87 % in most cases) and high chemoselectivity. Significantly, the reaction proceeds under an atmospheric pressure of CO and O2 (from two individual balloons), preventing the double carbonylation pathway and Pd-black precipitation. The use of oxygen as the second gas, which facilitates the reoxidation of the Pd0 species to PdII, mediated by CuII, and the key role of MeCN as a solvent (and Pd ligand) is particularly noteworthy. This new protocol can serve as an attractive alternative to the existing methods for the synthesis of a,b-unsaturated esters, such as Wittig-type alkenylation, cross-metathesis, Heck addition, and Suzuki–Miyaura coupling.[29] Of these methods, the new protocol is the most atom economical and sustainable because only two protons are lost from the reactants (one from the substrate olefin and one from MeOH).
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Communication Experimental Section General Procedure A 50 mL round-bottomed flask was charged with PdCl2 (5 mol %) and Cu(OAc)2·2 H2O (1.1 equivalents) and flushed first with N2, followed by CO. A CO balloon (diameter 15 cm) was then applied, MeCN (8 mL) was introduced by a syringe, and the reaction mixture was left to stir at 40 8C for 2 h. A solution of the substrate (0.5 mmol) in MeOH (4 mL) was added by a syringe, and an O2 balloon (diameter 7 cm) was applied. The reaction mixture was stirred at 60 8C for 24 h and then cooled. Ether (15 mL) was added and the mixture was washed with aqueous saturated NaHCO3 and brine and then dried over MgSO4. The solvent was evaporated under vacuum and the residue was purified by flash chromatography on silica gel (petroleum ether/Et2O 90:10) to afford a pure product. Note: a palladium deposit may occur during the reaction, but this can be easily re-dissolved by gentle shaking or swirling.[30] Experimental procedures, analytical and spectral data, and copies of the NMR spectra for the key compounds are available in the Supporting Information.
Acknowledgements We thank the EPSRC for grant EP/E011179/1 and Loughborough University for a fellowship to N. D. and other support. The Axel Wenner–Gren sabbatical scholarship awarded to P. K. and the additional support from COST through the ORCA action are also appreciated. Keywords: carbonylation · homogeneous catalysis · oxygen · palladium · solvent effects [1] B. Cornils, W. A. Herrmann, Applied Homogeneous Catalysis with Organometallic Compounds; Vol. 5: Applications, 2nd ed., Wiley-VCH, Weinheim, 2002, pp. 31 – 194. [2] a) P. P. Chiusoli, M. Costa in Handbook on Organopalladium Chemistry for Organic Synthesis Vol. 2, (Eds.: E. Negishi, A. de Meijere), Wiley, New York, 2002, pp. 2593 – 2623; b) J. Tsuji, Palladium Reagents and catalysts, Wiley-VCH, Weinheim, 2004, pp. 45 – 50; c) B. Gabriele, G. Salerno, M. Costa, Top. Organomet. Chem. 2006, 18, 239 – 272. [3] X.-F. Wu, H. Neumann, M. Beller, ChemSusChem 2013, 6, 229. [4] a) R. F. Heck, J. Am. Chem. Soc. 1969, 91, 6707 – 6714; b) R. F. Heck, J. Am. Chem. Soc. 1971, 93, 6896 – 6901; c) R. F. Heck, J. Am. Chem. Soc. 1972, 94, 2712 – 2716; d) D. M. Fenton, P. J. Steinwand, J. Org. Chem. 1972, 37, 2034 – 2035; e) D. E. James, L. F. Hines, J. K. Stille, J. Am. Chem. Soc. 1976, 98, 1806; f) D. E. James, J. K. Stille, J. Am. Chem. Soc. 1976, 98, 1810 – 1823; g) D. Zargarian, H. Alper, Organometallics 1991, 10, 2914 – 2921; h) S. C. A. Nefkens, M. Sperrle, G. Consiglio, Angew. Chem. 1993, 105, 1837 – 1838; Angew. Chem. Int. Ed. 1993, 32, 1719 – 1720; i) H. Zhou, J. Hou, J. Cheng, S. Lu, H. Fu, H. Wang, J. Organomet. Chem. 1997, 543, 227 – 228. [5] G. Cometti, G. P. Chiusoli, J. Organomet. Chem. 1979, 181, C14 – C16. [6] A. R. El’man, O. V. Boldyreva, E. V. Slivinskii, S. M. Loktev, Russ. Chem. Bull. 1992, 41, 435 – 438. [7] C. Bianchini, G. Mantovani, A. Meli, W. Oberhauser, P. Brggeller, T. Stampfl, J. Chem. Soc. Dalton Trans. 2001, 690 – 698. [8] C. Bianchini, A. Meli, W. Oberhauser, S. Parisel, O. V. Gusev, A. M. Kal’sin, N. V. Vologdin, F. M. Dolgushin, J. Mol. Catal. A 2004, 224, 35. [9] a) H. Chen, C. Cai, X. Liu, X. Li, H. Jiang, Chem. Commun. 2011, 47, 12224 – 12226. For the synthesis of b,g-unsaturated esters by carbonylation of allylic alcohols, see: b) B. Gabriele, G. Salerno, M. Costa, G. P. Chiusoli, J. Mol. Catal. A 1996, 111, 43 – 48; c) Q. Liu, L. Wu, H. Jiao, X. Fang, R. Jackstell, M. Beller, Angew. Chem. 2013, 125, 8222 – 8226; Angew. Chem. Int. Ed. 2013, 52, 8064 – 8068. Chem. Eur. J. 2014, 20, 4542 – 4547
www.chemeurj.org
[10] a) D. Milstein, Organometallics 1982, 1, 888 – 890; b) B. C. Sçderberg, B. kermark, S. S. Hall, J. Org. Chem. 1988, 53, 2925 – 2937. [11] a) A. V. Malkov, M. Barłg, L. Miller-Potuck, M. A. Kabeshov, L. J. Farrugia, P. Kocˇovsky´, Chem. Eur. J. 2012, 18, 6873 – 6884. For our earlier work, see: b) P. Kocˇovsky´, M. Pour, J. Org. Chem. 1990, 55, 5580 – 5589. [12] For reviews on the use of p-BQ, CuII, and other oxidants of Pd intermediates, see: a) J.-E. Bckvall, Acc. Chem. Res. 1983, 16, 335 – 342; b) P. G. Andersson, J.-E. Bckvall, in Handbook of Organopalladium Chemistry for Organic Synthesis (Eds.: E. Negishi, A. de Meijere), Wiley, New York, 2002, Vol. 2, pp. 1859 – 1874; For interception of the p-BQ-Pd complex as intermediate, see: c) H. Grennberg, A. Gogoll, J.-E. Bckvall, Organometallics 1993, 12, 1790 – 1793. For another use of p-BQ in the transmetalation of organomercurials with PdII, followed by carbonylation, see: d) P. Kocˇovsky´, J. M. Grech, W. L. Mitchell, Tetrahedron Lett. 1996, 37, 1125 – 1128; e) P. Kocˇovsky´, V. Dunn, J. M. Grech, J. Sˇrogl, W. L. Mitchell, Tetrahedron Lett. 1996, 37, 5585 – 5588. [13] a) J. Tsuji, I. Shimizu, K. Yamamoto, Tetrahedron Lett. 1976, 17, 2975 – 2976; b) T. Hosokawa, T. Uno, S. Inui, S. I. Murahashi, J. Am. Chem. Soc. 1981, 103, 2318 – 2323; c) T. Nishimura, N. Kakiuchi, T. Onoue, K. Ohe, S. Uemura, J. Chem. Soc. Perkin Trans. 1 2000, 1915 – 1918; d) B. Weiner, A. Baeza, T. Jerphagnon, B. L. Feringa, J. Am. Chem. Soc. 2009, 131, 9473 – 9474. [14] a) M. H. G. Prechtl, J. D. Scholten, J. Dupont, Molecules 2010, 15, 3441 – 3461; b) D. Zim, A. L. Monteiro, J. Dupont, Tetrahedron Lett. 2000, 41, 8199 – 8202; c) V. Cal, P. Giannocaro, A. Nacci, A. Monopoli, J. Mol. Catal. A 2004, 214, 45 – 56. For other effects of halide ions (in particular Cl) on the Pd-catalyzed reactions, see, e.g., ref. [12 a,b] and the following: d) P. Kocˇovsky´, Sˇ. Vyskocˇil, I. C sarˇov, J. Sejbal, I. Tisˇlerov, M. Smrcˇina, G. C. Lloyd-Jones, S. C. Stephen, C. P. Butts, M. Murray, V. Langer, J. Am. Chem. Soc. 1999, 121, 7714 – 7715; e) P. Kocˇovsky´, A. V. Malkov, Sˇ Vyskocˇil, G. C. Lloyd-Jones, Pure Appl. Chem. 1999, 71, 1425 – 1433; f) G. C. Lloyd-Jones, S. C. Stephen, M. Murray, C P. Butts, Sˇ. Vyskocˇil, P. Kocˇovsky´, Chem. Eur. J. 2000, 6, 4348 – 4357; g) I. J. S. Fairlamb, G. C. Lloyd-Jones, Sˇ. Vyskocˇil, P. Kocˇovsky´, Chem. Eur. J. 2002, 8, 4443 – 4453; h) L. Gouriou, G. C. Lloyd-Jones, Sˇ. Vyskocˇil, P. Kocˇovsky´, J. Organomet. Chem. 2003, 687, 525 – 537. [15] For an early use of Pd(TFA)2 in PdII-catalyzed reactions, see: a) J. E. McMurry, P. Kocˇovsky´, Tetrahedron Lett. 1984, 25, 4187 – 4190; b) J. E. McMurry, P. Kocˇovsky´, Tetrahedron Lett. 1985, 26, 2171 – 2172. [16] a) B. A. Steinhoff, S. R. Fix, S. S. Stahl, J. Am. Chem. Soc. 2002, 124, 766 – 767; b) T. Diao, P. White, I. Guzei, S. S. Stahl, Inorg. Chem. 2012, 51, 11898 – 11909. [17] B. V. Popp, S. S. Stahl, Chem. Eur. J. 2009, 15, 2915 – 2922. [18] For the use of MeC(OR)3 or HC(OR)3 in PdII-catalyzed reactions, see ref. [11a] and the following: a) H. Harayama, A. Abe, T. Sakado, M. Kimura, K. Fugami, S. Tanaka, Y. Tamaru, J. Org. Chem. 1997, 62, 2113 – 2122; b) B. Gabriele, L. Veltri, V. Maltese, R. Spina, R. Mancuso, G. Salerno, Eur. J. Org. Chem. 2011, 5626 – 5635; c) B. Gabriele, R. Mancuso, G. Salerno, L. Veltri, M. Costa, A. Dibenedeto, ChemSusChem 2011, 4, 1778 – 1786. [19] The protocol was modified from ref. [11a]. [20] For the stereocontrolled synthesis of the parent alcohols, see: a) A. V. Malkov, M. Orsini, D. Pernazza, K. W. Muir, V. Langer, P. Meghani, P. Kocˇovsky´, Org. Lett. 2002, 4, 1047 – 1049; b) A. V. Malkov, M. Bell, M. Orsini, D. Pernazza, A. Massa, P. Herrmann, P. Meghani, P. Kocˇovsky´, J. Org. Chem. 2003, 68, 9659 – 9668; c) A. V. Malkov, M. Bell, M. Vassieu, V. Bugatti, P. Kocˇovsky´, J. Mol. Catal. A 2003, 196, 179 – 186; d) A. V. Malkov, L. Dufkov, L. Farrugia, P. Kocˇovsky´, Angew. Chem. 2003, 115, 3802 – 3805; Angew. Chem. Int. Ed. 2003, 42, 3674 – 3677; e) A. V. Malkov, M. Bell, F. Castelluzzo, P. Kocˇovsky´, Org. Lett. 2005, 7, 3219 – 3222; f) A. V. Malkov, M.-M. Westwater, A. Gutnov, P. Ram rez-Lpez. F. Friscourt, A. Kadlcˇ kov, J. Hodacˇov, Z. Rankovic, M. Kotora, P. Kocˇovsky´, Tetrahedron 2008, 64, 11335 – 11348; g) A. V. Malkov, M. Bell, P. Ram rez-Lpez, L. Biedermannov, L. Rul sˇek, L. Dufkov, M. Kotora, F. Zhu, P. Kocˇovsky´, J. Am. Chem. Soc. 2008, 130, 5341 – 5348; h) P. Kocˇovsky´, A. V. Malkov, Pure Appl. Chem. 2008, 80, 953 – 966; i) A. V. Malkov, S. Stoncˇius, M. Bell, F. Castelluzzo, P. Ram rez-Lpez, L. Biedermannov, L. Rul sˇek, V. Langer, P. Kocˇovsky´, Chem. Eur. J. 2013, 19, 9167 – 9185. [21] a) P. Kocˇovsky´, Tetrahedron Lett. 1988, 29, 2475 – 2478; b) P. Kocˇovsky´, I. Stary´, J. Org. Chem. 1990, 55, 3236 – 3243. For an overview of the related coordination of Rh species to amide groups in catalytic hydrogenation
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[22]
[23]
[24]
[25]
[26] [27]
affording amino acids, see: C. Njera, J. M. Sansano, Chem. Rev. 2007, 107, 4584 – 4671. Allyl silanes R3SiCH2CH=CH2 (R = Me or Ph), subjected to methoxycarbonylation, afforded complex mixtures of products with a loss of the silicon group. This behavior shows that Pd can readily insert into the OSi or CSi bond, complicating the reaction. For dramatic ligand effects on the reactivity of Pd complexes, see: ref. [12d], ref. [12e] and the following: a) R. M. Trend, Y. K. Ramtohul, B. M. Stoltz, J. Am. Chem. Soc. 2005, 127, 17778 – 17788; b) T. Hayashi, K. Yamasaki, M. Mimura, Y. Uozumi, J. Am. Chem. Soc. 2004, 126, 3036 – 3037; c) J. S. Nakhla, J. W. Kampf, J. P. Wolfe, J. Am. Chem. Soc. 2006, 128, 2893 – 2901. Complexes of the type Ln(X)PdCO2Me have been prepared independently and characterized, see: ref. [4a] and the following: a) F. Rivetti, U. Romano, J. Organomet. Chem. 1978, 154, 323 – 326; b) D. Milstein, Acc. Chem. Res. 1988, 21, 428 – 434. For discussion of the interaction of PdX2 species with MYn salts, see, e.g.: ref. [11b] and the following: a) K. Takehira, T. Hayakawa, H. Orita, M. Shimidzu, J. Mol. Catal. 1989, 53, 15 – 21; b) T. Hosokawa, S. Murahashi, Acc. Chem. Res. 1990, 23, 49 – 54; c) M. F. Semmelhack, C. Kim, N. Zhang, C. Budurow, M. Sanner, W. Dobler, M. Meier, Pure Appl. Chem. 1990, 62, 2035 – 2040; d) P. Kocˇovsky´, Organometallics 1993, 12, 1969 – 1971. J. Tsuji, M. Morikawa, J. Kiji, J. Am. Chem. Soc. 1964, 86, 4851 – 4853. A CH activation of the vinylic group could also be suggested, but this scenario seems less likely in view of the behavior of 9 j and in light of the current work in progress. For recent examples of the true C=CH activation, see: N. Gigant, J.-E. Bckvall, Chem. Eur. J. 2013, 19, 10799 – 10803 and references therein.
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[28] E. M. Doherty, C. Fotsch, Y. Bo, P. P. Chakrabarti, N. Chen, N. Gavva, N. Han, M. G. Kelly, J. Kincaid, L. Klionsky, Q. Liu, V. I. Ognyanov, R. Tamir, X. Wang, J. Zhu, M. H. Norman, J. J. S. Treanor, J. Med. Chem. 2005, 48, 71 – 90. [29] For comparison of the efficiency of these methods in the synthesis of allylic alcohols, see: J. Sˇtambasky´, A. V. Malkov, P. Kocˇovsky´, Collect. Czech. Chem. Commun. 2008, 73, 705 – 732. [30] Although the use of a CO balloon at atmospheric pressure represents an intrinsic risk, this is a procedure that has been repeatedly used in the literature as a standard technique. We have not experienced any problem using balloons of CO and O2. Nevertheless, considering that they can create highly flammable mixtures, the reactions were carried out in a well-ventilated fumehood, free from any source of ignition. Note that the two gasses are mixed in the reaction vessel, whereas the back-leaking and mixing in the balloons is minimal due to the small gauge of the needle that connects the balloon with the reaction vessel through a septum. Furthermore, although the reaction temperature is kept at 60 oC, the balloons experience room temperature, which further reduces the risk of explosion. To alleviate the hazards of toxicity and flammability of CO, the reaction can be performed in an autoclave under the same conditions. In fact, the model reaction (Table 2, entry 1) was also carried out in a stainless steel autoclave with 0.5 atm of each of CO and O2 to give a full conversion of 5 a into 6 a, with 70 % isolated yield.
Received: December 6, 2013 Published online on March 11, 2014
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