Chung-Meng Chao

Asymmetric Gold‐Catalyzed Hydroarylation/Cyclization Reactions

Recent years have witnessed a substantial growth in the number of gold-catalyzed reactions implying C C, C O or C N bond-formation processes. Despite the rapid development of several synthetic applications, the enantioselective aspects still require investigations. Some reports described the transfer of chirality from allenes and propargylic esters, and the asymmetric hydroalkoxylation and hydroamination of allenes. Nevertheless examples are still scarce, most probably due to the linear geometry of chiral gold(I) complexes that explains a lack of steric interactions between the chiral inducer and the activated function of the substrate. Ito and Hayashi s groups pioneered the field of asymmetric gold catalysis by conceiving the addition of isocyanoacetates to aldehydes in the presence of a cationic gold catalyst and a chiral diphosphanyl ferrocene ligand. Other groups have recently challenged to discover new applications of linear chiral gold complexes, but to the best of our knowledge, only two of them implied alkyne activation. In the course of our research on metal-catalyzed cycloisomerization reactions of enynes, we and others have described novel rearrangements in the presence of external nucleophiles such as alcohols, electron-rich aromatic rings, amines, carboxylic acids and 1,3-dicarbonyl compounds (Scheme 1). Despite the fact that these reactions seem mechanistically related, they proved to be highly substrate and nucleophile dependent. This explains the fact that no general asymmetric version was described so far for these tandem atom-economical processes. We described the first asymmetric Pt-catalyzed alkoxycyclization reactions and Echavarren s group published the first analogous gold-catalyzed proACHTUNGTRENNUNGcess.[4a] In both cases, moderate to good enantioselectivities were observed and only one example has been reported with an ee higher than 90 %. We envisaged to study these challenging reactions and wish to present our preliminary results leading to enantiomerically enriched functionalized cyclic alkenes starting from 1,6-enynes. Initial efforts have focused on the optimization of an efficient system starting from enyne 1 a as a model substrate (Table 1). Based on our experience, we reasoned that the addition of electron-rich aromatic rings would be successful as the kinetics were fast and the steric hindrance of the nucleophile would favor an enantioselective process. According to previously described procedures, we prepared chiral Au catalysts with MeOBIPHEP, BINAP and 4MeO-3,5-(tBu)2-MeOBIPHEP ligands. The use of (R)MeOBIPHEP–(AuCl)2 associated with silver salt AgSbF6 in diethyl ether led to the formation of the desired product 2 a in excellent yield and 26 % enantiomeric excess (Table 1, entry 1). The influence of silver salts was investigated (Table 1, entries 2–4), silver triflate and silver bis(trifluoromethanesulfonyl)imidate giving the best results. The use of silver benzoate was particularly striking as no conversion was observed at room temperature for 240 h (Table 1, entry 2). Lowering the temperature to 0 8C increased the re[a] C.-M. Chao, Dr. M. R. Vitale, Dr. P. Y. Toullec, Prof. J.-P. GenÞt, Dr. V. Michelet Laboratoire de Synth se S lective Organique et Produits Naturels UMR 7573, Ecole Nationale Sup rieure de Chimie de Paris rue P. et M. Curie, 75231 Paris cedex 05 (France) Fax: (+33) 144-071-062 E-mail : veronique-michelet@enscp.fr Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200802341. Scheme 1. Metal-catalyzed cycloisomerization of 1,6-enynes in the presence of an external nucleophile.

Asymmetric Au-catalyzed cycloisomerization of 1,6-enynes: An entry to bicyclo[4.1.0]heptene.

Summary A comprehensive study on the asymmetric gold-catalyzed cycloisomerization reaction of heteroatom tethered 1,6-enynes is described. The cycloisomerization reactions were conducted in the presence of the chiral cationic Au(I) catalyst consisting of (R)-4-MeO-3,5-(t-Bu)2-MeOBIPHEP-(AuCl)2 complex and silver salts (AgOTf or AgNTf2) in toluene under mild conditions to afford functionalized bicyclo[4.1.0]heptene derivatives. The reaction conditions were found to be highly substrate-dependent, the best results being obtained in the case of oxygen-tethered enynes. The formation of bicyclic derivatives, including cyclopropyl pentasubstituted ones, was reported in moderate to good yields and in enantiomeric excesses up to 99%.