Enantioselective Synthesis of Epoxides Having a Tetrasubstituted Trifluoromethylated Carbon Center: Methylhydrazine-Induced Aerobic Epoxidation of β,β-Disubstituted Enones

摘要

Ever since the milestone of asymmetric epoxidation of allylic alcohols in the early 1980s by Katsuki and Sharpless, the catalytic asymmetric epoxidation of olefins has become one of the most powerful, well-explored, and reliable transformations in organic synthesis for providing enantiomerically enriched epoxides, which are versatile building blocks for the synthesis of biologically active molecules and advanced materials. A large number of catalytic systems for asymmetric epoxidation have been devised over three decades and can be categorized into three classes according to the combination of catalysts and oxidants: a) metal complex/ active oxidant, b) metal complex/molecular oxygen, and c) organocatalyst/active oxidant. Despite tremendous efforts by many groups, the catalytic asymmetric epoxidation of acyclic β,β-disubstituted enones is still a challenge, particularly for β,β-disubstituted enones bearing a trifluoro-methyl group at the β-position. In 2011, Yamamoto and coworkers provided a very nice solution to the catalytic asymmetric epoxidation of acyclic β,β-disubstituted enones with an iron complex consisting of Fe(OTf)2 and a carefully designed phenanthroline ligand. This chiral iron phenan-throline system is effective for the asymmetric epoxidation of a variety of acyclic β,β-disubstituted enones, however, no example was shown for the asymmetric epoxidation of β,β-disubstituted enones having a β-trifluoromethyl group. In 2012, Feng and co-workers investigated chiral N,N'-dioxide-metal complexes for the epoxidation of β-monosubstituted enones including a β-trifluoromethyl group using hydrogen peroxide and found that optically active epoxides could be obtained with excellent enantioselectivities, but method was not be applicable for β,β-disubstituted enones. We disclose herein the first asymmetric epoxidation of β,β-disubstituted enones 1, having a β-trifluoromethyl group, by the serendipitous discovery of an aerobic organocatalytic system consisting of methylhydrazine (H2NNHMe), a base, and a cinchona alkaloid phase-transfer catalyst (Scheme 1). Enantiomerically enriched trifluoromethylated epoxides with a tetrasubstituted carbon centers (3) were obtained for the first time, instead of the pyrazolines 2, in excellent yields, excellent diastereo-selectivities, and enantioselectivities (96-99 % ee).