Palladium-Catalyzed Asymmetric Hydrogenation of α-Acyloxy-1-arylethanones

摘要

α-Acyloxy-1-arylethanols, especially those possessing chiral centers, are a class of useful structural motifs commonly found in natural products and drug candidates. They can serve as important intermediates for the preparation of many bioac-tive and medicinal molecules (Figure 1). However, little attention has been focused on their synthesis and the general approaches to prepare them often involve the selective acylation of the corresponding chiral diol species. Strategies to directly obtain the chiral α-acyloxy-1-arylethanols from α-acyloxy-1-arylethanones are relatively unknown. The initial study on the asymmetric reduction of α-acyloxy ketones was achieved in 1985 by utilizing the mixed reducing agent of a chiral diamine and SnCl2. Although moderate yields and good enantioselectivities were obtained, 3 equivalents of the reducing agent were required. Santaniello and co-workers, Fujisawa and co-workers, and Ema et al. reported asymmetric reductions of prochiral α-acyloxy ketones, using either baker's yeast or similar enzymes, with excellent enantiose-lectivity but moderate regioselectivity. Kambourakis and co-workers developed an efficient ketoreductase-catalyzed asymmetric synthesis of chiral α-acyloxy-l-alkylethanols. These enzyme regulated asymmetric syntheses require harsh reaction conditions, often have limited substrate scope, and often involve the migration of the acyl group by hydrolysis. The asymmetric transfer hydrogenation of α-acyloxy-1-aryl-ethanones has also been accomplished but with low yield and enantioselectivity or limited substrate scope. To the best of our knowledge, a strategy using transition-metal-catalyzed asymmetric hydrogenation of α-acyloxy-1-arylethanones remains unexplored, despite it being one of the most powerful methods for preparing chiral compounds.