Highly enantioselective hydrogenation of styrenes directed by 2'-hydroxyl groups
Xiang Wang1, Anil Guram, Seb Caille
1Chemical Process Research and Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, United States. xiangw@amgen.com
Abstract:
A new synthetic strategy that turns styrene-type olefins into excellent substrates for Rh-catalyzed asymmetric hydrogenation by installing a 2'-hydroxyl substituent is described. This methodology accommodates trisubstituted olefinic substrates in various E/Z mixtures, leading to valuable benzylic chiral compounds including (R)-tolterodine. It is also demonstrated that the 2'-hydroxyl groups could be readily removed in high yield without loss of ee from the products. Thus, this technology represents an attractive alternative to the Ir(P-N) catalyst system for the asymmetric hydrogenation of unfunctionalized olefins.
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