Catalytic Enantioselective Intermolecular Desymmetrization of 3-Substituted Oxetanes

摘要

Enantioselective desymmetrization represents a powerful method to access chiral building blocks. For example, the enantioselective ring opening of meso epoxides has been a topic of intense investigations.In contrast, oxetanes, the immediate homologue of epoxides, have been much less studied in terms of enantioselective ring openings, although studies on their preparation and application have been well-documented. Oxetanes substituted at the 3-position are prochiral, and can lead to various useful three-carbon chiral building blocks upon enantioselective ring opening by nucleophiles. However, there have been only two reports to date. In 1996, Tomioka and co-workers reported the first (and only) example of intermolecular desymmetrization of 3-substituted oxetanes by organolithium reagents, but the reaction requires a stoichiometric amount of a chiral boron reagent and proceeds with low enantioselectivity (< 48% ee; Scheme 1a). Recently, Loy and Jacobsen reported an intramolecular desymmetrization catalyzed by [(salen)Co~(III)] complexes with good to excellent enantioselectivity (Scheme 1b). However, the same catalytic system could not be extended to an intermolecular reaction. Herein we describe the first catalytic enantioselective intermolecular desymmetrization of 3-substituted oxetanes leading to the efficient synthesis of useful chiral building blocks, bearing tertiary or quaternary chiral centers, with high enantioselectivity (Scheme 1c).