Enantioselective Ammonium Ylide Mediated One-Pot Synthesis of Highly Substitutedγ-Butyrolactones

An ammonium ylide mediated access towardstrans-beta,gamma-disubstituted,all-trans-alpha,beta,gamma-trisubstituted, and alpha,alpha,beta,gamma-tetrasubstituted gamma-butyrolactones bearing a broad variety of functionalities was developed. Starting from widely accessible benzylidene Meldrum's acid derivatives and alpha-bromo carbonyl compounds,gamma-butyrolactones were obtained in yields between 32-99% with up to excellent diastereoselectivities (>95:5)viaa DABCO-mediated [2+1] annulation. Utilization of enantiomerically pure cinchona alkaloid derivatives enables the first asymmetric ammonium ylide mediated method to provide (3R, 4R)-beta,gamma-disubstituted and (2R, 3R, 4R)-alpha,beta,gamma-trisubstituted gamma-butyrolactones in moderate to good yields with up to very good enantiomeric ratios (97:3). The scalability of the transformation was proven while determining the absolute configuration.