An Asymmetric Michael Addition of α,α-Disubstituted Aldehydes to Maleimides Leading to a One-Pot Enantioselective Synthesis of Lactones Catalyzed by Amino Acids
A highly enantioselective synthesis of a-branched acrylonitriles is reported featuring a one-pot sequential asymmetric Michael addition/retro-Dieckmann/retro-Michael fragmentation cascade. The method, which relies on a solid, bench-stable and commercially available acrylonitrile surrogate, is practical, scalable, highly versatile, and provides a direct access to a wide range of enantioenriched nitrile-containing building blocks. Most importantly, the method offers a new tool to incorporate an acrylonitrile moiety in an asymmetric fashion.<br>
A simple synthesis of prostaglandin E1 (PGE1) is described. The key steps are an asymmetric Michael addition to establish the desired (R)-configurations at C8 and C12 of the 2- (trimethylsilyl)ethoxymethyl- (SEM) protected PGE1 and its one-pot deprotection with magnesium bromide in high yield. This method is potentially useful for the preparation of other modified prostaglandins.
Direct Access to Highly Enantioenriched α-Branched Acrylonitriles through a one-pot Sequential Asymmetric Michael addition/retro-Dieckmann/retro-Michael Fragmentation Cascade