Diastereo- and enantioselective preparation of oxazolines via the base-catalysed aldol reaction of isocyanoacetates with aldehydes using cinchona alkaloids

Abstract

A diastereo- and enantioselective base-catalysed aldol reaction of t-butyl isocyanoacetate with aldehydes under phase-transfer catalytic conditions yielded 19 4,5-disubstituted oxazolines, 16 of which are novel. Key to success was the use of a free 9-OH-containing cinchona alkaloid-based quaternary ammonium salt bearing bulky and electron-withdrawing aryl groups on the N-benzyl moiety. This process tolerates both aromatic and aliphatic aldehydes, affording the corresponding chiral oxazoline products in diastereoselectivities up to 20:1 and enantioselectivities up to 78% ee.