The chiral guanidine-catalyzed conjugate addition of 5H-oxazol-4-ones to 2-chloroacrylonitrile was developed with high enantiomeric and diastereomeric control. Introduction of an electron-donating 4-methoxyphenyl group as an aromatic substituent (Ar) on 5H-oxazol-4-one was suitable for inhibiting undesirable cyclization and achieving high stereoselectivity in this conjugate addition. The derivatization of an obtained product was also performed to afford a chiral α-siloxyimide, which was subsequently converted to the corresponding α-siloxy-γ-lactam in a few steps.

In this Letter, a chiral guanidine-catalyzed 1,4-addition reaction of 5H-oxazol-4-ones to vinyl ketones is described. The 1,4-addition reaction proceeded with a high enantioselectivity using 5H-oxazol-4-ones, substituted with a 3-chloro-5-methylphenyl group, as pronucleophiles and a newly developed chiral guanidine as a catalyst. The optimized reaction conditions were also effective in achieving excellent enantioselectivity in the 1,6-addition to dienones. Subsequent solvolysis of the 1,4-addition adduct yielded the corresponding α-hydroxy-5-oxocarboxylates.

An asymmetric 1,4-addition reaction of 5H-oxazol-4-ones with alkynyl carbonyl compounds was developed, and, for the first time, high enantiomeric and geometric control was achieved to afford the thermodynamically unstable Z-isomer predominantly using chiral guanidine catalysts bearing a hydroxy group at the appropriate position. The method provides synthetically useful γ-butenolide ester bearing a chiral quaternary stereogenic center.

A new chiral bicyclic guanidine-catalyzed direct catalytic aldol reaction of 5H-oxazol-4-ones with aldehydes has been developed. The present aldol reaction proceeds smoothly with high enantioselectivity using bicyclic guanidines bearing a hydroxy group at the appropriate position, and various combinations of 5H-oxazol-4-ones and aldehydes are applicable. The method provides synthetically useful α,β-dihydroxycarboxylates bearing a chiral quaternary stereogenic center at the α-carbon atom.