A Convenient One-Pot Synthesis of Both Enantiomers of 1,3,5-Trisubstituted Hydantoins

Abstract

A novel one-pot asymmetric synthetic method for the direct conversion of bromoacetates into highly substituted hydantoins has been developed. Both enantiomers of 1,3,5-trisubstituted hydantoins were conveniently synthesized through a dynamic kinetic resolution of bromoacetates derived from either ethyl l-lactate or diacetone-d-glucose. The sequential three-component reaction permitted the preparation of (R)- or (S)-1,3,5-trisubstituted hydantoins in yields of 77–51% with enantiomeric ratios of up to 95:5.

Enantioselective construction of substituted hydantoins via chiral phosphoric acid catalyzed annulation/Heyns rearrangement of aryl-substituted ureas with glyoxals

“…In particular, chiral hydantoins have attracted considerable attention regarding their synthesis using amino acids as the starting materials. 5 However, the catalytic synthesis of hydantoins with high enantioselectivity has rarely been reported. Enantioselective hydrogenation using a chiral cobalt catalyst provided an elegant strategy to afford chiral hydantoins with up to 82% ee (Scheme 2a).…”

Asymmetric preparation of 2,4,6‐trisubstituted dihydropyridazinones

“…α‐Bromoacetates offer considerable versatility as intermediates for the synthesis of diverse heterocycles 5,6 . This utility is derived primarily from the bifunctional electrophilic character of α‐bromoacetates.…”