Synthesis of Optically Active Spirohydantoins by Asymmetric Induction. Hydantoin Formation from Amino Nitriles and Chlorosulfonyl Isocyanate

Article abstract of DOI:10.1021/jo00142a016

Conversion of 6-chloro- or 6-fluoro-2,3-dihydro-4H-1-benzopyran-4-one with optically active (S)-α-methylbenzylamine in the presence of TiCl4 to the ketimine followed by treatment in EtOH with HCN gas gives excellent yields of crystalline, enantiomerically pure (4S)-4-cyano-2,3-dihydro-6-chloro(or 6-fluoro)-4-<(S)-(1-phenylethyl)amino>-4H-1-benzopyran.These sterically hindered amino nitriles react smoothly with chlorosulfonyl isocyanate to give, after hydrolysis, the hydantoins (4S)-2,3-dihydro-6-chloro(or 6-fluoro)-3'-<(S)-1-phenylethyl>spiro<4H-1-benzopyran-4,4'-imidazolidine>-2',5'-dione.The α-methylbenzyl groups can be removed by aqueous HBr/acetic acid to give the unprotected spirohydantoins.