Highly Diastereoselective Aziridination of Imines with Trimethylsilyldiazomethane. Subsequent Silyl Substitution with Electrophiles, Ring Opening, and Metalation of C-SilylaziridinesA Cornucopia of Highly Selective Transformations

Abstract

Treatment of a range of N-sulfonyl (Ts and SES) imines derived from aromatic, heteroaromatic, aliphatic, and unsaturated aldehydes with trimethylsilydiazomethane gave C-silylaziridines in good yield (32−83%) and with high diastereoselectivity in favor of the cis product (80:20−100:0). In contrast, an α-imino ester gave predominantly the trans-aziridine (89:11) in high yield (91%). The synthetic potential of C-silylaziridines was investigated. Treatment with F^- (tetrabutylammonium triphenyldifluorosilicate was used) in the presence of aldehydes gave the α-hydroxyaziridines in high yield and high diastereoselectivity (86:14−98:2) for the newly created stereogenic center. Complete retention of configuration was observed in the substitution of the silyl group with electrophiles in all cases. Trapping with deuterium (using CDCl₃ as electrophile) was also successful, but trapping with phosphate [using ClP(O)(OPh)₂] and acetate (using Ac₂O) was unsuccessful. In these latter cases ring opening by chloride and acetate, respectively, was observed. Further ring-opening reactions were effected using azide and thiolate nucleophiles and in all cases complete regioselectivity in favor of attack at the silyl-bearing carbon occurred. Complete regioselectivity was also observed in the carbonylative ring expansion using Co₂(CO)₈ to give a β-lactam. Treatment of cis-1-tosyl-2-phenyl/butyl-3-trimethylsilylaziridines with n-BuLi and subsequent quenching with MeI followed completely different pathways, depending on the 2-substituent. In the case of the 2-phenylaziridine, metalation was initiated α to the phenyl group and led finally to a fused tricyclic adduct with four stereogenic centers as a single diastereoisomer. In the case of the 2-butylaziridine, metalation occurred α to the silyl group and led to a trisubstituted silylaziridine, probably via an azirine intermediate.