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

• Published in: Journal of organic chemistry 2002-04, Vol.67 (7), p.2335-2344
• Main Authors: Aggarwal, Varinder K, Alonso, Emma, Ferrara, Marco, Spey, Sharon E
• Format: Article
• Language: English
• Subjects: Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Organic chemistry; Preparations and properties
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo016312h

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.