Organocatalysts for the Asymmetric Neber reaction: Synthesis of Chiral 2‐(Tetrazol‐5‐yl)‐2H‐Azirines

Abstract

Abstract‐ Several novel organocatalysts derived from β‐ and γ‐lactam‐fused thiazolidines and L‐phenylalanine‐based thiazolidines were efficiently synthetized. These organocatalysts, as well as other previously developed thiazolidine‐derived thioureas, were tested in the asymmetric one‐pot Neber reaction of β‐ketoxime‐1H‐tetrazoles towards chiral 2‐(tetrazol‐5‐yl)‐2H‐azirines. The results obtained when using thioureas only differing in the lactam ring size demonstrate that the presence of the 6β‐lactam ring in the catalysts is a requirement to achieve high enantioselectivity in the studied transformation. The new 6β‐aminopenicillanic acid‐derived thiourea afforded the R enantiomer of 3‐phenyl‐2‐(tetrazol‐5‐yl)‐2H‐azirine with >99 % ee.