Facile Synthesis of β-Lactam Derivatives by the Staudinger Reaction Using 3,6-Dichlorotetrazine

Abstract

A versatile and convenient method for synthesis of β-lactams using 3,6-dichlorotetrazine as an acid activator in the ketene-imine cycloaddition is reported. Monocyclic and spirocyclic β-lactams are obtained in good to excellent yields. Easy purification of the products can be performed by aqueous workup and then crystallisation from ethyl acetate.

Recent Advances in the Synthesis of Spiro‐β‐Lactams and Spiro‐δ‐Lactams

“…Zarei and co-workers synthesized C3 spiro-βlactams 34 a and 34 b, containing the spiro-xanthene moiety, in high yields (86% and 87%, respectively) (Scheme 8a). [23] These molecules were obtained as products of the ketene-imine cycloaddition between xanthene-9-carboxylic acid (32) and aromatic imines 23 with 3,6-dichlorotetrazine (33) as the carboxylic acid activator. The use of diphosphorus tetraiodide as acid activator in the synthesis of two other xanthene-9carboxylic acid derived C3 spiro-β-lactams, 34 c and 34 d, was also reported allowing the synthesis of the target molecules in good yields (71-75%) (Scheme 8b).…”

“…Zarei and co‐workers synthesized C3 spiro‐β‐lactams 34 a and 34 b , containing the spiro‐xanthene moiety, in high yields (86% and 87%, respectively) (Scheme 8a) [23] . These molecules were obtained as products of the ketene‐imine cycloaddition between xanthene‐9‐carboxylic acid ( 32 ) and aromatic imines 23 with 3,6‐dichlorotetrazine ( 33 ) as the carboxylic acid activator.…”

An update on the synthesis and reactivity of spiro-fused β-lactams

“…36 To deal with these difficulties, the Zarei and Sardarian groups have independently devoted efforts to the preparation of a cyclic ketene from the corresponding xanthene-9-carboxylic acid 34 using different carboxylic activators 36 to synthesize spiro-β-lactams 37 by Staudinger reaction with imines 35 (Scheme 10, Table 1). 15,[36][37][38][39][40][41][42][43] The structure of 1-[3-(morpholin-4-yl)propyl]-4-(3-nitrophenyl)spiro[azetidine-3,9'-xanthen]-2-one -an analog of spiro-β-lactams 37 -was successfully determined for the first time by Akkurt via single-crystal X-ray analysis. 44…”