Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

Abstract

In this work, we report an efficient approach to 2-oxoazetidine-3-carboxylic acid derivatives based on a thermally promoted Wolff rearrangement of diazotetramic acids in the presence of nucleophiles. The method allows easy variation of the substituent in the exocyclic acyl group by introducing different N-, O-, and S-nucleophilic reagents into the reaction. The reaction of chiral diazotetramic acids leads exclusively to trans-diastereomeric β-lactams. The use of variously substituted diazotetramic acids, including spirocyclic derivatives, as well as a wide range of nucleophiles provides access to a structural diversity of medically relevant 2-oxoazetidine-3-carboxylic acid amides and esters.

Keywords

• β-lactams
• diazotetramic acids
• nucleophiles
• spirocycles
• thermolysis
• wolff rearrangement