Isoxazolidinones via Asymmetric Decarboxylative Protonation

Key words

decarboxylative protonation - isoxazolidinones - Meldrum’s acids

Significance

An organocatalytic approach for the synthesis of isoxazolidinones 3 is reported by the Brière group. The methodology is a tandem process promoted by the quinidine-derived catalyst A. An initial formal [3+2]-cycloaddition process couples 5-substituted Meldrum’s acids 1 and nitrones derived from sulfonamides 2. Then, an asymmetric decarboxylative protonation takes place via a putative stepwise mechanism. The desired products are generally obtained with good yields and with modest to good enantioselectivities.

Comment

Asymmetric protonation reactions are a fascinating topic in organic chemistry. In this area, decarboxylative protonation processes have attracted the interest of the scientific community due to the elegant in situ generation of the reacting enolate upon release of carbon dioxide (see Review below). Based on this concept, the authors present a novel straightforward approach to the synthesis of isoxazolidinones, which are useful precursors for β²-amino acids.

Review

J. Blanchet, J. Baudoux, M. Amere, M.-C. Lasne, J. Rouden Eur. J. Org. Chem. 2008, 5493–5506.