An Air- and Moisture-Stable Synthetic Reagent for Optically Active α-Branched Proline Derivatives

(2R,5S)-2-Trichloromethyl-3-oxa-1-azabicyclo[3.3.0]octan-4-one (1) is an efficient reagent usable for the introduction of functional groups onto the α-position of proline stereoselectively due to the concept of self-reproduction of chirality. Seebach et al. have been developed the original reagent 2 on the basis of its concept¹⁾ and the reagent 1 is its improved reagent with air- and moisture-stabilities.^2,6) The treatment of 1 with some base generates the enolate, followed by the reaction with electrophiles proceeding diastereoselectively to afford the desired products.^2-7) Afterwards, the sodium methoxide-promoted methanolysis leads to the methyl esters of optically active α-branched prolines via the formation of N-formylproline methyl esters. Generally, the hydrolysis of the N-formyl group proceeds slowly, but the rate of cleavage can be improved more rapidly by the addition of acetyl chloride.^4-6) In this synthetic manner, optically active proline amides are also given after the secondary amine-promoted aminolysis.⁸⁾