ABSTRACT
The desymmetrization of meso-hydrobenzoin is described using chiral phosphine catalysts 8b-d and 9-11. The best enantioselectivity at room temperature was obtained with the newly synthesized phospholane 8c and benzoic anhydride, but the reaction is very slow. Much faster reactions, but somewhat lower enantioselectivities were observed using the bicyclic phosphine catalyst 9. To obtain product 5a with >90% ee required conditions where the ee is upgraded due to the formation of the dibenzoate 6a. Among the new phospholane catalysts, 8b has the best selectivity in the kinetic resolution of benzylic alcohols, but not at the level observed previously with catalyst 11.
ABSTRACT
The synthesis and evaluation of chiral phosphines 11, 15a, 19a, 24a, and 28a as nucleophilic catalysts for anhydride activation and kinetic resolution of alcohols is described. The relative reactivity follows the order 11a > 11b > 15a > 1 in the monocyclic series, and 24a > 19a > 28ain the bicyclic series, with an overall rate advantage of ca. 2 orders of magnitude for the bicyclic phospholanes over the monocyclic analogues. The increased reactivity of the bicyclic phospholanes for the acylation of alcohols is attributed to conformational effects and ground-state destabilization in a highly associative mechanism. Kinetic resolution data demonstrate promising enantioselectivities for 24a.
