Inter- and Intramolecular Differentiation of Enantiotopic Dioxane Acetals through Oxazaborolidinone-Mediated Enantioselective Ring-Cleavage Reaction:  Kinetic Resolution of Racemic 1,3-Alkanediols and Asymmetric Desymmetrization of M eso-1,3-polyols

Acetals derived from racemic 1,3-alkanediols undergo kinetic resolution in chiral oxazaborolidinone-mediated ring-cleavage reaction with nucleophiles such as enol silanes and allylic silanes. Enantioselectivity of the reaction is affected by nucleophiles, the N-sulfonyl groups of oxazaborolidinones, and the substituents attached to the acetal carbon. For disubstituted acetals rac- 1 and for trisubstituted acetal rac-2, derived from syn-2,4-dimethyl-1,3-pentanediol, satisfactory enantioselectivity is obtained by using methallylsilane 7b,c as a nucleophile in combination with N-mesyloxazaborolidinone 4a. On the other hand, enantioselective reaction of trisubstituted acetal rac-3b, derived from anti-2,4-dimethyl-1,3-pentanediol, is realized by using silyl ketene acetal 5e in combination with N-tosyloxazaborolidinone 4b. The reaction conditions optimized for the kinetic resolution, or enantiomer differentiating reaction, of the racemic acetals are successfully applied to asymmetric desymmetrization of meso-1,3-polyols through intramolecular differentiation of the enantiotopic acetal moieties of the bis-acetal derivatives. The utility of the ring-cleavage reaction as a method for enantioselective terminal differentiation of prochiral polyols is demonstrated in convergent asymmetric synthesis of pentol derivative 35 corresponding to the C(19)−C(27) ansa-chain of rifamycin S.