On the Mechanism of the Unexpected Facile Formation of meso-Diacetate Products in Enzymatic Acetylation of Alkanediols

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Abstract
The mechanism of the unexpected facile formation of meso-diacetate previously observed in the enzymatic resolution of dl/meso mixtures of 2,4-pentanediol and 2,5-hexanediol with Candida antarctica lipase B has been elucidated. It was found that the formation of meso-diacetate proceeds via different mechanisms for the two diols. Enzyme-catalyzed acylation of AcO-d3 labeled (R)-monoacetates of meso-2,4-pentanediol and meso-2,5-hexanediol and analysis of the meso-diacetates obtained show that the former reaction proceeds via intramolecular acyl migration while the latter occurs via direct S-acylation of the alcohol. For the (R)-monoacetate of (R,S)-2,4-pentanediol the intramolecular acyl migration was fast and therefore direct S-acylation by the external acyl donor is suppressed. For the hexanediol monoacetate the rate ratio (pseudo E value) between (5R,2R)- and (5R,2S)-5-acetoxy-2-hexanol was experimentally determined to be kR,R/kR,S = 25, which is about 10−20 times lower than the E value for 2-pentanol and 2-octanol. In a preliminary experiment it was demonstrated that facile acyl migration in the 1,3-diol derivative can be utilized to prepare syn-1,3-diacetoxynonane (>90% syn) in high enantioselectivity (>99% ee) via a chemoenzymatic dynamic kinetic asymmetric transformation of a meso/dl mixture of 1,3-nonanediol.

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