Combining Organo- and Biocatalysis

Key words

1,3-diols - enzymatic reduction - aldol addition - chemoenzymatic sequence

Significance

The authors report a chemoenzymatic reaction sequence towards 1,3-diols. The reported route consists of the amine-1-catalyzed aldol addition of acetone to aromatic aldehydes with a subsequent alcohol dehydrogenase (ADH) catalyzed ketoreduction. The co-factor NADH or NADPH, depending on the involved enzyme, respectively, was used in only catalytic amounts, enabled by a substrate-coupled regeneration process. The stereochemical outcome of the reaction could be fully controlled. With the four possible combinations of (S,S)-1, (R,R)-1 and (S)-ADH, (R)-ADH all diastereoisomers of each product could be obtained with excellent diastereo- and enantiocontrol.

Comment

The preparation of 1,3-diols is a challenging synthetic task, often achieved via metal catalysis or enzymatic reactions relying on dynamic kinetic resolution. The elegance of the present procedure is that it enables the synthesis of all four possible diastereoisomers of the desired diols by simple variation of the catalyst combination. Furthermore, the involved catalysts and the reaction conditions are fully biocompatible, enabling ‘green chemistry’. Since the combination of bio- and metal catalysis has already been achieved (see Review below), the present work closes a gap, disclosing that in principle all three types of catalyses are compatible.

Review: O. Pàmies, J.-E. Bäckvall Chem. Rev. 2003, 103, 3247-3262.