β-Hydroxycarboxylic Acids from Simple Ketones by Carboxylation and Asymmetric Hydrogenation

We present a new asymmetric synthesis of beta-hydroxycarboxylic acids from ketones, performed by carboxylation using CO2 followed by asymmetric hydrogenation. First, the carboxylation of ketones gives beta-ketocarboxylic acids. The effects of temperature, reaction time, and amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) promoter on the carboxylation were investigated. The DBU can be recycled. For the second step, the asymmetric hydrogenation of these beta-ketocarboxylic acids, we determined the effect of solvent choice, H-2 pressure, and substrate substitution. Hydrogenation yield and enantioselectivity are solvent-dependent, and the mechanism could proceed through hydrogenation of either the enol or the keto forms of the bound substrate. This synthesis is industrially advantageous due to the limited number of reactants required, their low-cost, and the potential for recycling unused materials.