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

Abstract

We present a new asymmetric synthesis of b-hydroxycarboxylic acids from ketones, performed by carboxylation using CO 2 followed by asymmetric hydrogenation. First, the carboxylation of ketones gives b-ketocarboxylic acids. The effects of temperature, reaction time, and amount of 1,.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 b-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.

Making C–C Bonds from Carbon Dioxide via Transition-Metal Catalysis

“…In contrast, compounds containing less polarized C-M bonds (e.g., organocuprate, organozinc, organozirconium) typically require elevated temperatures and basic media [37][38][39]. Substrates bearing acidic C-H bonds can also undergo carboxylation, including alkynes, azoles, and carbonyl compounds [40][41][42][43][44][45].…”

Direct Carboxylation of C(sp3)-H and C(sp2)-H Bonds with CO2 by Transition-Metal-Catalyzed and Base-Mediated Reactions

“…In light of this view, an analysis of recent advances in this field and relevant developments of this chemistry over the last two decades are reported in the following two sections. Thanks to reports by Jessop [58] and Beckman [59], significant advances in the synthesis of β-keto carboxylic acids from ketones and CO 2 and their further conversion into β-ketoesters and β-hydroxycarboxylic acids have been introduced. Very recently an interesting example of base-promoted carboxylative cyclization reaction of 1-propenyl ketones to α-pyrones has been reported by Lu [85].…”

“…The Jessop group developed an efficient two step procedure for the synthesis of chiral β-hydroxycarboxylic acids from ketones, CO 2 and H 2 [58]. First β-ketocarboxylic acids (57) are synthesized in a DBU-promoted reaction, subsequently the acids are stereoselectively reduced with H 2 to chiral β-hydroxycarboxylic acids (58) by using the RuCl 2 [(S)-BINAP] catalyst (Scheme 25).…”

“…In this review, we inspect recent advances concerning direct CO2-based carboxylation reactions of C(sp 3 )-H and C(sp 2 )-H bonds encompassing both transition-metal-catalyzed and Brønsted-base mediated reactions. Also a few examples of For stoichiometric reactions falling under Scheme 2c, recent reports have dealt with the problem of Brønsted-base recycling [58,59] or Brønsted-base regeneration through electrodialysis [60] providing, on the overall, very efficient synthetic processes (see Sections 4.1 and 6.3).…”

“…For stoichiometric reactions falling under Scheme 2c, recent reports have dealt with the problem of Brønsted-base recycling [58,59] or Brønsted-base regeneration through electrodialysis [60] providing, on the overall, very efficient synthetic processes (see Sections 4.1 and 6.3).…”