Mechanism of α-Ketol-Type Rearrangement of Benzoin Derivatives under Basic Conditions

Abstract

The mechanism of base-catalyzed rearrangement of ring-substituted benzoins in aqueous methanol was examined by kinetic and product analyses. Substituent effects on the rate and equilibrium constants revealed that the kinetic process has a different electron demand compared to the equilibrium process. Reactions in deuterated solvents showed that the rate of H/D exchange of the α-hydrogen is similar to the overall rate toward the equilibrium state. A proton-inventory experiment using partially deuterated solvents showed a linear dependence of the rate on the deuterium fraction of the solvent, indicating that only one deuterium isotope effect contributes to the overall rate process. All these results point to a mechanism in which the rearrangement is initiated by the rate-determining α-hydrogen abstraction rather than a mechanism with initial hydroxyl hydrogen abstraction as in the general α-ketol rearrangement.

Base-Promoted Three-Component Cascade Reaction of α-Hydroxy Ketones, Malonodinitrile, and Alcohols: Direct Access to Tetrasubstituted NH-Pyrroles

“…Subsequently, intramolecular cyclization of F results in the formation of intermediate G , which can undergo hydration to give the final product 4 (path A). Alternatively, when R 1 = (hetero)­aryl and R 2 = alkyl, species A will preferentially attack the more electrophilic carbonyl group of 1′ , which is generated through α-ketol-type rearrangement of 1 under basic conditions, giving rise to intermediate B′ . Then, intermediate B′ would yield the product 4′ through path b, similar to path a.…”

Intramolecular Benzoin Reaction Catalyzed by Benzaldehyde Lyase from Pseudomonas Fluorescens Biovar I

“…Non‐enzymatic partial racemization of 6 was already observed under the reaction conditions of BAL catalysis (i.e., 50 % ee by chiral HPLC; see Figure S54). The racemization was strongly favored by the 2‐substituted hydroxy derivative, through an α‐ketol‐type rearrangement of benzoin derivatives under basic conditions . Therefore, the enantiopure product could only be obtained by the biocatalytic intramolecular benzoin reaction.…”

Double Proton Transfer during a Novel Tertiary α-Ketol Rearrangement in Ketol-Acid Reductoisomerase: A Water-Mediated, Metal-Catalyzed, Base-Induced Mechanism

“…The isomerization mediated by KARI can be considered an αketol rearrangement 16,17 in which 1,2-alkyl migration occurs after deprotonation of the OH group on C2 by a general base.…”

“…The first step (isomerization) is considered to be the rate-determining and more biologically important step. The isomerization mediated by KARI can be considered an α-ketol rearrangement , in which 1,2-alkyl migration occurs after deprotonation of the OH group on C2 by a general base. A similar rearrangement has been reported in the 1-deoxy- d -xylulose-5-phosphate (DXP) pathway, where DXP reductoisomerase (DXR) catalyzes the biosynthesis of 2- C -methyl- d -erythritol 4-phosphate. , …”