Carbene-Catalyzed Dynamic Kinetic Resolution of Carboxylic Esters

Abstract

Carbene-catalyzed reaction of carboxylic esters has the potential to offer effective synthetic solutions that cannot be readily achieved by using the more conventional aldehyde-type substrates. Here we report the first carbene-catalyzed dynamic kinetic resolution of α,α-disubstituted carboxylic esters with up to 99:1 er and 99% yield. The present study clearly illustrates the unique power of carbene-catalyzed reactions of readily available and easy to handle carboxylic esters.

Recent Progress in (Dynamic) Kinetic Resolution Catalyzed by N‐Heterocyclic Carbenes

“…In 2016, the Chi group reportedadynamic kinetic resolution of readily available and easy-to-handle carboxylic esters (Scheme 25). [35] Aw ide range of alcohols,i ncluding methanol and benzyla lcohol, weree xamined and diphenylmethanol was found to provide the highest enantioselectivity in this dynamic kinetic resolution reaction. The a-phenyl groups of ester substrates that contained different substituents were well-tolerated to providethe desired products with excellent enantioselectivities.…”

“…In 2016, the Chi group reported a dynamic kinetic resolution of readily available and easy‐to‐handle carboxylic esters (Scheme ) . A wide range of alcohols, including methanol and benzyl alcohol, were examined and diphenylmethanol was found to provide the highest enantioselectivity in this dynamic kinetic resolution reaction.…”

N‐Heterocyclic Carbene (NHC)‐Organocatalyzed Kinetic Resolutions, Dynamic Kinetic Resolutions, and Desymmetrizations

“…Esters and related carboxylic acid derivatives have since proved to be versatile reaction starting materials in asymmetric synthesis through various NHC‐catalytic activation modes . One of the best examples of this is the NHC‐catalyzed DKR process of racemic esters through an enantioselective trans ‐esterification reaction (Scheme ) . The α,α‐disubstituted carboxylic esters 72 were activated by NHC catalyst 74 and became racemized through an enolization process under basic conditions.…”

“…[56] One of the best examples of this is the NHC-catalyzed DKR process of racemic esters through an enantioselective transesterification reaction (Scheme18). [57] The a,a-disubstituted carboxylic esters 72 were activated by NHC catalyst 74 and becamer acemized through an enolization process under basic conditions. The esterificationr eaction of the NHC-activated esters with alcohol 73 was carried out in an enantioselective manner.…”

(Dynamic) Kinetic Resolution of Enamines/Imines: Enantioselective N‐Heterocyclic Carbene Catalyzed [3+3] Annulation of Bromoenals and Enamines/Imines

“…[2] Lately,t he NHCcatalyzed DKR of a-substituted ketones were then successfully established for [3+ +2] [3] and [4+ +2] [4] annulations with enals and b-methylenals for the synthesis of g-and d-lactones, respectively (Scheme 1b,c). TheN HC-catalyzed DKR of substituted ketones by the benzoin reaction [5] and the DKR of a-substituted esters by transesterification [6] were also developed (Scheme 1d,e). In addition, the NHC-catalyzed DKR of pyranone-dervied hemiacetals by esterification was reported (Scheme 1f).…”