Access to Optically Enriched α-Aryloxycarboxylic Esters via Carbene-Catalyzed Dynamic Kinetic Resolution and Transesterification

Abstract

Optically active α-aryloxycarboxylic acids and their derivatives are important functional molecules. Disclosed here is a carbene-catalyzed dynamic kinetic resolution and transesterification reaction for access to this class of molecules with up to 99% yields and 99:1 er values. Addition of a chiral carbene catalyst to the ester substrate leads to two diastereomeric azolium ester intermediates that can quickly epimerize to each other and thus allows for effective dynamic kinetic resolution to be realized. The optically enriched ester products from our reaction can be quickly transformed to chiral herbicides and other bioactive molecules.

Dynamic Kinetic Resolution of Carboxylic Esters Catalyzed by Chiral PPY N-Oxides: Synthesis of Nonsteroidal Anti-Inflammatory Drugs and Mechanistic Insights

“…Initially, the reaction of the 4-nitrophenol ester 1a with diphenylmethanol 2a was selected as the model reaction (Table ). First, when the chiral 2-substituted PPY N -oxide C9a was used as the catalyst, the desired ester 3a was generated in 52% yield with 62% ee (entry 1).…”

N‐Heterocyclic Carbene (NHC)‐Catalyzed Transformations Involving Azolium Enolates

“…[101] Recently, Chi and co-workers reported an NHC-catalyzed dynamic kinetic resolution of carboxylic esters 156 followed by a transesterification strategy using alcohol 157 for the enantioselective synthesis of α-aryloxy carboxylic esters 158 (Scheme 56). [102] The reaction proceeded via addition of the chiral NHC generated from ent-J to the ester substrate 156 to generate the two diastereomeric acylazolium intermediates, which can easily isomerize via the NHC-enolate. This selectively generated acylazolium was acylated using 157 to form the desired ester product 158.…”

Enantioselective N-heterocyclic carbene-catalyzed rearrangement of enol ε-lactones

“…The Chi group demonstrated an array of enantioselective α-, β-, and γ-functionalization reactions of para -nitro phenyl esters. 14 Other activated esters, such as N -hydroxyphthalimide esters 15 and 1-hydroxybenzotriazole esters, 16 are also good substrates for NHC activation. In these reactions, the OR group of esters as leaving groups becomes atomic waste after NHC activation.…”