Year: 2025
Type: article
Abstract: Despite the occurrence of the β‐hydroxy‐α,α‐dimethyl carboxylic ester motif in many natural products, no attempt is made to synthesize this core structure via a racemic and enantioselective Barbier reaction. In this study, the optimized reaction conditions for the achiral Barbier reaction between allyl bromide and a 2,2‐dimethyl‐3‐oxopropanoate are found, yielding the desired β‐hydroxy‐α,α‐dimethyl carboxylic ester in up to 64%. Therefore, different metals, additives, solvents, and solvent mixtures are tested. The optimized reaction conditions are then used to expand the substrate scope of the Barbier reaction by using five structurally different allylic and propargylic bromides. By using (+)‐cinchonine and (–)‐cinchonidine as chiral additives along with indium in a tetrahydrofuran/hexane solvent mixture, it is possible to obtain 10 different β‐hydroxy‐α,α‐dimethyl carboxylic esters in an enantioenriched fashion with up to 81% yield and 98%ee.
Authors: Jan Grammel, Jasmina Amrouch, Wolfgang Frey, Anna Zens, Sabine Laschat
Institution: University of Stuttgart
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,330
OpenAlex ID: W4409482761