Asymmetric Organocatalysed Synthesis of (R)‐Mandelic Acid Esters and α‐Alkoxy Derivatives from Commercial Sources
Year: 2024
Type: article
Abstract: Optically active mandelic acid esters represent a highly valuable class of building blocks in organic synthesis and recurrent motifs embedded in bioactive compounds and drugs. Herein, we provide an enantioselective one-pot synthesis based on Knoevenagel condensation/asymmetric epoxidation/domino ring-opening hydrolysis (DROH) sequence to the crude mandelic acids, which underwent a final esterification step to (R)-methyl mandelates. These products have been obtained in good to high overall yield and enantioselectivity, using commercially and widely available reagents and catalyst including aldehydes, phenylsulfonyl acetonitrile, cumyl hydroperoxide, water and an epi-quinine-derived urea as the organocatalyst. Moreover, the versatility of the process has been demonstrated to prepare the corresponding α-alkoxy esters in highly enantioselective manner, when using primary alcohols in a domino ring-opening esterification (DROE) step. This system is a first example of non-enzymatic catalytic one-pot protocol which allows a straightforward asymmetric synthesis of highly valuable mandelic acid derivatives from aldehyde feedstocks.
Source: Chemistry - A European Journal
Authors: Vincenzo Battaglia, Sara Meninno, Alessandra Lattanzi
Institution: University of Salerno
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,640
Awards: G5338858321, G5356308337
OpenAlex ID: W4404226458