Flow Asymmetric Propargylation: Development of Continuous Processes for the Preparation of a Chiral β-Amino Alcohol

Publication
Continuous flow
Drug substance
Process development

In our article published in Angewandte Chemie International Edition, we discuss how we developed of a flow chemistry process for asymmetric propargylation using allene gas as a reagent. The connected continuous process of allene dissolution, lithiation, Li-Zn transmetallation, and asymmetric propargylation provides homopropargyl β-amino alcohol 1 with high regio- and diastereoselectivity in high yield, enabling practical use of an unstable allenyllithium intermediate.

We outline how the process uses the commercially available and recyclable (1S,2R)-N-pyrrolidinyl norephedrine as a ligand to promote the highly diastereoselective (32:1) propargylation. Judicious selection of mixers based on the chemistry requirement and real-time monitoring of the process using process analytical technology (PAT) enabled stable and scalable flow chemistry runs. Read the article to learn more about this process.

View the full article (via Angewandte Chemie)