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Updated: Feb 27, 2026

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Flow Asymmetric Propargylation: Development of Continuous Processes for the Preparation of a Chiral β-Amino Alcohol
Hui Li1, Jillian W Sheeran1, Andrew M Clausen1
1Snapdragon Chemistry Inc., 85 Bolton St., Cambridge, MA, 02140, USA.
Abstract:
The development of a flow chemistry process for asymmetric propargylation using allene gas as a reagent is reported. 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. This flow process enables practical use of an unstable allenyllithium intermediate. 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.
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