Flow Asymmetric Propargylation: Development of Continuous Processes for the Preparation of a Chiral β‐Amino Alcohol. (7th July 2017)

• Record Type: Journal Article
• Authors: Li, Hui; Sheeran, Jillian W.; Clausen, Andrew M.; Fang, Yuan‐Qing; Bio, Matthew M.; Bader, Scott
• Is Part Of: Angewandte Chemie. Volume 129:Number 32(2017)
• Page Start: 9553
• Page End: 9557
• Publication Date: 2017-07-07
• Subjects: Allen-Lithiierung -- Asymmetrische Propargylierung -- Durchflusssynthese -- FlowIR -- Prozessanalysetechnik; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201704882
• Languages: English
• ISSNs: 0044-8249

Abstract

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 alcohol1 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 (1 S, 2 R )‐ 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.