Rapid Asymmetric Synthesis of Disubstituted Allenes by Coupling of Flow-Generated Diazo Compounds and Propargylated Amines

Jian-Siang Poh; Szabolcs Makai; Timo von Keutz; Duc N Tran; Claudio Battilocchio; Patrick Pasau; Steven V Ley

doi:10.1002/anie.201611067

Rapid Asymmetric Synthesis of Disubstituted Allenes by Coupling of Flow-Generated Diazo Compounds and Propargylated Amines

Angew Chem Int Ed Engl. 2017 Feb 6;56(7):1864-1868. doi: 10.1002/anie.201611067. Epub 2017 Jan 11.

Authors

Jian-Siang Poh¹, Szabolcs Makai¹, Timo von Keutz¹, Duc N Tran¹, Claudio Battilocchio¹, Patrick Pasau², Steven V Ley¹

Affiliations

¹ Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
² UCB Biopharma SPRL, Chemical Research R5, Chemin du Foriest, 1420, Braine-L'Alleud, Belgium.

Abstract

We report herein the asymmetric coupling of flow-generated unstabilized diazo compounds and propargylated amine derivatives, using a new pyridinebis(imidazoline) ligand, a copper catalyst and base. The reaction proceeds rapidly, generating chiral allenes in 10-20 minutes with high enantioselectivity (89-98 % de/ee), moderate yields and a wide functional group tolerance.

Keywords: allenes; asymmetric catalysis; copper; diazo compounds; flow chemistry.

Publication types

Research Support, Non-U.S. Gov't