Stereocontrolled Total Synthesis of (-)-Stemaphylline

Ana Varela; Lennart K B Garve; Daniele Leonori; Varinder K Aggarwal

doi:10.1002/anie.201611273

Stereocontrolled Total Synthesis of (-)-Stemaphylline

Angew Chem Int Ed Engl. 2017 Feb 13;56(8):2127-2131. doi: 10.1002/anie.201611273. Epub 2017 Jan 18.

Authors

Ana Varela¹, Lennart K B Garve¹, Daniele Leonori², Varinder K Aggarwal¹

Affiliations

¹ School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
² School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.

Abstract

Homologation of readily available α-boryl pyrrolidines with metal carbenoids is especially challenging even when good leaving groups (Cl^- ) are employed. By performing a solvent switch from Et₂ O to CHCl₃ , efficient 1,2-metalate rearrangement of the intermediate boronate occurs with both halide and ester leaving groups. The methodology was used in the total synthesis of the Stemona alkaloid (-)-stemaphylline in just 11 steps (longest linear sequence), with high stereocontrol (>20:1 d.r.) and 11 % overall yield. The synthesis also features a late-stage lithiation-borylation reaction with a tertiary amine containing carbenoid.

Keywords: Stemona alkaloids; boronic esters; lithiation-borylation; stereocontrol; total synthesis.

Publication types

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