Eight-Step Enantioselective Total Synthesis of (-)-Cycloclavine

Angew Chem Int Ed Engl. 2017 Jan 2;56(1):324-327. doi: 10.1002/anie.201608820. Epub 2016 Nov 18.

Abstract

The first enantioselective total synthesis of (-)-cycloclavine was accomplished in 8 steps and 7.1 % overall yield. Key features include the first catalytic asymmetric cyclopropanation of allene, mediated by the dirhodium catalyst Rh2 (S-TBPTTL)4 , and the enone 1,2-addition of a new TEMPO carbamate methyl carbanion. An intramolecular strain-promoted Diels-Alder methylenecyclopropane (IMDAMC) reaction provided a pivotal tricyclic enone intermediate with more than 99 % ee after crystallization. The synthesis of (-)-1 was completed by a late-stage intramolecular Diels-Alder furan (IMDAF) cycloaddition to install the indole.

Keywords: allene; clavine alkaloids; cycloaddition; cyclopropanation; enantioselectivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Crystallography, X-Ray
  • Indole Alkaloids / chemical synthesis*
  • Indole Alkaloids / chemistry
  • Models, Molecular
  • Molecular Structure
  • Stereoisomerism

Substances

  • Indole Alkaloids
  • cycloclavine