Stereodivergent assembly of tetrahydro-γ-carbolines via synergistic catalytic asymmetric cascade reaction

Nat Commun. 2019 Dec 5;10(1):5553. doi: 10.1038/s41467-019-13529-z.

Abstract

Enantiomerically enriched indole-containing heterocycles play a vital role in bioscience, medicine, and chemistry. As one of the most attractive subtypes of indole alkaloids, highly substituted tetrahydro-γ-carbolines are the basic structural unit in many natural products and pharmaceuticals. However, the syntheses of tetrahydro-γ-carbolines with high functionalities from readily available reagents are significant challenging. In particular, the stereodivergent syntheses of tetrahydro-γ-carbolines containing multi-stereogenic centers remain quite difficult. Herein, we report an expedient and stereodivergent assembly of tetrahydro-γ-carbolines with remarkably high levels of stereoselective control in an efficient cascade process from aldimine esters and indolyl allylic carbonates via a synergistic Cu/Ir catalyst system. Control experiments-guided optimization of synergistic catalysts and mechanistic investigations reveal that a stereodivergent allylation reaction and a subsequent highly stereoselective iso-Pictet-Spengler cyclization are the key elements to success.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbolines / chemical synthesis
  • Carbolines / chemistry*
  • Catalysis
  • Chromatography, High Pressure Liquid
  • Cyclization*
  • Drug Synergism
  • Indole Alkaloids / chemical synthesis
  • Indole Alkaloids / chemistry*
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Models, Chemical
  • Molecular Structure
  • Proton Magnetic Resonance Spectroscopy
  • Stereoisomerism

Substances

  • Carbolines
  • Indole Alkaloids
  • Indoles
  • gamma-carboline