Synthesis of bridged benzazocines and benzoxocines by a titanium-catalyzed double-reductive umpolung strategy

Chemistry. 2015 Feb 2;21(6):2339-42. doi: 10.1002/chem.201405852. Epub 2014 Dec 4.

Abstract

A sequence of two titanium(III)-catalyzed reductive umpolung reactions is reported that allows the rapid construction of benzazo- and benzoxozine building blocks. The first step is a reductive cross-coupling of quinolones or chromones with Michael acceptors. This reaction proceeds with complete syn-selectivity for the quinolone functionalization while the anti-diastereomers are obtained as the major products from chromones. With different reaction conditions, the stereochemical outcome can be altered to afford the syn-chromanone products as well. A subsequent reductive ketyl radical cyclization forges the tricyclic title compounds in good yields. A stereochemical model explaining the observed stereoselectivities is provided and the product configurations were unambiguously verified by X-ray analyses and 2D NMR spectroscopic experiments.

Keywords: catalysis; cyclization; electron transfer; titanium; umpolung.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Chromones / chemistry
  • Crystallography, X-Ray
  • Cyclization
  • Molecular Conformation
  • Oxocins / chemical synthesis
  • Oxocins / chemistry*
  • Stereoisomerism
  • Titanium / chemistry*

Substances

  • Chromones
  • Oxocins
  • Titanium