Copper-Catalyzed gem-Dichloroalkyl-Arylation of Unactivated Alkenes for the Synthesis of Dichloroalkyl-Azaheteropolycycles

TL;DR

A new copper-catalyzed method enables efficient synthesis of complex nitrogen-containing compounds with a gem-dichloroalkyl group, useful in drug development.

Contribution

A novel copper-catalyzed gem-dichloroalkyl-arylation method for synthesizing azaheteropolycycles with high regioselectivity and functional group tolerance.

Findings

The reaction enables tandem radical cyclization with high regioselectivity and short reaction times.

The method tolerates a broad array of functional groups and complex substrates.

The gem-dichloroalkyl group is efficiently installed as a valuable pharmacophore and building block.

Abstract

We report copper-catalyzed
dichloroalkyl-arylation of
terminal
alkenes containing a pendant aryl group bearing trichloroalkyl compounds
as radical precursors. Tandem radical cyclization proceeded with high
regioselectivity, short reaction times, and tolerance for a broad
array of functional groups and complex substrates, yielding fused
azaheterocycles such as pyrrolizidines and indolizidines, which serve
as important intermediates in total synthesis. This reaction sequence
affords the installation of the gem-dichloroalkyl
group, a potent pharmacophore and versatile building block in organic
synthesis.

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