Report

Modular radical cross-coupling with sulfones enables access to sp3-rich (fluoro)alkylated scaffolds

See allHide authors and affiliations

Science  18 Feb 2018:
eaar7335
DOI: 10.1126/science.aar7335

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Abstract

Cross-coupling chemistry is widely applied to carbon-carbon bond formation in the synthesis of medicines, agrochemicals, and other functional materials. Recently single-electron-induced variants of this reaction class have proven particularly useful in the formation of C(sp2)-C(sp3) linkages, though certain compound classes have remained a challenge. Here we report the use of sulfones to activate the alkyl coupling partner in nickel-catalyzed radical cross-coupling with aryl zinc reagents. This method’s tolerance of fluoroalkyl substituents proved particularly advantageous for the streamlined preparation of pharmaceutically-oriented fluorinated scaffolds that previously required multiple steps, toxic reagents, and non-modular retrosynthetic blueprints. Five specific sulfone reagents facilitate the rapid assembly of a vast set of compounds, many of which contain challenging fluorination patterns.

View Full Text