Modular radical cross-coupling with sulfones enables access to sp3-rich (fluoro)alkylated scaffolds | Health & Environmental Research Online (HERO)

Health & Environmental Research Online (HERO)

Print Feedback Export to File

This record has one attached file:

Citation
Tags

HERO ID

4239852

Reference Type

Journal Article

Title

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

Author(s)

Merchant, RR; Edwards, JT; Qin, T; Kruszyk, MM; Bi, C; Che, G; Bao, DH; Qiao, W; Sun, L; Collins, MR; Fadeyi, OO; Gallego, GM; Mousseau, JJ; Nuhant, P; Baran, PS

Year

2018

Is Peer Reviewed?

Journal

Science
ISSN: 0036-8075
EISSN: 1095-9203

Language

English

PMID

29456201

DOI

10.1126/science.aar7335

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.