Intermolecular C(sp3 )-H Amination of Complex Molecules

Nicholas D Chiappini; James B C Mack; J Du Bois

doi:10.1002/anie.201713225

Intermolecular C(sp³ )-H Amination of Complex Molecules

Angew Chem Int Ed Engl. 2018 Apr 23;57(18):4956-4959. doi: 10.1002/anie.201713225. Epub 2018 Mar 22.

Authors

Nicholas D Chiappini¹, James B C Mack¹, J Du Bois¹

Affiliation

¹ Department of Chemistry, Stanford University, Stanford, CA, 94305-5080, USA.

PMID: 29484792
DOI: 10.1002/anie.201713225

Abstract

A general and operationally convenient method for intermolecular amination of C(sp³ )-H bonds is described. This technology allows for efficient functionalization of complex molecules, including numerous pharmaceutical targets. The combination of pivalonitrile as a solvent, Al₂ O₃ as an additive, and phenyl sulfamate as a nitrogen source affords differential reaction performance and substrate scope. Mechanistic data strongly implicate a pathway for catalyst decomposition that initiates with solvent oxidation, thus providing rationale for the marked influence of pivalonitrile on this reaction process.

Keywords: C−H oxidation; amination; reaction mechanisms; rhodium; sulfamates.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't