Chemoselective Tertiary C−H Hydroxylation for Late-Stage Functionalization with Mn(PDP)/Chloroacetic Acid Catalysis

Rachel K. Chambers, Jinpeng Zhao, Connor P. Delaney, M. Christina White

Research output: Contribution to journalArticlepeer-review

Abstract

Aromatic and heterocyclic functionality are ubiquitous in pharmaceuticals. Herein, we disclose a new Mn(PDP) catalyst system using chloroacetic acid additive capable of chemoselectively oxidizing remote tertiary C(sp3)−H bonds in the presence of a broad range of aromatic and heterocyclic moieties. Although catalyst loadings can be lowered to 0.1 mol% under a Mn(PDP)/acetic acid system for aromatic and non-basic nitrogen heterocycle substrates, the Mn(PDP)/chloroacetic acid system generally affords 10–15% higher isolated yields on these substrates and is uniquely effective for remote C(sp3)−H hydroxylations in substrates housing basic nitrogen heterocycles. The demonstrated ability to perform Mn(PDP)/chloroacetic acid C(sp3)−H oxidations in pharmaceutically relevant complex molecules on multi-gram scales will facilitate drug discovery processes via late-stage functionalization. (Figure presented.).

Original languageEnglish (US)
Pages (from-to)417-423
Number of pages7
JournalAdvanced Synthesis and Catalysis
Volume362
Issue number2
DOIs
StatePublished - Jan 23 2020

Keywords

  • C−H hydroxylation
  • chemoselective
  • late stage functionalization
  • oxidation
  • site-selective

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

Fingerprint Dive into the research topics of 'Chemoselective Tertiary C−H Hydroxylation for Late-Stage Functionalization with Mn(PDP)/Chloroacetic Acid Catalysis'. Together they form a unique fingerprint.

Cite this