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Chemoselective Tertiary C−H Hydroxylation for Late‐Stage Functionalization with Mn(PDP)/Chloroacetic Acid Catalysis
Author(s) -
Chambers Rachel K.,
Zhao Jinpeng,
Delaney Connor P.,
White M. Christina
Publication year - 2020
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201901472
Subject(s) - chloroacetic acid , chemistry , catalysis , hydroxylation , oxidizing agent , acetic acid , surface modification , combinatorial chemistry , organic chemistry , enzyme
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( sp 3 )−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( sp 3 )−H hydroxylations in substrates housing basic nitrogen heterocycles. The demonstrated ability to perform Mn(PDP)/chloroacetic acid C( sp 3 )−H oxidations in pharmaceutically relevant complex molecules on multi‐gram scales will facilitate drug discovery processes via late‐stage functionalization.