Chemoselective Tertiary C−H Hydroxylation for Late‐Stage Functionalization with Mn(PDP)/Chloroacetic Acid Catalysis. Issue 2 (26th December 2019)

• Record Type: Journal Article
• Authors: Chambers, Rachel K.; Zhao, Jinpeng; Delaney, Connor P.; White, M. Christina
• Is Part Of: Advanced synthesis & catalysis. Volume 362:Issue 2(2020)
• Page Start: 417
• Page End: 423
• Publication Date: 2019-12-26
• Subjects: C−H hydroxylation -- oxidation -- chemoselective -- site-selective -- late stage functionalization; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.201901472
• Languages: English
• ISSNs: 1615-4150

Abstract

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( 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. Abstract :