Chemoselective Tertiary C-H Hydroxylation for Late-Stage Functionalization with Mn(PDP)/Chloroacetic Acid Catalysis
| Autor: | M. Christina White, Connor P. Delaney, Jinpeng Zhao, Rachel K. Chambers |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
010405 organic chemistry
Chloroacetic acid chemistry.chemical_element General Chemistry 010402 general chemistry 01 natural sciences Combinatorial chemistry Nitrogen Article 0104 chemical sciences Catalysis Hydroxylation chemistry.chemical_compound Acetic acid chemistry Oxidizing agent Surface modification Molecule |
| Zdroj: | Advanced synthesiscatalysis. 362(2) |
| ISSN: | 1615-4150 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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