Cobalt-Catalyzed Oxidase C-H/N-H Alkyne Annulation: Mechanistic Insights and Access to Anticancer Agents

Ruhuai Mei; Hui Wang; Svenja Warratz; Stuart A. MacGregor; Lutz Ackermann

doi:10.1002/chem.201601101

Cobalt-Catalyzed Oxidase C-H/N-H Alkyne Annulation: Mechanistic Insights and Access to Anticancer Agents

Ruhuai Mei, Hui Wang, Svenja Warratz, Stuart A. MacGregor^*, Lutz Ackermann

^*Corresponding author for this work

School of Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Cp-free cobalt-catalyzed alkyne annulations by C-H/N-H functionalizations were accomplished with molecular O₂ as the sole oxidant. The user-friendly oxidase strategy proved viable with various internal and terminal alkynes through kinetically relevant C-H cobaltation, providing among others step-economical access to the anticancer topoisomerase-I inhibitor 21,22-dimethoxyrosettacin. DFT calculations suggest that electronic effects control the regioselectivity of the alkyne insertion step. Mit O₂: Co(OAc)₂ enabled the aerobic C-H/N-H functionalization with O₂ as the sole oxidant under Cp∗-free conditions, which enabled step-economical access to anticancer isoquinolones by highly selective C-H activation (see scheme, Cp∗=pentamethylcyclopentadienyl).

Original language	English
Pages (from-to)	6759-6763
Number of pages	5
Journal	Chemistry - A European Journal
Volume	22
Issue number	20
DOIs	https://doi.org/10.1002/chem.201601101
Publication status	Published - 10 May 2016

Keywords

annulation
C-H activation
cobalt
density functional calculations
isoquinolones
oxidase

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10.1002/chem.201601101

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title = "Cobalt-Catalyzed Oxidase C-H/N-H Alkyne Annulation: Mechanistic Insights and Access to Anticancer Agents",

abstract = "Cp-free cobalt-catalyzed alkyne annulations by C-H/N-H functionalizations were accomplished with molecular O2 as the sole oxidant. The user-friendly oxidase strategy proved viable with various internal and terminal alkynes through kinetically relevant C-H cobaltation, providing among others step-economical access to the anticancer topoisomerase-I inhibitor 21,22-dimethoxyrosettacin. DFT calculations suggest that electronic effects control the regioselectivity of the alkyne insertion step. Mit O2: Co(OAc)2 enabled the aerobic C-H/N-H functionalization with O2 as the sole oxidant under Cp∗-free conditions, which enabled step-economical access to anticancer isoquinolones by highly selective C-H activation (see scheme, Cp∗=pentamethylcyclopentadienyl).",

keywords = "annulation, C-H activation, cobalt, density functional calculations, isoquinolones, oxidase",

author = "Ruhuai Mei and Hui Wang and Svenja Warratz and MacGregor, {Stuart A.} and Lutz Ackermann",

note = "Publisher Copyright: {\textcopyright} 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

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doi = "10.1002/chem.201601101",

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AU - Mei, Ruhuai

AU - Wang, Hui

AU - Warratz, Svenja

AU - MacGregor, Stuart A.

AU - Ackermann, Lutz

PY - 2016/5/10

Y1 - 2016/5/10

N2 - Cp-free cobalt-catalyzed alkyne annulations by C-H/N-H functionalizations were accomplished with molecular O2 as the sole oxidant. The user-friendly oxidase strategy proved viable with various internal and terminal alkynes through kinetically relevant C-H cobaltation, providing among others step-economical access to the anticancer topoisomerase-I inhibitor 21,22-dimethoxyrosettacin. DFT calculations suggest that electronic effects control the regioselectivity of the alkyne insertion step. Mit O2: Co(OAc)2 enabled the aerobic C-H/N-H functionalization with O2 as the sole oxidant under Cp∗-free conditions, which enabled step-economical access to anticancer isoquinolones by highly selective C-H activation (see scheme, Cp∗=pentamethylcyclopentadienyl).

AB - Cp-free cobalt-catalyzed alkyne annulations by C-H/N-H functionalizations were accomplished with molecular O2 as the sole oxidant. The user-friendly oxidase strategy proved viable with various internal and terminal alkynes through kinetically relevant C-H cobaltation, providing among others step-economical access to the anticancer topoisomerase-I inhibitor 21,22-dimethoxyrosettacin. DFT calculations suggest that electronic effects control the regioselectivity of the alkyne insertion step. Mit O2: Co(OAc)2 enabled the aerobic C-H/N-H functionalization with O2 as the sole oxidant under Cp∗-free conditions, which enabled step-economical access to anticancer isoquinolones by highly selective C-H activation (see scheme, Cp∗=pentamethylcyclopentadienyl).

KW - annulation

KW - C-H activation

KW - cobalt

KW - density functional calculations

KW - isoquinolones

KW - oxidase

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ER -

Cobalt-Catalyzed Oxidase C-H/N-H Alkyne Annulation: Mechanistic Insights and Access to Anticancer Agents

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