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Synthesis of [5,6]-Bicyclic Heterocycles with a Ring-Junction Nitrogen Atom: Rhodium(III)-Catalyzed C-H Functionalization of Alkenyl Azoles.

ABSTRACT: The first syntheses of privileged [5,6]-bicyclic heterocycles, with ring-junction nitrogen atoms, by transition metal catalyzed C-H functionalization of C-alkenyl azoles is disclosed. Several reactions are applied to alkenyl imidazoles, pyrazoles, and triazoles to provide products with nitrogen incorporated at different sites. Alkyne and diazoketone coupling partners give azolopyridines with various substitution patterns. In addition, 1,4,2-dioxazolone coupling partners yield azolopyrimidines. Furthermore, the mechanisms for the reactions are discussed and the utility of the developed approach is demonstrated by iterative application of C-H functionalization for the rapid synthesis of a patented drug candidate.

SUBMITTER: Halskov KS

PROVIDER: S-EPMC5564303 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Synthesis of [5,6]-Bicyclic Heterocycles with a Ring-Junction Nitrogen Atom: Rhodium(III)-Catalyzed C-H Functionalization of Alkenyl Azoles.

Halskov Kim Søholm KS Roth Howard S HS Ellman Jonathan A JA

Angewandte Chemie (International ed. in English) 20170705 31

The first syntheses of privileged [5,6]-bicyclic heterocycles, with ring-junction nitrogen atoms, by transition metal catalyzed C-H functionalization of C-alkenyl azoles is disclosed. Several reactions are applied to alkenyl imidazoles, pyrazoles, and triazoles to provide products with nitrogen incorporated at different sites. Alkyne and diazoketone coupling partners give azolopyridines with various substitution patterns. In addition, 1,4,2-dioxazolone coupling partners yield azolopyrimidines. F ...[more]

PMID: 28586164

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