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Cobalt-Catalyzed Alkylation of Drug-Like Molecules and Pharmaceuticals Using Heterocyclic Phosphonium Salts.

ABSTRACT: Alkylated pyridines are common in pharmaceuticals, and metal catalysis is frequently used to prepare this motif via Csp2-Csp3 coupling processes. We present a cobalt-catalyzed coupling reaction between pyridine phosphonium salts and alkylzinc reagents that can be applied to complex drug-like fragments and for late-stage functionalization of pharmaceuticals. The reaction generally proceeds at room temperature, and 4-position pyridine C-H bonds are the precursors in this strategy. Given the challenges in selectively installing (pseudo)halides in complex pyridines, this two-step process enables sets of molecules to be alkylated that would be challenging using traditional cross-coupling methods.

SUBMITTER: Zhang X

PROVIDER: S-EPMC6814195 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Cobalt-Catalyzed Alkylation of Drug-Like Molecules and Pharmaceuticals Using Heterocyclic Phosphonium Salts.

Zhang Xuan X McNally Andrew A

ACS catalysis 20190422

Alkylated pyridines are common in pharmaceuticals, and metal catalysis is frequently used to prepare this motif via Csp2-Csp3 coupling processes. We present a cobalt-catalyzed coupling reaction between pyridine phosphonium salts and alkylzinc reagents that can be applied to complex drug-like fragments and for late-stage functionalization of pharmaceuticals. The reaction generally proceeds at room temperature, and 4-position pyridine C-H bonds are the precursors in this stra ...[more]

PMID: 31656687

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