Enantioselective Iridium-Catalyzed C-H Bond Alkylation for the Synthesis of N-N Atropisomeric Phosphines

对映选择性铱催化CH键烷基化反应合成NN轴手性膦

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Abstract

Over the past few decades, atropisomeric biaryl phosphines have emerged as privileged scaffolds in the design of chiral ligands, bioactive molecules, and drug candidates. However, despite their considerable potential, the enantioselective synthesis of N-N atropisomeric phosphines remains underdeveloped. Herein, we report an iridium-catalyzed, enantioselective C-H alkylation for constructing N-N atropisomeric monophosphines, employing a phosphine(III) group as a directing motif. This method enables ready access to a diverse range of N-N-linked indole-pyrrole and indole-indole frameworks with up to 98% ee. Furthermore, the utility of this approach is demonstrated through a series of synthetic transformations and catalytic applications.

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