Enantio- and Regioselective Ni-Catalyzed para-C–H Alkylation of Pyridines with Styrenes via Intermolecular Hydroarylation

Direct asymmetric functionalization of the pyridyl C–H bond represents a longstanding challenge in organic chemistry. We herein describe the first enantioselective para-C–H activation of pyridines through the use of a Ni–Al bimetallic catalyst system and N-heterocyclic carbene (NHC) ligand for inter...

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Published inJournal of the American Chemical Society Vol. 144; no. 30; pp. 13643 - 13651
Main Authors Ma, Jun-Bao, Zhao, Xia, Zhang, Dongju, Shi, Shi-Liang
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 03.08.2022
Amer Chemical Soc
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Summary:Direct asymmetric functionalization of the pyridyl C–H bond represents a longstanding challenge in organic chemistry. We herein describe the first enantioselective para-C–H activation of pyridines through the use of a Ni–Al bimetallic catalyst system and N-heterocyclic carbene (NHC) ligand for intermolecular hydroarylation of styrenes. The reaction procceds in high to excellent enantioselectivities (up to 98.5:1.5 er) and high site-selectivities for both styrene and pyridine components (up to >98:2). Consequently, a broad range of enantioenriched 1,1-diarylalkanes containing pyridine moieties could be prepared in a single step with 100% atom economy. Computational studies supported a mechanism involving a ligand-to-ligand H-transfer (LLHT) and reductive elimination sequence, with LLHT being the rate- and enantioselectivity-determining step. DFT studies indicate that the π–π stacking interaction between the NHC aryl fragment and trans-styrenes is critical for high reactivity and enantiocontrol.
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ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.2c04043