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 in | Journal of the American Chemical Society Vol. 144; no. 30; pp. 13643 - 13651 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
American Chemical Society
03.08.2022
Amer Chemical Soc |
Subjects | |
Online Access | Get full text |
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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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0002-7863 1520-5126 |
DOI: | 10.1021/jacs.2c04043 |