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Abstract There is a pressing need, particularly in the field of drug discovery, for general methods that will enable direct coupling of tertiary alkyl fragments to (hetero)aryl halides. Herein a uniquely powerful and simple set of conditions for achieving this transformation with unparalleled generality and chemoselectivity is disclosed. This new protocol is placed in context with other recently reported methods, applied to simplify the routes of known bioactive building blocks molecules, and scaled up in both batch and flow. The role of pyridine additive as well as the mechanism of this reaction are interrogated through Cyclic Voltammetry studies, titration experiments, control reactions with Ni(0) and Ni(II)‐complexes, and ligand optimization data. Those studies indicate that the formation of a BINAPNi(0) is minimized and the formation of an active pyridine‐stabilized Ni(I) species is sustained during the reaction. Our preliminary mechanistic studies ruled out the involvement of Ni(0) species in this electrochemical cross‐coupling, which is mediated by Ni(I) species via a Ni(I)‐Ni(II)‐Ni(III)‐Ni(I) catalytic cycle.
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Deciphering the mechanism of the Ni-photocatalyzed C‒O cross-coupling reaction using a tridentate pyridinophane ligand
Abstract Photoredox nickel catalysis has emerged as a powerful strategy for cross-coupling reactions. Although the involvement of paramagnetic Ni(I)/Ni(III) species as active intermediates in the catalytic cycle has been proposed, a thorough spectroscopic investigation of these species is lacking. Herein, we report the tridentate pyridinophane ligandsRN3 that allow for detailed mechanistic studies of the photocatalytic C–O coupling reaction. The derived (RN3)Ni complexes are active catalysts under mild conditions and without an additional photocatalyst. We also provide direct evidence for the key steps involving paramagnetic Ni species in the proposed catalytic cycle: the oxidative addition of an aryl halide to a Ni(I) species, the ligand exchange/transmetalation at a Ni(III) center, and the C–O reductive elimination from a Ni(III) species. Overall, the present work suggests theRN3 ligands are a practical platform for mechanistic studies of Ni-catalyzed reactions and for the development of new catalytic applications.
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- Award ID(s):
- 1925751
- PAR ID:
- 10364089
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 13
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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