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Nickel-Electrocatalytic Decarboxylative Arylation to Access Quaternary Centers

Laudadio, Gabriele ; Neigenfind, Philipp ; Péter, Áron ; Rubel, Camille Z. ; Emmanuel, Megan A. ; Oderinde, Martins S. ; Ewing, Tamara El-Hayek ; Palkowitz, Maximilian D. ; Sloane, Jack L. and Gillman, Kevin W. , et al. (2024) In Angewandte Chemie International Edition 63(8). p.202314617-202314617
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)
... (More)
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. (Less)
Abstract (Swedish)
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
keywords
Arylation, Cross-Coupling, Decarboxylative, Electrochemistry, Quaternary Centers
in
Angewandte Chemie International Edition
volume
63
issue
8
pages
202314617 - 202314617
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:38181042
  • scopus:85182453288
DOI
10.1002/anie.202314617
language
English
LU publication?
no
id
705e48b7-a78d-41cc-88df-10c7136ed4ce
date added to LUP
2025-08-06 19:40:13
date last changed
2025-09-01 11:14:59
@article{705e48b7-a78d-41cc-88df-10c7136ed4ce,
  abstract     = {{There is a pressing need, particularly in the field of drug discovery, <br>
for general methods that will enable direct coupling of tertiary alkyl <br>
fragments to (hetero)aryl halides. Herein a uniquely powerful and simple<br>
 set of conditions for achieving this transformation with unparalleled <br>
generality and chemoselectivity is disclosed. This new protocol is <br>
placed in context with other recently reported methods, applied to <br>
simplify the routes of known bioactive building blocks molecules, and <br>
scaled up in both batch and flow. The role of pyridine additive as well <br>
as the mechanism of this reaction are interrogated through Cyclic <br>
Voltammetry studies, titration experiments, control reactions with Ni(0)<br>
 and Ni(II)-complexes, and ligand optimization data. Those studies <br>
indicate that the formation of a BINAPNi(0) is minimized and the <br>
formation of an active pyridine-stabilized Ni(I) species is sustained <br>
during the reaction. Our preliminary mechanistic studies ruled out the <br>
involvement of Ni(0) species in this electrochemical cross-coupling, <br>
which is mediated by Ni(I) species via a Ni(I)-Ni(II)-Ni(III)-Ni(I) <br>
catalytic cycle.}},
  author       = {{Laudadio, Gabriele and Neigenfind, Philipp and Péter, Áron and Rubel, Camille Z. and Emmanuel, Megan A. and Oderinde, Martins S. and Ewing, Tamara El-Hayek and Palkowitz, Maximilian D. and Sloane, Jack L. and Gillman, Kevin W. and Ridge, Daniel and Mandler, Michael D. and Bolduc, Philippe N. and Nicastri, Michael C. and Zhang, Benxiang and Clementson, Sebastian and Petersen, Nadia Nasser and Martín-Gago, Pablo and Mykhailiuk, Pavel and Engle, Keary M. and Baran, Phil S.}},
  keywords     = {{Arylation; Cross-Coupling; Decarboxylative; Electrochemistry; Quaternary Centers}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{202314617--202314617}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Angewandte Chemie International Edition}},
  title        = {{Nickel-Electrocatalytic Decarboxylative Arylation to Access Quaternary Centers}},
  url          = {{http://dx.doi.org/10.1002/anie.202314617}},
  doi          = {{10.1002/anie.202314617}},
  volume       = {{63}},
  year         = {{2024}},
}