Yu Kawamata1,2, Julien C Vantourout1, David P Hickey3,2, Peng Bai4,2, Longrui Chen5, Qinglong Hou5, Wenhua Qiao5, Koushik Barman3,2, Martin A Edwards3,2, Alberto F Garrido-Castro1, Justine N deGruyter1, Hugh Nakamura1, Kyle Knouse1, Chuanguang Qin1, Khalyd J Clay1, Denghui Bao5, Chao Li1, Jeremy T Starr6, Carmen Garcia-Irizarry6, Neal Sach7, Henry S White3,2, Matthew Neurock4,2, Shelley D Minteer3,2, Phil S Baran1,2. 1. Department of Chemistry , The Scripps Research Institute , 10550 North Torrey Pines Road , La Jolla , California 92037 , United States. 2. Center for Synthetic Organic Electrochemistry , 315 South 1400 East , Salt Lake City , Utah 84112 , United States. 3. Department of Chemistry , University of Utah , 315 South 1400 East , Salt Lake City , Utah 84112 , United States. 4. Department of Chemical Engineering and Materials Science , University of Minnesota , Minneapolis , Minnesota 55455 , United States. 5. Asymchem Life Science (Tianjin) , Tianjin Economic-Technological Development Zone, Tianjin 300457 , China. 6. Discovery Sciences, Medicine Design , Pfizer Global Research and Development , 445 Eastern Point Road , Groton , Connecticut 06340 , United States. 7. Department of Chemistry , La Jolla Laboratories, Pfizer , 10770 Science Center Drive , San Diego , California 92121 , United States.
Abstract
C-N cross-coupling is one of the most valuable and widespread transformations in organic synthesis. Largely dominated by Pd- and Cu-based catalytic systems, it has proven to be a staple transformation for those in both academia and industry. The current study presents the development and mechanistic understanding of an electrochemically driven, Ni-catalyzed method for achieving this reaction of high strategic importance. Through a series of electrochemical, computational, kinetic, and empirical experiments, the key mechanistic features of this reaction have been unraveled, leading to a second generation set of conditions that is applicable to a broad range of aryl halides and amine nucleophiles including complex examples on oligopeptides, medicinally relevant heterocycles, natural products, and sugars. Full disclosure of the current limitations and procedures for both batch and flow scale-ups (100 g) are also described.
C-N cross-coupling is one of the most valuable and widespread transformations in organic synthesis. Ln class="Chemical">argely dominated by Pd- and Cu-based catalytic systems, it has proven to be a staple transformation for those in both academia and industry. The current study presents the development and mechanistic understanding of an electrochemically driven, Ni-catalyzed method for achieving this reaction of high strategic importance. Through a series of electrochemical, computational, kinetic, and empirical experiments, the key mechanistic features of this reaction have been unraveled, leading to a second generation set of conditions that is applicable to a broad range of aryl halides and amine nucleophiles including complex examples on oligopeptides, medicinally relevant heterocycles, natural products, and sugars. Full disclosure of the current limitations and procedures for both batch and flow scale-ups (100 g) are also described.
Authors: Sepideh Sharif; David Mitchell; Michael J Rodriguez; Jennifer L Farmer; Michael G Organ Journal: Chemistry Date: 2016-09-05 Impact factor: 5.236
Authors: Joseph P Tassone; Emma V England; Preston M MacQueen; Michael J Ferguson; Mark Stradiotto Journal: Angew Chem Int Ed Engl Date: 2019-01-24 Impact factor: 15.336
Authors: Alexander G O'Brien; Akinobu Maruyama; Yasuhide Inokuma; Makoto Fujita; Phil S Baran; Donna G Blackmond Journal: Angew Chem Int Ed Engl Date: 2014-09-10 Impact factor: 15.336
Authors: Dillon T Flood; Shota Asai; Xuejing Zhang; Jie Wang; Leonard Yoon; Zoë C Adams; Blythe C Dillingham; Brittany B Sanchez; Julien C Vantourout; Mark E Flanagan; David W Piotrowski; Paul Richardson; Samantha A Green; Ryan A Shenvi; Jason S Chen; Phil S Baran; Philip E Dawson Journal: J Am Chem Soc Date: 2019-06-12 Impact factor: 15.419
Authors: Christian A Malapit; Margarida Borrell; Michael W Milbauer; Conor E Brigham; Melanie S Sanford Journal: J Am Chem Soc Date: 2020-03-24 Impact factor: 15.419
Authors: Cian Kingston; Maximilian D Palkowitz; Yusuke Takahira; Julien C Vantourout; Byron K Peters; Yu Kawamata; Phil S Baran Journal: Acc Chem Res Date: 2019-12-11 Impact factor: 22.384
Authors: Hai-Jun Zhang; Longrui Chen; Martins S Oderinde; Jacob T Edwards; Yu Kawamata; Phil S Baran Journal: Angew Chem Int Ed Engl Date: 2021-08-15 Impact factor: 16.823