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Abstract Methods to synthesize alkylated pyridines are valuable because these structures are prevalent in pharmaceuticals and agrochemicals. We have developed a distinct approach to construct 4‐alkylpyridines using dearomatized pyridylphosphonium ylide intermediates in a Wittig olefination‐rearomatization sequence. PyridineN‐activation is key to this strategy, andN‐triazinylpyridinium salts enable coupling between a wide variety of substituted pyridines and aldehydes. The alkylation protocol is viable for late‐stage functionalization, including methylation of pyridine‐containing drugs. This approach represents an alternative to metal‐catalyzedsp2‐sp3cross‐coupling reactions and Minisci‐type processes.
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A Pyridine–Pyridine Cross‐Coupling Reaction via Dearomatized Radical Intermediates
Abstract A pyridine–pyridine coupling reaction has been developed between pyridyl phosphonium salts and cyanopyridines using B2pin2as an electron‐transfer reagent. Complete regio‐ and cross‐selectivity are observed when forming a range of valuable 2,4′‐bipyridines. Phosphonium salts were found to be the only viable radical precursors in this process, and mechanistic studies indicate that the process does not proceed through a Minisci‐type coupling involving a pyridyl radical. Instead, a radical–radical coupling process between a boryl phosphonium pyridyl radical and a boryl‐stabilized cyanopyridine radical explains the C−C bond‐forming step.
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- Award ID(s):
- 1753087
- PAR ID:
- 10120580
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 58
- Issue:
- 42
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 14882-14886
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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