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Abstract We report that O‐selective arylation of 2‐ and 4‐pyridones with arylboronic acids is affected by a modular, bismacycle‐based system. The utility of this umpolung approach to pyridyl ethers, which is complementary to conventional methods based on SNAr or cross‐coupling, is demonstrated through the concise synthesis of Ki6783 and picolinafen, and the formal synthesis of cabozantib and golvatinib. Computational investigations reveal that arylation proceeds in a concerted fashion via a 5‐membered transition state. The kinetically‐controlled regioselectivity for O‐arylation—which is reversed relative to previous BiV‐mediated pyridone arylations—is attributed primarily to the geometric constraints imposed by the bismacyclic scaffold.
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Ag I ‐Catalyzed Reaction of Enol Diazoacetates and Imino Ethers: Synthesis of Highly Functionalized Pyrroles
Abstract An unprecedented AgI‐catalyzed efficient method for the coupling of imino ethers and enol diazoacetates through a [3+2]‐cycloaddition/C−O bond cleavage/[1,5]‐proton transfer cascade process is reported. The general class of imino ethers that includes oxazolines, benzoxazoles and benzimidates are applicable substrates for these reactions that provide direct access to fully substituted pyrroles with uniformly high chemo‐ and regioselectivity. High variability in substitution at the pyrrole 2‐, 5‐ and N‐positions characterizes this methodology that also presents an entry point for further pyrrole diversification via facile modification of resulting N‐functional pyrroles.
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- Award ID(s):
- 1763168
- PAR ID:
- 10226911
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 60
- Issue:
- 24
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 13394-13400
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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