Isochromenes are important pharmacophores present in biologically active molecules and natural products. Their synthesis is generally limited to cyclization of phenyl propargyl ether precursors under transition metal catalyzed conditions. Herein, we present a novel disconnection that rapidly constructs isochromene derivatives through a cascade radical cyclization strategy. Generation of aryl radicals by SET reduction of 2‐iodo benzyl allenyl ethers is followed by radical cyclization to construct the isochromene core with formation of an allylic radical. The allylic radical then undergoes coupling with the azaallyl radical to give products in good to excellent yields. The elaborated 2‐iodo phenyl propargyl ether precursors can be used to construct isochromenes bearing various functional groups.
Herein, we present 2‐azaallyl anions as colored super‐electron‐donors capable of reducing a collection of aryl halides via a single electron transfer and coupling with the corresponding radicals to forge new C−C bonds. This offers a robust approach for the arylation of 2‐azaallyls. Mechanistic studies demonstrate that the reactions proceed via either a radical pathway for aryl bromides and chlorides or a SNAr mechanism for activated aryl fluorides. Moreover, we demonstrate that irradiation of the colored 2‐azaallyl anions with visible light can further extend their reducing power, enabling radical‐mediated coupling with otherwise unreactive electron‐rich aryl halides. Isolated yields up to 94% are obtained and the overall relevance and utility is demonstrated by the derivatization of both a known pharmaceutical agent and a popular fluorophore.
- NSF-PAR ID:
- 10060092
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Synthesis & Catalysis
- Volume:
- 360
- Issue:
- 15
- ISSN:
- 1615-4150
- Page Range / eLocation ID:
- p. 2854-2868
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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