Regioselective C−H Functionalization of Heteroarene N‐Oxides Enabled by a Traceless Nucleophile

Although N‐alkenoxyheteroarenium salts have been widely used as umpoled synthons with nucleophilic (hetero)arenes, the use of electron‐poor heteroarenes has remained unexplored. To overcome the inherent electron deficiency of quinolinium salts, a traceless nucleophile‐triggered strategy was designed...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie 2020-12, Vol.132 (50), p.22864-22872
Main Authors: Mathi, Gangadhar Rao, Kweon, Byeongseok, Moon, Yonghoon, Jeong, Yujin, Hong, Sungwoo
Format: Article
Language:English
Subjects:
Aromatic compounds
Chemistry
Computer applications
C−H functionalization
Electrons
N-alkenoxyheteroarenium salts
Organic compounds
Oxides
Phenanthridine
Pyridines
Quinolines
Regioselectivity
Room temperature
Salts
traceless nucleophile
umpolung
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although N‐alkenoxyheteroarenium salts have been widely used as umpoled synthons with nucleophilic (hetero)arenes, the use of electron‐poor heteroarenes has remained unexplored. To overcome the inherent electron deficiency of quinolinium salts, a traceless nucleophile‐triggered strategy was designed, wherein the quinolinium segment is converted into a dearomatized intermediate, thereby allowing simultaneous C8‐functionalization of quinolines at room temperature. Experimental and computational studies support the traceless operation of a nucleophile, which enables the previously inaccessible transformation of N‐alkenoxyheteroarenium salts. Remarkably, the generality of this strategy has been further demonstrated by broad applications in the regioselective C−H functionalization of other electron‐deficient heteroarenes such as phenanthridine, isoquinoline, and pyridine N‐oxides, offering a practical tool for the late‐stage functionalization of complex biorelevant molecules. The regioselective C−H functionalization of heteroarene N‐oxides with a range of alkynes was developed by exploiting a traceless operation of a nucleophile to override the intrinsic electron deficiency of N‐alkenoxyheteroarenium salts. Generality was demonstrated in the regioselective C−H functionalization of electron‐deficient heteroarenes.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202010597