Tunable molecular editing of indoles with fluoroalkyl carbenes.
Nat Chem
; 16(6): 988-997, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38443494
ABSTRACT
Building molecular complexity from simple feedstocks through precise peripheral and skeletal modifications is central to modern organic synthesis. Nevertheless, a controllable strategy through which both the core skeleton and the periphery of an aromatic heterocycle can be modified with a common substrate remains elusive, despite its potential to maximize structural diversity and applications. Here we report a carbene-initiated chemodivergent molecular editing of indoles that allows both skeletal and peripheral editing by trapping an electrophilic fluoroalkyl carbene generated in situ from fluoroalkyl N-triftosylhydrazones. A variety of fluorine-containing N-heterocyclic scaffolds have been efficiently achieved through tunable chemoselective editing reactions at the skeleton or periphery of indoles, including one-carbon insertion, C3 gem-difluoroolefination, tandem cyclopropanation and N1 gem-difluoroolefination, and cyclopropanation. The power of this chemodivergent molecular editing strategy has been highlighted through the modification of the skeleton or periphery of natural products in a controllable and chemoselective manner. The reaction mechanism and origins of the chemo- and regioselectivity have been probed by both experimental and theoretical methods.
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MEDLINE
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En
Ano de publicação:
2024
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Article