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Cobalt(III)-Catalyzed Regio- and Chemoselective [4 + 2]-Annulation of N-Chlorobenzamides/Acrylamides with 1,3-Dienes at Room Temperature

Balu Ramesh and Masilamani Jeganmohan*

*Department of Chemistry, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India, Email: mjeganmohaniitm.ac.in

B. Ramesh, M. Jeganmohan, J. Org. Chem., 2022, 87, 6902-6909.

DOI: 10.1021/acs.joc.2c00072


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Abstract

Co(III)-catalyzed regio- and chemoselective redox-neutral C-H annulation of arylamides/acrylamides with 1,3-dienes provides 3,4-dihydroisoquinolinones in good yields. Furthermore, the prepared 3,4-dihydroisoquinolinones can be converted into useful oxirane derivatives in good yields.

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proposed mechanism



Details

The article discusses a cobalt(III)-catalyzed regio- and chemoselective [4 + 2]-annulation of N-chlorobenzamides/acrylamides with 1,3-dienes at room temperature. This method effectively synthesizes pharmaceutically important 3,4-dihydroisoquinolinones in good yields. The process is notable for its compatibility with less-reactive 1,3-butadiene and the conversion of the synthesized dihydroisoquinolinones into oxirane derivatives. The reaction mechanism involves ortho C−H cobaltation, supported by kinetic isotopic effect (KIE) studies and competition experiments. The study highlights the use of the N−Cl bond as an internal oxidant, eliminating the need for external oxidants. Various substituted benzamides and 1,3-dienes were tested, demonstrating the method's broad applicability and tolerance for different functional groups. The article also explores the reaction's versatility with different 1,3-dienes and the synthesis of oxirane-substituted dihydroisoquinolinones. The findings suggest that the ortho C−H bond activation is a rate-limiting step, and the proposed mechanism involves a cobaltacycle intermediate. This research provides a cost-effective and less-toxic alternative for synthesizing complex heterocyclic compounds under mild conditions, contributing significantly to the field of organic synthesis.


Key Words

3,4-dihydroisoquinolinones


ID: J42-Y2022