Facile access to -substituted piperazin-2-ones and mianserin derivative enabled by chemoselective carbene insertion and cyclization cascade

• Published in: Chemical communications (Cambridge, England) England), 2024-05, Vol.6 (44), p.5691-5694
• Main Authors: Kumar, Dharmendra, Unnikrishnan, Urmila, Kuram, Malleswara Rao
• Format: Article
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/d4cc00959b

The chemoselective N-H insertion of unsymmetrical diamines into carbene is a longstanding challenge. A simple copper-catalyzed strategy for synthesizing C -substituted piperazinones is described, employing easily accessible diazo compounds and 1,2-diamines. The reaction proceeded via chemo-selective carbene insertion at the comparatively less nucleophilic amine, followed by instantaneous cyclization. The protocol was further extended to access NH-free piperazinone, and the synthesis of a Mianserin derivative. A simple method to synthesize carbon-substituted piperazinones achieved from donor-acceptor diazo compounds and 1,2-diamine derivatives under Cu-catalyzed conditions.