N-Heterocyclic Carbene-Promoted [4+2] Annulation of α-Chloro Hydrazones with α-Chloro Aliphatic Aldehydes to Access Enantioenriched Dihydropyridazinones

• DOI: 10.1021/acs.joc.1c02581
• Publication Date: 2022-01-14T17:40:46Z
• Authors: Yipeng Zhou; Hongwei Zhou; Jianfeng Xu
• Keywords: Stereocenter; Annulation

An expeditious protocol for the assembly of chiral 4,5-dihydropyridazin-3(2H)-ones from α-chloro hydrazones and aliphatic aldehydes via N-heterocyclic carbene (NHC) catalysis is outlined. These in situ-generated 1,2-diaza-1,3-dienes undergo asymmetric [4+2] annulation with NHC-bound enolates to afford desired products bearing a stereogenic center at C4 position. The notable features this approach include good excellent enantioselectivities, high functional group tolerance, mild reaction conditions, simple operating procedures, compatibility gram-scale synthesis.