Organocatalyzed Double C(sp3)−H Alkylation of Cyclic N‐Sulfonyl Ketimines with 3‐Chloropropiophenones: Selective Access to 2,3,6‐Trisubstituted Pyridines

Abstract

AbstractAn efficient sequential one‐pot, two‐step pseudo‐four‐component reaction between 3/4‐methyl N‐sulfonyl ketimines with 3‐chloropropiophenones triggered by DIPEA/NaHCO3 as a cooperative base and subsequent aza‐cyclization using NH4OAc is reported. This transition‐metal‐oxidant‐free technique concocts new C−C/C=C/C=N−C bonds selectively, guaranteeing acceptable yields of 2,3,6‐trisubstituted pyridines possessing ortho‐hydroxyaryl/benzenesulfonamide and propiophenone moieties at C2 and C3 positions, respectively. Interestingly, while replacing methyl‐substituents with straight alkyl chains of N‐sulfonyl ketimines, only a monoalkylation reaction happened with in situ‐generated vinyl ketones to deliver promising yields of 3‐picoline derivatives. Moreover, the synthetic transmutation of prepared pyridine derivative led to several important classes of pyridocoumarin, 5H‐chromenopyridine, and di(pyridin‐3‐yl) methane derivatives.