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

An 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.