Soft Fluorination of 4-Alkylpyridines

Stability and reactivity of alkylidene dihydropyridines

“…In view of their utility, we have recently developed a suite of reactions to make modified 4-alkylpyridines, including their allylation, 3 dehydrogenation, 4 and addition to pyridines 5 and unsaturated ketones 6 oxidation and fluorination. 7 These reactions proceed through the corresponding alkylidene dihydropyridines (we call them ADHPs) as discrete but unstable intermediates. ADHPs are readily prepared through dearomatization with chloroformate reagents and mild base, exploiting the imine-like moiety embedded within the pyridine ring.…”

Site-selective benzylic C–H hydroxylation in electron-deficient azaheterocycles

“…33,34 Given the widespread presence of azaheterocycles in medicines and materials, [35][36][37][38][39][40] there have been many efforts to develop benzylic C-H functionalization reactions that favour positions adjacent to heterocycles such as pyridine. 41 Recent examples of these efforts have resulted in the selective formation of C-N, 42 C-F, [43][44][45][46][47] C-S, 21,44,48 C-Cl, 49 C-C, [50][51][52][53][54] and CvO 55,56 bonds adjacent to electron-deficient heterocycles in the presence of more electron-rich benzylic C-H bonds. To our eyes, notably absent from this list was the direct formation of C-O bonds at positions where over-oxidation was possible.…”