C-Sulfonylation of 4-Alkylpyridines: Formal Picolyl C–H Activation via Alkylidene Dihydropyridine Intermediates

Abstract

4-Picoline derivatives are converted to the corresponding aryl picolyl sulfones upon treatment with aryl sulfonyl chlorides and Et 3 N in the presence of catalytic DMAP. The reaction proceeds smoothly for a variety of alkyl and aryl picolines using a range of aryl sulfonyl chlorides. The reaction is believed to involve N-sulfonyl 4alkylidene dihydropyridine intermediates and results in formal sulfonylation of unactivated picolyl C−H bonds.

Electrochemical Post-Ugi Cyclization for the Synthesis of Highly Functionalized Spirolactams

“…Sulfuric acid deprotected the tert -butyl group, producing acetamide [ E ], which generated tricyclic product [ F ] via an intramolecular aza-Michael addition proceeding via a 6- exo - trig pathway. Furthermore, the tert -butyl cation generated from iso-butene and acid attacked the para position of the benzene thiol group, generating the desired product 8a …”

Stability and reactivity of alkylidene dihydropyridines

“…8 Pigge has also used these intermediates in Mizoroki-Heck cyclizations 9 and methylenation with Eschenmoser's salt, 10 and applied them to the synthesis of 1,2,4-triazoles 11 and bis-piperidines. 12 Other methods for functionalization of 2-and 4-heterobenzylic positions of pyridines via transient dearomatization have been reported recently [13][14][15][16][17][18] but they do not involve the discrete ADHP and do not use chloroformate as the activating agent.…”

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.…”