Palladium‐Catalyzed C‐2 Selective CH Olefination of Pyridines

Abstract

A novel and efficient protocol for the C-2 selective olefination of pyridines via a palladiumcatalyzed oxidative cross-coupling reaction has been developed. A wide range of pyridines and olefin substrates including acrylic ester, styrene, and acrylamide are compatible. The products are highly useful building blocks for the synthesis of bioactive alkaloid natural products and drug molecules.

Pivalic Acid

“…Pivalic acid enhanced both yield and selectivity for the C2-selective olefination of pyridine. 33 Other acid additives performed inferiorly to pivalic acid; 2.5 equiv of PivOH was the ideal amount to maximize product yield. Silver(I) acetate functioned as a terminal oxidant and also positively influenced yield and selectivity.…”

Synthesis and Late-Stage Functionalization of Complex Molecules through C–H Fluorination and Nucleophilic Aromatic Substitution

“…7 However, these reactions are limited to the formation of C–C bonds, and the reaction conditions and scope suggest that these reactions are not suitable for complex substrates. 8 Other functionalizations of heteroaryl C–H bonds involve cross-coupling at the most acidic C–H bond; these methods occur most commonly with five-membered ring heteroarenes.…”

“…Most closely related to the work reported here, C–H functionalization reactions at the 2-position of pyridines and pyridine N -oxides have been developed with transition metal catalysts. 7 However, these reactions are limited to the formation of C–C bonds, and the reaction conditions and scope suggest that these reactions are not suitable for complex substrates. 8 Other functionalizations of heteroaryl C–H bonds involve cross-coupling at the most acidic C–H bond; these methods occur most commonly with five-membered ring heteroarenes.…”

Photoredox-catalyzed branch-selective pyridylation of alkenes for the expedient synthesis of Triprolidine

“…The cross-coupling of alkenes and aryl halides in the presence of palladium catalyst, the Heck reaction [11][12][13] , is a powerful protocol for the construction of aryl-substituted alkenes. Nevertheless, there are few examples of Heck coupling of alkenes with pyridines, probably due to the potential coordination between the nitrogen atom and metal catalyst [14][15][16][17][18][19] . Alternatively, several examples of Pd-catalyzed cross-coupling of alkenes with pyridine N-oxides have been reported, while only delivering vinylpyridine derivatives with linear selectivity [20][21][22][23] .…”