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

Abstract

Alkenylpyridines are important pharmaceutical cores as well as versatile building blocks in organic synthesis. Heck reaction represents one of the most powerful platform for the construction of aryl-substituted alkenes, nevertheless, examples for Heck type coupling of alkenes with pyridines, particularly with branched selectivity, remain elusive. Here we report a catalytic, branch-selective pyridylation of alkenes via a sulfinate assisted photoredox catalysis. This reaction proceeds through a sequential radical addition/coupling/elimination, by utilizing readily available sodium sulfinates as reusable radical precursors as well as traceless elimination groups. This versatile protocol allows for the installation of important vinylpyridines with complete branched selectivity under mild conditions. Furthermore, this catalytic manifold is successfully applied to the expedient synthesis of Triprolidine.

The Persistent Radical Effect in Organic Synthesis

“…The azidyl radical adds terminally to the alkene, and subsequent trapping of the adduct radical with 68 provides, after cyanide fragmentation, the β‐arylated alkyl azides (Figure h). In analogy to this transformation, the 1,2‐sulfonylarylation of styrenes was reported (Figure i) . By eliminating sulfinic acid from the 1,2‐sulfonylarylation product, a 1,1‐diarylethene is formed as the final product and methanesulfinate is regenerated.…”

Redox-neutral photochemical Heck-type arylation of vinylphenols activated by visible light

“…7a-c,8,9 However, the redox-neutral photochemical Heck-type arylation of alkenes under visible light is still a challenge and the only known example was reported by Chu and co-workers for the pyridylation of alkenes. 16 Evidently, development of new powerful photo-reductants that operate using mild visible light and do not require sacricial reductants is highly warranted to alleviate side reactions and expand the synthetic applicability of aryl radicals from (hetero)aryl halides. Phenolate anions have been used as an attractive model system for a photoinduced electron ejection mechanism study; 17 nevertheless, the photochemical reactivities of excited phenolate anions have received little attention.…”

Advances in the Synthesis of Imine‐Containing Azaarene Derivatives via Photoredox Catalysis

“…À and H + after azaarylation, providing αaryl-substituted vinylazaarenes. [69] This elegant work was described by the Chu group.…”