Details

Autor(en) / Beteiligte

• Bissonnette, Noah B
• Ellis, J. Michael
• Hamann, Lawrence G
• Romanov-Michailidis, Fedor

Titel

Expedient access to saturated nitrogen heterocycles by photoredox cyclization of imino-tethered dihydropyridines

Ist Teil von

• Chemical science (Cambridge), 2019-11, Vol.1 (41), p.9591-9596

Ort / Verlag

England: Royal Society of Chemistry

Erscheinungsjahr

2019

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• A large proportion of medicinally relevant molecules bear nitrogen and sp 3 -hybridized carbon functionalities. Overwhelmingly, these atoms are found as part of (hetero)cyclic structures. Despite their importance, synthetic approaches to saturated nitrogen heterocycles are limited to several established stoichiometric alkylation techniques, as well as a few methods involving C-H bond activation. The synthetic community remains interested in more general, mild, and sustainable ways to access these motifs. Here we describe a dual-catalyst system composed of an iridium photocatalyst and a lithium phosphate base that is capable of selectively homolyzing the N-H bond of 4-alkyl-1,4-dihydropyridines, presumably by proton-coupled-electron-transfer (PCET), and mediating efficient cyclization of the resultant carbon-centered radicals with tethered imines. The outcome of this transformation is access to a broad range of structurally complex nitrogen heterocycles obtainable from simple aldehyde starting materials in a highly chemoselective manner. This work describes an expedient access to sp 3 -rich nitrogen heterocycles via mild photoredox cleavage of 4-alkyl-1,4-dihydropyridines followed by cyclization of the resultant carbon-centered radicals with tethered imines.