- Expedient access to saturated nitrogen heterocycles by photoredox cyclization of imino-tethered dihydropyridines
-
A large proportion of medicinally relevant molecules bear nitrogen and sp3-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.
- Bissonnette, Noah B.,Ellis, J. Michael,Hamann, Lawrence G.,Romanov-Michailidis, Fedor
-
p. 9591 - 9596
(2019/11/05)
-
- Catalytic Synthesis of N-Unprotected Piperazines, Morpholines, and Thiomorpholines from Aldehydes and SnAP Reagents
-
Commercially available SnAP (stannyl amine protocol) reagents allow the transformation of aldehydes and ketones into a variety of N-unprotected heterocycles. By identifying new ligands and reaction conditions, a robust catalytic variant that expands the substrate scope to previously inaccessible heteroaromatic substrates and new substitution patterns was realized. It also establishes the basis for a catalytic enantioselective process through the use of chiral ligands. SnAPcat! The identification of new ligands and reaction conditions provides a robust catalytic method for the synthesis of N-unprotected heterocycles using SnAP reagents. This catalytic variant expands the substrate scope to include previously inaccessible piperazines, morpholines, and thiomorpholines and establishes the basis for a catalytic enantioselective process through the use of chiral ligands.
- Luescher, Michael U.,Bode, Jeffrey W.
-
supporting information
p. 10884 - 10888
(2015/09/15)
-
- SnAP reagents for the transformation of aldehydes into substituted thiomorpholines - An alternative to cross-coupling with saturated heterocycles
-
It's a SnAP! The transformation of aldehydes into N-unsubstituted 3-thiomorpholines provides a convenient alternative to metal-catalyzed cross-coupling reactions, which are generally unsuited to the functionalization of saturated N-heterocycles. A copper-mediated radical cyclization is the key to the mild conditions, high functional group tolerance, and broad substrate scope offered by these reagents. Copyright
- Vo, Cam-Van T.,Mikutis, Gediminas,Bode, Jeffrey W.
-
supporting information
p. 1705 - 1708
(2013/04/10)
-