1017481-31-0Relevant articles and documents
Continuous Flow Synthesis of Morpholines and Oxazepanes with Silicon Amine Protocol (SLAP) Reagents and Lewis Acid Facilitated Photoredox Catalysis
Jackl, Moritz K.,Legnani, Luca,Morandi, Bill,Bode, Jeffrey W.
, p. 4696 - 4699 (2017)
Photocatalytic coupling of aldehydes and silicon amine protocol (SLAP) reagents enables the simple, scalable synthesis of substituted morpholines, oxazepanes, thiomorpholines, and thiazepanes under continuous flow conditions. Key to the success of this process is the combination of an inexpensive organic photocatalyst (TPP) and a Lewis acid additive, which form an amine radical cation that is easily reduced to complete the catalytic cycle. Di- and trisubstituted SLAP reagents are formed in one step by an iron-catalyzed aminoetherification of olefins.
An integrated console for capsule-based, automated organic synthesis
Bode, Jeffrey W.,Bordi, Samuele,Chen, Kuang-Yen,Jiang, Tuo,McMillan, Angus E.,Nichols, Paula L.,Saito, Fumito,Wanner, Benedikt M.
, p. 6977 - 6982 (2021/06/06)
The current laboratory practices of organic synthesis are labor intensive, impose safety and environmental hazards, and hamper the implementation of artificial intelligence guided drug discovery. Using a combination of reagent design, hardware engineering, and a simple operating system we provide an instrument capable of executing complex organic reactions with prepacked capsules. The machine conducts coupling reactions and delivers the purified products with minimal user involvement. Two desirable reaction classes-the synthesis of saturated N-heterocycles and reductive amination-were implemented, along with multi-step sequences that provide drug-like organic molecules in a fully automated manner. We envision that this system will serve as a console for developers to provide synthetic methods as integrated, user-friendly packages for conducting organic synthesis in a safe and convenient fashion. This journal is
Expedient access to saturated nitrogen heterocycles by photoredox cyclization of imino-tethered dihydropyridines
Bissonnette, Noah B.,Ellis, J. Michael,Hamann, Lawrence G.,Romanov-Michailidis, Fedor
, p. 9591 - 9596 (2019/11/05)
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.
Catalytic Synthesis of N-Unprotected Piperazines, Morpholines, and Thiomorpholines from Aldehydes and SnAP Reagents
Luescher, Michael U.,Bode, Jeffrey W.
supporting information, p. 10884 - 10888 (2015/09/15)
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.
SnAP reagents for the synthesis of piperazines and morpholines
Luescher, Michael U.,Vo, Cam-Van T.,Bode, Jeffrey W.
, p. 1236 - 1239 (2014/03/21)
Substituted piperazines and morpholines are valuable structural motifs in biologically active compounds, but are not easily prepared by contemporary cross-coupling approaches. In this report, we introduce SnAP reagents for the transformation of aldehydes into N-unprotected piperazines and morpholines. This approach offers simple, mild conditions compatible with aromatic, heteroaromatic, aliphatic, and glyoxylic aldehydes and provides mono- and disubstituted N-heterocycles in a single step.