108303-99-7Relevant articles and documents
Transition-Metal-Free Deconstructive Lactamization of Piperidines
Romero-Iba?ez, Julio,Cruz-Gregorio, Silvano,Sandoval-Lira, Jacinto,Hernández-Pérez, Julio M.,Quintero, Leticia,Sartillo-Piscil, Fernando
, p. 8867 - 8871 (2019)
One of the major challenges in organic synthesis is the activation or deconstructive functionalization of unreactive C(sp3)–C(sp3) bonds, which requires using transition or precious metal catalysts. We present here an alternative: the deconstructive lactamization of piperidines without using transition metal catalysts. To this end, we use 3-alkoxyamino-2-piperidones, which were prepared from piperidines through a dual C(sp3)–H oxidation, as transitory intermediates. Experimental and theoretical studies confirm that this unprecedented lactamization occurs in a tandem manner involving an oxidative deamination of 3-alkoxyamino-2-piperidones to 3-keto-2-piperidones, followed by a regioselective Baeyer–Villiger oxidation to give N-carboxyanhydride intermediates, which finally undergo a spontaneous and concerted decarboxylative intramolecular translactamization.
Generation of aminoacyl radicals from 1-carbamoyl-1-methylcyclohexa-2,5-dienes: A new tin-free homolytic route to β- and γ-lactams
Jackson,Walton
, p. 2327 - 2328 (2000)
Radical induced homolyses of 1-carbamoyl-1-methylcyclo-hexa-2,5-dienes took place cleanly to yield aminoacyl radicals, with no competition from the alternative dissociation to methyl radicals: β- and γ-lactams were obtained from ring closures of suitably
Photochemical generation of acyl and carbamoyl radicals using a nucleophilic organic catalyst: Applications and mechanism thereof
Balletti, Matteo,De Pedro Beato, Eduardo,Mazzarella, Daniele,Melchiorre, Paolo
, p. 6312 - 6324 (2020/08/24)
We detail a strategy that uses a commercially available nucleophilic organic catalyst to generate acyl and carbamoyl radicals upon activation of the corresponding chlorides and anhydrides via a nucleophilic acyl substitution path. The resulting nucleophilic radicals are then intercepted by a variety of electron-poor olefins in a Giese-type addition process. The chemistry requires low-energy photons (blue LEDs) to activate acyl and carbamoyl radical precursors, which, due to their high reduction potential, are not readily prone to redox-based activation mechanisms. To elucidate the key mechanistic aspects of this catalytic photochemical radical generation strategy, we used a combination of transient absorption spectroscopy investigations, electrochemical studies, quantum yield measurements, and the characterization of key intermediates. We identified a variety of off-the-cycle intermediates that engage in a light-regulated equilibrium with reactive radicals. These regulated equilibriums cooperate to control the overall concentrations of the radicals, contributing to the efficiency of the overall catalytic process and facilitating the turnover of the catalyst. This journal is
Palladium-Catalyzed Construction of Quaternary Stereocenters by Enantioselective Arylation of γ-Lactams with Aryl Chlorides and Bromides
Jette, Carina I.,Geibel, Irina,Bachman, Shoshana,Hayashi, Masaki,Sakurai, Shunya,Shimizu, Hideki,Morgan, Jeremy B.,Stoltz, Brian M.
supporting information, p. 4297 - 4301 (2019/02/27)
Herein, we report the first Pd-catalyzed enantioselective arylation of α-substituted γ-lactams. Two sets of conditions were developed for this transformation, allowing for the use of either aryl chlorides or bromides as electrophiles. Utilizing a highly electron-rich dialkylphosphine ligand we have been able to construct α-quaternary centers in good yields (up to 91 % yield) and high enantioselectivities (up to 97 % ee).
Palladium-Catalyzed Hydrocarbonylative C-N Coupling of Alkenes with Amides
Zhou, Xibing,Zhang, Guoying,Gao, Bao,Huang, Hanmin
supporting information, p. 2208 - 2212 (2018/04/30)
An efficient palladium-catalyzed hydrocarbonylative C-N coupling of alkenes with amides has been developed. The reaction was performed via hydrocarbonylation of alkenes, followed by acyl metathesis with amides. Both intermolecular and intramolecular react
Carbazole-containing amides and ureas: Discovery of cryptochrome modulators as antihyperglycemic agents
Humphries, Paul S.,Bersot, Ross,Kincaid, John,Mabery, Eric,McCluskie, Kerryn,Park, Timothy,Renner, Travis,Riegler, Erin,Steinfeld, Tod,Turtle, Eric D.,Wei, Zhi-Liang,Willis, Erik
supporting information, p. 293 - 297 (2018/01/04)
A series of novel carbazole-containing amides and ureas were synthesized. A structure–activity relationship study of these compounds led to the identification of potent cryptochrome modulators. Based on the desired pharmacokinetic/pharmacodynamic parameters and the results of efficacy studies in db/db mice, compound 50 was selected for further profiling.
Palladium(II)-Catalyzed Allylic C H Oxidation of Hindered Substrates Featuring Tunable Selectivity Over Extent of Oxidation
Xing, Xiangyou,O'Connor, Nicholas R.,Stoltz, Brian M.
supporting information, p. 11186 - 11190 (2016/07/06)
The use of Oxone and a palladium(II) catalyst enables the efficient allylic C H oxidation of sterically hindered α-quaternary lactams which are unreactive under known conditions for similar transformations. This simple, safe, and effective system for C H activation allows for unusual tunable selectivity between a two-electron oxidation to the allylic acetates and a four-electron oxidation to the corresponding enals, with the dominant product depending on the presence or absence of water. The versatile synthetic utility of both the allylic acetate and enal products accessible through this methodology is also demonstrated.
Iridium-Catalyzed Single-Step N-Substituted Lactam Synthesis from Lactones and Amines
Kim, Kicheol,Hong, Soon Hyeok
, p. 4152 - 4156 (2015/05/04)
Catalytic lactam synthesis was achieved directly from lactones and amines using an Ir catalyst. Three sequential transformations - aminolysis of lactone, N-alkylation of amine with hydroxyamide, and intramolecular transamidation of aminoamide - afforded the corresponding N-substituted lactams. (Figure Presented).
CARBAZOLE-CONTAINING AMIDES, CARBAMATES, AND UREAS AS CRYPTOCHROME MODULATORS
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Paragraph 0293, (2015/10/28)
The subject matter herein is directed to carbazole-containing amide, carbamate, and urea derivatives and pharmaceutically acceptable salts or hydrates thereof of structural formula I wherein the variable R1, R2, R3, R4, R5, R6, R7, A, D, E, G, J, L, M, Q, a, and b are accordingly described. Also provided are pharmaceutical compositions containing the compounds of formula I to treat a Cry-mediated disease or disorder, such as diabetes, complications associated with diabetes, Cushing's syndrome, NASH, NAFLD, asthma, and COPD.
Synthetic studies towards the core structure of nakadomarin a by a thioamide-based strategy
Chavda, Jai K.,Procopiou, Panayiotis A.,Horton, Peter N.,Coles, Simon J.,Porter, Michael J.
, p. 129 - 139 (2014/01/06)
The tricyclic BCD substructure of the marine natural product nakadomarin A has been synthesised. The strategy utilised a key carbon-carbon bond-forming reaction between a furan and an N-acyliminium ion derived from a secondary thiolactam. In addition, a novel three-component coupling reaction between a thioamide, an allylic bromide and an isocyanate, leading to the establishment of two new stereogenic centres, is reported. Two key steps in a projected total synthesis of nakadomarin A have been realised by using the unique chemistry of thioamides. Formation of the carbocyclic B ring can be effected by nucleophilic attack of a furan on a thiolactam-derived iminium ion, and the key quaternary centre can be established by a novel three-component coupling reaction.
