Categories: C=N Bond Formation >
Synthesis of nitrones
Simple thermal conditions, previously found to minimize hydroxylamine decomposition (t-BuOH, 110 °C), allow the condensation of ketones and hydroxylamines to form exocyclic, acyclic, and α,β-unsaturated ketonitrones with benzylic, linear, and branched nitrogen substituents in modest to excellent isolated.
J. Y. Pfeiffer A. M. Beauchemin, J. Org. Chem., 2009, 74, 8381-8383.
The reaction of N-alkylhydroxylamines and aqueous hydroxylamine with monosubstituted allenes gives nitrones and oximes, respectively, in good yields. DFT calculations support a proposed concerted, five-membered Cope-type hydroamination process, and calculated transition state energies are in excellent agreement with experimental observations.
J. Moran, J. Y. Pfeiffer, S. I. Gorelsky, A. M. Beauchemin, Org. Lett., 2009, 11, 1895-1898.
A general, efficient and metal-free protocol for the direct oxidation of secondary amines to nitrones tolerates other functional groups or existing stereogenic centers using Oxone in a biphasic basic medium as the sole oxidant.
C. Gella, È. Ferrer, R. Alibés, F. Busqué, P. de March, M. Figueredo, J. Font, J. Org. Chem., 2009, 74, 6365-6367.
An Ir-catalyzed reductive formation of functionalized nitrones from N-hydroxyamides via dehydrosilylation and hydrosilylation showed high chemoselectivity in the presence of sensitive functional groups, such as methyl esters. The reaction was successfully applied to the synthesis of cyclic and macrocyclic nitrones, which are known to be challenging compounds.
S. Katahara, S. Kobayashi, K. Fujita, T. Matsumoto, T. Sato, N. Chida, J. Am. Chem. Soc., 2016, 138, 5246-5249.
A direct coupling of N-nosylhydrazones with nitrosoarenes enables an efficient and transition-metal-free synthesis of (Z)-N-arylnitrones under mild conditions. The protocol is compatible with a wide range of functional groups and provides the corresponding nitrones in very good yields by a simple recrystallization process.
T. Liu, Z. Liu, Z. Liu, D. Hu, Y. Wang, Synthesis, 2018, 50, 1728-1736.
Cu catalysis enables the synthesis of N-alkylated unsaturated ketonitrones from propargyloxyamines. The rearrangement reaction proceeds via Cu-catalyzed intramolecular hydroamination, followed by thermally induced electrocyclic ring opening.
I. Nakamura, T. Onuma, R. Kanazawa, Y. Nishigai, M. Terada, Org. Lett., 2014, 16, 4198-4200.
Solvothermal treatment of magnesium iodide (MgI2) with sodium hydride (NaH) provides magnesium hydride (MgH2), which can be used for hydromagnesiation of 1,3-enynes. Downstream functionalization of the resulting propargylmagnesium intermediates with organo nitro compounds affords α-alkynylnitrones.
Y. Li, J. S. Ng, B. Wang, S. Chiba, Org. Lett., 2021, 23, 5028-5032.
4-Dimethylaminopyridine (DMAP) catalyzes a single-step preparation of nitrones from benzyl halides and nitrosoarenes under mild reaction conditions. The reaction provides both keto- and aldonitrones in good yields. As an application of the reaction, methyl 2-bromo-2-phenylacetate was used to prepare the corresponding isoxazolidine by a sequential one-pot synthesis.
Y. Jung, J. E. Hong, J.-H. Kwak, Y. Park, J. Org. Chem., 2021, 86, 6343-6350.
Oxidations of organic substrates such as sulfides, secondary amines, N-hydroxylamines, and tertiary amines with molecular oxygen in the presence of 5-ethyl-3-methyllumiflavinium perchlorate catalyst and hydrazine monohydrate in 2,2,2-trifluoroethanol occur highly efficiently to give the corresponding oxidized compounds in excellent yields.
Y. Imada, H. Iida, S. Ono, S.-I. Murahashi, J. Am. Chem. Soc., 2003, 125, 2868-2869.