Intramolecular aerobic oxidative amination

The CDC between A-f-butyl nitrones and terminal alkynes to form alkynylated nitrones in good to excellent yields, catalysed by zinc trifiate, was achieved using 3,3, 5,5 -tetra-tertbutyldipheno-quinone and O2 as oxidants. The alkynylated nitrones were transformed to regioisomerically pure 3,5-disubstituted isoxazoles. Experimental and DFT computational studies of Pd(OAc)2/pyridine-catalysed intramolecular aerobic oxidative amination of alkenes supported a stepwise mechanism that involved (i) the formation of a Pd(ll)-amidate-alkene chelate with release of 1 equiv. of pyridine and AcOH from the catalyst centre, (ii) insertion of alkene into a Pd—N bond. 

Liu and coworkers reported a base-modulated regioselective Pd-catalyzed intramolecular aerobic oxidative amination of alkenes for five- or seven-memberedring products by varying the reaction conditions [12]. 

Very recently, Liu and coworkers reported a palladium-catalyzed intramolecular aerobic oxidative allylic amination of unactivated alkenes [34]. The reaction of 22... 

J.K. Cha et al. developed a stereocontrolled synthesis of bicyclo[5.3.0]decan-3-ones from readily available acyclic substrates. Acyclic olefin-tethered amides were first subjected to the intramolecular Kulinkovich reaction to prepare bicyclic aminocyclopropanes. This was followed by a tandem ring-expansion-cyclization sequence triggered by aerobic oxidation. The reactive intermediates in this tandem process were aminium radicals (radical cations). The p-anisidine group was chosen to lower the amine oxidation potential. This substituent was crucial for the generation of the aminium radical (if Ar = phenyl, the ring aerobic oxidation is not feasible). 

The mechanism proposed for Cu(02CCF3)2-catalysed aerobic oxidative intramolecular alkene C—H amination of (130), leading to formation of A-heterocycles in good to excellent yields, is summarized in Scheme 14. ... 

The mechanism of Gutknecht pyrazine synthesis has been studied and is well understood. Reduction of the a-oximino ketone affords an a-amino ketone. If the reduction is carried out under acidic conditions, the a-amino ketone may be isolated as an acid salt. These acid addition salts are entirely stable. In these salts the ketone carbonyl may be hydrated, and this is particularly true for a-amino aldehydes. However, as soon as the free base of the amine is generated, either from the salt or during reduction of the oxime if this is carried out under neutral or basic conditions, rapid bimolecular imine formation occurs, which is then followed by rapid intramolecular formation of a second imine to afford a dihydropyrazine. Oxidation to the pyrazine may occur spontaneously upon exposure to air, particularly in the presence of transition metals, and it is this facile aerobic oxidation that doubtless accounts for the isolation of pyrazines by early workers in the field. 

In 2009, Stahl and coworkers described the synthesis of the enantiomeri-cally resolved seven-membered ring NHC-Pd dimer 87 [75]. This complex was examined as a chiral catalyst under aerobic conditions in the intramolecular oxidative amination reaction of alkene 88 (Scheme 3.49). In the best case, an enantioselectivity of 63% ee was obtained with low yield (35%), while the other substrates underwent cyclization to afford essentially racemic products. 

Fu et al. developed an efficient Cu(OAc)2-catalyzed synthesis of imidazobenz-imidazole derivatives via aerobic oxidative intramolecular C(sp )-H amination in excellent yields (Scheme 8.55). 1,10-Phenanthroline was chosen as the ligand and NaOAc was used as the base. Molecular oxygen acts as the oxidant to recycle the copper catalyst [95]. Kaliappan and coworkers reported an efficient, one-pot, copper-catalyzed C(sp )-H cascade amination to synthesize various imidazobenzimidazole derivatives from various azoles and aryl bromides or 2-bromopyridines [96]. 

An intramolecular Cu(OAc)-catalyzed aerobic oxidative C(sp )-H amination of hydrazones to pyrazoles and indazoles using 2(1 atm) as the sole oxidant is reported by Jiang and coworkers (Scheme 8.66). A broad substrate scope and good functional group tolerance show that this aerobic oxidative transformation shows... 

An efficient Cu(CF3C02)2-catalyzed aerobic oxidative intramolecular alkene C(sp )-H amination leading to 1,4-dihydropyrazine derivatives from substituted 3-methyleneisoindolin-l-ones using air as the oxidant was developed by Fu and coworkers (Scheme 8.109). The corresponding Af-heterocycles 1,4-dihydropyrazine derivatives were obtained in good to excellent yields with wide functional group tolerance [183]. 

Intramolecular carbon-nitrogen bond formation may result from the Ullmann coupling of l,3-bis(2-iodoaryl)propan-2-amines catalysed by copper. Using (i )-BINOL, l,l -Bi-2-naphthol, ligands, the enantioselective formation of indolines and 1,2,3,4-tetrahydroquinolines was achieved. Copper catalysis has also been used in the intramolecular formation of imidazobenzimidazole derivatives. The reaction is likely to involve the formation of intermediates, such as (16), which on aerobic oxidation yield the product. There is evidence for an intramolecular 0- -N Smiles rearrangement, as... 

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