Retro-oxidative Cyclization

Retro-oxidative cyclization was initially reported in the thermolysis of titanacy-clopentane, which generated ethylene together with 1-butene via P-hydride elimination (Scheme 1.60) [78]. Nickellacyclopentane also underwent retro-oxidative cyclization to afford ethylene, together with cyclobutane and 1-butene [79]. 

The ethylene moiety of zircona- and hafnacyclopentane can be replaced with more strongly coordinating ligands. Trimethylphosphine induces retro-oxidative cyclization of a zirconacyclopentane and replaces one ethylene ligand to afford a monoethylene trimethylphosphine complex (Scheme 1.63) [82]. Alkynes, nitriles, and aldehydes also substitute the olefin moiety through retro-oxidative cyclization and re-oxidative cyclization to afford thermodynamically more stable zirconacy-cles (Scheme 1.64) [83]. The replacement reaction has been applied to the selective synthesis of polysubstituted benzenes and pyridines [84]. 

It has been reported that a retro-oxidative cyclization process proceeds in catalytic C-C bond cleavage reactions. For example, a six-membered cyclic allylic carbonate 38 underwent a palladium-catalyzed decarboxylative C-C bond cleaving reaction to afford dienyl aldehyde 40 (Scheme 7.12) [15]. It is proposed that oxidative addition of the allylic carbonate to palladium(O) followed by elimination of carbon dioxide generates the palladacycle 39. Subsequent retro-oxidative cyclization produces the diene and aldehyde functionalities. 

Cyclic 2-azidoalcohol 41 was converted to pyridine 46 upon treatment with a palladium(II) catalyst (Scheme 7.13) [16]. Mechanistically, palladium(II) reacts with the azidoalcohol 41 to form the palladacycle 42, which undergoes retro-oxidative cyclization (p-carbon elimination) to form a-azidoalkylpalladium 43. 

A new synthesis of isoxazoles is by successive treatment of a ketoxime with butyllithi-um, the ester of a carboxylic acid and sulfuric acid, e.g. 1 -> 2 (94S989). Hitrovinyl oximes 3 (R1, R3 = alkyl or aryl) undergo oxidative cyclization to isoxazoles 4 by the action of DDQ or iodine/potassium iodide (94JHC861). Flash-vacuum pyrolysis of the 1,3-dipolar cycloadduct 5 of acrylonitrile oxide to norbornadiene results in a retro-Diels-Alder reaction to give cyclopentadiene and 3-vinylisoxazole 6 (94CC2661). 

Compound 568 is transformed into 569 by heating in DMF, evidently via ring opening (retro-Michael addition) and subsequent oxidative cyclization <1998HCA718>. 

Oxazolium oxides, which can be generated by cyclization of a-amido acids, give pyrroles on reaction with acetylenic dipolarophiles.144 These reactions proceed by formation of oxazolium oxide intermediates. The bicyclic adduct can then undergo a concerted (retro 4 + 2) decarboxylation. 

It arises from 54 by cyclization and retro-Claisen loss of an ethoxycar-bonyl group. Brettle suggested that 54 was formed from radical disproportionation followed by Michael addition of the carbanion to the resulting ethyl methyleneacetoacetate. Alternatively, 52 could likewise be derived from a-carbonyl cation intermediates formed by one-electron oxidation of 51. 

Methylquinazolin-4(3//)-one was obtained in over 62% yield by reacting the phosphorane (25) with sodium hydride in methyl cyanide. The phos-phorane was readily formed from anthranilamide and prop-2-ynyltriphenyl-phosphonium bromide. When anthranilamide was fused with benzoin and a trace of acid at 150°C, it gave 2-phenylquinazolin-4(3H)-one together with o-iV-(a-benzoyl benzyl)aminobenzamide. The latter was cyclized, with ethyl orthoformate, to l-(a-benzoylbenzyl)quinazolin-4-one. If anthranilamide and benzoin were boiled in benzene with azeotropic removal of water, then the Schiff base (26) was formed. This gave 2-phenylquinazolin-4(3Jf/)-one and benzoic acid on heating alone at 150°C or with ethyl orthoformate. The mechanism of this reaction is not clear unless a retro-benzoin condensation and oxidation are occurring. 

An intramolecular vinylogous amide photocycloaddition, retro-Mannich fragmentation and final Mannich cyclization cascade provided a useful method for the synthesis of the complex ABCE ring system [91], The preparation of the requisite photosubstrate is outlined in Scheme 28. After cluomatographic separation, the cis alcohol was irradiated and led to the formation of aminals in a 2 1 ratio. Equilibration studies of the Swem oxidation products revealed that exposure of the minor diketone to sodium methoxide in methanol effected conversion to the manzamine-unlike... 

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