O-Aryl oximes

The [3,3]-sigmatropic rearrangement of O-aryl oximes was first described by Sheradsky and it has been used as an adequate route to benzofuran ring, a structural unit largely present in natural products. 

One potential approach for the preparation of benzofuran derivatives involves the acid-catalyzed cyclization of O-aryl oximes 1193. 39 (equation 36). The transformation is analogous to well-known Fisher indole synthesis. The reaction proceeds through a [3,3]-sigmatropic rearrangement of enehydroxylamine 120 to compound 121 followed... 

The use of a chiral auxiliary to induce stereochemical selectivity in the 3-aza -oxa-Cope rearrangement of O-aryl oximes 142 was reported by Citivello and Rapoport ... 

Thiolate anions37 38 and oxime alkoxides38 react under phase transfer conditions to give aryl sulfides and O-aryl oximes, respectively the o-dichloro benzene complex can be converted selectively to the monosubstitution product (equation 9). The arylation of oximes leads to a simple process for benzofuran formation (equation 10). Simple primary and secondary amine nucleophiles react smoothly in the absence of added base, in a very general and efficient process for aniline derivatives.49... 

Oximes are good precursors to reductive cyclization. A reductive base-induced cyclization of O-aryl oxime 4 will yield the tetrahydroquinoline <1998CL437>. The reduction prevented the normal dihydro-cyclization product from disproportionating to the quinoline and tetrahydroquinoline <1998BCJ2945>. By adding 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) after cyclization, the quinoline is the sole product (Scheme 9). 

Thiolate anions and oxime aUcoxides react under phase transfer conditions to give aryl thio ethers and O-aryl oximes, respectively the o-dichlorobenzene complex can be converted selectively to the monosubstitution product (equation 97). 

Thermal hetero Cope [3,3] - rearrangement of O-arylated oximes (Sheradsky) or acid catalyzed anionic hetero [3,3] and [3,5] - rearrangement of hydroxylamines with N-O bond cleavage.(see 1st edition). 

From O-Aryl-oximes and Alkanethiols (TypeF ). 4-Amino-isothiazoles (2 X = NH2) are obtained from the reaction between ArON=CR CN and R CH2SH, via the intermediates R CH2SN=CR CN, and these have subsequently been converted into various bicyclic isothiazoles (see later). 

SCHEME 1.212 Formation of 2-methyl-6-nitro-l,2,3,4-tetrahydrobenzofuro[3,2-c]pyri-dine from the functionalized O-aryl oxime. 

Interestingly, O-aryl oximes, close congeners of O-vinyl oximes, rearrange not into the pyrroles but into the corresponding furans (Scheme 1.211) [409-414]. The intermediate product of this rearrangement, 4-hydroxy-3-(2-iminopropyl)benzoni-trile, has been isolated [413]. 

Mooradian, A. 1967. Rearrangement of substituted O-aryl oximes to 5- and 7-substituted benzofurans. Tetrahedron Lett 8 (5) 407 08. 

Mooradian, A. and RE. Dupont. 1967. The rearrangement of O-aryl oximes. Tetrahedron... 

The general approach to 0-arylation of hydroxylamines involves N-protection followed by O-arylation. Activated aryl halides and heteroaryl halides easily alkylate oxime salts (equation 25), N-aUcyl hydroxamic acids and N-hydroxysuccinimide . N-Hydroxyph-thalimide can be also 0-phenylated through a reaction with diphenyliodonium salt, although in lower yield . ... 

Thermal synthesis of 2-substituted phenanthroxazoles and related compounds by cyclization of O-methyl o-quinone oximes with compounds ArCH2Y (Ar = aryl, hetaryl Y = H, OH, Cl, Br, OAc, SH, COR, NH2) or with amines (PhCHiNMej, PhNHMe, PhNMe2) has been described. Cyclization of a-oxooximes in the system alkyl halide or sulfate/DMF/K2C03 also leads to oxazole derivatives . 

Enehydroxylamines (102) are invoked as intermediates in the rearrangement of O-vinyl, acyl or aryl oximes (101) (equation 31). Varlamov and coworkers demonstrated that the heterocyclization of ketoximes (103) with acetylene in snper basic medium and in the presence of metal hydroxides proceeds by a [3,3]-sigmatropic rearrangement of the enehydroxylamine 105 of the corresponding oxime vinyl ethers 104 (equation 32). The unreactivity of 3-methyl-2-azabicyclo[3.3.1]nonan-9-one oxime (106) in the same reaction conditions was explained by its inability to isomerize to the corresponding enehydroxylamine. 

Polyakov, V.A., Nelen, M.I., Nazarpack-Kandously, N., Ryabov, A.D., Eliseev, A.V. Imine exchange in O-aryl and O-alkyl oximes as a base reaction for aqueous dynamic combinatorial libraries. A kinetic and thermodynamic study. J. Phys. Org. Chem. 1999, 12, 357-363. 

Arylamines.1 A novel method for amination of organometallic reagents involves activation of an O-tosylhydroxylamine by attachment to an auxiliary group that can be recycled. Thus aryl Grignard or lithium reagents react with the O-tosylate oxime of tetraphenylcyclopentadienone (1) to form an imine (2) with elimination of the tosylate anion. The imine is then converted into an ary lamine and the original oxime by treatment with excess hydroxylamine in aqueous pyridine. 

In an analogous manner, the generation of alkyl radicals in benzene solution by the O-acyl oxime method results in the formation of alkylbenzenes with moderate to good yields for simple acids (equation 55). Use of pyridine as solvent leads to the formation of alkylpyridines as mixtures of ortho, meta and para isomers in which the para isomer predominates. The 0-acyI benzophenone oxime chemistry can also be applied to aryl acids in benzene or pyridine, resulting in the formation of mixed biaryls. A closely related method involves photolysis of mixed anhydrides of arenecarboxylic acids with the hydrox-amic acid A -hydroxy-Z-pyridone in benzene solution (equation 56). 

Table 12 Reduction of O-Alkyl, O-Aryl and O-Acyl Oximes to O-Substituted Hydroxylamines... 

Benzofurans and Other Annelated Furans.-A new synthesis of benzofurans (73) is by the reaction of the phosphonium salt (72) with acid chlorides RCOCl in the presence of triethylamine. The benzofuran (74) results from the condensation of hexafluorobenzene with acetylacetone. Three instances of the formation of benzofurans from O-aryl-hydroxylamines, i.e. the oxygen analogue of the Fischer indole synthesis, have been reported O-phenylhydroxylamine hydrochloride and benzenesulphonylacetone give a 2 1 mixture of compounds (73 R = CH2S02Ph) and (75), the oxime ether (76) is converted into the aldehyde (77 ... 

Portela-Cubillo F, Scott JS, Walton JC (2008) Microwave-assisted syntheses of iV-hetero-cycles using aUcenone-, alkynone- and aryl-carbonyl o-phenyl oximes formal synthesis of neocryptolepine. J Org Chem 73 5558-5565... 

A variety of 2-arylbenzo[ ]furans were obtained in good yields by the O-arylation of oximes with diaryliodonium triflates, followed by the treatment with HCl in 1,4-dioxane with warming to initiate a [3,3]-sigmatropic reaction (14H2122). 

Scheme 4.26 shows the development of two general reactions based on copper(I) thiophene-2-carboxylate (CuTC) or Cu(OAc)2 for the formal arylation of imtnes with arylboronic acids [62]. The O-acetyl or O-pentafluorophenyl oximes react with a wide range of electron-rich, electron-poor and electron-neutral boronic acids, and even ortho-substituted substrates react well. The mechanism is proposed to proceed, as shown in Scheme 4.27, via an initial oxidative addition of the copper(I) species, either CuTC or through reduction of Cu(OAc)2 by the boronic acid, to the ketoxime O-carboxylate. This is followed by transmetallation and reductive elimination to generate the final product and regenerate the catalytically active copper(I) species. 

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