Cyclization of oximes

Aminoisoxazoles 22 have been synthesized by nucleophilic addition of lithiated alkyl nitriles to a-chloroximes <06OL3679>. The cyclization of oxime dianions with diethyl oxalate afforded isoxazole-5-carboxylates 23 by acid-mediated dehydration of intermediate hydroxyisoxazolines <06S2515>. 

Cyclization of oximes containing y-,d-, or oo-alkenyl substituents, upon treatment with /V-bromosuccinimide (NBS) or iodine leads in good yields to the corresponding cyclic nitrones or their dimeric H- bonded hydriodide salts (290). 

Synthesis of novel bicyclic heterocyclic systems involving aziiidine ring formation has been described. The sodium salts of tosylhydrazones 11 decomposed by heating in benzene and gave aziridinopyrroloindoles 12 in yields up to 73% (equation 5) . Intramolecular cyclization of oxime ether 13 in the presence of base (for example, DBU) in acetonitrile afforded aziridinopyrrolidine 14 in yields up to 51% (equation 6) °. 

Synthesis of dihydrofuran derivatives by cyclization of oxime derivatives has been described. Thus, reduction of 2-quinolineacetaldoxime (26) with H2/Pt02 afforded fura-noquinoline 27 as a single product (equation 1. 4-Formy l-3-hydroxy-5-hydroxymethyl-2-methylpyridine oxime (28) in the system NaN02/HCl/H20 cyclized to furopyridine 29 (equation 13). ... 

Radical cyclization of oxime ethers having allylic substiffients to five-membered rings including furan and pyrrole derivatives was described in reviews A thiophenol-promoted radical cyclization of oxime ethers into tetrahydrofurans was recently described. For example, oxime derivative 36 in the presence of thiophenol and azobisisobuty-ronitrile (AIBN) afforded substimted tetrahydrofurans 37 and 38 in a ratio 1.2-3 1 (equation 17) . Radical cyclization of oxime ethers 39 to tetrahydrofurans 40 was successfully realized in the presence of alkyl iodides and EtsB in refluxing toluene (equation 18) . ... 

Heck-type cyclization of oxime ethers which contain a halogenated aryl group is a new route to dihydroindole oxime ethers. Thus, oxime ethers 70 in the system Pd(PPh3)4/ K2C03/dioxane afforded dihydroindoles 71 in 59-89% yields (equation 30) °. ... 

The intramolecular cyclization of oximes with alkene substituents to dihydropyrroles in the presence of radical initiator or by heating was also describedThus, oxime 83 underwent a tandem 1,2-prototropy-cycloaddition sequence and gave an unstable cycloadduct 84, which on treatment with NaOH afforded indolizine 85 (equation 36). ... 

Radical cyclization of oximes or oxime ethers having allylic substituents or an aldehyde group to tetrahydropyrrole derivatives was described Thus, Sm -induced 5-exo-trig radical cyclization of oxime ethers containing a formyl group was found to be particularly effective for the preparation of cyclic trans-wimo alcohols. For example, oxime 96 in the system SmE/THF/f-BuOH at 25 °C or —78°C afforded pyrrolidin-3-ols 97 and 98 in a ratio 3 2 or 9 1 (equation 41) . Cyclization of oxime ether 99 in the... 

Bromoallyloxy)phenyl oxime O-ethers 290 have been cyclized with BusSnH and azoisobutyronitrile (AIBN) to alkoxyamino-3-methylidenechromanes 291 (equation 125). The cyclization of oxime 290 proceeds through formation of vinyl radicals . 

Hydroxy-l,2,3,4-tetrahydroquinolines 304 were obtained by cyclization of oxime 2,4-dinitrophenyl ethers 303 in the presence of system NaBH3CN/NaH/l,4-dioxane (equation 131) . If the reductive cyclization was followed by oxidation with DDQ (2,3-dichloro-4,5-dicyano-p-benzoquinone) the corresponding 8-hydroxyquinolines 305 were obtained . ... 

Desilylative cyclization of oxime silyl ethers 319 in the presence of TBAT (tetra-butylammonium triphenyldrflnorosiliconate)/THF or benzene afforded tetrahydropyridine A-oxides 320 in 67-71% yields (equation 138) . 

A free radical cyclization of oxime ethers tethered to an aldehyde has been used in the synthesis of azepine derivatives . For example, oxime ether 389 is cyclized to azepine 390 by reaction with Sml2 in HMPA and f-BuOH at —78°C (equation 170) . Similar free radical cyclization of oxime ethers can be carried out also in the presence of Bu3SnH/AIBN in benzene . Oxime 0-methyl ether 391 underwent thermal cyclization in refluxing o-dichlorobenzene (ODCB) leading to the mixture of two products 392 and 393 in ratio 69 31 in overall yield of 91% (equation 171) °. Rearrangement of oxime 0-tosylates in the presence of piperidine also leads to azepine ring formation . ... 

Cycloaddition of Nitroalkanes/Nitroalkenes to Unsaturated Compounds. 9.2 Inter- and Intramolecular Cyclization of Oximes... 

A previous review has highlighted the following methods of ring synthesis intramolecular cyclization of oximes, nitro alkenes, and nitrones, and [4+2] cycloaddition reactions <1996CHEC-II(6)279>. In addition to that, this review includes the intramolecular cyclization of hydroxylamines, hydroxamates, hetero-Diels-Alder [4+2], 1,3-dipolar cycloaddition of nitrile oxides to alkenes, and [3+3] cycloaddition reactions. This review does not cover cycloaddition reactions of the [4+2] [3+2] and [4+2] [3+2] [3+2] types which primarily led to heterocycle-fused oxazine ring systems. 

Another widely used approach is the cyclization of oximes either under acidic, as in the conversion (147 ->148) (71MI22700), or basic conditions (149- 150) (78JOC2020). Cyclopropyl ketones (151) also react with hydroxylamine hydrochloride to give dihydro-1,2-oxazines (153), probably via the protonated oxime (152). If this is so then this reaction represents a rare example of a 6-endo-tet ring closure <80AG(E)199). 

The cyclization of oximes under acid conditions is well documented. Lewis acid-catalyzed conditions prevail in the synthesis of quinoline 2 (Equation 4) <1995CL5>. 

The 3-unsubstituted indoxazenes are so unstable towards alkali that it is not possible to prepare them by basic cyclization of oximes.7 The same applies to attempted preparations of the 3-carboxylic acid by this route.20,21 The ring opening with alkali probably goes through the carbanion (41), which then undergoes ring opening to form the phenoxy anion (42).60... 

Stannyl radical addition-cyclization of oxime ether 183 [31] was also examined (Scheme 44). In this case vinyl stannane 185 was obtained in 77% yield. 

Keck, G E, McHardy, S F, Murry, J A, Diastereoselective 6-exo radical cyclizations of oxime ethers total s3mthesis of 7-deox3fpancratistatin, J. Org. Chem., 64, 4465-4476, 1999. 

Cyclization of oximes 15 with HCl gave the N-oxides 16, which were reduced with PCI3 to give the corresponding 14 (74MI1 75JPR705). 

Formation of functionalized heterocycles in Et20 BF3-catalyzed radical cyclization of oxime ethers 03YZ285. 

The cyclization of oxime 3 yields 2-(chloromethyl)-4-phenylpyrido[3,2-c/]pyrimidine 3-ox-ide (4).426... 

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