Oximes cyclization reactions

During hydrogenation, intermediate aromatic hydroxylamines may undergo various cyclization reactions in molecules containing a suitably disposed carbonyl group, or carbonyl derivative, such as an oxime (13). The cyclized product may or may not maintain the N—OH bond, depending on the solvent, the catalyst, and the electrophilicity of the carbonyl (27,28,29,32,67,68). 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

This chapter, therefore, ends the monograph with a potpourri of reactions all of which occur without a change in oxidation state. In many cases, the reaction is one of nucleophilic attack at an electrophilic C-atom. The result is often hydrolytic bond cleavage (e.g., in carbohydrate conjugates, disubstitut-ed methylene and methine groups, imines, oximes, isocyanates, and nitriles, and various ring systems) or a nucleophilic substitution (e.g., hydrolytic de-halogenation of halocarbons and chloroplatin derivatives, and cyclization reactions). The formation of multiple bonds by dehydration is a special case to be discussed separately. 

Novel polycyclic heterocyclic systems including the isoxazoline ring were described. Thus, oximes 191 and 193 in the presence of sodium hypochlorite afforded heterocycles 192 or 194, respectively (equations 83 and 84). Intramolecular cycloaddition of nitrile oxide was used in the synthesis of the A-ring fragments of la,25-dihydrovitamin D3 and taxane diterpenoids, sulphur-containing isoxazoles, fluoro-substituted aminocyclopentanols and aminocyclopentitols . New gem- and vic-disubstituted effects in such cyclization reactions have been reviewed by Jung. ... 

When the oxime precursor for the Beckmann rearrangement contains one or more oxygen atoms placed in the appropriate position, a cyclization reaction may occur. One example of a Beckmann rearrangement-cyclization involving an oxygen atom as... 

The electrophile-induced cyclization of heteroatom nucleophiles onto an adjacent alkene function is a common strategy in heterocycle synthesis (319,320) and has been extended to electrophile-assisted nitrone generation (Scheme 1.62). The formation of a cyclic cationic species 296 from the reaction of an electrophile (E ), such as a halogen, with an alkene is well known and can be used to N-alkylate an oxime and so generate a nitrone (297). Thus, electrophile-promoted oxime-alkene reactions can occur at room temperature rather than under thermolysis as is common with 1,3-APT reactions. The induction of the addition of oximes to alkenes has been performed in an intramolecular sense with A-bromosuccinimide (NBS) (321-323), A-iodosuccinimide (NIS) (321), h (321,322), and ICl (321) for subsequent cycloaddition reactions of the cyclic nitrones with alkenes and alkynes. 

Among the electrophilic handles proposed for head-to-tail and side-chain-to-tail cyclization of peptides on solid support by intrachain aminolysis with concurrent detachment of the product from the resin in the protected form (see Section 6.8.3.1.3), generally the oxime resin (also called Kaiser resin)1364 365 and a thioester resin[363l are recommended (see Scheme 14). In addition to the classical head-to-tail cyclization,[3431 the oxime resin is used for side-chain cyclizations as well as for the synthesis of multicyclic peptides vide infra). Due to its dual functions, the oxime resin can be employed only with Boc/Bzl chemistry it is not compatible with Fmoc/tBu chemistry where the basic N -deprotection leads to free amino groups and thus to premature cyclization reactions. To avoid this premature cleavage of the... 

The use of aldehyde derivatives serves in lieu of the carboalkoxy group in cyclization reactions. The oxime 473, when allowed to react with triethyl orthoformate, gives the -oxide 474 (Equation 177) <1996H(43)389>. 

The total synthesis of ( )-xenovenine 100 ° was carried out by applying the present cyclization reaction as shown in Scheme 47. Closure of oxime 98j proceeded successfully by treatment with NaH, sesamol 97, and 1,4-cyclohexadiene in 1,4-dioxane at 50 °C, giving 3,4-dihydro-2f/-pyrrole 99j in 87% yield. 

The thermal cyclization reactions of A -alkenyl hydroxylamines and /V-alkenyl oximes are concerted (2n + 2s + 27t) processes proceeding through cyclic five-membered transition states7. 

The same methodology was employed by Tiecco to effect the cyclizations of 0-allyl oximes 164 indicated in Scheme 25. Treatment of the intermediate iminium salt 165 with sodium borohydride affords M-alkyl isoxazolidines 166 [95]. Alternatively, 165 can be treated with water to produce M-unsubstituted isoxazolidines 167 [96]. This synthesis of M-alkyl isoxazolidines represents a valid alternative to that described in Scheme 23. Moreover, the present cyclization reaction is much more stereoselective than the cyclization of 0-allyl hydro-xylamines. In fact, when the methyl derivative 168 was employed, the two isomeric isoxazolidines 153 and 154 were obtained in a ratio of 95 5. The same two products were, in contrast, formed in a 1 1 ratio when the reaction was carried out starting from the corresponding 0-allyl hydroxylamines. Clearly, the steric requirements for the selenium-induced cyclization of the 0-allyl oximes are much greater than those for the corresponding 0-allyl hydroxylamines. 

Bromotellurenylbenzaldehyde (or its oxime) serves as the precursors to another tellurium-containing heterocyclic system, namely benzoisotellurazole 34 (78JHC865). The reaction of the aldehyde with ammonia proceeds through the formation of imine 35 followed by its dehydrobromination. The cyclization reaction of oxime 36 is catalyzed by polyphosphorous acid (Scheme 19). 

Cyclization reactions. 3-Cyano-V-alkoxyindoles are formed when a-cyanobenzyl oxime ethers are oxidized with FeCls (a one-electron oxidant). Cyclization follows the generation of the benzylic radicals. ... 

Naito and coworkers [65] have reported the synthesis of hexahydroazepine part of balanol employing a radical addition of an aldehyde to an oxime ether. Treatment of the aldehyde 260 with Bu3SnH and AIBN furnished a 1 2 mixture of cis and trans amino alcohols 261 via a 1-exo trig radical cyclization reaction. The effi-... 

Oxime ethers and imines are viable intramolecular radical acceptors. Advanced precursors of (—)-tetrodotoxin were prepared via radical cyclization reactions using oxime ethers as radical acceptors [105]. In the synthesis of (+)-7-deoxypancratistatin (160) [106] (Scheme 55), the intermediate 159 was prepared via tandem radical cyc-lizations of the precursor 158 possessing an A -aziridinylimine and an 0-benzyloxime moiety. Direct formation of lactones is possible as shown in the reaction of the (2,2-diphenylhydrazono)acetate 161, which afforded the hydrazino lactone 162 along with the epimer 163. (-t-)-Furanomycin (164) was synthesized from 162 [107] (Scheme 56). Normally, use of nitrile radical acceptors is limited to cyclopentanone synthesis, but the rigidity of the 1,6-anhydro scaffolding in the bromide 166 enabled radical cyclization to give the tricyclic ketone 167, which comprises the entire skeletal framework of tetrodotoxin [108] (Scheme 57). 

Radicals are also produced by manipulation of the a-carboxy and amino groups. The former usually results in decarboxylation, with the products no longer being a-amino acids [61]. Aminyl radicals have been generated from sulfenamide precursors and exploited in cyclization reactions, as illustrated in Scheme 11 [62]. Radical additions to imines [63], oximes [64], isothiocyanates [65] and isocyanides [66] of a-... 

Radical cyclization continues to be one of the most popular radical reaction classes used in synthesis. By far the majority of published cyclization reactions are 5-exo in nature and this year is no exception. The rates of 5-exo cyclization reactions continue to be measured. For example, the rate constants for the 5-exo cyclizations of the 6,6-diphenylhex-5-enyl, 1-methyl-6,6-diphenylhex-5-enyl and the 1,1-dimethyl-6,6-diphenylhex-5-enyl radicals have been measured by laser flash photolysis studies and Arrhenius parameters determined. The relative rate constants for cyclization, and the reaction with PhSeH, were determined at 20 °C. At 20 °C the rates of the three primary, secondary and tertiary radicals with PhSeH were approximately (1.2 0.1) X 10 lmol s The rate constants for alkyl radicals calibrated by competition reactions with PhSeH and PhSH were found to be 30-40% smaller than previously reported and thus it was concluded that derived rate constants for some fast radical reactions may have to be adjusted accordingly. The rate constants for the 5-exo cyclization of secondary radicals on to hydrazones and oxime ethers have been determined. The fastest rate constants were observed for the IV-benzoylhydrazone acceptor. The rate constants were found to be approximately 800 times faster than for the corresponding 5-exo cyclization on to alkenes." Other work has measured the rate constants of cyclization of a range of fluorinated hex-5-enyl, hept-6-enyl, oct-7-enyl and non-8-enyl radicals. Not only were the rate constants measured but the regioselectivity of cyclization was compared with that for the aU-carbon homologues." The 6-exo cyclization of 1,1,2,2-tetrafluoro- and l,l,2,2,3,3,4,4-octafluorohept-6-enyl radicals were found to be approximately 10 times faster than those for the parent... 

H. Miyabe, M. Ueda, K. Fujii, A. Nishimura, T. Naito, Tandem carbon-carbon bond-forming radical addition-cyclization reaction of oxime ether and hydrazone, J. Org. Chem. 68 (2003) 5618-5626. 

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