Oxime ethers, synthesis

Shen, Y., and Jiang, G.-E, Sequential transformations of phosphonates. One-pot synthesis of ethoxycarbonyl allyl substituted oxime ethers. Synthesis, 502, 2000. 

MILLER - SNYDER Aiyl Cyanide Synthesis Synthesis of benzonitnies from aldehydes via oxime ethers Formation of p-cyanophenol from p nrtrobenzaldoxime and p-nitiobenzonitnle (used as a sometimes recyclable chain carrier)... 

Compound 14 can be dismantled in a productive fashion by ret-rosynthetic cleavage of the indicated bonds (see Scheme 4). The intermolecular attack of the amino group in 15 upon the keto function in 16 would be expected to result in the formation of the desired oxime ether after loss of a water molecule. A few functional group manipulations would then complete the synthesis of intermediate 14. A valuable structural feature of 15 is the C-2 oxygen substituent. Although this oxygen atom is not expressed in the natural product, it would certainly play an important role in our... 

The synthesis of alkoxy amines 2 by addition of organometallic reagents to the C-N double bond of oxime ethers 1 is plagued by the propensity for proton abstraction a. to the C-N double bond, the lability of the N-O bond and the poor electrophilicity of the oxime ethers. Therefore, frequently no products, undesired products or complex mixtures are obtained. The result depends on the substrate, organometallic reagent, solvent, temperature and additives1 6. 

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... 

Nazarpack-Kandlousy, N. Nelen, M. I. Goral, V Eliseev, A. V. Synthesis and mass spectrometry studies of branched oxime ether libraries. Mapping the substitution motif via linker stability and fragmentation pattern. J. Org. Chem. 2002, 67, 59-65. 

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) °. 

Total synthesis of (-l-)-lycoricidine, (—)-lycoricidine and (-l-)-narciclasine via 6-exo cyclization of substituted vinyl radicals with oxime ethers has been reported . Thus, interaction of oxime ether 321 with thiophenol and then with Sml2 and TFA afforded (-l-)-lycoricidine 322 in good overall yield (equation 139). 

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 . ... 

A new synthetic method of benzofuran was reported (equation 39). The [3,31-sigma-tropic rearrangement of Af-trifluoroacetyl enehydroxylamines 136 obtained in situ by acylation of oxime ethers 135 in the presence of trifluoroacetic anhydride lead to the synthesis of cyclic or acyclic dihydrobenzofurans 138. The effects of base and temperature on the reaction products were studied. A similar pathway to that of Fisher indolization was proposed. The acylimine formed by the [3,3]-sigmatropic rearrangement of the V-trifluoroacetyl enehydroxylamine 136 gave the dihydrobenzofuran 137 by an intramolecular cyclization or the benzofuran 138 after elimination. 

A new approach to this synthesis category involves the dimerization of halogenated oxime ethers 705 by reaction with Grignard reagents, where the C-2 atom of the product 706 arises from a rearrangement that is proposed to proceed via azirene intermediates <2002JA9032, 2004CL122>. 

Radical cyclizations are often used in ring formations and are an effective methodology in the synthesis of piperidines. The intramolecular cyclization of an oxime ether, such as 63 onto an aldehyde or ketone gives a new entry into cyclic amino alcohols <99JOC2003, 99H(51)2711>. Similarly, reaction of a terminal acetylene with BujSnH generates a vinyl radical, which will cyclize with an imine moiety to give 3-methylenepiperidine <99TL1515>. The indolizidine alkaloid ipalbidine was prepared by a sulfur-controlled 6-exo-selective radical cyclization of an a/p/ia-phenylthio amide <99H(50)31>. 

The phenylthionocarbonate procedure was also used for the cyclization of a 5-oxime-ether radical (Scheme 6) [17]. The stereochemical outcome of this reaction is almost identical with that observed for a closely related 6-methoxyhex-5-enyl radical cyclization [12,14]. A related glucosamine-derived radical cyclization has been employed for the synthesis of allosamizoline 13 [18]. Other examples in this area include the cyclization of... 

Strategies that lead to the formation of isoxazoles during cleavage from an insoluble support include the oxidative cleavage of /V-(4-alkoxybenzyl)isoxazolidincs with DDQ to yield isoxazolines (Entry 14, Table 15.16), the nucleophilic cleavage of 2-acyl enamines with hydroxylamine (Entry 15, Table 15.16), and the acidolysis of 2-cyano-phenols etherified with an oxime resin (Entry 17, Table 15.16). The required oxime ethers for the latter synthesis were prepared by reaction of the corresponding 2-fluorobenzonitriles with Kaiser oxime resin [203],... 

Sulfonyl oxime ethers function as efficient radical Cl acceptors [45]. The instance in Scheme 6.26, in which a bissulfonyl oxime ether is used as a radical Cl acceptor, showcases the strategic aspect of this unique method for the synthesis of... 

A subsequent similar synthesis of a-amino acids was then reported by Naito et al. which used the indium-mediated alkylation and allyation reaction of the Oppolzer camphorsultam derivative of glyoxylic oxime ether <02CC1454>. 

An asymmetric synthesis of aminocyclopentitols 134-137 has been used in the synthesis of trehazolin via free-radical cycloisomerization of enantiomerically pure, alkyne-tethered oxime ethers derived from D-mannose (Scheme 17).84 Treatment of 2,3 5,6-di-(9-isopropylidene-D-mannofuranose (128)85 with ethynylmagnesium bromide gave compound 129, which underwent sequential one-pot acid hydrolysis plus diol cleavage to give 130, oximation of which afforded the radical precursor 131, in 41% overall yield from 129. The free hydroxyl group of 131 was protected as acetate 132 and tert-butyldimethylsilyl ether 133, which were isolated as inseparable... 

J. L. Chiara, J. Marco-Contelles, N. Khira, P. Gallego, C. Destabel, and M. Bemabe, Intramolecular reductive coupling of carbonyl-tethered oxime ethers promoted by samarium diiodide A powerful method for the stereoselective synthesis of aminocyclopentitols, J. Org. Chem., 60 (1995) 6010-6011. 

---