Reaction with oxime ethers

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... 

The stereochemistry of the reactions of oxime ethers and crotylboronates (22) and (23) have been discussed earlier (Scheme 8). The reactions of the corresponding oximes with (22) and (23) appear to follow a similar stereochemical course (Scheme 14). Stereoselectivity, however, is not as high with the isobutyraldehyde and pentanal oximes as it is with phenylaldoxime. The reaction of MeaSi-substituted allylboronate (90) and acetaldehyde oxime performed in refluxing CCU similarly provides a 79 21 mixture of the anti and syn product diastereomers (MeaSi replacing Me in 25 and 26). Excellent stereoselectivity for syn-homoallylamines has been achieved via the Lewis acid catalyzed reactions of aldimines and crotyltributylstannane. ... 

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). 

Pattenden, G. and Schulz, D.J. (1993) Cascade Radical Reactions in Synthesis. A New Radical Mediated Double Ring Expansion-Cyclization Process with Oxime Ethers, Tetrahedron Lett. 34, 6787-6790. 

As one would expect, oximes and nitroso-compounds are frequently encountered starting materials throughout the chemistry of this group of heterocycles. Further examples of their reactions have appeared. Reaction with enol ethers produces dihydro-oxazines (260), which may be converted to pyridine N-oxides upon treatment with HCl. Dihydro-oxazines are also obtained upon treatment of 7,6-unsaturated dicarbonyl compounds with nitrous acid. Thermolysis of these products leads to nitrones (261). 

Driver et al. also studied the reactivity of aryl azides with oxime ethers 66 toward the synthesis of benzopyrazoles 67 through Fe(II)-catalyzed formation of an N—N bond (Scheme 16.30) [49]. In the reactions of oxime derivatives 66, the (Z)-isomer could not afford any desired product. It was suggested that N—N bond formation occurs through intermediate A produced from ( )-66 by coordination of the iron(II) catalyst to the terminal N atom of the azide. Subsequent nucleophilic attack of the oxime nitrogen on the activated azide forms an N—N bond, which is followed by extrusion of N2 and dissociation of the iron catalyst to provide the benzopyrazoles 67. 

SCHEME 10.45 Reaction of oxime ethers with cyclopropanes. 

TABLE 10.15 Intramolecular Reaction of Oxime Ethers with Cyclopropanes... 

Z-oxy-immiuin spedes SCHEME 10.47 Mechanism of intramolecular reaction of oxime ethers with cyclopropanes. 

Reaction with Oximes Deprotection of Ketones. Regeneration of protected ketones from their oximes can be achieved by refluxing the oxime in di-n-butyl ether with one equiv of Fe(CO)s and a catalytic amount of a Lewis acid (eq 20). ... 

Acetaldehyde can be isolated and identified by the characteristic melting points of the crystalline compounds formed with hydrazines, semicarbazides, etc these derivatives of aldehydes can be separated by paper and column chromatography (104,113). Acetaldehyde has been separated quantitatively from other carbonyl compounds on an ion-exchange resin in the bisulfite form the aldehyde is then eluted from the column with a solution of sodium chloride (114). In larger quantities, acetaldehyde may be isolated by passing the vapor into ether, then saturating with dry ammonia acetaldehyde—ammonia crystallizes from the solution. Reactions with bisulfite, hydrazines, oximes, semicarb azides, and 5,5-dimethyl-1,3-cyclohexanedione [126-81 -8] (dimedone) have also been used to isolate acetaldehyde from various solutions. 

Vinyl chloride reacts with sulfides, thiols, alcohols, and oximes in basic media. Reaction with hydrated sodium sulfide [1313-82-2] in a mixture of dimethyl sulfoxide [67-68-5] (DMSO) and potassium hydroxide [1310-58-3], KOH, yields divinyl sulfide [627-51-0] and sulfur-containing heterocycles (27). Various vinyl sulfides can be obtained by reacting vinyl chloride with thiols in the presence of base (28). Vinyl ethers are produced in similar fashion, from the reaction of vinyl chloride with alcohols in the presence of a strong base (29,30). A variety of pyrroles and indoles have also been prepared by reacting vinyl chloride with different ketoximes or oximes in a mixture of DMSO and KOH (31). 

If the carbonyl grou]) in the 3-position of N-methylisatin or tlii-ana])hthencquinone is blocked by formation of an oxime (cf. 112), A -methylation of the oxime group occurs instead of ring expansion on reaction with diazomethane. In methanol, thianaphthenequinone oxime iV-mcthyl ether (113) then undergoes ring opening catalyzed by diazoniethane (113 114). 

The pharmacological versatility of this general substitution strategy is further illustrated by diazonium coupling of 14 with 2-nitrobenzenediazonium chloride to produce biarylal-dehyde 18. Formation of the oxime with hydroxylamine is followed by dehydration to the nitrile. Reaction with anhydrous methanolic hydrogen chloride leads to imino ether and addition-elimination of ammonia leads to the antidepressant amid-ine, nitrafudam (20). ... 

A mixture of 202 g 2-amino-5-chlorobenzophenone, 190 g hydroxylamine hydrochloride, 500 cc pyridine and 1,200 cc alcohol was refluxed for 16 hours, then concentrated in vacuc to dryness. The residue was treated with a mixture of ether and water. The water was separated, the ether layer containing a considerable amount of precipitated reaction product was washed with some water and diluted with petroleum ether. The crystalline reaction product, 2-amino-5-chlorobenzophenone-0 -oxime, was filtered off. The product was recrystallized from a mixture of ether and petroleum ether forming colorless prisms, MP 164° to 167°C. 

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