A-Keto-oxime

Fluoride ion catalyzed 1,3-dipolar cycloaddition of bromo nitrile oxide, obtained in situ from dibromoformaldehyde oxime 184, to nonactivated alkynes provides a new approach to the synthesis of neuroactive isoxazoles. However, the regioselectivity of cycloaddition in this case is not high—products 185 and 186 are obtained in a 1 1 to 1 1.4 ratio (equation 80). Cycloaddition reaction of hydroximoyl chlorides and acetylene was snc-cessfully carried out also in the presence of NaHCOs as a base. For instance, a-keto oximes 187 were reacted with acetylene and NaHCOs to give isoxazoles 188 in good yields (equation 81). 

One attractive possibility is the use of the a-keto-oxime chromophore. It has a strong absorption at 220 nm whose tail, which extends to 240-250 nm, would improve the absorption characteristics of PMMA. Also, the esters possess a N-O bond which is photochemically labile yet sufficiently thermally stable so as to be compatible with the various processing steps. The solution degradation of a-keto oximino methacrylate esters upon irradiation with light of X365 nm has been reported by Delz-enne (2), and we proceeded to investigate the solid state photodegradation of similar copolymers and their possible utility as deep UV photoresists. 

In an effort to improve PMMA s photosensitivity further, methyl methacrylate has been copolymerized with higher percentages of the a-keto-oxime methacrylate and terpolymerized with varying amounts of methacrylonitrile. The resulting effects on resist properties, e.g., sensitivity, contrast and resolution, and plasma resistance, are reported here. The terpolymers are up to 85 times more sensitive than PMMA, and retain its high resolution characteristics. 

A representative sample of terpolymers was exposed to a variety of etchants for polysilicon and silicon dioxide, and the results are given in Table V. The ratio of the etch rate of the substrate to the etch rate of the resist must be at least 2 1 for the resist to be a viable etch mask. Inspection of Table V, shows that the materials examined are unacceptable for only the QFj — CF3CI (4 1) plasma. The etch rates are comparable to those for PMMA the a-keto-oxime exhibits essentially no effect on that rate and the nitrile affords a slight decrease in the plasma etch rate. The etch rates of some commercially available materials are shown for comparison. 

Reaction of DAMN with x-Keto Aldehydes, a-Keto Oximes, and x-Diketones... 

DAMN reacts readily with a-keto aldehydes, a-keto oximes, and x-diketones to give mono- and disubstituted aryl/alkyl dicyanopyrazines (127) in good yield (Scheme 45). 

Oximes carrying a second group like a hydroxyl, carbonyl, or car-balkoxyl may form cyclic products, such as pyrazines from a-keto oximes and pyrrolidones from y-oximino esters, upon reduction. ... 

Preparation of heterocyclic compounds by coupling two constituents with a titanium Lewis acid is shown in Eqs (241) and (242). A C-labeled nitrogen heterocycle was synthesized by condensation of a keto-oxime and a-aminonitrile in the presence... 

One of the identified causes of the low sensitivity of PMMA to DUV radiation is the low absorption coefficient of the material in this region of the spectrum and the poor match of its absorption spectrum with the emission of the Xe-Hg lamp. Incorporating acyloximino groups into the base polymer has been reported to overcome this deficiency and significantly enhance the photospeed of the resist (Scheme 7.19). The a-keto-oxime chromophore, first introduced by Delzenne et al., has a strong broad absorption band in the DUV, centered around 225 nm it is photolabile and is relatively thermally stable.The incorporation... 

Base-induced ring closure of a keto oxime has been reported to give a 45% yield of (37) (Scheme 13) <81CL1561>, while intramolecular Pictet-Spengler condensation affords a fused-ring hexahydro derivative (43) (Equation (9)) <89TL6809>. 

This reaction was initially reported by Forster in 1915. It is the synthesis of diazoketones, especially for the cyclic diazoketones from a-keto oximes by the reaction with chloramines. Therefore, it is known as the Forster reaction. Although two mechanisms have been proposed for this reaction,experimental evidence favors the one involving the attack of NH2CI by the lone-pair electrons of the oxime nitrogen. " This reaction has been modified via the generation of chloramine in situ, which is used in the preparation of 2-diazo-1 -indanones. ... 

The Hoch-Campbell reaction of a-hydroxy ketoximes do not alter the course of the reaction although deprotonation probably took place concurrently for both the alcohol and the oxime. Treatment of oxime 40 afforded aziridine 42 in 30%, presumably via the intermediacy of azirine 41. a-Keto ketoximes would behave similarly to the a-hydroxy ketoximes in the Hoch-Campbell reaction after addition of the first equivalent of the Grignard reagent to the ketone. Therefore, the reaction between a-keto ketoxime 43 and phenylmagnesium bromide gave aziridine 45 in 41% yield, presumably via the intermediacy of azirine 44. 

The starting semicarbazones were most often prepared directly from the a-keto acids. Godfrin proceeded from a-alkyl acetoacetates, which were converted by oxidation with nitrosylsulfuric acid to a-keto-acid oximes and the latter transformed to semicarbazones or thioseraicarbazones by applying semicarbazide or thiosemicarbazide. For glyoxylic acid semicarbazone a very convenient procedure was employed, making use of the hydrolysis of nonisolated chloral semicarbazone. ... 

It yields a monobromide melting at 41°, a semi-carbazone melting at 220° to 221 °, and an oxime melting at 106°. When reduced with sodium and alcohol it yields a secondary alcohol, which forms large crystals melting at 51°. On oxidation by cold 3 per cent, solution of potassium permanganate it yields geronic acid, a keto-acid of the constitution—... 

This transformation can also be carried out under solvent-free conditions in a domestic oven using acidic alumina and ammoniiun acetate, with or without a primary amine, to give 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazoles, respectively (Scheme 15A) [69]. The automated microwave-assisted synthesis of a library of 2,4,5-triarylimidazoles from the corresponding keto-oxime has been carried out by irradiation at 200 ° C in acetic acid in the presence of ammonium acetate (Scheme 15B) [70]. Under these conditions, thermally induced in situ N - O reduction occurs upon microwave irradiation, to give a diverse set of trisubstituted imidazoles in moderate yield. Parallel synthesis of a 24-membered library of substituted 4(5)-sulfanyl-lff-imidazoles 40 has been achieved by adding an alkyl bromide and base to the reaction of a 2-oxo-thioacetamide, aldehyde and ammonium acetate (Scheme 15C) [71]. Under microwave-assisted conditions, library generation time was dramatically re-... 

Certain ketoximes can be converted to nitriles by the action of proton or Lewis acids. Among these are oximes of a-diketones (illustrated above), a-keto acids, a-dialkylamino ketones, a-hydroxy ketones, p-keto ethers, and similar compounds. These are fragmentation reactions, analogous to 17-25 and 17-26. For example, ot-dialkylamino ketoximes also give amines and aldehydes or ketones besides nitriles. 

Catalytic asymmetric hydrogenation is a relatively developed process compared to other asymmetric processes practised today. Efforts in this direction have already been made. The first report in this respect is the use of Pd on natural silk for hydrogenating oximes and oxazolones with optical yields of about 36%. Izumi and Sachtler have shown that a Ni catalyst modified with (i ,.R)-tartaric acid can be used for the hydrogenation of methylacetoacetate to methyl-3-hydroxybutyrate. The group of Orito in Japan (1979) and Blaser and co-workers at Ciba-Geigy (1988) have reported the use of a cinchona alkaloid modified Pt/AlaO.i catalyst for the enantioselective hydrogenation of a-keto-esters such as methylpyruvate and ethylpyruvate to optically active (/f)-methylacetate and (7 )-ethylacetate. 

Indium-mediated allylation reactions of a-keto imides derived from Oppolzer s sultam proceeded in aqueous THF in good yields and excellent diastereoselectivity (Eq. 11.43).74 The indium-mediated allylation of the Oppolzer camphorsultam derivatives of glyoxylic oxime ether... 

The scope and efficiency of [4+2] cycloaddition reactions used for the synthesis of pyridines continue to improve. Recently, the collection of dienes participating in aza-Diels Alder reactions has expanded to include 3-phosphinyl-l-aza-l,3-butadienes, 3-azatrienes, and l,3-bis(trimethylsiloxy)buta-l, 3-dienes (1,3-bis silyl enol ethers), which form phosphorylated, vinyl-substituted, and 2-(arylsulfonyl)-4-hydroxypyridines, respectively <06T1095 06T7661 06S2551>. In addition, efforts to improve the synthetic efficiency have been notable, as illustrated with the use of microwave technology. As shown below, a synthesis of highly functionalized pyridine 14 from 3-siloxy-l-aza-1,3-butadiene 15 (conveniently prepared from p-keto oxime 16) and electron-deficient acetylenes utilizes microwave irradiation to reduce reaction times and improve yields <06T5454>. 

A closely related protocol for the synthesis of imidazoles was independently investigated by Sparks and Combs (Scheme 6.199) [362]. Here, the authors employed readily available unsymmetrical keto-oximes as building blocks, initially leading to N-hydroxyimidazoles. Diaryl keto-oximes were condensed with various aldehydes (1.1 equivalents) in the presence of 4 equivalents of ammonium acetate under microwave conditions at 160 °C. In this way, the N-hydroxyimidazoles were formed... 

Recently, Kim and colleagues have described a new efficient method for the preparation of a-keto esters 48 via a free-radical acylation approach using (phenylsulfonyl) methoxycarbonyl oxime ether 46 as carbonyl equivalent radical acceptor (Scheme 28). The oxime 46 was conveniently prepared from readily available methylphenylsulfonyl acetate 44 by a two-step sequence (via oxime 45) as shown in Scheme 28. Nitrosation of 44 with isoamyl nitrite in the presence of sodium methoxide gave oxime 47 in 78% yield. 

Reaction with alcohols is general for diazo compounds, but it is most often performed with diazomethane to produce methyl ethers or with diazo ketones to produce a-keto ethers, since these kinds of diazo compounds are most readily available. With diazomethane593 the method is expensive and requires great caution. It is used chiefly to methylate alcohols and phenols that are expensive or available in small amounts, since the conditions are mild and high yields are obtained. Hydroxy compounds react better as their acidity increases ordinary alcohols do not react at all unless a catalyst such as HBF4594 or silica gel595 is present. The more acidic phenols react very well in the absence of a catalyst. Oximes, and ketones that... 

Hydroxydihydro-l,2-oxazines (20) are in equilibrium with the corresponding open-chain keto oximes (21) (70T1315), and a related tautomerism is exhibited by certain TV-oxides (22), the seco forms (23) of which are nitronic acids (78TL2339). 

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