Ketones oxime ethers

Asymmetric Reduction of Ketone Oxime Ethers with (-)-(25, 3 )-2-Aiiiino-3-methyl-l,l-diphenylpentanol-Borane Reagent General Procedure33 ... 

In addition to the reduction of ketones (e.g., aromatic and aliphatic ketones, a-halo ketones, hydroxyketones, enones, and ketoesters), oximes can be reduced to the corresponding amine with this reagent. In general, ketone oxime ethers, such as 39, can give rise to amines 40 in excellent chemical yield with good to excellent optical purity.5d... 

Fluorination. In a freon solvent, this powerful fluorinating agent is able to convert compounds containing C=N (ketone oxime ethers, hydrazones) and C=S groups to gew-difluorides. Trifluoromethyl derivatives are directly obtained from alkyl dithioates. Caution must be paid to avoid the use of oxygenated solvents with which BrFi reacts violently. 

A method for protecting ketones and aldehydes is the formation of oximes, but sometimes further protection of the oximes is required. For this purpose, the oximes can be protected as allyl ethers. The oxime ethers ean be eleaved with triethylammonium formate in boiling dioxane[444]. The allyl ether of oximes is eleaved under mild conditions without attaeking the aeetal group in 677. 

The radical alkylation of ketones is achieved by their conversion into the desired N-silyloxy enamines 81 (Scheme 13). The reaction of 81 with diethyl bromomalonate in the presence of EtsB (0.5 equiv) in benzene was performed in open air and stirred at room temperature for 3h. With nitro compounds it is achieved by their conversion into the desired ]V-bis(silyloxy)enamines (82) (Scheme 13). When the reaction is carried out with 82 and alkyl iodides with an electron-withdrawing substituent at the a-position, using V-70 as radical initiator (2,2 -azobis(4-methoxy-2,4-dimethylvaleronitrile)), it underwent a clean radical alkylation reaction to yield an oxime ether. Successful radical alkylation of... 

On the other hand, since oxime ethers were electrochemically more inert than ketones under the electroreduction conditions, the electroreductive intra- and inter-molecular coupling of ketones with oxime ethers proceeded via anion radicals in good yields (equations 5 and 6) °4i. Moreover, cobaloxime-mediated intramolecular radical addition onto oxime functions in the electrolysis media proceeded to afford the cyclized aminoethers (equation 7). ... 

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>. 

Intermolecular reactions between 0-benzyl oximes and ketones (or aldehydes) are limited to those with formaldehyde O-benzyl oxime. However, intramolecular coupling proceeds with carbonyl-tethered oxime ethers (Equation (69)). 

An oxidized stage of isohexide nitrates, wherein the remaining hydroxyl group is transformed into the ketone, gives rise to a number of derivatives 161, such as oximes, semicarbazones, acyclic and cyclic acetals, and hydra-zones.154 Among them, 3-amino-2-hydroxypropyl-substituted oxime ethers... 

The reaction of methyl (3-hydroxypyridin-2-yl)ketone oxime (487) with thionyl chloride, trichloroacetyl isocyanate or chlorosulfonyl isocyanate gave 3-methylisoxazolo[4,5-6]pyridine (488) in varying yields dependent upon the temperature and solvent (Equation (43)) <87H(26)292l>. Trichloroacetyl isocyanate was particularly effective in the formation of compound (488) in either diethyl ether or tetrahydrofuran, at ambient temperature or at reflux, affording 60-78% yields. The treatment of 2-acetyl-3-hydroxypyridine (489) with hydroxyamine 0-sulfonic acid afforded a 1 1 mixture of compound (488) and 2-methyloxazolo[4,5-6]pyridine (490) (Equation (44)). The formation of the isomer (490) results from a Beckmann rearrangement. 

Deoximiation Oximes, oximic ethers, or oxime 0-acetates can be converted into the corresponding ketones by reaction with Fe,(CO)9 in CH,OH at 60°. This reaction proceeds particularly readily and in good yield with oxime acetates. 

Several other 1,3,2-oxazaborolidines have been successfully used as chiral catalysts or reagents in borane-promoted reduction of ketones, imines and oxime ethers, and lactones as well as in aldol condensations, Diels-Aldercycloadditions, and ally Imetal additions to aldehydes. ... 

To a warm solution (50 °C) of the 2-aminodiphenyl ketone oxime (70 g, 0.33 mol) in glacial HOAc (420 mL) was added chloroacetyl chloride (74.6 g, 0.66 mol). The mixture was left at rt for 48 h, saturated with anhyd HCl (g), and concentrated in vacuo. The residue was dissolved in CHjClj and washed with ice-cold NajCO soln. The organic solution was dried, concentrated to a small volume, and diluted with petroleum ether. The precipitated crystals were filtered. The mother liquid yielded an additional crop. After recrystallization, the product formed as yellow needles yield 67.8 g (76%) mp 160-161 °C. 

Oximes Amides Ketones Aldehydes Ethers Esters... 

When electroreduction was used, it was even possible to obtain cross-products, by coupling a ketone to an O-methyl oxime O-Methyl oxime ethers are coupled... 

Treatment of benzaldehyde oxime ether (166) with butyllithium (pentane/-10 C) demonstrates the complexity of the reaction (Scheme 32) as the desired alkoxyamine (167 R = Bu) is accompanied by other oxime-derived side products" (entry 1, Table 12). Selectivity is reagent/solvent dependent as allyl Grignard (ether)," allylzinc bromide (THF)," and butyllithium (THF)" treatment produce predominantly amine (171 R = allyl) (the Beckmann rearrangement derived product), alkoxyamine (167 R = allyl) (the oxime addition product) and ketone (169 R = Bu) (the nitrile-derived pro ct), respectively (entries 2-4, Table 12). 

Primary amines (RNH2) also add reversibly to ketones or aldehydes to give imines (Schiff bases) and related compounds via the intermediate hemiaminals. The position of the equilibrium depends on the structure of the amine and the carbonyl compound. With alkylamines, the equilibrium favors the carbonyl compound, but it can be driven to the imine by removal of H20. With hydrazines (R2NNH2) and hydroxyl-and alkoxylamines (RONH2), the equilibrium greatly favors the hydrazone, oxime, or oxime ether, and it is difficult to drive the reaction in the reverse direction. Secondary amines (R2NH) can form hemiaminals, but they cannot form imines. 

Up until the end of the 1980s, radical carbonylation chemistry was rarely considered to be a viable synthetic method for the preparation of carbonyl compounds. In recent years, however, a dramatic change has occurred in this picture [3]. Nowadays, carbon monoxide has gained widespread acceptance in free radical chemistry as a valuable Cl synthon [4]. Indeed, many radical methods can allow for the incorporation of carbon monoxide directly into the carbonyl portion of aldehydes, ketones, esters, amides, etc. Radical carboxylation chemistry which relies on iodine atom transfer carbonylation is an even more recent development. In terms of indirect methods, the recent emergence of a series of sulfonyl oxime ethers has provided a new and powerful radical acylation methodology and clearly demonstrates the ongoing vitality of modem free radical methods for the synthesis of carbonyl compounds. 

A similar method for cyclic ketone synthesis via an intramolecular carbonyl ad-dition/elimination strategy has been reported by Kim and Jon, who used acylsul-fides and acylselenides as radical acceptors (Scheme 4-21) [41]. As has previously been observed in the cases of sulfonyl oxime ethers which liberate sulfonyl radicals, thiyl and selenenyl radicals react with ditin to propagate the chain. Generally acylselenides are more efficient substrates than acylsulfides due to the better leaving ability of the phenylseleno group. As shown in the third example in Scheme 4-21, a tandem cyclization leading to a tricyclic ketone has also been effected. 

Replacement of the normal pyrethroid ester by alternative linkages usually leads to diminution of biological activity. One important exception to this general phenomena is several oxime ether derivatives, in particular, 3-phenoxybenzyl derivatives of various alkyl aryl ketones. Pyrethroid esters derived from certain 2-substituted-[1,1 -biphenyl]-3-methanols have been shown to possess initial and residual activity surpassing that of esters derived from 3-phenoxybenzyl alcohol. Now it has been demonstrated that the same enhancement of activity was observed for alkyl aryl oxime ethers of certain [1,1 -biphenyl]-3-methanols compared to the corresponding 3-phenoxybenzyl alcohol derived oximes. The synthesis, biological activity, including soil activity, structure-activity relationships and toxicity of several of these biphenylmethyl oxime ethers are described. 

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