Oxime ethers hydrides

Complex hydrides are reagents of choice for reduction of oximes, oxime ethers and nitrones. Hydrogenation is rarely used for reduction of these compounds although several examples are known. Other methods, especially reduction with silanes in the presence of acid, can also be useful for providing alternative stereochemical outcomes. 

Enantioselective reduction of ketoxime ethers with chiral boron hydrides produces chiral 0-alkylhydroxylamines with variable ee. Reduction of oxime ethers of type 94 (equation 65) with norephedrine-derived oxazoborolidine 95 proceeds with very high ee. However, an analogous reduction of acyclic aromatic oximes with chiral oxab-orazolidines produced a mixture of amine and hydroxylamine . 

J. Marco-Contelles, P. Gallego, M. Rodriguez-Femandez, N. Khiar, C. Destabel, M. Bemanbe, A. Marinez-Grau, and J. L. Chiara, Synthesis of aminocyclitols by intramolecular reductive coupling of carbohydrate derived <5- and 8-functionalized oxime ethers promoted by tributyltin hydride or samarium diiodide,./. Org. Chem., 62 (1997) 7397-7412. 

Miyabe et al. developed a tandem addition/cycUzation reaction featuring an unprecedented addition of alkoxycarbonyl-stabihzed radicals on oxime ethers [117], and leading to the diastereoselective formation of /1-amino-y-lactone derivatives [118,119]. The reaction proceeds smoothly in the absence of toxic tin hydride and heavy metals via a route involving a triethylborane-mediated iodine atom-transfer process (Scheme 37). Decisive points for the success of this reaction are (1) the differentiation of the two electrophilic radical acceptors (the acrylate and the aldoxime ether moieties) towards the nucleophilic alkyl radical and (2) the high reactivity of triethylborane as a trapping reagent toward a key intermediate aminyl radical 125. The presence of the bulky substituent R proved to be important not only for the... 

Oxime ethers are the first of three different types of C=N bonds to be used as radical acceptors. After the cyclization of an alkyl radical onto the oxime ether using zinc-trimethylchlorosilane was first reported by Corey in 1983 [5], n-tributyltin hydride-mediated radical cyclization onto oxime ethers has been successfully applied to the conversion of carbohydrate derivatives to carbocycles (Scheme 1) [6]. Parker employed the oxime ether as the radical trap in the synthesis of the morphine skeleton... 

The Keck group used a slightly different approach in a synthesis of (+)-7-deoxypancratistatin (Scheme 11) [72]. Once again 104 served as the starting material. A 3-step sequence provided 107, and an additional 6 steps afforded hydrazone-oxime ether 108. Treatment of this substrate with triphenyltin hydride gave tandem-cyclization product 110 in 78% yield. The first cyclization involves powerful methodology introduced by Kim in which a free radical adds to a hydra-... 

Standard conversion of the alcohol of 87 into a phenylthionocarbonate derivative, then reaction with tributyltin hydride-AIBN, produced a radical centred at C-5 which added to the oxime ether double bond to produce the corresponding cyclitol. Further standard conversions gave 88. ... 

Oxime ethers derived from hydroxy aldehydes, upon conversion to their phenyl thionocarbonate esters, undergo radical cyclizations resulting in the formation of carbocycles. For example, an oxime ether obtained from D-glucose is converted into its phenyl thionocarbonate ester at C-5 and, upon heating in benzene in the presence of tributyltin hydride, affords cyclopentanes in 93% yield as a 62 38 mixture of two diastereomers (eq 7). In general, only low to modest stereoselectivity between the newly formed stereocenters is observed in a number of substrates examined. 

The treatment of ketoximes with lithium aluminum hydride is usually a facile method for the conversion of ketones into primary amines, although in certain cases secondary amine side products are also obtained. Application of this reaction to steroidal ketoximes, by using lithium aluminum deuteride and anhydrous ether as solvent, leads to epimeric mixtures of monodeuterated primary amines the ratio of the epimers depends on the position of the oxime function. An illustrative example is the preparation of the 3(x-dj- and 3j5-di-aminoandrostane epimers (113 and 114, R = H) in isotopic purities equal to that of the reagent. 

Triphenyl- 1,2,4-butanetrione oxime in chloroform with hydrogen chloride cyclized in 70-75% yield to the purple 2,4,5-triphenyl-3f/-pyrrol-3-one 1-oxide (61) (30JA1590), along with an isoxazoline derivative. The pyrrlone was reduced by lithium aluminum hydride in ether [76JCS(P 1)2259] to l-hydroxy-2,3,5-triphenylpyrrole 62. 

Sodium hydride (11 mmol) was added to 50 ml DMF, 4 portions of chloroacetophenone oxime (1.7 g) added, and the mixture stirred at ambient temperature 30 minutes. Thereafter, the product from Step 3 (10 mmol) dissolved in 10 ml DMF was added dropwise. The mixture stirred at ambient temperature 2 hours, poured into cold 2 M HCl, and the product extracted with methyl t-butyl ether. The combined organic phases were washed with water, dried, concentrated, purified by chromatography on silica gel using methyl t-butyl ether/n-hexane, and the product isolated in 80% as a colorless oil. HNMR data supplied. 

Reduction, An original report by a Czechoslovak group indicated that organic compounds are reduced with difficulty and in poor yields by magnesium aluminum hydride. However, James has reported recently that the reagent (suspended in ether) reduces aldehydes, ketones, acids, and oximes in high yield in a reasonable time (4 12 hr.). The reagent thus rivals lithium aluminum hydride in efficiency, but not in convenience. 

The reductive Beckmann rearrangement of oximes has been effected with several types of aluminum hydride reagents. Early examples exhibited only moderate regioselectivity, giving mixtures of primary amines and rearranged secondary amines. Recently, diisobutylaluminum hydride was reported to be most satisfactory for this type of transformation (equation 20). Here dichloromethane is the solvent of choice, and attempted use of ethereal solvents results in the formation of a mixture of primary and secondary amines. ... 

Dihydroxylation of the stilbene double bond in the trans isomers of Combretastatin A-1 and A-4 produced diols which by treatment with boron trifluoride in ethyl ether [44] or with trifluoroacetic acid [17] resulted in pinacolic rearrangement to produce an aldehyde. The aldehyde was converted in a variety of derivatives, as illustrated in the Scheme 20, via the following reaction sequence reduction with sodium borohydride to primary alcohol which was derivatized to the corresponding mesylate or tosylate, substitution with sodium azide and final reduction to amine with lithium aluminum hydride. Alternatively the aldehyde was converted to oxime which was catalitically hydrogenated to amine [17]. 

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