Reduction oxime ethers

Jacobsen epoxidation 359 -, Katsuki epoxidation 361 -, Mukaiyama-aldol reaction 367 f. -, oxime ether reduction 363 -, Sharpless asymmetric dihydroxyla-tion 361... 

Table 5. Addition of Organolithium Reagents R2Li to Oxime Ethers 4 and Reduction of the Resulting Alkoxyamines 5 to Amines 6"...

Several lupin alkaloids have been derived from the unsaturated quinalozidine 433, that was obtained in the treatment of amine 431 with ortho-quinone 432. This quinone behaves as a model of topaquinone, the cofactor of copper-containing amine oxidases. The cyclization step involved a nucleophilic attack of the piperidine nitrogen of 431 onto a side-chain aldehyde function that is unmasked by the oxidative deamination. Quinolizine 433, when treated with dehydropiperidine, gave the oxime ether 434 that, on ozonolysis followed by reduction, afforded sparteine 10, presumably via the bis(iminium) system 435 (Scheme 102) <1996JOC5581>. 

The other study3 of oxime ethers focused on radical cyclizations to alkoxyami-nocyclopentanes and -cyclohexanes (equations III and IV). Yields decrease as chain length of the precursors is increased, mainly because of reduction. The cyclizations... 

Asymmetric reduction of oxime ethers,2 The complex (1) of (- )-norephedrine with BH3 (2 equiv.) reduces prochiral oxime ethers to optically active amines the... 

In the asymmetric reduction of ketones, stereodifferentiation has been explained in terms of the steric recognition of two substituents on the prochiral carbon by chirally modified reducing agents40. Enantiomeric excesses for the reduction of dialkyl ketones, therefore, are low because of the little differences in the bulkiness of the two alkyl groups40. In the reduction of ketoxime ethers, however, the prochiral carbon atom does not play a central role for the stereoselectivity, and dialkyl ketoxime ethers are reduced in the same enantiomeric excess as are aryl alkyl ketoxime ethers. Reduction of the oxime benzyl ethers of (E)- and (Z)-2-octanone with borane in THF and the chiral auxiliary (1 R,2S) 26 gave (S)- and (R)-2-aminooctane in 80 and 79% ee, respectively39. 

Schiff bases are obtained from 2-aminoimidazothiadiazoles with aldehydes (77M665). Hydrazones and oxime ether formation of imidazothia-diazole-5-carbaldehydes and -5-ketoesters was reported (84FES585 95EUP662477). Reduction of 122 with Al/FIg yields the tautomeric imine 128 of the corresponding amine (83JHC1003). 

C. Hydroxylamines through Reduction of Oximes, Oxime Ethers... 

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. 

Sodium cyanoborohydride is the most commonly used reagent for reduction of oximes and oxime ethers. Although this reaction is highly versatile, and does not interfere with a majority of functional groups, careful control of reaction conditions is necessary. A considerable problem in the reduction, especially for aldoximes 80 (equation 57), is the reaction of initially formed A-alkylhydroxylamine 81 with the starting oxime 80. The obtained nitrone 82 is subsequently reduced to A,A-dialkylhydroxylamine 83, which was found to be a major reaction product at pH = 4 and above. This side reaction can be avoided by adjusting the pH of the reaction mixture to 3 or below. 

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 . 

The samarium diiodide-mediated reductive cyclization of a sugar-derived oxime ether provides a trace amount of an unexpected cyclized product <1997JOC7397>. It is thought that its formation probably arises from an intermediate (methylthio)methyl ether formed with the excess of Swern reagent used to generate the aldehyde in situ after cyclization (Equation 59). 

Chu, Y, Shan, Z., Liu, D. and Sun N. Asymmetric Reduction of Oxime Ethers Promoted by Chiral Spiroborate Esters with an O3BN Framework. J. Org. Chem. 2006, 71, 3998-4001. 

Usually, 3- and 4-substituted thianes are prepared from the 3- and 4-oxothians by the common techniques applicable to alicyclic chemistry. Reduction affords alcohols which may be etherified or halogenated, while oximation and reduction produces the amino derivatives, which are also accessible via the halo compounds. 2-Alkoxy and 2-alkylthio compounds are made by acid catalyzed addition of alcohols and thiols to 3,4-dihydro-2H-thiopyran (75MI22502) in a reaction analogous to the use of dihydropyran for protection of alcohols as THP ethers. 

Enantioselective reduction of oxime ethers promoted by chiral spiroborate esters (10) with an O3BN framework is reported. In the presence of (R,S)-10, aralkyloxime ethers are reduced by borane-THF at give (S)-l-aralkylamine in high yield and excellent enatiomeric excess (up to 98% ee). A possible mechanism (Scheme 13) of the catalytic reduction is suggested.310... 

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. 

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