Ketoxime ethers, reduction

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. 

B. Reduction of Ketoximes and Ketoxime Ethers with Chiral Metal... 

Syn stereoselectivity in reduction of acylic chiral ketoxime ethers of type 91 (equation 63) can be obtained using bulky tetramethylammonium triacetoxyborohydride that produces FeUdn-type products with high selectivity . Reaction of a-tolylsulfinylketoximes 92 (equation 64) with L-Selectride also results in syn products 93. 

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 reduction of ketoxime ethers by borane in the presence of (—)-norephedrine yields (S)-amines from a/ i-kctoximcs and (/ )-isomers from. s i/ -ketoximes, e.g. from phenyl-4-tolyl-methyl ketoxime methyl ether40. 

During the last decade, use of oxazaborolidines and dioxaborolidines in enantioselective catalysis has gained importance. [1, 2] One of the earliest examples of oxazaborolidines as an enantioselective catalyst in the reduction of ketones/ketoxime ethers to secondary alco-hols/amines was reported by Itsuno et al. [3] in which (5 )-valinol was used as a chiral ligand. Since then, a number of other oxazaborolidines and dioxaborolidines have been investigated as enantioselective catalysts in a number of organic transformations viz a) reduction of ketones to alcohols, b) addition of dialkyl zinc to aldehydes, c) asymmetric allylation of aldehydes, d) Diels-Alder cycloaddition reactions, e) Mukaiyama Michael type of aldol condensations, f) cyclopropana-tion reaction of olefins. 

The one-step transformation of 2- or 3-(l-hydroxyalkyl)-2,3-dihydrobenzofurans to 2- or 3-acylbenzofurans with A -bromosuccinimide was performed with good yields <97H(45)1657>. The asymmetric reduction of dihydrobenzofuran ketoxime ethers to enantiomerically enriched chiral hydroxylamines with reagents prepared from borane and norephedrine has been investigated <97TA497>. An enzymatic resolution of a 3-hydroxymethylbenzofuran using Candida rugosa lipase provides an enantioselective synthesis of vitamin E related antioxidants <97TA45>. 

Enantiomerically pure boranes have a long history in the reduction of prochiral ketones/ Amongst the early results using stoichiometric oxazaborolidines, the work of Itsuno is of particular interest. For example, acetophenone (3.32) could be reduced with the oxazaborohdines (3.113) or (3.114) where the ratio of amino alcohol to borane was 1 2, implying that one equivalent of oxazaborolidine and one equivalent of borane were present in the transition state. Itsuno also reported that the oxazaborohdine reagent (3.114) could be used catalytically in the reduction of prochiral ketoxime ethers. ... 

Scheme11.19 OAB-induced reduction of ketoxime ether derivatives.

An early approach to the formation of chiral amines by nonenzymatic asymmetric synthesis was the reduction of prochiral ketoximes and their O-tetrahydropyranyl and O-methyl derivatives with lithium aluminum hydride-3-0-benzyl-1,2-0,0-cyclohexylidene-a-D-glucofuranose complex (16)33 in ether and prochiral ketoximes... 

Enantioselective Reduction of Oxime 0-Ethers. In addition to the reduction of prochiral ketones, oxazaborolidine (3) has been used (both stoichiometrically and catalytically with borane-THF) to catalyze the enantioselective reduction of prochiral ketoxime O-ethers to the corresponding amine (eq Unlike the ketone reduction described above, the... 

Table 2 Enantioselective Reduction of Prochiral Ketoxime O-Ethers 1-...

Reduction using 0.25 mol equiv of the catalyst with excess borane-THF. Reduction using the catalyst derived from (5)-diphenyl-O-benzyltyrosenol. AICI3 added to the ketoxime O-ether prior to reduction. 

Enantioselective Reduction of Imines and Ketoxime O-Ethers. In addition to the reduction of prochiral ketones, chiral oxazaborolidines have been employed as enantioselective reagents and catalysts for the reduction of imines (eq 11) and ketoxime O-ethers (eq 12) - to give chiral amines. It is interesting to note that the enantioselectivity for the reduction of ketoxime O-ethers is opposite that of ketones and imines. For more information, see 2-Amino-3-methyl-l,l-diphenyl-I-butanol. 

Based on a comparative study for asymmetric reduction of oxime ethers of acetophenone and 2-hepitanone using different classes of OABs, such as la, 2a, and 6a, Cho and Ryu reported the 6a-induced borane reduction of ketoxime O-trimethylsilyl ethers in moderate to good enantioselectivities (Scheme 11.19) [83a, bj. Similarly, ben-zylic amine derivatives were obtained with high enantioselectivities by stoichiometric reduction of oxime ethers using ent-6a-BHj or la-BH (Scheme 11.20) [84-86],... 

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