Asymmetric transformation of ketoxime

Products from the asymmetric transformation of ketoximes to chiral amides via the DKR of amines. 

The DKR processes for secondary alcohols and primary amines can be slightly modified for applications in the asymmetric transformations of ketones, enol esters, and ketoximes. The key point here is that racemization catalysts used in the DKR can also catalyze the hydrogenation of ketones, enol esters, and ketoximes. Thus, the DKR procedures need a reducing agent as additional additive to enable asymmetric transformations. 

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>. 

With the help of a bifiinctional thiourea catalyst 55, Mukherjee and coworkers contemporaneously developed a related catalytic asymmetric iodoetherification of oximes (Scheme 2.31). A variety of p.y-unsaturated ketoximes were cyclized using commercially available A-iodosuccinimide (NIS) as the iodine source and iodine as the cocatalyst to furnish A -isoxazolines containing a quaternary stereogenic center in high yields and good to excellent enantioselectivities [47]. Besides, the oxime iodoetherification products could be subjected to a number of synthetically useful transformations to produce other important organic compounds. 

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