Oximes asymmetric

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

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

Catalytic asymmetric hydrogenation is a relatively developed process compared to other asymmetric processes practised today. Efforts in this direction have already been made. The first report in this respect is the use of Pd on natural silk for hydrogenating oximes and oxazolones with optical yields of about 36%. Izumi and Sachtler have shown that a Ni catalyst modified with (i ,.R)-tartaric acid can be used for the hydrogenation of methylacetoacetate to methyl-3-hydroxybutyrate. The group of Orito in Japan (1979) and Blaser and co-workers at Ciba-Geigy (1988) have reported the use of a cinchona alkaloid modified Pt/AlaO.i catalyst for the enantioselective hydrogenation of a-keto-esters such as methylpyruvate and ethylpyruvate to optically active (/f)-methylacetate and (7 )-ethylacetate. 

Hanessian reported the synthesis of enantiomerically pure or highly enriched allylglycine and its chain-substituted analogs from the reaction of the sultam derivatives of O-benzyl glyoxylic acid oxime with ally he bromides in the presence of zinc powder in aqueous ammonium chloride (Eq. 11.41).72 Brown noticed the critical importance of water in the asymmetric allylboration of /V-trimethylsilyIbcnzaldimines with B-allyldiisopinocampheylborane.73 The reaction required one equivalent of water to proceed (Eq. 11.42). 

I.2. Oxidation of Amines Oxidation of primary amines is often viewed as a particularly convenient way to prepare hydroxylamines. However, their direct oxidation usually leads to complex mixtures containing nitroso and nitro compounds and oximes. However, oxidation to nitrones can be performed after their conversion into secondary amines or imines. Sometimes, oxidation of secondary amines rather than direct imine oxidation seems to provide a more useful and convenient way of producing nitrones. In many cases, imines are first reduced to secondary amines which are then treated with oxidants (26). This approach is used as a basis for a one-pot synthesis of asymmetrical acyclic nitrones starting from aromatic aldehydes (Scheme 2.5) (27a) and 3,4-dihydroisoquinoline-2-oxides (27b). 

Asymmetric catalytic reduction reactions represent one of the most efficient and convenient methods to prepare a wide range of enantiomerically pure compounds (i.e. a-amino acids can be prepared from a-enamides, alcohols from ketones and amines from oximes or imines). The chirality transfer can be accomplished by different types of chiral catalysts metallic catalysts are very efficient for the hydrogenation of olefins, some ketones and oximes, while nonmetallic catalysts provide a complementary method for ketone and oxime hydrogenation. 

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. 

The 36d-LAH complex was applied to the reduction of ketone oximes and their O-tetrahydropyranyl and O-methyl derivatives to optically active amines (69). Results for a variety of phenyl alkyl and dialkyl ketones are shown in Table 4. The predominant amines formed all were of the S absolute configuration with optical purities up to 56%. The oxime hydroxy group presumably reacts with the less hindered H2 in the 36d-LAH complex (cf. Scheme 6) to form an oxime complex (45), which probably undergoes infermolecular hydride transfert of H2 from a second molecule of the 36d-LAH complex (Scheme 8). Asymmetric reduction with the ethanol-modified 36d-LAH reagent gave amines of R con-... 

The asymmetric reduction of C=N double bonds in prochiral oximes afforded a maximum of 18% ee [380, 384, 385]. Prochiral azomethines were reduced to the corresponding 1,2-diamines and secondary amines using 36 optically active supporting electrolytes. The dimers were optically inactive, while the monomers showed low optical inductions (<11% ee). The effect of electrolyte, substrate concentration, temperature, pH, and cathode potential on the induction was studied. It was proposed that the enantioselectivity... 

A further example of the use of a chiral anion in conjunction with a chiral amine was recently reported by Melchiorre and co-workers who described the asymmetric alkylation of indoles with a,P-unsaturated ketones (Scheme 65) [212]. The quinine derived amine salt of phenyl glycine (159) (10-20 mol%) provided the best platform with which to perform these reactions. Addition of a series of indole derivatives to a range of a,P-unsaturated ketones provided access to the adducts with excellent efficiency (56-99% yield 70-96% ee). The substrates adopted within these reactions is particularly noteworthy. For example, use of aryl ketones (R = Ph), significantly widens the scope of substrates accessible to iminium ion activation. Expansion of the scope of nucleophiles to thiols [213] and oximes [214] with similar high levels of selectivity suggests further discoveries will be made. 

Carbon chemical shifts were employed in studies of conformational effects on aldoximes and ketoximes. They appear in the region 145 to 163 ppm and several values are illustrated in Table 2. Such resonances are some 50 ppm to higher field relative to the corresponding carbonyl resonance. Where substimtion is asymmetrical, differences in oxime carbon chemical shifts are observed, depending upon the conformation of the oxime N—OH. Such conformational isomerism also has a profound effect upon the chemical shift of the a-carbon. 

Scheme 6.138 Product range of the 121-catalyzed asymmetric (3-hydroxylating Michael addition of oximes to aliphatic nitroalkenes. The product configurations were not determined.

The asymmetric reduction of oximes of 2-trifluoroacetyl furan, by using diborane with a chiral amino alcohol, has also allowed synthesis of both enantiomers of trifluoroalanines in an elegant manner. The key step in this synthesis is the separation of the (Z) and ( ) isomers of the oximes (Figure 5.4). ... 

Optically active aldehydes are available in abundance from amino and hydroxy acids or from carbohydrates, thereby providing a great variety of optically active nitrile oxides via the corresponding oximes. Unfortunately, sufficient 1,4- or 1,3-asymmetric induction in cycloaddition to 1-alkenes or 1,2-disubstituted alkenes has still not been achieved. This represents an interesting problem that will surely be tackled in the years to come. On the other hand, cycloadditions with achiral olefins lead to 1 1 mixtures of diastereoisomers, that on separation furnish pure enantiomers with two or more stereocenters. This process is, of course, related to the separation of racemic mixtures, also leading to both enantiomers with 50% maximum yield for each. There has been a number of applications of this principle in synthesis. Chiral nitrile oxides are stereochemicaUy neutral, and consequently 1,2-induction from achiral alkenes can fully be exploited (see Table 6.10). 

An alternative and elegant approach to bicyclo[3.3.0]isoxazolidines from alkenyl oximes was developed by Grigg (205) and applied in asymmetric reactions by Hassner et al. (206-209) and others (210). The optically active L-serine derived oxime 130 was proposed to be in a thermal tautomeric equilibrium with the nitrone tautomer 131, which underwent an intramolecular 1,3-dipolar cycloaddition to form the product 132 in 80% yield as a single stereoisomer (Scheme 12.44) (209). 

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. 

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