Oximes stereoselective reduction

Another synthetic route via the Beckmann rearrangement, which is promoted by organoaluminum reagent along with alkylation, involves a new stereoselective reduction of the imino group. The starting oxime sulfonate (228) was synthesized from cyclopentanone (226) in three steps Reaction of 226 with 1-undecene in the presence of silver oxide produced the a-undecylcyclopentanone (227) which on successive treatment with hydroxylamine and methanesulfonyl chlo-ride-triethylamine gave the mesylate (228). Treatment of the oxime mesylate... 

A 7 -Hydroxycephalosporins.2 Reaction of the 7-oxocephem 1 with hydroxyl-amine gives a single oxime (2). Reduction of 2 with BH3-pyridine leads stereoselectively to the N7-hydroxycephalosporin 3. 

The stereoselective reduction of a tricyclodecyl oxime has been described 486) ... 

The second synthesis of lasubine II (6) by Narasaka et al. utilizes stereoselective reduction of a /3-hydroxy ketone O-benzyl oxime with lithium aluminum hydride, yielding the corresponding syn-/3-amino alcohol (Scheme 5) 17, 18). The 1,3-dithiane derivative 45 of 3,4-dimethoxybenzaldehyde was converted to 46 in 64% yield via alkylation with 2-bromo-l,l-dimethoxyethane followed by acid hydrolysis. Treatment of the aldol, obtained from condensation of 46 with the kinetic lithium enolate of 5-hexen-2-one, with O-benzylhydroxylamine hy-... 

The in situ generated catalyst from ATBH and trimethyl borate has also been used in the stereoselective reduction of a-oxoketoxime ethers to prepare the corresponding chiral 1,2-amino alcohols. Thus the asymmetric borane reduction of buta-2,3-dione monoxime ether followed by acidic work-up and subsequent reaction with benzyloxycarbonyl chloride affords a 90% yield of 7V-(Z)-3-aminobutan-2-ol with excellent enantioselectivities (eq 5). A trityl group in the oxime ether is required for high enantioselectivity. This method has been successively applied to both cyclic and acyclic a-oxoketoxime ethers. 

Although the metal-NHs reduction of unhindered cyclohexanones usually affords equatorial alcohols with greater stereoselectivity then metal hydride reductions, this method has not been used frequently in synthesis. An exception is the highly stereoselective reduction of ketoxime (19 equation 10), an intermediate in the synthesis of ( )-perhydrohistrionicotoxin, which gave an excellent yield of equatorial alcohol (20) on reduction with Na-NHs. This reduction is noteworthy in that the oxime survives the reduction, which was carried out below the boiling point of liquid NH3 for a relatively short period of time (30 min). ... 

The stereoselective, one-step synthesis of (l,4)-5-thiodisaccharides (7-2) is a classical example (Scheme 2) of exploiting the excellent functionality of levoglucosenone as Michael reaction acceptor. The methodology of functionalization of C-2 either via conventional and stereoselective reduction, or oximation and then stereoselective reduction of the oximino functionality is unique in providing both classes of 5-thio-disaccharides. Moreover, the C-2 amino functionalized nonhydrolyzable 5-thio-disaccharide, after deprotection of C-2 acetamido function represents a convenient molecular scaffold for the generation of diverse libraries of peptidomimetics as a selected class of glycoconjugates. 

The intermediate ketone addition product offers potential for the synthesis of precursors of certain amino sugars as reported by us earlier (/-5), through conventional oximation and highly stereoselective reduction of the oxime function at C-3 to the corresponding amino group. 

The stereoselective reduction of ex-hydroxy oxime ethers with borane allows the synthesis of civ-1,2-amino alcohols in 86% yield5. 

Next, Wood and Stolz [46] treated (+)-80 with NH2OH.HCI to produce corresponding oxime (-)-83 in 95% yield. In contrast to ketone (+)-80, bis-methylation of (-)-83 under phase transfer conditions (Mel, KOH, and n-Bu4NBr in THF) occurred cleanly to afford (-)-84 and set the stage for a stereoselective reduction (H2/Pt02) that furnished amine (+)-85a. Mono-methylation and deprotection then afforded (+)-staurosporine (1) in 67% yield (two steps. Scheme 11). 

Chiral tricyclic fused pyrrolidines 29a-c and piperidines 29d-g have been synthesized starting from L-serine, L-threonine, and L-cysteine taking advantage of the INOC strategy (Scheme 4) [19]. L-Serine (23 a) and L-threonine (23 b) were protected as stable oxazolidin-2-ones 24a and 24b, respectively. Analogously, L-cysteine 23 c was converted to thiazolidin-2-one 24 c. Subsequent N-allylation or homoallylation, DIBALH reduction, and oximation afforded the ene-oximes, 27a-g. Conversion of ene-oximes 27a-g to the desired key intermediates, nitrile oxides 28 a-g, provided the isoxazolines 29 a-g. While fused pyrrolidines 29a-c were formed in poor yield (due to dimerization of nitrile oxides) and with moderate stereoselectivity (as a mixture of cis (major) and trans (minor) isomers), corresponding piperidines 29d-g were formed in good yield and excellent stereoselectivity (as exclusively trans isomers, see Table 3). 

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. 

Electrochemical reduction of camphor-and norcamphoroxime at a Hg cathode proceeds with a high degree of stereoselectivity to give products of opposite stereochemistry to those formed in the dissolving metal (Na-alcohol) reduction of the oximes. The electrolyses are proposed to proceed by a kinetically controlled attack by the electrode on each oxime from the less hindered side (Fig. 62) [348]. In contrast, the corresponding N-phenyl imines yield products of the same stereochemistry as those isolated from a dissolving metal reduction. Cyclic voltammetry and polarographic data point to RH and intermediates in this case that are proto-nated from the least hindered side [349]. 

Reduction of chiral ketoximes results in formation of a new stereogenic center. Although mixtures of stereoisomers are generally obtained, kineticaUy controlled reduction of cyclic oximes (e.g. 86, equation 59 and 87, equation 60) with sodium cyanoborohydride can proceed with high diastereoselectivity Stereoselectivity in these reactions closely resembles that of reduction of ketones with complex hydrides featuring attack from the least hindered side. 

Opposite stereoselectivity in reduction of cyclic oximes (e.g. 88, equation 61) can be achieved with silane-trifluoroacetic acid . ... 

Stereoselectivity in reductions of acyclic oximes depends on the configuration of C=N bond. ( )-Isomer of oxime 89 produced syn-hydroxylamine 90 in excellent stereoselectivity in reaction with phenyldimethylsilane-trifluroacetic acid while giving anti-product in the reaction with lithium aluminium hydride. Stereoselectivity in reductions of (Z)-isomers of 89 was substantially lower in both cases (equation 62) . It can be assumed that the rules of stereoselectivity established in diastereoselective reduction of ketones can be applied to reduction of oximes as well. 

Oximes undergo hydrogenation to hydroxylamines and/or amines depending on reaction conditions. Platinum oxide is the most frequently used catalyst for selective hydrogenation of oximes to hydroxylamines. Reduction of chiral oxime 96 over palladium catalyst (equation 66) proceeds in high yield and stereoselectivity. High stereoselectivity was observed in catalytic hydrogenation of a-alkoxyoximes . 

A high degree of stereoselectivity was achieved in reductive radical cyclizations with Coordination of the oxime function (e.g. 108) with samarium cation seems to play an important role, since the identical reaction with a tributyltin hydride/radical initiator system produces poor stereoselectivity (equation 79). ... 

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. 

As described here, both enantiomers of 3 can be prepared In three steps from commercially available diethyl D- and L-tartrate in up to 70% over-all yield.2 3 5 Procedures to obtain the benzylidene acetal,11 12 with the ensuing reduction step,11. 2 are based on previous literature reports. Both enantiomers of 3 have been used in highly stereoselective nitroaldol additions.3 13 Imines, nitrones, oximes, and nitrile oxides derived therefrom were recently employed in a variety of additions/cycloadditions.14 15 (-)-2-0-Benzyl-L-glyceraldehyde has further been used... 

Stereoselectivity of Reductions of Cyclic Oximes and Oxime Derivatives... 

Entry 9 in Table 15 illustrates another synthetically useful stereocontrolled reduction of cyclic oxime ethers (isoxazolines) to alicyclic amino alcohols using LAH. The stereoselectivity obtained is further enhanced by the incorporation of a 4a-hydroxy group which, upon reduction, affords almost entirely the erythro isomer (equation High diastereoselectivity in the reductive cleavage of isoxazolines has... 

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