Diastereomeric oximes

Lanthanide shift reagents have been used to differentiate diastereomeric oximes, dinitrophenyl-hydrazones 304,305, and nitrones 306. A collision complex model to rationalize aromatic solvent induced shifts in the spectra of oximes and hydrazones has been developed305,307. 

Halpem [8] described the reaction of cyclic ketones containing an asymmetric carbon a to the carbonyl function with (- -)-2,2,2-trifluoro-l-phenylethylhydra-zine (47) (see Section 4.4.2 for structures of numbered reagents) to form diastereomeric hydrazones, which were resolved by GC. However, some racemization was noted and it was recommended that the reaction should not be considered for ketones containing a hydrogen a to the asymmetric carbon. The enantiomers of cyclic ketones have also been separated as diastereomeric oximes by Pappo [114] in this reaction the racemic ketone was treated with R-2-amino-oxy-4-methylvaleric acid (48) in methanol/pyridine (10 1) at room temperature for 18 h. The diastereomers were separated on silica... 

It is the same reaction as if it were a primary amine reacting with the ketone. But, instead of getting an imine, we get something that we call an oxime. Rememher to always look if the starting ketone is nnsynunetrical. If it is, we should expect to form two diastereomeric oximes ... 

The addition of allylboronates 1 to the chiral oxime 2 results in the formation of a hydroxyl-amine. This is a general method for the subsequent reductive generation of primary homoallyl-amines, but with poor diastereoselectivity in the case of 3 and 4. A diastereomeric ratio of 90 10 is achieved in the addition reaction, using the chiral allylboronate 59 (double stcrcodifferenti-ation). 

The addition of ( )-(3-trimcthylsilylallyl)boronate (10) to the racemic oxime 9 has been used in connection with a total synthesis of cannabisativine n. The results are congruent with the application of ( )-crotylboronatc as organometallic reagent9,, 0. The reaction is anti selective and generates the diastereomeric hydroxylamines 11 and 12, where 11 is converted to a tetrahydropyridine 13, a useful intermediate for the synthesis of cannabisativine11. 

After the formation of tautomeric anions A=A. the anion A a rearranges to give the anion B, which reacts with the second nitroso acetal molecule to form a mixture of stereoisomers of silyl derivative 509a. After desilylation of 509a, oxime 510a is isolated. The reaction with the fluoride anion proceeds at low temperature, whereas the use of triethylamine is efficient only at room temperature. The yield of oxime (510a) is virtually independent of the reaction conditions, whereas the diastereomeric ratio varies substantially. 

Dihydrooxadiazoles 106 have been syntheised in moderate to high diastereomeric excess by the addition of aromatic nitrile oxides across the C=N bond of the hydrazones 105. The N-N bond can subsequently be cleaved with formic acid, and the chiral auxiliary recycled <99H(50)995>. The oxadiazolone 108 was produced (56%) from the oxime 107 by heating it with phenyl isocyanate <99SC3889>. ... 

Diastereomeric thial 5-oxides have been investigated, including a mixture of ( )- and (Z)-propanethial 5-oxide (R = C2H5) which is the lacrimatory factor of onions. The Z-isomer is the major component308. The methods used for structural assignments of oximes and hydrazones286 have been used successfully for thial 5-oxides. 

Pyrazino[l,2-5]isoquinolin-5-ium 2-oxide perchlorate and its 3-methyl and 3-phenyl derivatives were obtained by cyclization of the appropriate 3-oximidomethyl-l-acylmethylisoquinolinium salt (or its oxime) through heating in an acidic medium (72JHC177). Swern oxidation of 2-acyl-3-hydroxymethyl-l,2,3,4-tetrahydroisoquinolines (298) proceeded smoothly to yield a diastereomeric mixture of l-hydroxy-l,3,4,6,ll,lla-hexahydro-2//-pyrazino[l, 2-5] isoquinolin-4-ones 136 (87TL4065). Heating (3-carboxy-... 

The diastereomeric ratio is high only for ( )-disubstituted alkenes and norbornene, but low for cyclic and (Z)-alkenes, reflecting the order of stability of the intermediate complexes. The loss of stereochemical purity is probably due to base-catalyzed nitroso-oxime tautomerization during the reduction. However, the use of diisobutylaluminum hydride, before adding lithium aluminum hydride, allows (3/ , 4S )-3,4-hexanediamine to be obtained from (Z)-3-hexene with d.r. [(3R, 4S )IQR AR )] 90 10. 

The photoaddition of an excess of 1-nitrosopiperidine to 3-methylcyclohexene is diastereo-selective and afforded exclusively rran. -2-methyl-6-(l-piperidinyl)cyclohexanone oxime (4) as a mixture of (E)- and (Z)-isomers. The reaction with Ar-nitrosodimethylamine was less efficient and also produced a small amount (2%) of the (E)-trans-regioisomer the major product was separated and reduced to the corresponding 1,2-diamines 5 with slightly different diastereo-selectivity32. The relative ratio of diastereomeric diamines and the relative stereochemistry of the three substituents in the predominant diamine diastereomer were established by HNMR of the. V-acetyl derivative, while those of the minor diastereomer were proposed from mechanistic considerations. The photoaddition of A -nitrosodimethylamine with 4-fer/-butylcyclohex-ene, however, afforded a mixture of diastereomers and regioisomers21,32. 

Cyclization of the oxime 1, performed with iodine in dichloromethane, gave the nitrone 2 in quantitative yield as a diastereomeric mixture174. 

Chiral nitrones 59 prepared from unprotected D-glucopyranosyl oxime underwent 1,3-dipolar cycloadditions with A-arylmaleimides to give the anfi-isoxazolidinones 60 as the major isomers [49]. The iyn-diastereomers 61 were formed with a diastereomeric excess of more than 90% only when the Ar group was a 2,6-disubstituted arene (Scheme 10.20). The hydrogen bond between the... 

Nicotra et al. observed that 144 or 145, obtained by mercury-induced cycli-zation of 142 and 143, could not be converted to the desired iodo compound 146. The workers had to resort to introducing the 2-deoxynitrogen substituent after the phosphonate had been introduced as shown in Scheme 30. The ketone was converted to an oxime and with diborane gave the gluco isomer 149 in 64% diastereomeric excess [41]. 

In a related study, Heathcock reported that ketone 42 reacted with hydroxylamine hydrochloride under similar conditions to produce 44 (87JOC226). The intermediate oxime 43 that was first formed could be isolated under milder conditions. Whereas heating oxime 43 at reflux in acetonitrile for 30 h gave 44 in 92% yield, heating 43 in DMF formed a 1 1-mixture of the diastereomeric cycloadducts 44 and 45. 

The addition of ( )--y-(trimethylsilyl)allylboronate (93) to racemic oxime (92) has been utilized by Wuts and Jung in connection with a total synthesis of cannabisativine (Scheme 7). Paralleling the investigations of Hoffmann and Endesfelder using ( )-crotylboronate (87 see equation 20), the reaction of (93) is anti selective and affords diastereomeric hydroxylamines (94) and (95). The diastereofacial se-... 

Synthesisfromo-glyceraldehyde D-Glyceraldehyde acetonide (17) has been used for the synthesis of a protected nectrisine 23 (Scheme 4). Compound 17 was converted into 3,3-diethoxy-2-hydroxypropanal (18), which underwent transketolase-mediated condensation with hydroxypyruvate 19 to afford the triol 20 in 56% yield. Silylation of 20 using TBSOTf and NEts (74%) followed by treatment with hydroxylamine gave the oxime 21 in 82% yield. Reduction of 21 using Raney nickel afforded the diastereomeric mixture of... 

The readily available 2,3,4,6-fefra-O-benzyl-D-glucopyranose (11) can be used for the synthesis of both nojirimycin (1) and 1-deoxynojirimycin (2) (Schemed).It was treated with EtSH to furnish 12, which was oxidized to the corresponding ketone 13 using TPAP, while the Swern oxidation method failed to produce 13. Treatment of 13 with mercury(ll) salts in the presence of methanol followed by treatment with hydroxylamine hydrochloride in the presence of pyridine afforded the oxime 14 in 73% yield. Treatment of 14 with LiAlH4 in diethyl ether followed by N-protection of the resulting diastereomeric mixture of amines with di-rert-butyl dicarbonate furnished 15 and 16 in 65 and 15% yield, respectively. Pearlman s catalytic hydrogenation of 15 over palladium hydroxide in ethanol followed by treatment of the resulting tetrol with SO2 in water furnished the sulfonic acid 17 in 80% yield. Conversion of 17 into 1 was accomplished by treatment with Dowex 1X2 (OH ) resin. 

See Chapter 2 for a discussion of anti- and synperiplanar requirements in E2 elimination reactions.) In each diastereomeric diazonium ion in the example, the bond that is antiperiplanar to the C—N2 bond migrates selectively. (Draw a Newman projection or make a model if you have trouble seeing this.) The same phenomenon is observed in the Beckmann rearrangement, in which an oxime is converted into an amide after a 1,2-alkyl shift and addition of H2O. The group that is trans to the OH group (i.e., antiperiplanar) shifts selectively. 

---