Catalytic epimerization

A related palladium(O)-catalyzed epimerization of y-aziridinyl-a,P-enoates 244 was also reported by Ibuka, Ohno, Fujii, and coworkers (Scheme 2.60) [43]. Treatment of either isomer of 244 with a catalytic amount of Pd(PPh3)4 in THF yielded an equilibrated mixture in which the isomer 246 with the desired configuration predominated (246 other isomers = 85 15 to 94 6). In most cases the isomer 246 could be easily separated from the diastereomeric mixture by a simple recrystallization, and the organocopper-mediated ring-opening reaction of 246 directly afforded L,L-type (E)-alkene dipeptide isosteres 243. 

Epimerization of 50 at C-3 furnished carba-a-DL-allopyranose (60). Stepwise, 0-isopropylidenation of 50 with 2,2-dimethoxypropane afforded compound 56. Ruthenium tetraoxide oxidation of 56 gave the 3-oxo derivative 57, and catalytic hydrogenation over Raney nickel converted 57 into the 3-epimer 58 exclusively. Hydrolysis of 58, and acetylation, provided the pentaacetate 59, which was converted into 60 on hydrolysis. ... 

Formal isomerization of the double bond of testosterone to the 1-position and methylation at the 2-position provides yet another anabolic/androgenic agent. Mannich condensation of the fully saturated androstane derivative 93 with formaldehyde and di-methylamine gives aminoketone 94. A/B-trans steroids normally enolize preferentially toward the 2-position, explaining the regiospecificity of this reaction. Catalytic reduction at elevated temperature affords the 2a-methyl isomer 95. It is not at all unlikely that the reaction proceeds via the 2-methylene intermediate. The observed stereochemistry is no doubt attributable to the fact that the product represents the more stable equatorial isomer. The initial product would be expected to be the p-isomer but this would experience a severe 1,3-diaxial non-bonded interaction and epimerize via the enol. Bromination of the ketone proceeds largely at the tertiary carbon adjacent to the carbonyl (96). Dehydrohalogenation... 

For example, 10% Pd/C in CH2Cl2 with catalytic amounts of p-TsOH was used for 56 hours to reduce benzyl alcohol.47 Likewise, the catalytic hydrogenolysis of an epimeric mixture of another benzyl alcohol was performed in dry ethanol using 10% Pd/C and two drops of HC104 for 3 hours at room temperature and atmospheric pressure.48... 

During the asymmetric synthesis of a-aminophosphonates (14 in Fig. 4.4), numerous attempts to cleave the benzylic C—N bond, involving catalytic or transfer hydrogenolysis, resulted in epimerization at the a-carbon.319... 

Tetrahydropyrido[2,1 -HI 1,4 oxazinc-7,9-dicarboxylate 278 was obtained from the 1,8-dihydro derivative 277 by hydrogenation over a Pd/C catalyst (Equation 51) <1997CAP2188071 >. Catalytic hydrogenation of an epimeric mixture of (4.S, 9a.S )-l -trimcthylsilyloxy-4-phenyl-3,4,6,7-tetrahydro-l//-pyrido[2,1 -HIl,4]oxazine over Raney-Ni afforded perhydro derivatives <2000SC2565>. 

The kinetic resolution using a chiral zirconocene-imido complex 286 took place with high enantioselectivity to result in chiral allenes 287 (up to 98% ee) (Scheme 4.74) [116]. However, a potential drawback of these methods is irreversible consumption of half of the allene even if complete recovery of the desired enantiomer is possible. Dynamic kinetic resolutions avoid this disadvantage in the enantiomer-differentiating reactions. Node et al. transformed a di-(-)-L-menthyl ester of racemic allene-l,3-dicarboxylate [(S)- and (RJ-288] to the corresponding chiral allene dicarbox-ylate (R)-288 by an epimerization-crystallization method with the assistance of a catalytic amount of Et3N (Scheme 4.75) [117]. 

Based on nucleophilic addition, racemic allenyl sulfones were partially resolved by reaction with a deficiency of optically active primary or secondary amines [243]. The reversible nucleophilic addition of tertiary amines or phosphanes to acceptor-substituted allenes can lead to the inversion of the configuration of chiral allenes. For example, an optically active diester 177 with achiral groups R can undergo a racemization (Scheme 7.29). A 4 5 mixture of (M)- and (P)-177 with R = (-)-l-menthyl, obtained through synthesis of the allene from dimenthyl 1,3-acetonedicar-boxylate (cf. Scheme 7.18) [159], furnishes (M)-177 in high diastereomeric purity in 90% yield after repeated crystallization from pentane in the presence of catalytic amounts of triethylamine [158], Another example of a highly elegant epimerization of an optically active allene based on reversible nucleophilic addition was published by Marshall and Liao, who were successful in the transformation 179 — 180 [35], Recently, Lu et al. published a very informative review on the reactions of electron-deficient allenes under phosphane catalysis [244]. 

Interesting information about the catalytic systems was obtained by studying the stereochemistry of the reaction of the catalyst precursor 1 with methacrylonitrile. The water molecule of complex 1 is readUy displaced by methacrylonitrile rendering complex [(t -C5Me5)Ir (/ )-Prophos (methacrylonitrile)] (SbFg)2 (9) as a mixture of the two possible epimers at metal, namely, R iJic and 5ir,/ c, in 34% diastereomeric excess in the former (Scheme 20). In acetone, at 50°C, the R r,Rc isomer slowly epimerizes to the thermodynamically preferred epimer. From the solution, pure samples of the latter can be isolated that have been employed as stoichiometric catalysts for the DCR between methacrylonitrile and nitrones IV and V. 

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