Racemization column chromatography

Three general methods exist for the resolution of enantiomers by Hquid chromatography (qv) (47,48). Conversion of the enantiomers to diastereomers and subsequent column chromatography on an achiral stationary phase with an achiral eluant represents a classical method of resolution (49). Diastereomeric derivatization is problematic in that conversion back to the desired enantiomers can result in partial racemization. For example, (lR,23, 5R)-menthol (R)-mandelate (31) is readily separated from its diastereomer but ester hydrolysis under numerous reaction conditions produces (R)-(-)-mandehc acid (32) which is contaminated with (3)-(+)-mandehc acid (33). 

A solution of racemic 3-(2-ethylhexyIoxy)phthaIonitriIe (5 2 g, 7.8 mmol) in 2-(dimcthylainino)cthanol was heated with NiCl2 (0.26 g, 2 mmol) for 24 h at 140 C. The solvent was distilled off under vacuum and the product was purified several times by column chromatography (silica gel, toluene/hexane 7 3). A dark-blue solid was obtained yield 0.22 g (10%). 

All the y-sultines were obtained as diastereomeric mixtures (ca 1 1, by NMR), and each one of y-sultines ( + )-49 and ( + )-51 (R = t-Bu) was separated into two diastereomers A and B by column chromatography. The oxidation of y-sultines (— )-49A and (+ )-49B to the corresponding optically active sultones (+ )-52A,B, which lack a chiral sulfur, may be taken as proof that the observed optical activity in the sultines is also due to the y-carbon. This result seems to exclude the intermediacy of vinylsulfene in the reaction mechanism, since its disrotatory closure would lead to racemic y-carbon in the product. 

Fig. 4a. Resolution of racemic (67) by column chromatography on microcrystalline cellulose triacetate (column B) and by recrystallization 35) C = crystals M = mother liquor the index following C or M gives the number of recrystallizations the fraction has undergone. The value of [ot] ° is given, followed by the quantity obtained...

On the other hand, telluronium imides 13 were isolated for the first time in 2002 by optical resolution of their racemic samples on an optically active column by medium-pressure column chromatography.27 The relationship between the absolute configurations and the chiroptical properties was clarified on the basis of their specific rotations and circular dichroism spectra. The racemization mechanism of the optically active telluronium imides, which involved the formation of corresponding telluroxides by hydrolysis of the telluronium imides, was proposed (Scheme 6). 

Resolution of a racemic mixture is still a valuable method involving fractional crystallization [113], chiral stationary phase column chromatography [114] and kinetic resolutions. Katsuki and co-workers demonstrated the kinetic resolution of racemic allenes by way of enantiomer-differentiating catalytic oxidation (Scheme 4.73) [115]. Treatment of racemic allenes 283 with 1 equiv. of PhIO and 2 mol% of a chiral (sale-n)manganese(III) complex 284 in the presence of 4-phenylpyridine N-oxide resulted... 

A. ( )-1-(Dimethylphenylsilyl)-1-buten-3-ol (2a). A solution of 10.0 g (0.143 mol) of racemic 3-butyn-2-ol (Note 1) dissolved in 255 mL of tetrahydrofuran (THF, Note 2) in a 1-L, round-bottomed flask equipped with a reflux condenser and nitrogen atmosphere is prepared. Dimethylphenylsilane (21.4 g, 0.157 mol) (Note 3) and a small piece of sodium metal (ca. 5 mg) (Note 4) are placed in the reaction mixture. The solution is stirred for 15 min and 12 mg (2.05 x 10 5 mol) of bis(q-divinyltetramethyldisiloxane)tri-tert-butylphosphineplatinum(O) (Note 5) is added. The reaction mixture is then heated under reflux for 12 hr. The orange solution is cooled to ambient temperature, and the solvent is removed under reduced pressure to yield a crude orange residue containing 2a. The oil is subjected to column chromatography on silica gel (Note 6) (gradient elution 5, 10, 20, 35% EtOAc/hexanes) providing 25.4 g (123.23 mmol, 86%) of pure 2a as a yellow oil (Note 7). 

A lOOmL three-necked, round-bottomed flask equipped with magnetic stirrer was charged with racemic 1,2-diphenylethylenediamine (1.02 g, 4.8 mmol), triethy-lamine (2mL, 14.3 mmol) and dry tetrahydrofuran (10 mL) followed by dropwise addition of p-toluenesulfonyl chloride (0.91 g, 4.8 mmol) dissolved in 10 mL of dry tetrahydrofuran. The reaction mixture was stirred at ambient temperature for 12 h and a white salt was obtained. The salt was filtered and washed with ether. The combined filtrate was concentrated and purified by flash column chromatography (eluent petroleum ether/ethyl acetate = 1/1) to give 7/-p-toluenesulfony 1-1,2-diphenyl-1,2-ethylenediamine (1.02g, 58.0% yield ). 

The structure of A1(acac)3 contains an octahedral A106 core, with At—O distance of 189.2 pm. Differences of the monoclinic a form and orthohombic y form (a racemate) lie chiefly in the orientations of molecules within the crystal bond distances are almost identical.181 Resolution of the optical isomers of Al(acac)3 has twice been achieved by column chromatography at low temperature.182183 The hexafluoro compound, Al[(OCCF3)2CH]3, m.p. 74 °C, is more volatile than Al(acac)3. Its structure, determined by vapour phase ED,184 reveals a slightly distorted A106 unit in which the A1—O distance of 189.3 pm is the same as that in Al(acac)3. Comparative studies have been made of the Raman spectra of M(acac)3 (M= Al, Ga or In)185 and of other j8-diketonates of these metals.186... 

This type of disconnection is mainly used for the preparation of dipeptides of type Xaai >[ , CH=CH]Gly. It allows control of the stereochemistry of the Xaa residue by starting from chiral a-amino aldehydes. For the construction of the /ram -p,y-unsaturated carboxylic acid moiety, the use of the triphenylphosphonium salt 31 (Scheme 9) derived from 3-chloro-propanoic acid was not suitable.14 Instead, the trimethylsilylprop-2-ynyl phosphonium salt 33 serves as a three-carbon unit, which can be converted into the P,y-unsaturated acid by hydroboration and oxidation. The required Boc-protected a-amino aldehyde 32 can be prepared using virtually racemization-free procedures. 37 However, at the end of the reaction sequence, racemization has been detected, especially for Boc-Phet )[ , CH=CH]Gly-OH, but not for the Ala and Pro analogues. 63 A mixture of E- and Z-enynes 34 and 35 is formed (8 2 to 9 1), which can be separated by column chromatography. 4,48 50 53 64 65 ... 

Scheme 15)62. After terminating the reaction at a conversion of 38% (relative to total amount of substrate rac-78), the product (S)-43 was separated from the nonreacted substrate by column chromatography on silica gel and isolated on a preparative scale in 71% yield (relative to total amount of converted rac-78) with an enantiomeric purity of 95% ee. Recrystallization led to an improvement of the enantiomeric purity by up to >98% ee. The biotransformation product (S)-43 is the antipode of compound (/ )-43 which was obtained by enantioselective microbial reduction of the acylsilane 42 (see Scheme 8)53. The nonreacted substrate (/ )-78 was isolated in 81% yield (relative to total amount of nonconverted rac-78) with an enantiomeric purity of 57% ee. For further enantioselective enzymatic hydrolyses of racemic organosilicon esters, with the carbon atom as the center of chirality, see References 63 and 64. 

Enantioselective enzymatic ester hydrolyses have also been used for the preparation of optically active silicon compounds with the silicon atom as the center of chirality. An example of this is the kinetic resolution of the racemic 2-acetoxy-l-silacyclohexane rac-(SiR,CR/SiS,CS)-79 with porcine liver esterase (PLE E.C. 3.1.1.1) (Scheme 16)65. Under preparative conditions, the optically active l-silacyclohexan-2-ol (SiS,CS)-80 was obtained as an almost enantiomerically pure product (enantiomeric purity >96% ee) in ca 60% yield [relative to (SiS,CS )-79 in the racemic substrate]. The biotransformation product could be easily separated from the nonhydrolyzed substrate by column chromatography on silica gel. 

---