Binaphthol chromatography

It has been reported that Horeau s method can be applied to micromolar quantities of secondary alcohols, if the enantiomeric composition of the remaining 2-phenylbutanoic anhydride is determined by means of gas chromatography. To the acylation mixture an optically active amine [(+)-(R)-l-phenylethanamine] is added which reacts rapidly with the excess of 2-phenylbutanoic anhydride. The resulting diastereomeric amides are then characterized by GLC. The amine salts of 2-phenylbutanoic acid do not interfere. Success is dependent upon rapid amide formation (without significant resolution of the anhydride by the amine)236. The application of this method to (+)-(A/)-binaphthol (9) is shown237. 

In contrast, the phosphoramidites comprising (R) -binaphthol or (S) -binaphthol moieties (1) are obtained as a diastereomeric mixture and can be separated. The separation of the diastereomers has been achieved for many derivatives exploiting the different solubility profiles of the two diastereomers. Alternatively, the separation could be accomplished by column chromatography. These methodologies need to be optimized for each diastereomeric pair, thus representing currently the synthetic bottleneck for the rapid generation of different QUINAPHOS derivatives. 

Lienne et al. [170] resolved the enantiomers of albendazole sulfoxides on a column derived from the 6S )-/V-(3,5-dinitrobcnzoyl)tyrosinc chiral selector. The developed method was applied for the enantiomeric resolution of albendazole sulfoxides in plasma samples. Witherow et al. [171] immersed a commercially available thin-layer plate (thin-layer chromatography) into a solution of N-(3,5-dinitrobenzoyl)-L-leucine solution. The developed plate was used for the chiral resolution of 2,2,2-trifluoro-(9-anthryl)ethanol and l,l -binaphthol enantiomers. 

In this section, the application of equilibrium theory is illustrated for a fairly complex multireaction system. The problem to be considered is that of the separation of binaphthol enantiomers through using achiral chromatography. This problem was studied by Baciocchi et al. [1] among others, who in particular made the following experimental observations. When a pulse with a racemic composition of enantiomers was injected on to the column, no separation occurred. However in all cases... 

R. Baciocchi, G. Zenoni, M. Mazzotti, et al., Separation of binaphthol enantiomers through achiral chromatography. J. Chromatogr. 

Racemic mixture and meso form, 19 separation of meso form racemate by chromatography, 223 irradiation converts the meso form to the racemate (R)-W enantiomer does not form a 19 complex with (5)-binaphthol,... 

Purify the residue by flash chromatography on silica, eluting first with diethyl ether [110 mL to separate (S)-binaphthol 53] then diethyl ether THF (1 1) to yield (/ )-4-(5,5-dimethyl-2-oxo-2x5-[1,3,2]dioxaphosphinan-2-yl)-2,2,5,5-tetramethyl-3-thiazolidine, 57 (87 mg, 99%, 99% e.e.), as a solid. 

The in situ prepared trialkoxy(chloro)titanium complex is dissolved in CH2C1, (ca. 5 mL per mmol). At -30CC ca. 0.8 equiv of methyl acrylate (5), and after 30 min at the same temperature ca. 2 3 equiv of cyclopcntadiene, are added dropwise. The mixture is kept overnight (ca. 15 h) at - 30 =C, then hydrolyzed with ca. 20 niL of 2 N HC1 and extracted with Ft20. When (R)-binaphthol (7) is used it is extracted with 2 N NaOH. In the case of the 1.3-dioxolanc derivatives it is precipitated by the addition of pentane to the crude reaction mixture, then filtered off. The crude product is purified by flash chromatography. For determination of the oplical rotation a sample is purified by Kugclrohr distillation (130 fC/l 5 Torr). When (3 )-binaphthol (7) is used the adduct is obtained in 77% yield with 50% cc of the (-)-(f )-enantiomer. With the (R.R)-diol 8 derived from tartrate, the (-)-(S)-adduct is predominant (55% yield) with 46% ee. 

To ensure high enantiomeric purity of the product there should be <0.5% 1,1 -bi-2-naphthol or its monoester in this solution. The relative amounts of binaphthol species can be accurately determined by HPLC on a reverse-phase column eluted with a water-acetonitrile gradient (50-100% over 10 min). Both 1,1 -bi-2-naphthol and its dipentanoate have equal (within 2%) extinction coefficients at 254 nm. The monopentanoate absorbs more strongly the relative extinction coefficient at 254 nm is 1.13. Alternatively, the solution composition can be estimated using thin layer chromatography silica gel eluted with 1 4 ethyl acetate/cyclohexane 1,T-bi-2-naphthol, Rf 0.39 monopentanoate, Rf 0.56 dipentanoate, Rf 0.71. 

The binaphthol host 10b was found to be very effective for enantiomeric separation of some sulfoxides. When a solution of 10b and two molar equivalents of rac-me-thyl m-methylphenyl sulfoxide (85c) in benzene-hexane was kept at room temperature for 12 h, a 1 1 complex of 10b and (-i-)-85c was obtained, after one recrystallization from benzene, as colorless prisms in 77% yield. Chromatography of the complex on sihca gel gave (-i-)-85c of 100% ee in 77% yield [32]. By the same procedure, rac-85d was separated by 10b to give (-i-)-85d of 100% ee in good yield. However, rac-85a was poorly separated with 10b, giving approximately 5% ee enantiomer, while 85b and 85e did not form complexes with 10b. In order to establish why the chirality of the m-substituted derivatives 85c and 85d is so precisely recognized by 10b, the crystal structure of the complex of 10b and (-i-)-85c was studied by X-ray analysis [33]. 

The well known chiral carbon skeleton designated as binaphthyl hinge has been introduced into asymmetric synthesis and resolution of racemates in the form of the derivatives of 2,2 -dihydroxy-l,r-binaphthyl (84, binaphthol). The application of chiral crown compounds containing this binaphthyl tmit for the separation of amino acids and amino acid esters by use of liquid/liquid chromatography has been described particularly by Cram et al. in detail... 

To a stirred ice-cooled solution of (5)-binaphthol (4, 1.43 g, 5 mmol) in benzene (100 ml) and pyridine (10 ml) was slowly added a slightly excess amount of l-bromo-2-naphthoic chloride (659, 3.23 g, 12 mmol). The reaction mixture was diluted with benzene (50 ml), and then 2 M HCl (50 ml) was added. The aqueous layer was extracted with benzene (3><30 ml). The combined organic phases were washed successively with 2 M aqueous hydrochloric acid, 1 M sodium sulfite, and water, then dried over Na2S04 in the presence of activated charcoal. The filtrate was evaporated under a reduced pressure, and the crude diester 551 was purified by column chromatography, m.p. 180-182 °C, [a]o +34.7° (c = 0.922, acetone) [13]. 

The resolution of the enantiomers of bridged bis(indenyl) metallocene dichlorides has been accomplished by the replacement of both halides by one enantiomer of binaphthol, followed by chromatography (179). Direct synthesis of enantiomer-ically pure precursors via chiral epoxides has been reported (180). Polymerization of a-olefins using such precursors does not lead to the production of appreciably chiral pol5mier due to the de facto mirror plane which exists in an isotactic poly(a -olefin) of reasonably high degree of polymerization (Fig. 10). 

Lepri et al. investigated the chromatographic behavior of racemic dinitropyridyl, dinitrophenyl, dinitrobenzoyl, 9-fluorenylmethoxycarbonyl amino acids, tryptophanamides, lactic acid derivatives, and unusual enantiomers such as binaphthols on reversed phase TLC plates developed with aqueous-organic mobile phase containing bovine serum albumin (BSA) as chiral agent. More than 75 racemates has been separated in these experiments with planar chromatography using BSA in mobile phase. BSA showed enantioselectivity towards racemates with structures completely different from amino acids, their derivatives, and similar compounds such as hydroxy acids. 

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