Resolution, OF 1,1 -BI-2-NAPHTHOL

Kinetic resolution of 1,1 -bi-2-naphthol with a crude extract containing cholesterol... 

Best results were obtained with noncommercial AC-40 + CMC plates and, in particular, on layers of microcrystalline cellulose triacetate (MCTA Fluka, Switzerland) + CMC for all the investigated racemates with the exception of 1,1 -bi-2-naphthol, l-(l-naphthyl)ethanol, and flurbiprofen. The addition of silica gel GF254 to plates prepared with MCTA and the use of aqueous organic eluents, containing high percentages of water, also yielded the resolution of ( )-flurbiprofen (see Table 4.2). 

R)-1,1 -Bi-2-naphthol was prepared by resolution employing the N-benzylammonium chloride salt of (-)-cinchonidine to form separable diastereomeric clathrate complexes. Hu, Q-S. Vitharama, D. Pu, L. Tetrahedron Asymmetry 1995, 6, 2123. 

R = (R)-1,1-bi-2-naphthol Scheme 1233 Kinetic resolution of racemic nucleophiles [56]. 

The ready accessibility of Cu(II) Cu(I) - Cu(0) redox pathways together with the high insolubility of many copper(I) compounds causes simple copper(II) salts to be potent oxidants under appropriate conditions. One practical outcome is that copper(II) salts show facile C-H activation behaviour towards aromatic alcohols. Of particular interest is the ready formation of ( )-l,l -bi-2-naphthol 36 from 2-naphthol (Scheme 1.10)/ as enantiomerically enriched 36 is a popular ligand for many asymmetric transformations. The mechanism of this reaction is believed to involve oxidation of intermediate [L Cu2(OCioH7)2] complexes by internal and/or external redox processes. A number of attempts have been made to carry out this reaction in an asymmetric fashion, with varying degrees of success. " Nevertheless, the racemic version has its merits as a number of effective low cost resolutions of 36 have appeared. - ... 

When optically inactive polystyrene was used as adsorbent, no difference in the relative peak intensity at m/z 288 to 286 was detected. Moreover, in the resolution of (RS)-1,1 -bi-2-naphthol and (if5)-l,l,-bi-2-naphthol-rf2 on the CSP, no isotope effect was observed. These findings indicate that the difference in EI-MS spectra is due to the difference in desorption between the enantiomers from the chiral adsorbent tris(5-f uoro-2-methylphenylcarbamate). This method can be used to discriminate the chirality of other enantiomers of small molecules if they show peaks in their EI-MS spectra in the presence of chiral polymers. Similar chiral recognition was detected by negative ion fast-atom bombardment mass spectrometry [34],... 

Ohkubo and coworkers studied the photooxidative racemic resolution of rac-1, T-bi-2-naphthol (rac-38) with the axially chiral ruthenium complex A-[Ru(menbpy)3]2+ (39, menbpy = 4,4 -dimenthoxycarbonyl-2,2 -bipyridine)... 

Recrystallization of a 1 1 molecular complex formed from several sulfoxides and (R)-( + )-2,2 -dihydroxy-l, l -binaphthyl (7) allowed resolution of the former22. Conversely, using the optically pure sulfoxide, it was possible to resolve racemic bis-naphthol 7. 

If bi-2-naphtol was stereoselectively oxidized, the kinetic resolution of bi-2-naphthol was achieved. Actually, the S enantiomer of bi-2-naphtol is more rapidly consumed than the R enantiomer with an enantiomer excess of 15.2% after 1 h and 2 h reactions and 11.0% after a 12 h reaction. 

The most frequently applied ligands are 2,2 -binaphthol (BINOL la) and 2,2 -bis(diphenyl-phosphino)binaphthyl (BINAP lb). Both antipodes of these compounds are commercially available in enantiopure form, though not at little cost [3]. It is rewarding, therefore, to become acquainted with the syntheses of these compounds, which have been described in detail [4J and have been simplified substantially on the basis of recent publications [5J. The iron(lIl)-catalyzed dimerization of 2-naphthol (2) to give racemic BINOL (rac)-la succeeds smoothly and on a large scale (Scheme 1). Its resolution can be achieved easily with N-benzylcinchoidinium chloride (3) and yields both (/ )- and (5 )-la in high enantiomeric excesses. After conversion into the ditri-flate 4, enantiopure la can be coupled with diphe-nylphosphine (or, in lower yield, with cheaper chlorodiphenylphosphine) in a nickel-catalyzed... 

In conclusion, simple, convenient methods have been developed for the resolution of racemic bi-2-naphthol 1, the diols 7, 8, the amino alcohol derivatives 9, 10 and 11 and purification of the diastereomeric amino alcohol 13. Since some of these chiral diols and amino alcohols are widely used in large scale in asymmetric syntheses, it is anticipated that the new resolution procedures involving diastereomeric borate complexes described here will also find wide applicability. 

Preparative Methods racemic l,l -bi-2,2 -naphthol (BINOL) is most conveniently prepared by the oxidative coupling reaction of 2-naphthol in the presence of transition metal complexes (eq 1). The resolution of racemic BINOL with cinchonine may be performed via the cyclic phosphate (eq 2). An alternative procedure to provide directly optically active BINOL is the oxidative coupling of 2-naphthol catalyzed by Cu salt in the presence of chiral amines (eq 3). The best procedure uses (+)-amphetamine as the chiral ligand and provides BINOL in 98% yield and 96% ee. Above 25 °C the Cu /(+)-amphetamine/(5)-BINOL complex precipitates, while the more soluble Cu /(+)-amphetamine/(I )-BINOL complex is slowly transformed into the former complex. 9,9 -Biphenanthrene-10,10 -diol has also been prepared in 86% yield and with 98% ee by a similar asymmetric oxidative coupling of 9-phenanthrol in the presence of (I )- 1,2-diphenylethylamine. ... 

Table IIo Resolution of Some Bi-g-naphthols Upon CSP 1 Using 10-20% 2-Propanol in Hexane.

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