Binaphthyl compounds, resolution

The salt precursor was prepared according to the following route as shown in Scheme 4. The desired enantiopure binaphthyl compound (5)-4 was made from 2-methyhiaphtalene (3) over five steps, which also included a resolution step [31-33]. The final precursor (5)-5 was obtained in 41% yield via a deprotonation of (5)-4 followed by the reaction with methyltrimethoxysilane and a subsequent reduction. 

CL Cooper, JB Davis, MJ Sepaniak. Mechanisms of enantiomeric resolution in cyclodextrin-modified capillary electrophoretic separations of binaphthyl compounds. Chirality 7 401-408, 1995. 

To prepare salt 2 compound 5 was first prepared according to Scheme 16.2. Binaphthyl compound (S)-4 was prepared from 2-methylnaphthalene (3) over five steps. Owing to a resolution step the compound was obtained enantiopure [32-34]. In the last step precursor (S)-5 was synthesized in 41% yield as shown in Scheme 16.2. 

Chiral 1,1 -binaphthol derivatives are well established as readily available chiral catalysts and auxiliaries for the production of various useful optically active compounds. Tanabe et al. investigated [11] a crystalline-liquid resolution of (1R) -// . v - c h rysanthemic acid utilizing l,l -binaphthyl monoethyl ether (25) (Scheme 3). 

This compound, in common with other suitable substituted biphenyls, possesses a chiral axis (p. 6) and is isolated from the reaction as a racemate. Although several resolution procedures have been reported, the superior method to date4 is that in which the binaphthol is first converted by treatment with phosphorus oxychloride into the binaphthyl phosphoric acid (14). Resolution is then effected by formation of diastereoisomeric salts with (+ )-cinchonine, appropriate fractional crystallisation and recovery of the (S)-( + )-binaphthyl phosphoric acid. Suitable hydrolysis gives (S)-( — )-l,l -bi-2-naphthol (15). 

Among the preparative methods used for obtaining P-chiral phosphorus compounds, there are procedures involving the use of optically pure auxiliaries like (—)-menthol [40], (—)-ephedrin [41,42], or more recently, the kinetic resolution of 1-hydroxymethylalkylphenylphosphine oxides using Pseudomonas or Candida antarctica lipases [43], It has been found that some [(alkyl-substituted)arene] phosphinates and phosphine oxides can also be resolved efficiently by inclusion complexation with optically active 2,2 -dihydroxy-1, 1 -binaphthyl (17) [44],... 

Toda, F., and Tanaka, K. (1997) New Chiral Ammonium Salt Hosts Derived from Amino Acids Very Efficient Optical Resolution of 2,2 -Dihydroxy-l,r-binaphthyl by Complexation with These Host Compounds, Chem. Commun., 1087-1088. 

Diols such as the optically active 1,1 -binaphthyl-2-2 -diol (BINOL) have been used as versatile templates and chiral auxiliaries in catalysts employed successfully in asymmetric synthesis. The application of enzymes in the enantioselective access to axially dissymmetric compounds was first reported by Fujimoto and coworkers.83 In aqueous media, the asymmetric hydrolysis of the racemic binaphthyl dibutyrate (the ester) using whole cells from bacteria species afforded the (A)-diol with 96%ee and the unreacted substrate (A)-ester with 94% ee at 50 % conversion. Recently, in non-aqueous media, lipases from Pseudomonas cepacia and Ps. fluorescens have been employed in the enantioselective resolution and desymmetrization of racemic 6,6 -disubstituted BINOL derivatives using vinyl acetate.84 The monoacetate (K)-73 (product) was obtained in 32-44 % chemical yields and 78-96% ee depending on the derivatives used. The unreacted BINOL (S)-72 was obtained in 30-52 % chemical yield and 55-80% ee. 

Analytical Properties Resolution of such enantiomeric compounds as 2,2 -dihydroxy-1,1 -binaphthyl and frans-1,2-cyclo hexandiol Reference 29... 

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... 

For the 3,3 -dimethyl derivative 8, several other methods have been developed. The racemic 3,3 -dimethy] compound can be prepared by aminomcthylation of binaphthol with subsequent conversion of the aminomethy] function to a methyl group, and resolved analogously to binaphthol via the phosphoric acid derivative15. Another possibility is the preparation [oxidation of 3-hydroxy-2-naphthoic acid with iron(III) chloride] and resolution [with (S)-leucine methyl ester] of 2,2 -dihydroxy-1,l -binaphthyl-3,3 -dicarboxylic acid (7). 

Toda procedure for obtaining enantiomeri-cally pure compounds will find broad application very soon. This development could make preparative HPLC with chiral columns obsolete and be applied to distillable amino acid derivatives as well. After all, analytical resolution of amino acids was quite successful by host/guest complexation chromatography with reversed-phase packings loaded with Cram s chiral 1,1 -binaphthyl crown ethers (similar to 1). [20]... 

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... 

At first we tried to address the problem with Moreau s method of kinetic resolution which has been applied with great success to compounds of central chirality (ref. 18). To our knowledge this technique has not yet been used for compounds with axial chirality. To be on safe ground, we had to calibrate the effects first with compounds of similar structure and known absolute configuration. We selected 2,2 -dihydroxy-1,1 -binaphthyl (31) as an example and reacted it in the usual way with an excess of racemic 2-phenyl butanoic anhydride in the presence of pyridine. The optical excess in the remaining anhydride was determined by means of the gas chromatographic variant of Brooks and Gilbert (ref. 19) (Scheme 6). 

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