Binaphthyls

The SHG/SFG technique is not restricted to interface spectroscopy of the delocalized electronic states of solids. It is also a powerful tool for spectroscopy of electronic transitions in molecules. Figure Bl.5.13 presents such an example for a monolayer of the R-enantiomer of the molecule 2,2 -dihydroxyl-l,l -binaphthyl, (R)-BN, at the air/water interface [ ]. The spectra reveal two-photon resonance features near wavelengths of 332 and 340 mu that are assigned to the two lowest exciton-split transitions in the naphtli-2-ol... 

Triflates of phenols are carbonylated to form aromatic esters by using PhjP[328]. The reaction is 500 times faster if dppp is used[329]. This reaction is a good preparative method for benzoates from phenols and naphthoates (473) from naphthols. Carbonylation of the bis-triflate of axially chiral 1,1 -binaphthyl-2,2 -diol (474) using dppp was claimed to give the monocarboxy-late 475(330]. However, the optically pure dicarboxylate 476 is obtained under similar conditions[331]. The use of 4.4 equiv. of a hindered amine (ethyldiisopropylamine) is crucial for the dicarbonylation. The use of more or less than 4.4 equiv. of the amine gives the monoester 475. 

Phosphine oxides are prepared similarly[644]. Selective monophosphiny-lation of 2,2 -bis[(lrifluoromethanesulfonyl)oxy]-l,1 -binaphthyl (784) with diphenylphosphine oxide using dppb or dppp as a ligand takes place to give optically active 2-(diarylphosphino)-1,1 -binaphthyl (785). No bis-substitution is observed[645,646]. 

Chiral separations are concerned with separating molecules that can exist as nonsupetimposable mirror images. Examples of these types of molecules, called enantiomers or optical isomers are illustrated in Figure 1. Although chirahty is often associated with compounds containing a tetrahedral carbon with four different substituents, other atoms, such as phosphoms or sulfur, may also be chiral. In addition, molecules containing a center of asymmetry, such as hexahehcene, tetrasubstituted adamantanes, and substituted aHenes or molecules with hindered rotation, such as some 2,2 disubstituted binaphthyls, may also be chiral. Compounds exhibiting a center of asymmetry are called atropisomers. An extensive review of stereochemistry may be found under Pharmaceuticals, Chiral. 

Catalytic asymmetric hydrogenation was one of the first enantioselective synthetic methods used industrially (82). 2,2 -Bis(diarylphosphino)-l,l -binaphthyl (BINAP) is a chiral ligand which possesses a Cg plane of symmetry (Fig. 9). Steric interactions prevent interconversion of the (R)- and (3)-BINAP. Coordination of BINAP with a transition metal such as mthenium or rhodium produces a chiral hydrogenation catalyst capable of inducing a high degree of enantiofacial selectivity (83). Naproxen (41) is produced in 97% ee by... 

The dynamic stereochemishy of biaryls is conceptually similar. The energy barrier for racemization of optically active 1,1 -binaphthyl (Scheme 2.2, enhy 3, p. 83) is 21-23 kcal/mol. The two rings are not coplanar in the ground state, and the racemization takes place by rotation about the l,l -bond. 

Not long thereafter, Tarnowski and Cram reported the first example of a hinged bis-crown ether. The compound was prepared in the usual Williamson reaction by heating a mixture of 2,2, 3,3 -tetrahydroxy-l, r-binaphthyl with pentaethylene glycol ditosylate and KOH in aqueous THF solution. The product (mp 159.5—161°) shown in Eq. (3.30) was obtained in 30% yield. This compound was shown to complex bis-ammonium cations of several varieties . 

Two different all-aromatic crowns have been reported ". In 1975, de Jong, Siegel and Cram reported the synthesis of a tri-binaphthyl system in which each oxygen was bound to a naphthalene ring, but aliphatic bridges were used to join the binaphthyl units. Relatives of this compound are discussed further in Sect. 3.13. The synthesis of this molecule (Structure 17, below) was not simple, but was relatively straightforward. An interesting feature of it was the use of ethyl chloroacetate followed by LAH reduction to attach ethyleneoxy units to the naphthol unit. 

A large number of chiral crowns have been prepared by numerous groups. The reader is directed to the tables at the end of this chapter to obtain an overview of these structures. It would not be useful to try to recount the synthetic approaches used in the preparation of all of these compounds we have chosen rather to subdivide this mass of compounds into three principal groups. The groups are (1) Cram s chiral binaphthyl systems (2) chiral crowns based on the tartaric acid unit and (3) crowns incorporating sugar subunits. These are discussed in turn, below. 

Cram and his coworkers have pioneered the use of bis-binaphthyl crowns as chiral com-plexing agents for ammonium salts and amino acid salts. In these systems, the chiral binaphthyl unit provides a steric barrier within the macrocycle which allows discrimina-... 

In Cram s first synthesis of a chiral bis-binaphthyl system, optically pure binaph-thol and diethylene glycol ditosylate were heated at reflux in tetrahydrofuran solution for 15 h with potassium f-butoxide, two products were obtained. The 1 + 1 product (mp 230—231°) was isolated in 5% and the 2 + 2 product (mp 123—126°) was obtained in 31% yield. The reaction is shown in Eq. (3.51). 

The structural variations reported by Cram and coworkers relate to an appreciable extent to the various ancillary functions which have been appended to the binaphthyl units or elsewhere in the macrocyclic system. Enhancements of the chiral barrier or functionalization through arms has generally been effected at the 3-or 6-positions. These positions are adjacent to the hydroxyl group or directly across the second ring from it, respectively. 

The six-position may be functionalized by electrophilic aromatic substitution. Either bromination (Br2/CH2Cl2/-5°) acetylation (acetyl chloride, aluminum chloride, nitrobenzene) " or chloromethylation (chloromethyl methyl ether, stannic chloride, -60°) " affords the 6,6 -disubstituted product. It should also be noted that treatment of the acetyl derivative with KOBr in THF affords the carboxylic acid in 84% yield. The brominated crown may then be metallated (n-BuLi) and treated with an electrophile to form a chain-extender. To this end, Cram has utilized both ethylene oxide " and dichlorodimethyl-silane in the conversion of bis-binaphthyl crowns into polymer-bound resolving agents. The acetylation/oxidation sequence is illustrated in Eq. (3.54). 

Just as selective oxidation can be carried out on these systems, reduction also occurs with considerable selectively. Hydrogenation of binaphthol (Pd catalyst) in glacial acetic acid at room temperature for seven days affords the octahydro (bis-tetrahydro) derivative in 92% yield with no apparent loss of optical activity when the reaction is conducted on optically pure material. The binaphthol may then be converted into the bis-binaphthyl crown in the usual fashion. 

The principal variations on the normal crown synthesis methods were applied in preparing mixed crowns such as those shown in Eq. (3.55) and in forming isomers of the dibinaphthyl-22-crown-6 systems. The latter has been discussed in Sect. 3.5 (see Eq. 3.21) . The binaphthyl unit was prepared to receive a non-naphthyl unit as shown in Eq. (3.57). Binaphthol was allowed to react with the tetrahydropyranyl ether or 2-chloroethoxyethanol. Cleavage of the THP protecting group followed by tosyla-tion of the free hydroxyl afforded a two-armed binaphthyl unit which could serve as an electrophile in the cyclization with catechol. Obviously, the reaction could be accomplished in the opposite direction, beginning with catechol". ... 

Crown compounds containing a single 2,2 -binaphthyl subunit.116... 

Table 3.20. Crown compounds containing two 2,2 -binaphthyl subunits...

Cram has published several studies indicating that complexation of ammonium salts was greatly enhanced by using cyclic polyethers over the corresponding acyclic ones. These molecules were analogs of the binaphthyl systems under study and were generally prepared by phenoxide substitution on the appropriate tosylate. The approach is illustrated below in Eq. (7.9). ... 

Table 7.4. Podands containing the biphenyl or binaphthyl subunit...

Lehn and his coworkers have prepared a number of chiral cryptands based upon the 2,2 -binaphthyl unit " . In a typical preparation, the binaphthyl units are treated with bromoacetic acid to form the phenoxyacetic acid derivatives which are then converted into the corresponding diacyl chlorides (75). Reaction of 15 with l,10-diaza-18-... 

If a bridged bis-crown is used instead of diaza-18-crown-6, the cryptand contains two macrorings facing each other (see Table 8.5). Note also that the 2,2 -binaphthyl unit has been used extensively by Cram and his coworkers to provide chirality to mono-cyclic systems as well (see Sect. 3.13). 

The 1,2 naphthalyne can be trapped by reaction with excess furan to give the Diels-Alder adduct In the absence of furan, 1,2-naphthalyne can react with heptafluoro-2-naphthyllithium to yield a mixture of monohydrotndecafluoro-binaphthyls (equation 14)... 

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