Binaphthol host

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 binaphthol 13 is different from 1 and 7 owing to the lower acidity of its functional groups. Therefore, crystalline complexes of 13 with amines (see Table 3) are not expected to have a salt character. The 13 imidazole 1 2 complex (Fig. 22)81) was studied in the light of the general interest in this guest partner and its relation to alcohol functions in biological ensembles. The host molecule adopts ideal twofold... 

Some other resolutions by inclusion complexation with achiral host and by distillation technique are also described. In the last section, progress of the resolution of binaphthol, biphenols and related compounds is described. 

Some amide derivatives have been reported to form inclusion complex with a wide variety of organic compounds.9 Optically active amide derivatives are expected to include one enantiomer of a racemic guest selectively. According to this idea, some amide derivatives of tartaric acid (11-13) were designed as chiral hosts.10 As will be described in the following section, these amide hosts were found to be useful for resolution of binaphthol (BNO) (14) and related compounds (15,16). 

As the inclusion capacity of a host compound cannot be precisely predicted as yet, the work of the preparative chemist at the time being is reduced to systematic variation, design and further development of substance families, which are knoivn to constitute clathrate formers. The numerous complex forming agents derived from binaphthol have been mentioned already in section 2A. 

If host and guest molecules mutually recognize their chiralities at inclusion formation, the process could be used for optical resolution. In other words, when the host compound is optically active, one enantiomer of the guest compound should be included selectively. In turn, if an optical active guest molecule forms a crystal inclusion with one enantiomer of the host compound selectively, the host compound yields resolved. This section deals with the resolution via inclusion formation using host compounds such as alkaloids, 2-propyn-l-ols, 2,4-hexadiyne-l,6-diols, 2,2 -dihydroxy-l,r-binaphthol (7), and 2,2 -dihydroxy-9,9 -spirobifluorene (10a). 

L. The DSC traces were also unremarkable, all displaying an endotherm for desolvation, followed by an endotherm corresponding to fusion of the desolvated binaphthol. Single crystal X-ray analyses were performed to establish the precise mode of inclusion of the solvent molecules in the crystals as well as the molecular interactions between the host and guest molecules. All of the solvent molecules are located within channels in the respective solvates and the primary interactions are hydrogen bonds of the type 0-H--N with 0-N in the range 2.794(2)-2.826(3) A. 

Figure 10. Chemical structures of the host molecule binaphthol 13 and solvent molecules 2,6-lutidine 2,6-L, 2,4-lutidine 2,4-L and 3,5-lutidine 3,5-L.

An established area of application of macrocyclic polyethers is the stereoselective complexation of chiral guest primary alkylammonium salts by optically active host macrocycles. Full details of the resolution, optical stability, and inclusion into chiral hosts of the binaphthol (84), and also of the chiral recognition properties of crowns [e.g. (85)] based on simple carbohydrate precursors, have been reported this year. An extension of the latter work" utilizes derivatives of the more complex carbohydrates D-glucose and D-galactose. The macrobicyclic polyethers (86) derived from D-glycerol or pentaerythritol have been suggested as potential chiral (at the bridgeheads) cryptands. 

The chiral macrocyclic polyether (U)-d-(521) and its (5)-D-diastereoisomer have been derived from D-mannitol and (R)- or (S )-binaphthol, respectively. Significant changes were observed in the n.m.r. spectra of (/ )-d-(521) and its diastereoisomer in the presence of primary alkylammonium salts [e.g. (+)-(2 )-, (-)-(5 )- and ( )-(i 5 )-a-phenylethylammonium hexafluorophos-phate], indicating that both diastereoisomers act as hosts to suitable guest molecules. The chiral hosts dd-(523) and dd-(524) have been obtained from l,2 5,6-di-0-isopropylidene-D-mannitol by the routes outlined in Scheme 100. The temperature dependence of the H n.m.r. spectrum of the 1 1 complex of dd-(524) and benzylammonium thiocyanate in [ Ha]dichloromethane was interpreted... 

Chiral Crown Ethers. Perhaps the most extensive work in this area has been performed by Cram and his group, who utilize the chirality of 2,2 -binaphthol. Starting from optically pure materials, optically active crown ethers such as the (R,R)-macrocycles (55) can be synthesized, and these host molecules will form diastereo-meric complexes with the enantiomeric forms of chiral guest molecules, such as alkylammonium ions. For example, the more stable complex formed between... 

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