Chiral inclusion crystal

Tanaka, K., Fujimoto, D., Oeser, T., Imgartinger, H., and Toda, F. (2000) Chiral Inclusion Crystallization of Tetra(p-bromophenyl)ethylene by Exposure to the Vapor of Achiral Guest Molecules A Novel Racemic-to-Chiral Transformation Through Gas-Solid Reaction, Chem. Commun., 413-414. 

Figure 10 Molecular structure of 2a and crystal packing of (a) the chiral inclusion crystal 2a (- )4 and (b) the chiral crystal of 2a on its own. (c) Space-filling representation of molecular structure of 2a as found in the two crystal structures. Conformations are similar in the two cases.

It is well known that spontaneous resolution of a racemate may occur upon crystallization if a chiral molecule crystallizes as a conglomerate. With regard to sulphoxides, this phenomenon was observed for the first time in the case of methyl p-tolyl sulphoxide269. The optical rotation of a partially resolved sulphoxide (via /J-cyclodextrin inclusion complexes) was found to increase from [a]589 = + 11.5° (e.e. 8.1%) to [a]589 = +100.8 (e.e. 71.5%) after four fractional crystallizations from light petroleum ether. Later on, few optically active ketosulphoxides of low optical purity were converted into the pure enantiomers by fractional crystallization from ethyl ether-hexane270. This resolution by crystallization was also successful for racemic benzyl p-tolyl sulphoxide and t-butyl phenyl sulphoxide271. 

Scheme 3 illustrates intriguing enantioselection in organic reactions that proceed in chiral crystalline lattices (5). When inclusion crystals of a ketone and an optically active diol host are treated with BH3-ethyl-enediamine complex, the optically active alcohol is obtained in... 

In this chapter, enantioselective photoreactions of achiral molecules in their own chiral crystals and in inclusion crystals with a chiral host compound that have been carried out mainly in our research groups are described. 

Even for the oxoamides which do not form chiral crystals, enantioselective photoconversion to optically active (3-lactams can easily be accomplished by photoirradiation in their inclusion crystals with an optically active host compound. For example, irradiation of a 1 1 inclusion complex crystal of 9 with 11 [8] gave (-)-10 of 100% ee in a quantitative yield [9], The host compound 11 is recovered and can be used again. The chiral arrangement of 9 molecules in the inclusion complex was studied by x-ray analysis [9], A schematic stereoview of the inclu-... 

Intramolecular [2 + 2] photocyclization reactions of 2- /V-(2-propcnyl)amino]cy-clohex-2-enones (67) are also controlled enantioselectively by carrying out irradiation in inclusion complex with a chiral host compound. When inclusion crystals of 67 with 12 are irradiated in the solid state, optically active 9-azatricyclo[5.2.1.0]-decan-2-ones (68) were obtained in the chemical and optical yields indicated in Table 3 [30],... 

Enantioselective photocyclization of 2-(arylthio)-3-methylcyclohexan-l-ones (75) to dihydrobenzothiophene derivatives 77 was also achieved in inclusion crystals using chiral host molecules. Photoirradiation of the 1 1 inclusion crystals of 75g with (-)-12b as a water suspension gave the corresponding photocyclization product (+ )-m-77g of 82% ee in 83% yield. Similar photoirradiation of the... 

The chiral arrangement of 80a molecules in the complex with (—)-12c is also easily detected by measurement of CD spectra as Nujol mulls. For example, the inclusion crystal of 80a with (—)-12c showed a (—)-Cotton effect, and that of 80a with (+)-12c showed a (+)-Cotton effect at around 260 and 310 nm, respec-... 

When a mixture of powdered ketone and NaBH4 is kept at room temperature, reduction of the ketone occurs to give the corresponding alcohol [2], When the reaction is carried out in inclusion crystals containing a chiral host compound, the optically active alcohol can be obtained by enantio-control of the reaction by the chiral host. For example, treatment of inclusion crystals of acetophenone (2a) or o-methylacetophenone (2b) and (S,S)-(-)-1,6-bis(o-chlorophenyl)-1,6-diphenylhexa-2,4-diyne-l,6-diol (1) [3] with powdered BH3-ethylenediamine complex (3) in the solid state gave 4a of 44 % ee (96 % yield) or 4b of 59 % ee (57 % yield), respectively [4],... 

Although mechanism of the precise chiral recognition between host and guest molecules in their inclusion crystal has been studied in detail by X-ray structural analysis, these X-ray structures are not shown in this chapter, since this chapter deals with practical procedures of optical resolutions. 

In the case of volatile racemic guest, optical resolution can be carried out by using distillation technique in the presence of a non-volatile chiral host compound. The resolution by distillation is summarized in the section of 5. In the section 5, optical resolution by inclusion crystallization in a suspension medium in hexane or water is also described. 

In order to clarify mechanism of the precise chiral recognition between aliphatic secondary alcohols and 9a or 10a in their inclusion crystal, X-ray structure of a 1 1 inclusion crystal of 9a and (+)-l,3-butanediol (58) was investigated. Finally, it was found that hydrogen bond between the OH group of 9a and that on the chiral carbon of 58 plays an important role to arrange both molecules at close positions to be able to recognize the chirality each other.24... 

Mechanism of the mutual chiral recognition between 14b and (+)-116c was studied by X-ray analysis of their inclusion crystal. By this study, the absolute configuration of the (+)-116c was determined to be the (R)47... 

It was found that efficient inclusion crystallization can be accomplished simply by mixing powdered crystalline host and a hydrophobic guest compound in hexane or water. By using the inclusion crystallization in suspension media, very efficient optical resolution method was established. Furthermore, when inclusion complexation between chiral host and rac-guest in the solid state is combined with a distillation procedure, optical resolution can easily be accomplished by the fractional distillation procedure. 

Toda, F., Tanaka, K., and Kuroda, R. (1997) Isolation of a Nearly Eclipsed Chiral Rotamer of 1,2-Dichloroethane as an Inclusion Crystal with a Chiral Host Compound, Chem. Commun., 1227-1228. 

It should be noted that benzyl methyl sulfoxide was included without the recognition of their chirality (entry 7 in Table 4).26 By single crystal X-ray analyses of this inclusion compound, it was elucidated that the molecules of 1 form the layer structure similar to the one of the above alkyl phenyl sulfoxide-inclusion crystals, and the sulfoxides are included between these layers. There are two different recognition cavities on the upper side for its S enantiomer and on the lower side for its K enantiomer. The upper side cavity can be illustrated by motif A, and the lower side one by motif B in Figure 16. 

Cramer, F., and Dietsche, W. 378 (1959) Occlusion compounds. XV. Resolution of racemates with cyclodextrins, Chem. Ber. 92 b) Toda, F., and Tohi, Y. (1993) Novel optical resolution methods by inclusion crystallization in suspension media and by fractional distillation,/. Chem. Soc., Chem. Commun., 1238-1240 c) Toda, F., and Tanaka, K. (1988) A new chiral host compound... 

Reactions using chiral crystals of 2a were carried out using one single crystal in order to avoid the mixture of crystals with opposite chirality. The ee of several independent reactions was 56% on average [53]. The smaller value compared with that seen for the inclusion crystals must be due to weaker confinement of molecules in the crystal lattice compared with the case of the inclusion crystal, which has hydrogen bonds between host and guest molecules. 

Enantioselective Michael addition of thiols to enones is a useful reaction for the synthesis of sex pheromones [26] and terpenes [27]. For example, enantioselective Michael additions of thiols to 2-cyclohexenone (64) and maleic acid esters in the presence of chiral bases such as cinchona alkaloids [28, 29] and optically active amino alcohols [30, 31] have been reported. It has also been found that the enantioselective Michael addition reaction proceeds efficiently in an inclusion crystal... 

The mechanism of the very effective enantioselective photocyclization of 88 was clarified by X-ray analysis of its inclusion crystal with 2c. In this inclusion crystal, the 88 molecules are arranged in a chiral form so as to give only chiral 89 but not 90 upon iiradiation [50]. 

Enantioselective intramolecular photocyclization reactions of enones as inclusion crystals with chiral host compounds proceeds very efficiently. Several examples of such reactions are described in this Chapter. 

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