Chiral cocrystal

TABLE 3. Asymmetric autocatalysis in reaction of 87 initiated by chiral inorganic crystals, inorganic-organic hybrid materials and chiral cocrystals of achiral compounds... 

All the 311 molecules adopt a P-helical conformation in the central hexatriene part (this crystal is named (P)-311 NpF). Single crystals with the opposite chirality, (M)-311 NpF, in which 311 is in an M-helical conformation, were also obtained from the same sample batch. The chiral cocrystals underwent photochromism. Upon irradiation with 365 nm light, the colorless crystal turned blue. 

Nagano, M., and Yu H. (2003) Photoreaction of 9-Methylbenz[c]acridine with Diphenylacetic Acid in the Chiral Cocrystal, Heterocycles, 60, 2251-2258... 

Chiral cocrystals (from achiral organic molecules) Chiral crystals of achiral hippuric acid... 

We have used chiral cocrystals composed of two different molecules [10]. When one of the two components is chiral, a cocrystal of a chiral space group is necessarily obtained. Combination of an electron donor molecule with an electron acceptor molecule, or a photoinert molecule with a photosensitizer molecule, in a cocrystal can induce new photoreactivity as well as intermolecular photoreaction. 

When two different achiral molecules form a chiral cocrystal by spontaneous chiral cocrystallization, the occurrence of absolute asymmetric intermolecular photoreaction can be expected. In fact, we have achieved enantio- and diastereo-selective photodecarboxylative condensation, as well as absolute asymmetric pho-todecarboxylative condensation. The development of intermolecular photoreao tions leads to an extension of the scope of solid-state chiral photochemistry. Reactivity in a cocrystal is controlled by the crystal packing arrangement, so the key point is the preparation of photoreactive cocrystals. 

Figure 3 Chiral cocrystals formed from two different achiral molecules.

Despite acridine and diphenylacetic acid being achiral molecules, it was found that these two compounds formed a chiral cocrystal on spontaneous crystallization, and further irradiation of this caused photodecarboxylation and then enantio-selective radical coupling to give a chiral condensation product (Scheme 35) [31]. This kind of absolute asymmetric photodecarboxylation is not a topochemical reaction but is accompanied by gradual decomposition of the initial crystal structure as the reaction proceeds. This pathway is different from the four examples of [2 + 2] photocycloadditions described above. 

The chiral cocrystal 150 DPA was prepared by crystallization from a 1 1 solution of acridine 150 and diphenylacetic acid DPA in acetonitrile. The crystal... 

Scheme 36 Possible reaction mechanism on irradiation of the chiral cocrystal of acridine and diphenylacetic acid.

Kawasaki T, Jo K, Igarashi H, Sato I, Nagano M, Koshima H, Soai K (2005) Asymmetric amplification using chiral cocrystals formed from achiral organic molecules by asymmetric autocatalysis. Angew Chem IntEd 44 2774—2777. doi 10.1002/anie.200462963... 

A. Lemmerer, N.B. Bathori, S.A. Bourne, Chiral carboxylic acids and their effects on melting-point behavior in cocrystals with isonicotinamide, Acta Cryst. B64 (2008) 780-790. 

Cocrystal Chiral molecule Moderate-high enantiodifferentiation... 

This kind of chiral crystallization of an achiral molecule always gives both right- and left-handed crystals. However, under ordinary crystallization conditions, enantiomorphous control is not possible. We have reported that a cocrystal is formed by the crystallization of a solution of a 1 1 mixture of 3-indolepropionic acid and phenanthridine in acetonitrile [28]. When the acetonitrile solution was divided into six parts and spontaneously evaporated in six containers, P-crystals appeared in four containers and M-crystals in two. If such chiral crystallization is carried out using a much larger number of flasks, the ratio of the formation of both enantiomeric crystals will approach 1 1. 

Acridine 94 and (R)-( — )-2-phenylpropionic acid (R)-95 formed the chiral 3 2 cocrystal 94 (/ )-95. Irradiation of these cocrystals gave enantiomeric products 96 and 98 as well as the diastereomeric product 97 through photodecarboxylative condensation, with all positive [a]j> values (Scheme 22) [94]. Similarly, the opposite handed cocrystal afforded 96-98 with negative [a] d values. In contrast, photolysis of a 1 1 solution of 94 and (/ )-95 in acetonitrile resulted injhe formation of racemic 96 and biacridane 99. 

Terahertz time-domain-spectroscopy has been used to distinguish between chiral and racemic hydrogen-bonded cocrystals, and could readily distinguish between the isostructural cocrystals of theophylline with the chiral and racemic forms of both malic and tartaric acids [29]. These findings are of importance since it was concluded that while the respective cocrystal systems were almost identical in molecular structure and supramolecular architecture, the use of terahertz spectroscopy was comparable in sensitivity to X-ray diffraction and more sensitive than Raman spectroscopy to changes in cocrystal architecture. Solid-state nuclear... 

Thanks to the exploratory work of Schmidt et al. [42], the concept of absolute asymmetric induction starting from chiral crystals of achiral molecules is now very commonly known [1,43]. A 1 1 hydrogen-bonded cocrystal of acridine and diphenylacetic acid 17-h is chiral (space group P2i2,2,). Upon irradiation, the cocrystal underwent mainly hetero coupling to give chiral HNArH-R in a relatively low optical yield (37% ee. Scheme 17) [41]. 

In addition, a number of carboxylic acid cocrystals, of which some are of course chiral, are being reported in Aust. J. Chem. and by Japanese workers. For example. Lynch, D.E. Latif, T. Smith, G. Byriel, K.A. Kennard, C.H.L. Parsons, S. Aust. 

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