Crystal achiral —» chiral

In a special case of this type of asymmetric synthesis, a compound (47) with achiral molecules, but whose crystals are chiral, was converted by UV light to a single enantiomer of a chiral product (48). ... 

The culmination of the studies on asymmetric photodimerization reactions in the solid state was the successful elaboration of chemical systems that are achiral but crystallize in chiral structures, and that yield, on irradiation, dimers, trimers, and higher oligomers in quantitative enantiomeric yield (175,258). 

Systematic studies of topochemical reactions of organic solids have led to the possibility of asymmetric synthesis via reactions in chiral crystals. (A chiral crystal is one whose symmetry elements do not interrelate enantiomers.) (Green et al, 1979 Addadi et al, 1980). This essentially involves two steps (i) synthesis of achiral molecules that crystallize in chiral structures with suitable packing and orientation of reactive groups and (ii) performing a topochemical reaction such that chirality of crystals is transferred to products. The first step is essentially a part of the more general problem of crystal engineering. An example of such a system where almost quantitative asymmetric induction is achieved is the family of unsymmetrically substituted dienes ... 

Recrystallization of the achiral oxo amide /V,/V-diisopropylphenylglyoxylamide (la) from benzene gave colorless chiral prisms [1], Each crystal is chiral and shows a CD spectrum in Nujol mulls (Fig. 1). One type of chiral crystal shows a (+)-Cotton effect and the other type shows a (-)-Cotton effect (Fig. 1). Crystals of (+)-la and (-)-la can easily be prepared in large quantities by seeding with finely powdered crystals of (+)-la or (-)-la during recrystallization of la from benzene. Measurement of the CD spectrum of chiral crystals as Nujol mulls is now well established [2],... 

In the case of 18, however, photoreaction in its chiral crystals gave 19 (22% yield, 32% ee) in the low chemical and optical yields as indicated, together with the side product 20 (17% yield, 46% ee) [15]. The reason for the low optical yield is not clarified. As the photoreaction in the chiral crystal proceeds, chiral arrangement of the achiral molecules of 18 in their crystal would be disturbed and racem-ized. 

Kondepudi and McBride indicate that stirred crystallization is effective to accelerate the enantiomeric excess (ee) of crystals in the recrystallization step. [7] Kondepudi reported that the ee of the crystal greater than 95% can easily be obtained in stirred crystallization of achiral materials that crystallize in chiral form, such as sodium... 

Sakamoto et al. provided an example of absolute asymmetric synthesis involving hydrogen abstraction by thiocarbonyl sulfur (Scheme 6). [24] Achiral A -diphenylacetyl-iV-isopropylthiobenzamide 33 and Y-diphenylacetyl-A-isopropyl(p-chloro)thio-benzamide 33 crystallize in chiral space group P2 2 2. Photolysis of the chiral crystals in the solid state gave optically active azetidin-2-ones whereas achiral thioketones were obtained as main products. When 33a was irradiated in the solid state at -45°C followed by acetylation (at -78°C), 2-acetylthio-3,3-dimethyl-l-diphenylacetyl-2-phenylaziridine (34a 39% yield, 84% ee), 4-acetylthio-5,5-dimethyl-2-diphenylmetyl-4-phenyloxazoline (35a 10% yield, 50% ee), 3,3-diphenyl-1-isopropy 1-4-... 

Similar absolute asymmetric synthesis was demonstrated in the solid-state photoreaction of A-(P,y-unsaturated carbonyl)thiocarbamate 41. [27] Achiral 0-methyl AT-(2.2-dmeth ibut-3-enoyl)-iV-phenylthiocarbarnate 41 crystallized in chiral space group P2i, and irradiation of these crystals gave optically active thiolactone in 10-31% ee. A plausible mechanism for the formation of 42 is rationalized on the basis that photolysis of 41 undergoes [2 + 2] cyclization to thietane and is subsequently followed by rearrangement to thiolactone 42. 

In the envelope conformation (A) the peroxide bond and the two carbon atoms are all coplanar (with the C-O-O-C dihedral angle being close to 0°) while the ethereal oxygen atom can be displaced by as much as 0.65 A to either side of this plane. In conformation B the peroxide bond straddles the plane of the remaining three atoms and this dihedral is around 50°. While conformation A is achiral, B has C.y symmetry. Usually ozonides crystallize in chiral space groups however, both enantiomorphic forms of B are usually encountered in the crystal lattice. Furthermore, disorder of the peroxide oxygen atoms over several occupancies is frequent, and in recent analyses, due mostly to improvement in the structure refinement algorithms, this disorder could be taken into account and suitably refined models could be built from the diffraction data. 

A great number of chiral TTFs have been prepared [31,32], and some of their charge transfer salts have been crystallised. The 7r-donor 1 can be elec-trocrystallised to give a salt 12 PF6, which has a conductivity of 5 2 1 cm 1 at room temperature and metallic behaviour when cooled down [33]. While the structure of the crystals is chiral, the structure of this salt and other related ones [34] has an essentially achiral stack of donor molecules, which are pseudo-centrosymmetric [35]. The methyl groups at the periphery of the molecule are apparently not sufficient to cause a truly chiral stack of donors, which prefer to stack in parallel arrangements with partial overlap of the tr-systems in the solid state, a situation which is true for the majority of the efforts to prepare salts of this type (even if the salts are metallic). 

Dibenzobarrelene diisopropylester 12 is an achiral molecule, but it forms dimorphic crystals. A chiral crystal, P212121, can be obtained by crystallization from the molten state. Irradiation of such crystals gives 13 in over 95% enantiomeric excess (ee) (Scheme 4.6) [8]. 

Sakamoto et al. have provided an example of absolute asymmetric synthesis involving [i-hydrogen abstraction by thiocarbony] sulfur (Scheme 4.68) [102]. The achiral benzothioamides 126 crystallize in chiral space group P212121. When the chiral crystals were irradiated in the solid state at —45 °C, followed by acetylation with AcCl at —78 °C, the aziridines 127 were obtained as a main product in a highly enantioselective cyclization. 

This approach involves formation of salts most commonly between prochiral carboxylic acid-containing photoreactants and optically pure nonabsorbing amines. While the carboxylic acids are achiral the salts are chiral and these salts, which necessarily crystallize in chiral space groups, provide the asymmetric media in which to carry out the reactions. Clearly the opposite approach, namely forming a salt using a reactive achiral amine and a chiral acid, is also valid. 

The crystallization of achiral molecules in chiral space groups, while rare and unpredictable, is well documented. Molecules with a C2 symmetry axis tend to crystallize in chiral structures, according to Jacques and coworkers, but despite impressive work on crystal engineering, predictions of a correlation between crystal symmetry and molecular structures are still hard to make [6]. 

Irradiation of a benzene solution of 5-phenyl Af-benzoylformyl-A-p-tolylthiocar-bamate 48a (Scheme 23) gave 5-phenyl-5-phenylthio-3-p-tolyloxazolidine-2,4-dione 49a in 61% yield accompanied by oxazolidine-2,4-dione dimer (15%), p-tolyl isocyanate (22%), and diphenyl disulfide [29]. Photolysis of 48a in the solid state gave oxazolidine-2,4-dione 49a in 96% yield. For the N-methyl derivative, 48b, compared to the solution photochemistry in which only 8% of oxazolidinedi-one 49b was obtained with a complex mixture, radical cyclization proceeds selectively to give oxazolidinedione in 75% yield in the solid state. Whereas N-p-tolyl and A-methyl derivatives, 48a and 48b, formed achiral crystals, the N-benzyl derivative 48c crystallized in chiral space group P2. Photolysis of the chiral... 

Recently, Sakamoto et al. reported an absolute asymmetric synthesis using the frozen chirality generated by chiral crystallization. Achiral asymmetricly substituted imide 68, which bonds between the nitrogen atom and the tetrahydronaph-tyl (TENAP) group, rotates freely at room temperature, crystallized in a chiral fashion, and the enantiomerization owing to the bond rotation was suppressed at low temperature (Scheme 33). Furthermore, the frozen molecular chirality could be transferred to optically active products in fluid solution [35]... 

Even if a molecule is achiral, chiral crystals can form by spontaneous chiral crystallization [26]. The big advantage in utilizing a crystal as a reactant is that absolute asymmetric synthesis can be achieved by solid-state photoreaction of such a chiral crystal. The initial chiral environment in the crystal lattice is retained during the reaction process, owing to the low mobility of molecules in the crystalline state, and leads to an optically active product. The process represents transformation from crystal chirality to molecular chirality. This kind of absolute asymmetric synthesis does not need any external asymmetric source in the entire synthetic procedure [9-14]. 

The achiral compound 136 crystallized in chiral space group P2i2i2i. Enantioselective di-TT-methane photorearrangement took place on irradiation to afford preparative quantities of 137 and 138 in respective enantiomeric excesses of < 44% and 96%, respectively (Scheme 31) [111]. The absolute configurations of the reactant and the products were not determined. 

Recrystallization of the achiral oxo amide MAf-diisopropylphenylglyoxylamide (78a) from benzene gave colorless chiral prisms. Each crystal is chiral and shows... 

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