Crystals, chiral, absolute asymmetric transformation

In the solid-state photochemical reaction of N,N-disubstituted a,(3-unsatu-rated thioamides 24, a crystal-to-crystal nature was observed in 24c furthermore, absolute asymmetric transformation in the chiral crystalline environment was performed in the photoreaction of 24b, 24c, and 24e. 

SPONTANEOUS CHIRAL CRYSTALLIZATION OF ACHIRAL MATERIALS AND ABSOLUTE ASYMMETRIC TRANSFORMATION IN THE CHIRAL CRYSTALLINE ENVIRONMENT... 

Absolute Asymmetric Transformation from Nonchiral Molecules in Chiral Crystals... 

Penzien and Schmidt reported the first absolute asymmetric transformation in a chiral crystal. [10] They showed that enone 4,4 -dimethylchalcone 1, although being achiral itself, crystallizes spontaneously in the chiral space group P2 2 2 (Scheme 1). When single crystals of this material are treated with bromine vapor in a gas-solid reaction, the chiral dibromide 2 is produced in 6-25% ee. In this elegant experiment, it is the reaction medium, the chiral crystal lattice, that provides the asymmetric influence favoring the formation of one product enantiomer over the other, and the chemist has merely provided a non-chiral solvent (ethyl acetate) for the crystallization and a nonchiral reagent (bromine) for the reaction. 

The concept of absolute asymmetric synthesis using a chiral crystal was applied to unimolecular photochemistry, and now many fine examples are reported. Scheffer et al. reported elegant unimolecular absolute asymmetric transformations (Scheme 4). [19] This group demonstrated that the well-studied solution-phase di-ir-mcthane photorearrangement can also occur in the solid state. Of over 20 symmetrical and unsymmetrical dialkyl 9,10-ethanoanthracene-l 1,12-decarboxylate 22, only two compounds were found to undergo absolute asymmetric di-ir-methane... 

II. ABSOLUTE ASYMMETRIC TRANSFORMATION FROM NONCHIRAL MOLECULES IN CHIRAL CRYSTALS... 

Table 2 Absolute Asymmetric Transformation Using Chiral Crystals via Intermolecular Reactions...

Spontaneous Chiral Crystallization of Achiral Materials and Absolute Asymmetric Transformation in the Chiral Crystalline Environment by Sakamoto, M. (2007) in Enantiomer Separation Fundamentals and Practical Methods (ed. Toda, R), Kluwer Academic, Dordrecht/Boston, pp. 103-133. 

A subsequent paper (05TA1969) reported the preparation of four pyrrolo fused TBs, 34a, 34b, 35a and 35b from 33a,b (no chiral induction was observed) (see reaction of 30, 31a,b and 32). The absolute configuration of 34a, [a]o = -193, was determined by X-ray crystallography. A CIAT experiment (crystallization-induced asymmetric transformation) allows the transformation of the crude mixture of 34b and 35b into pure 35b (Scheme 7). The thiophene derivative WADPIB (03AX(E)o745) (see VI.A) also belongs to this section. 

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]. 

Centrosymmetric crystals can be transformed into chiral or polar mixed crystals and this enables us to obtain novel means for absolute asymmetric synthesis. The principle is based on selective introduction of a guest molecule into a centrosymmetric host structure, thus reducing the symmetry of the mixed crystal. Crystallization of (E)-cinnamamide (space group P2i/c) in the presence of (E)-... 

Scheme 24) [52], The reaction was much more efficient in the solid state than in solution. When o-divinylbenzene was used, an absolute asymmetric induction leading to the chiral cycloadduct (71% and 95% ee at 15°C and -70 °C, respectively) was observed to occur via a single-crystal-to-single-crystal transformation (P2, P2.). 

The asymmetric polymerization in crystalline architectures provides an excellent environment to conduct the absolute asymmetric synthesis of polymers, and also provides an effident route for the ampHfication of chirality. Mirror-symmetry breaking might occur either through total asymmetric transformations, either in enantiomorphous crystals that have self-assembled from achiral molecules, or within racemic crystalline architectures which are delineated by chiral rims or surfaces when one of the chiral faces is blocked by an interface. The self-assembly of nonracemic mixtures into a mixture comprising eutectic compositions of a racemic compound and an enantiomorphous assembly, followed by asymmetric transformation, provides a series of thermodynamically controlled, alternative routes for the effident ampHfication of homochirality. 

Atropisomerization of the C-amide bond can be suppressed by introducing a bulky f-butyl group in the naphthalene by an S Ar reaction. Addition of crystals of (+)-l 15/116 to f-BuLi in cold toluene provides with good ee s the naphthalene derivatives 117/118 of undetermined absolute configuration. Kinetic resolutions of racemic amines were also performed using the provisional chiral molecular conformation derived from chiral crystals [94]. Despite the attractive features of these examples, planning of absolute asymmetric S Ar transformation remains a difficult task since only about 10% of achiral substrates crystallize in a chiral fashion. 

In some systems, as in one which we shall describe here in some detail, it is possible to generate chiral crystals of one handedness only, starting from achiral or from chiral-racemic molecules, and produce chiral non-racemic products by reaction in these crystals. Thus these coupled processes of crystallization and solid-state reaction provide an asymmetric synthesis in the absence of any outside chiral agent. The term absolute asymmetric synthesis is used to describe such processes which start with achiral materials and lead to non-racemic chiral products in the absence of chiral agents. In this sense our coupled processes of crystallization and solid-state reaction provide such a synthesis. It is clear that the chirality is here in fact introduced in the crystallization step the chemical reaction then transforms the chirality of the crystal into that of the product. The purist may object to the use of the word absolute however it is accepted by polymer chemists in this context [3, 5]. It can be said that the only outside chirality is that of the observer, the role of whom is to detect the asymmetry of the synthesis. On the other hand in a classical transformation, such as Pasteur s famous experiment [6], the role of the observer is to sort crystals of different handednesses, and thus to introduce the chiral element. 

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