Spontaneous absolute asymmetric synthesis

E. Stochastic Production of S- and /7-Enantiomers without Adding a Chiral Source by Asymmetric Autocatalysis Spontaneous Absolute Asymmetric Synthesis... 

Absolute asymmetric synthesis refers to the situation in which an asymmetric induction occurs in the absence of an externally imposed source of chirality [5]. Such reactions are invariably carried out in the crystalline state, where the asymmetric influence governing the enantioselectivity derives from the spontaneous crystallization of an achiral compound in a chiral space group. This phenomenon, which is analogous to the spontaneous crystallization of racemates as... 

We describe highly enantioselective asymmetric autocatalysis with amplification of chirality and asymmetric autocatalysis initiated by chiral triggers. Asymmetric autocatalysis correlates between the origin of chirality and the homochirality of organic compounds. We also describe spontaneous absolute asymmetric synthesis in combination with asymmetric autocatalysis. 

Spontaneous absolute asymmetric synthesis, that is the statistical formation of enantioenriched compounds from achiral reagents without the intervention of any chiral auxiliary, has been proposed as one of the origins of chirality. Without using... 

Spontaneous absolute asymmetric synthesis is described in the formation of enantiomerically enriched pyrimidyl alkanol from the reaction of pyrimidine-5-car-baldehyde and /-Pr2Zn without adding chiral substance in combination with asymmetric autocatalysis. The approximate stochastic distribution of the absolute conhgurations of the product pyrimidyl alkanol strongly suggests that the reaction is a spontaneous absolute asymmetric synthesis. 

In this reaction, achiral A-methacryloylthiobenzanilide 39 gave chiral crystals by spontaneous crystallization, and absolute asymmetric synthesis was performed by the solid-state photoreaction leading to optically active thietane-fused 3-thiolactam. The reaction mechanism for the cyclization was elucidated on the basis of the correlation between the absolute structures of both the prochiral starting monothioimide and the photoproduct. 

Spontaneous Absolute Asymmetric Synthesis in Conjunction with Asymmetric Autocatalysis... 

Scheme 19 Spontaneous absolute asymmetric synthesis of pyrimidyl alkanol without the addition of a chiral substance...

We have demonstrated the stochastic formation of (S)- and (,R)-5-pyrimidyl alkanol 12 from pyrimidine-5-carbaldehyde 11 and i-V Zn without the intervention of a chiral auxiliary. Even in the reactions performed in toluene alone, stochastic behavior of the formation of (S)- and (A)-12 was observed in the presence of achiral silica gel. We believe that the approximate stochastic behavior in the formation of alkanols fulfils one of the conditions necessary for chiral symmetry breaking by spontaneous absolute asymmetric synthesis. 

One of the main features of asymmetric autocatalysis and the formation of the helix is that the initial extremely low enantioenrichment is amplified significantly to near enantiopure. These processes of amplification of chirality have become powerful tools to elucidate the origin of chirality of organic compounds. For example, by using asymmetric auto catalysis, spontaneous absolute asymmetric synthesis without the intervention of any chiral factor has been realized. 

The first use of crystals to achieve asymmetric induction in a chemical reaction was reported by Penzien and Schmidt in 1969 [3]. In what the authors termed an absolute asymmetric synthesis because it occurs in the absence of any external source of optical activity, Penzien and Schmidt showed that the achiral compound 4,4 -dimethylchalcone 1 crystallizes spontaneously from ethyl acetate in the chiral space group P2i2121, and when enantiomorphously pure... 

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]. 

Of course, these reactions are not true examples of absolute asymmetric synthesis because the first excess of the i -enantiomer formed on the base of stochastic distribution served as the trigger for the next repeated reactions similar to the iniating crystal in spontaneous crystallization. 

Suzuki, K Hatase, K. Nishiyama, D. Kawasaki, T. Soai, K. Spontaneous Absolute Asymmetric Synthesis Promoted by Achiral Amines in Gonjunction with Asymmetric Autocatalysis. /. Syst. Chem. 2010,1, 5. 

Before considering in detail the different approaches to asymmetric synthesis, it is worth looking briefly at all the methods available to obtain chiral compounds in non-racemic form. Some methods, such as the spontaneous crystallisation of enantiomers and absolute asymmetric synthesis using circularly polarised light, are of little general value and will not be considered here. 

Keywords Amplification of ee Asymmetric autocatalysis Automultiplication Chiral discrimination Circularly polarized light Quartz Isotope chirality Origin of chirality Pyrimidyl alkanol Spontaneous absolute asymmetric synthesis... 

Meanwhile, we noticed a short review by Wynberg in the same year on asymmetric autocatalysis [22]. He introduced the theoretical paper of Frank [23] on spontaneous asymmetric synthesis. He explained that no experimental realization of asymmetric autocatalysis had ever been achieved. He also described the potential difficulties to realize asymmetric autocatalysis (1) chiral product should have the catalytic activity for producing itself, (2) asymmetric autocatalyst of certain absolute configuration should induce the same absolute configuration of the product, and (3) enantiomeric excess of the product should not decrease because the repeated... 

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