Asymmetric synthesis, autocatalysis

Another achievement in recent asymmetric reaction study is the so-called chiral autocatalysis—where the product itself catalyzes its own asymmetric synthesis. In this process, the chiral catalyst and the products are the same in an asymmetric autocatalytic reaction. The separation of chiral catalyst from the product is not required, because the product itself is the catalyst. Starting from an optically active product with very low ee, this process allows the formation of a product with high ee values.106,114... 

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 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. 

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

In the absence of any chiral factors, the probability of the formation of S- and 77-enantiomers is 1 to 1. However, the numbers of the resulting two enantiomers are not exactly the same in almost all cases. Mislow197 described the inevitability of small enantiomeric enrichment in absolute asymmetric synthesis. According to the statistics, it is expected that a fluctuation in the ratio of the S- and 77-enantiomers becomes more and more likely as the numbers in the enantiomer mixture become smaller198. Thus, if the asymmetric autocatalysis is initiated without adding any chiral substance, small fluctuations of enantiomers produced in the initial stage could be enhanced by consecutive asymmetric autocatalytic reaction of pyrimidyl alkanol with amplification of chirality. 

In 1953, Frank proposed a reaction mechanism without showing any chemical structure for the molecules, in which a chiral product acts as a chiral catalyst for its own production (asymmetric autocatalysis) and prohibits the formation of its antipode [411. In such a reaction, if it exists, the enantiomeric purity of the product would increase as the reaction progresses. Since then, asymmetric autocatalysis has attracted considerable conceptual interest [42], However, it was not until 1990 that the first asymmetric autocatalysis in asymmetric synthesis was reported [43]. 

Unlike conventional catalytic asymmetric synthesis, asymmetric autocatalysis possesses the following novel features ... 

Thus, asymmetric autocatalysis is one of the most energy- and resource-saving processes in asymmetric synthesis. 

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

Soai K Shibata T (2000) Asymmetric amplification and autocatalysis In Ojima I (ed) Catalytic asymmetric synthesis, 2nd ed, chap 9. Wiley-VCH, New York, p 699... 

Fig. 17 Absolute asymmetric synthesis observed by 1H NMR. The lower trace is a solution of the racemic square planar dimer in toluene-ds with separate signals for (R, S [low field]) and (R, R ) forms. The upper trace shows the final product of autocatalysis without initial added catalyst, giving a product of >80% ee...

Abstract The addition of diisopropylzinc to prochiral pyrimidine carbaldehydes (Soai reaction) is the only known example of spontaneous asymmetric synthesis in organic chemistry. It serves as a model system for the spontaneous occurrence of chiral asymmetry from achiral initial conditions. This review describes the possible kinetic origin of specific experimental features of this reaction. It is shown that generic kinetic models, including enantioselective autocatalysis and mutual inhibition between the enantiomers,... 

During classical asymmetric synthesis, the amplitude of these fluctuations are expected to decrease during the course of the reaction because more and more chiral molecules are formed and eeeXp declines. However, in the presence of chiral autocatalysis, the small ee caused by such fluctuations can be amplified. In such cases, the system is likely to be most sensitive in the initial stage of reaction when the concentration of chiral molecules is still small. If the autocatalytic species are concentrated they can be either in a racemic or optically active state but if they are highly diluted, as at the beginning of the reaction, statistical fluctuations can become significant so that the state... 

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. 

Asymmetric amplification in reactions involving partially resolved chiral auxiliaries is now a well-established phenomenon that is very attractive since it gives improved enantioselectivities witb respect to expectations based upon the ee of the auxiliary. It may have practical application in that enantiomerically pure chiral auxiliaries are not always required for highly selective asymmetric synthesis. Asymmetric amplification is also of fundamental importance in order to achieve efficient asymmetric autocatalysis. Finally, evidence of an asymmetric amplification is a very useful piece of information in mechanistic studies. 

K. Soai, T. Shibata, Asymmetric Amplification and Autocatalysis, in Catalytic Asymmetric Synthesis (I. Ojima, Ed.), Wiley-VCH, New York, 2nd ed., 2000, 699-726. 

The cpl-induced asymmetry in photoreactions as described in Sec. B. of this chapter is not very pronounced. In order to obtain ees in excess of a few percent, photodestruction must be chosen and most of the reactant material must be sacrificed. Therefore amplification mechanisms for all types of cpl-induced asymmetric photoreactions would be highly desirable. Autocatalysis, i.e., an asymmetric synthesis where a chiral product acts as a catalyst for its own production [128], and autoinduction, i.e., the stimulation of a chiral catalyst by a chiral product [44,129], are options. Autocatalytic systems that will tilt to one enantiomeric side were introduced by Frank [130] and Seelig [131]. 

Soai K., Sato I., Shibata T., Komiya S., Hayashi M., Matsueda Y., Imamura H., Hayase T., Morioka H., Tabira H., Yamamoto J. and Kowata Y. (2003) Asymmetric synthesis of pyrimidyl alkanol without adding chiral substances by the addition of diisopropylzinc to pyrimidine-5-carbaldehyde in conjunct-tion with asymmetric autocatalysis, Tetrahedr. Asymm. 14, 185-188. 

Singleton, D. A. Vo, L. K. A Few Molecules Can Control the Enantiomeric Outcome. Evidence Supporting Absolute Asymmetric Synthesis Using the Soai Asymmetric Autocatalysis. Org. Lett. 2003,5, 4337. 

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. 

Blackmond, D. G. Kinetic Aspects of Non-Linear Effects in Asymmetric Synthesis, Catalysis, and Autocatalysis. Tetrahedron Asymmetry 2010, 21, 1630-1634. 

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... 

Barabas B, Toth J, Palyi G (2010) Stochastic aspects of asymmetric autocatalysis and absolute asymmetric synthesis. J Math Chem 48 457-489. doi 10.1007/sl0910-010-9680-8... 

Barabas B, Caglioti L, Micskei K, Palyi G (2009) Data-based stochastic approach to absolute asymmetric synthesis by autocatalysis. Bull Chem Soc Jpn 82 1372-1376. doi 10.1246/ bcsj.82.1372... 

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