Autocatalysis, asymmetric

Design of chiral catalysis and asymmetric autocatalysis for diphenyl-(l-methyl-pyrrolidin-2-yl) methanol-catalyzed enantioselective additions of organozinc reagents 97YGK994. 

Another attempt to explain the homochirality of biomolecules is based on autocatalysis. The great advantage of asymmetric catalysis is that the catalyst and the chiral product are identical and thus do not need to be separated (Buschmann et al., 2000). The racemic mixture must have been affected by a weak perturbation in order that autocatalysis, which acts as an amplifier of enantioselectivity, could have led to only one of the two enantiomeric forms. This perturbation could have been due to the slight energy difference of the enantiomers referred to above, or to statistical fluctuations. 

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... 

Another practically perfect asymmetric catalysis has been observed in reactions using (2-alkynyl-5-pyrimidyl)alkanols as the catalyst. The asymmetric autocatalysis shown in Scheme 8-59 gives the corresponding product in high yield with over 99% ee.116... 

ASYMMETRIC AUTOCATALYSIS WITH AMPLIFICATION OF CHIRALITY AND ORIGIN OF CHIRAL HOMOGENEITY OF BIOMOLECULES... 

Significant progress has been witnessed in asymmetric catalysis/ In conventional asymmetric catalysis, the asymmetric catalyst C provides the enantioenriched product P, whose structures are generally different from those of the asymmetric catalysts. In contrast, asymmetric autocatalysis is an automultiphcation of a chiral compound P, in which the chiral product P acts as a chiral catalyst P for its own production/ ... 

Asymmetric autocatalysis has the following intrinsic merits (1) the efficiency is high because the process is automultiplication (2) in an ideal asymmetric autocatalysis, no decrease in the amount of catalyst and no deterioration of the catalytic activity should be observed because the amount of catalyst increases during the reaction and (3) there is no need to separate the catalyst from the product because their structures are identical. Frank proposed a kinetic model of asymmetric autocatalysis without mentioning a specific compound or reaction." ... 

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. 

When (5)-2-a]kynyl-5-pyrimidyl alkanol 2c with >99.5% ee was employed as an asymmetric autocatalyst, (5)-2c with >99.5% ee composed of both the newly formed 2c and the initially used 2c was obtained. The yield of the newly formed 2c was >99%. To make use of the advantage of asymmetric autocatalysis—that the structures of the asymmetric autocatalyst and the product are the same—the 2c obtained in the first round was used as an asymmetric autocatalyst for the following round. Again, the product (5)-2c and the initial autocatalyst had an ee of >99.5% and the yield of the newly formed (S)-2c was >99%. The product 2c was therefore used as an asymmetric autocatalyst for the following round. Even after the 10th round, the yield of 2c was >99% and the ee was >99.5%. Thus, 2-aIkynyl-5-pyrimidyl alkanol 2c served as a virtually perfect asymmetric autocatalyst. Moreover, the amount of (S)-2c automultiplied by a factor of 60 million during the 10 rounds ... 

Asymmetric autocatalysis using (5)-pyrimidyl alkanol 2a with only 2% ee afforded (5)-2a with an increased ee of 10%, [Eq. (9.4)]. The (5)-2a obtained with 10% ee was then used as an asymmetric autocatalyst for the following asymmetric autocatalysis. (5)-Pyrimidyl alkanol 2a with an increased ee of 57% was obtained. The subsequent consecutive asymmetric autocatalysis and the use of that product as an asymmetric autocatalyst for the following round gave (5)-pyrimidyl alkanol 2a with 81 % and 88% ee, respectively. Thus, the overall process was the asymmetric autocatalysis of (5)-2a starting from a low ee of 2% with significant amplification of chirality to 88% ee, with the increase in the amount without need for other chiral auxiliary. ° This stands as the first example of an asymmetric autocatalysis with amplification of ee. In addition, one-pot asymmetric autocatalysis of pyrimidyl alkanol 2b also significantly increased the chirality from 0.28 to 87% ee. ... 

ASYMMETRIC AUTOCATALYSIS AND ITS ROLE IN THE ORIGIN AND AMPLIFICATION OF CHIRALITY... 

Asymmetric Autocatalysis Triggered by Organic Compounds Induced by Circularly Polarized Light... 

Irradiation of CPL to racemic alkylidenecyclohexanone induces a small enantiomeric imbalance, which triggers the subsequent asymmetric autocatalysis to afford highly enantioenriched pyrimidyl alkanol 2c with the absolute configuration corre-... 

Thus, a slight enantiomeric imbalance in compounds induced by CPL was correlated for the first time to an organic compound with very high ee by asymmetric autocatalysis with amplification of chirality. Moreover, various chiral organic compounds such as 1,1-binaphthyl,[2.2]paracyclophanes, and primary alka-nols due to deuterium substitution have been found to serve as chiral triggers in asymmetric autocatalysis. 

We have demonstrated the enantioselective synthesis of near-enantiopure compounds by asymmetric photodegradation of racemic pyrimidyl alkanol 2c by circularly polarized light followed by asymmetric autocatalysis. This is the first example of asymmetric autocatalysis triggered directly by a chiral physical factor CPL. 

Asymmetric Autocatalysis Triggered by Chiral Inorganic Crystals... 

In addition, helical silica and chiral organic-inorganic hybrid silica were found to serve as chiral triggers of asymmetric autocatalysis ... 

As described, a chiral organic compound with high ee is formed using chiral inorganic crystals in conjunction with asymmetric autocatalysis. 

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