Autocatalysis chiral organic compounds

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. 

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

Asymmetric Autocatalysis Triggered by Chiral Organic Compounds... 

Scheme 9 Asymmetric autocatalysis initiated with chiral organic compounds...

We reasoned that chiral organic compounds with low ee induced by CPL can act as a chiral trigger in the enantioselective addition of z -Pr2Zn to pyrimidine-5-carbaldehyde, and that the subsequent asymmetric autocatalysis of pyrimidyl alkanol, formed in situ, amplifies its ee to produce highly enantioenriched pyrimidyl alkanol with an absolute configuration corresponding to that of the handedness of the CPL. 

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. 

In these systems, after the crystal chirality induced the chirality of asymmetric carbon in external organic compound, the subsequent asymmetric autocatalysis gives the greater amount of enantiomerically amplified product. These results clearly demonstrate that the crystal chirality of achiral organic compound is responsible for the enantioselective addition of /-Pr2Zn to pyrimidine-5-carbalde-hyde Ic. 

As described, asymmetric autocatalysis with amplification of chirality is a powerful tool to correlate the origin of chirality with highly enantioenriched organic compounds. 

As shown in Scheme 9, various organic compounds can act as a chiral initiator of asymmetric auto catalysis. 2-Methylpyrimidine-5-carbaldehyde 9 was subjected to the addition of z-Pr2Zn in the presence of chiral butan-2-ol, methyl mandelate and a carboxylic acid [74], When the chiral alcohol, (S)-butan-2-ol with ca. 0.1% ee was used as a chiral initiator of asymmetric autocatalysis, (S)-pyrimidyl alkanol 10 with 73% ee was obtained. In contrast, (,R)-butan-2-ol with 0.1% ee induced the production of (A)-10 with 76% ee. In the same manner, methyl mandelate (ca. 0.05% ee) and a chiral carboxylic acid (ca. 0.1% ee) can act as a chiral initiator of asymmetric autocatalysis, therefore the S- and IC enantiomers of methyl mandelate and carboxylic acid induce the formation of (R)- and (S)-alkanol 10, respectively. Chiral propylene oxide (2% ee) and styrene oxide (2% ee) also induce the imbalance of ee in initially forming the zinc alkoxide of the pyrimidyl alkanol in the addition reaction of z-Pr2Zn to pyrimidine-5-carbaldehyde 11 [75]. Further consecutive reactions enable the amplification of ee to produce the highly enantiomerically enriched alkanol 12 (up to 96% ee) with the corresponding... 

Scheme 11 Asymmetric autocatalysis with amplification of chirality triggered by CPL-induced organic compound with small ee...

Thus, low enantioenrichments in compounds induced by CPL have been correlated for the first time to an organic compound with very high enantioenrichments by asymmetric autocatalysis with amplification of chirality. 

The achiral inorganic ionic sodium chlorate (NaClOs) and sodium bro-mate (NaBrOs) crystallize in enantiomeric forms belonging to the P2i3 space group for which the same crystal structures exhibit opposite optical rotation [89]. The levo-(Z) and dextrorotatory (d) crystals can be obtained in equal proportions [90]. The chiral ionic crystals of NaClOs and NaBrC>3 were subjected to asymmetric autocatalysis as the initial seed of chirality to study the correlation between the organic compound with high ee and the chiral inorganic crystal composed of achiral ionic components. 

Enantioselective Synthesis Mediated by Chiral Crystals of an Achiral Organic Compound in Conjunction with Asymmetric Autocatalysis... 

Some achiral organic compounds form chiral crystals, with each crystal exhibiting one of two possible enantiomorphs [9-13]. These chiral crystals composed of an achiral organic compound may serve as an efficient chiral seed in a prebiotic world, therefore, a study of asymmetric autocatalysis using these chiral organic crystals is an interesting subject. 

When pyrimidine-5-carbaldehyde 11 was treated with z-Pr2Zn in the presence of powdered [CD(+)260]-crystal, (S)-pyrimidyl alkanol with 73% ee was obtained in 88% yield (Scheme 16). On the other hand, in the presence of [CD(-)260]-crystal, the opposite enantiomer (R)-12 with 89% ee was isolated in 89% yield. When the crystals, grown from the stirred methanol solution of hippuric acid using each enantiomorph of hippuric acid as the seed crystal, were used in asymmetric autocatalysis, the same correlation between the chirality of crystal and the product 12 was observed with excellent reproducibility. It should be noted that nearly enantiopure (S)- and (K)-pyrimidyl alkanols 12 with > 99.5% ee were obtained by consecutive asymmetric autocatalysis [64], In this system, after the enantiomorphs of the crystal induced the chirality of an external organic compound, the subsequent asymmetric autocatalysis gave a greater amount of enantiomerically amplified product. 

On the other hand, the IOM samples from which several percent amounts of organic compounds had been removed by hydrothermolytic treatment (IOM-H) gave results that are in sharp contrast to the above-mentioned meteoritic sample. Here, both (R)- and (S)-pyrimidyl alkanol 12 were obtained equally and indicate the absence of chiral factors in the IOM-H sample, i.e., the results are stochastic. Similar stochastic results were obtained on conducting the asymmetric autocatalysis in the presence of Murchison powders from which all the organic material had been removed by exposure to oxygen plasma. 

Chiral organic crystals composed of achiral compounds such as hippuric acid act as the initial source of chirality of asymmetric autocatalysis to produce the highly enantiomerically pure product. In this reaction, chiral organic crystals are utilized as a chiral inducer, not as a reactant. Therefore, these results are the realization of the process in which the crystal chirality of achiral organic compounds induces asymmetry in another organic compound whose chirality was amplified to produce a large amount of enantiomerically pure organic compound, pyrimidyl alkanol in conjunction with asymmetric autocatalysis. 

Highly sensitive chiral discrimination of amino acids with low ee was described. Amino acids with low ee act as a chiral initiator of asymmetric autocatalysis. In the presence of amino acids with low ee, pyrimidine-5-carbaldehyde was treated with z-P Zn to produce chiral pyrimidyl alkanol with the absolute configuration correlated with that of the amino acid by the consecutive asymmetric autocatalysis with amplification of ee. In addition, direct examination of extraterrestrial chirality was performed using meteorites by applying the asymmetric autocatalysis as the chiral sensor. The results indicated the presence of some chiral factor in the meteorites other than known organic compounds such as amino acids. 

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. 

TABLE 3. Asymmetric autocatalysis in reaction of 87 initiated by chiral inorganic crystals, inorganic-organic hybrid materials and chiral cocrystals of achiral compounds... 

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