2-Alkynyl-5-pyrimidyl alkanol

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... 

Soai et al. established highly enantioselective asymmetric autocatalysis in the asymmetric isopropylation of pyrimidine-5-carbaldehyde 27 (Scheme 14) [44], quinoline-3-carbaldehyde [45], and 5-carbamoylpyridine-3-carbaldehyde [46]. Among these, 2-alkynyl-5-pyrimidyl alkanol is a practically perfect asymmetric autocatalysis [47]. When 0.2 equivalents of 2-alkynyl-5-pyrimidyl alkanol 28b with >99.5% ee was employed as an asymmetric autocatalyst in the isopropylation of 2-alkynylpyrimidine-5-carbaldehyde 27b, it automultiplies in a yield of >99% without any loss of ee (>99.5% ee). When the product was used as an asymmetric autocatalyst for the next run, pyrimidyl alkanol 28b with >99.5% ee was obtained in >99%. Even after tenth round, pyrimidyl alkanol 28b with >99.5% ee was formed in a yield of >99% [47]. 

Moreover, when these alkanols with low ee are utilized as asymmetric autocatalysts, 5-pyrimidyl alkanol 28 [48], 3-quinolyl alkanol [49],and 5-carbamoyl-3-pyridyl alkanols [50] with higher ees were obtained. The successive reactions were performed in order to make the best use of the autocatalysis, that is, the products of one round served as the asymmetric autocatalysts for the next. In the case of pyrimidyl alkanol, staring from (S)-alkanol 28a with only 2% ee, the ee reached almost 90% after four rounds [48] without the assistance of any other chiral auxiliary (Scheme 14). 2-Alkynyl-5-pyrimidyl alkanol 28b [5] and 2-... 

We found that chiral 5-pyrimidyl alkanol, 3-quinolyl alkanol and 5-carbamoyl-3-pyridyl alkanol are highly enantioselective asymmetric autocatalysts for the addition of z-Pr2Zn to the corresponding aldehydes, respectively. Among these, 2-alkynyl-5-pyrimidyl alkanol is a highly efficient asymmetric auto-... 

Scheme 3 Strong chiral amplification in the Soai reaction by using a starting ee of 0.00005% and obtaining the 2-alkynyl-5-pyrimidyl alkanol with an ee of 57% in the first reaction cycle...

Practically perfect asymmetric autocatalysts of the (2-alkynyl-5-pyrimidyl)alkanol series have been identified. A /-butylalkynyl residue fulfills the role of proper bulkiness and moderate electron-withdrawing power. Quartz also induces enantioselective addition of (-Pr2Zn to this heterocyclic aldehyde, by virtue of its morphological chirality and acidity, which enable differentiation of the enantiofaces of the aldehyde upon coordination with the oxygen and nitrogen atoms. Chiral sodium chlorate crystals have the same effect. ... 

Sato I., Omiya D., Igarashi H., Kato K. Ogi Y., Tsukiyama K. and Soai K. (2003) Relationship between the time, yield and enantiomeric excess of asymmetric autocatalysis of chiral 2-alkynyl-5-pyrimidyl alkanol with amplification of enantiomeric excess, Tetrahedr. Asymm. 14, 975-979. 

In summary, we have described how we find out the asymmetric autocatalysis with amplification of chirality in the reaction between pyrimidine-5-carbaldehyde and i-Pr2Zn. 2-Alkynyl-5-pyrimidyl alkanol is a highly enantioselective asymmetric autocatalyst with greater than 99.5% enantioselectivity for the addition of i-Pr2Zn to the corresponding pyrimidine-5-carbaldehydes. Furthermore, it was found that enantiomeric excess of asymmetric autocatalyst enhances during the reaction. Thus, (5)-pyrimidyl alkanol with as low as ca. 0.00005% ee enhanced its ee to... 

This result supports the view that diverse ways exist to obtain chiral biomolecules via CPL or chiral inorganic or organic crystals combined with asymmetric autoctalysis. Kenso Soai and his team studied the effect of the structure of the substituents at position 2 of the pyrimidyl alkanol (Shibata et al. 1996). They found that using 2-alkynyl-pyrimidyl alkanol after three rounds of asymmetric autocatalysis, an astonishing amplification factor of 630,0000 was reached. In the reaction, either (+) or (—) crystals of Cytosine serve as initiators that were formed spontaneously by stirring. In the Soai reaction of chiral amplification, it is crucial that dimers of the O-Zinc diisopropyl intermediate are the active catalysts Racemic pyrimidine alcohols subjected to photolysis with either right- or left-handed CPL produced an ee of one isomer as shown in Fig. 3.4. 

When 2-(ferf-bulylethynyl)pyrimidine-5-carbaldehyde 11, instead of the 2-methyl derivative 9, was subjected to reaction with z-P Zn in the presence of chiral leucine, highly enantioenriched pyrimidyl alkanol 12 with the absolute configuration corresponding to that of chiral leucine was also obtained. But it should be noted that the resulting alkanol 12 showed the opposite enan-tioselectivity to that of alkanol 10, i.e., L-leucine induces the production of (S)-alkanol 12 and D-leucine induces (R)-12, respectively [82]. The asymmetric amplification of 12 with an alkynyl substituent is more significant than that of the 2-methyl derivative 10 to increase to 96% ee (Scheme 11). 

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