Soai asymmetric autocatalysis

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. 

A transient alkoxyacetal intermediate formed by 1 2 combination of (40) and (41) has been observed by NMR for reaction of /-Pr2Zn with (40) promoted by Soai asymmetric autocatalysis by (41) (Scheme 29)... 

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]. 

In the course of the continuing study [9a,b] on the enantioselective addition of dialkylzincs to aldehydes by using chiral amino alcohols such as diphenyl(l-methyl-2-pyrrolidinyl)methanol (45) (DPMPM) [48] A. A -dibutylnorephedrine 46 (DBNE) [49], and 2-pyrrolidinyl-l-phenyl-1-propanol (47) [50] as chiral catalysts, Soai et al. reacted pyridine-3-carbaldehyde (48) with dialkylzincs using (lS,2/ )-DBNE 46, which gave the corresponding chiral pyridyl alkanols 49 with 74-86% ee (Scheme 9.24) [51]. The reaction with aldehyde 48 proceeded more rapidly (1 h) than that with benzaldehyde (16 h), which indicates that the product (zinc alkoxide of pyridyl alkanol) also catalyzes the reaction to produce itself. This observation led them to search for an asymmetric autocatalysis by using chiral pyridyl alkanol. 

Soai K, Shibata T (1999) Asymmetric autocatalysis and biomolecular chirality In Palyi G, Zucchi C, Caglioti L (eds) Advances in biochirality, chap 11. Elsevier, Oxford, p 125... 

Soai K, Sato I, Shibata T (2004) Asymmetric autocatalysis and the origin of homochirality of biomolecules. In Malhotra SV (ed) Methodologies in asymmetric catalysis. J Am Chem Soc, Washington, DC, p 85... 

Soai K, Kawasaki T (2008) Asymmetric Autocatalysis with Amplification of Chirality. 284 1-33... 

Examples of asymmetric autocatalysis are difficult to find. Only quite recently have Soai et al. shown that a catalyzed diorganozinc addition to aldehydes may be... 

Soai and co-workers have developed additions of diisopropylzinc to 2-alkynylpyrimidyl-5-carbaldehydes. The resulting alcohol allows a practically perfect asymmetric autocatalysis.216 Recently, they reported that an efficient amplification by a catalyst with as low as 10 5%ee gives practically enantiomerically pure (>99.5%ee) product in only three consecutive cycles.217 The product formed in situ with enhanced ee serves as an asymmetric autocatalyst. Thus, addition of diisopropylzinc to the carbaldehyde 64 in presence of 20 mol% of the alkanol (61-65 with 10 s% ee gives after 1.5 h (6)-65 with 57% ee. A new addition of the mixture diisopropylzinc/carbaldehyde 64 to the reaction... 

In 1995, Soai and coworkers reported a highly enantiose-lective asymmetric autocatalysis of pyrimidyl alkanol in the enantioselective addition reaction of I-Pr2Zn to pyrimidine-5-carboxaldehyde (equation 63). When a 5-pyrimidyl alkanol with a small enantiomeric excess such as 5x10 % is added to j-Pr2Zn and pyrimidine-5-carboxaldehyde, then the reaction... 

Soai, K. Shibata, T. Sato, I. Enantioselective Automultiplication of Chiral Molecules by Asymmetric Autocatalysis, Acc. Chem. Res. 2000,55, 382-390. 

Soai, K. Asymmetric Autocatalysis and Biomolecular Chirality, Adv. Biochirality, Palyi, G. Zucchi, C. Caglioti, L., Eds. Elsevier Amsterdam, The Netherlands, 1999. 

Soai has reported the remarkable example of asymmetric autocatalysis in carbonyl-addition reactions of diisopropylzinc [40- 3, 45]. Usually, zinc alkoxide forms an inactive tetramer. However, the use of pyridyl aldehyde as a substrate to give pyridyl alcohol product can loop the catalytic cycle without formation of the inac-... 

Soai et al. discovered and developed asymmetric autocatalysis (Figure 9), in which the structures of the chiral catalyst (5)-54 and the chiral product (5)-54 are the same after the addition of diisopropylzinc to aldehyde 53. Consecutive asymmetric autocatalysis starting with (S)-54 of 0.6% ee amplifies its ee, and yields itself as the product with >99.5% ee. Even chiral inorganic crystals, such as quartz or sodium chlorate, act as chiral inducers in this reaction. Soai et alls asymmetric autocatalysis gives us an insight to speculate on the early asymmetric reactions on this planet Earth. However, it can be argued whether such strictly anhydrous organometallic reactions are possible under the nonartificial conditions or not. 

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. 

Direct asymmetric autocatalysis amplified the slight excess of one enantiomer, leading to the enantiopure compound by reaction with diisopropylzinc. It is widely accepted that enantiomerically enriched products must form from achiral precursors merely because of statistical fluctuations. Usually, however, enantiomeric enrichment by fluctuations is very low. Thus, an amplification process of enantiomeric enrichment is required. Detailed kinetic analysis revealed that autocatalysis and inhibition are the major players in asymmetric autocatalytic synthesis. It turned out that tetramers serve as catalyst in the Soai reaction. The transition state for the Soai reaction implicates two molecules of pyrimidine alcohols or alcoxides as the dimeric catalysts and one molecule of prochiral aldehyde substrate (Buono and Blackmond 2003). Further kinetic studies using different ratios of substrate and reagent showed that a tetramer template is used. 

Shibata T, Morioka H, Hayase T, Choji K, Soai K (1996) Highly enantioselective catalytic asymmetric auto-multiplication of chiral pyrimidyl alcohol. J Am Chem Soc 118 471-472 Soai K, Kawasaki T (2006) Discovery of asymmetric autocatalysis with amplification of chirality and its implication in chiral homogeneity of biomolecules. Chirality 18 469-478 Szostak JW (2010) On the origins of primitive cells from nutrient intake to elongation encapsulated nucleotides. Angew Chem 49 3738-3750 Szostak JW et al (2001) Synthesizing life. Nature 409 387-390... 

This is easily demonstrated in what Soai calls practically perfect asymmetric autocatalysis with the special aldehyde 221 using 20mol% of the previously prepared product 222 as catalyst and enough i-Pr2Zn to allow for the conversion of the catalyst to the zinc alkoxide. There is considerable amplification if the catalyst 222 has 5.5% ee, the product (also 222) is 70% ee. But if enantiomerically pure catalyst is used, the yield and the ee of the product are practically perfect. Each molecule of catalyst produces five molecules of itself as product. The amplification factor is six and if the whole of the product is used in a second reaction with five times as much aldehyde a second batch of 222, 36 times as much, is the product.51... 

Several scientists had pointed out the importance of asymmetric autocatalysis but it remained a theoretical system until Soai found an asymmetric alkylation of pyridine-3-carbaldehyde the 3-pyridylalkanol functions as an asymmetric autocatalyst in an enantioselective alkylation of pyridine-3-carbaldehyde us-... 

Recently it has been shown that optically active quartz crystals as asymmetric inductors become very effective in autocatalytic enantioselective reactions. Soai et al. have shown that in asymmetric autocatalysis, the action of small amounts of chiral reaction products (involved in the reaction cycle) may enhance the enantioselective excess by a factor of 94 after introduction of an intermediate into the reaction. Optically active synthetic quartz crystals were used in this reaction with ratios of 1 1.9 quartz to aldehyde and 1 2.2 quartz to diisopropyl-zinc. 

Soai K., Shibata T., Morioka H. and Choji K (1995) Asymmetric autocatalysis and amplification of enantiomeric excess of a chiral... 

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. 

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. 

Soai K, Kawasaki T Discovery of asymmetric autocatalysis with amplification of chirality and its implication in chiral homogeneity of biomolecules. Chirality 2006, 18(7) 469-478. 

J. M. Brown, I. Gridnev and J. Klankermayer, Asymmetric Autocatalysis with Organozinc Complexes Elucidation of the Reaction Pathway , in Topics in Current Chemistry, ed. K. Soai, Springer GmbH, 2008, vol. 284, Amplification of Chirahty, p. 35. 

Soai, K. Shibata, T Morioka, H. Shoji, K. Asymmetric Autocatalysis and Amplification of Enantiomeric Excess of a Chiral Molecule. Nature 1995,378, 767. 

Soai, K. Kawasaki, T. Discovery of Asymmetric Autocatalysis with Amplification of Chirality and Its Implications in Chiral Homogeneity of Biomolecules. Chirality 2006, 18, 469. 

Kawasaki, T Soai, K. Asymmetric Induction Arising from Enantiomerically Enriched Carbon-13 Isotopomers and Highly Selective Chiral Discrimination by Asymmetric Autocatalysis. Bull. Chem. Soc. Jpn. 2011,84, 879-892. 

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. 

Gehring, T. Quaranta, M. Odell, B. Blackmond, D. G. Brown, J. M. Observation of a Transient Intermediate in soai s Asymmetric Autocatalysis Insights from Turnover in Real Time. Angew. Chem. Int. Ed. 2012, 51, 9539-9542. 

Soai K, Shibata T, Sato I (2000) Enantioselective automultiplication of chiral molecules by asymmetric autocatalysis. Acc Chem Res 33 382-390. doi 10.1021/ar9900820... 

Soai K, Shibata T, Sato I (2004) Discovery and development of asymmetric autocatalysis. Bull Chem Soc Jpn 77 1063-1073. doi 10.1246/bcsj.77.1063... 

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