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Spontaneous absolute asymmetric synthesis promoted by achiral amines in conjunction with asymmetric autocatalysis

Journal of Systems Chemistry volume 1, Article number: 5 (2010) Cite this article

Abstract

The origin of homochirality of organic compounds such as L-amino acids and D-sugars have intrigued many scientists, and several hypotheses regarding its homochirality have been proposed. According to the statistical theory, small fluctuations in the ratio of the two enantiomers are present in a racemic mixture obtained from the reaction of achiral molecules.

We report herein the reaction of pyrimidine-5-carbaldehyde and diisopropylzinc in the presence of achiral amine such as N,N'-dimethylpiperazine, N,N'-diethylpiperazine or N-methylmorpholine but in the absence of a chiral substance. The stochastic formation of (S)- and (R)-pyrimidyl alkanols with detectable ee was observed. This study shows that the slight fluctuation of the enantiomeric ratio of pyrimidyl alkanol produced at the initial reaction step can be enhanced significantly in conjunction with asymmetric autocatalysis with amplification of enantiomeric excess. We believe that the stochastic behavior in the formation of pyrimidyl alkanol constitutes one of the conditions necessary for spontaneous absolute asymmetric synthesis.

Background

The origin of biomolecular homochirality such as L-amino acids and D-sugars is an interesting mystery [1–6]. Spontaneous absolute asymmetric synthesis [1], that is, the synthesis of enantioenriched products from achiral conditions in the absence of a chiral substance, has been proposed as one of the origins of chirality. Spontaneous asymmetric crystallization of achiral compounds is another of the proposed mechanisms of homochirality [7–10]. However, spontaneous absolute asymmetric synthesis without using chiral compounds differs from crystallization in that it is possible for an increase in the amount of chiral compound to occur. Experimental realization of spontaneous absolute asymmetric synthesis via asymmetric autocatalysis has been a challenge, although the theories have been proposed [11–13].

During our continuing studies of asymmetric autocatalysis [14–25], we have observed asymmetric autocatalysis of 5-pyrimidyl alkanols in the enantioselective addition of diisopropylzinc (i-Pr2Zn) to pyrimidine-5-carbaldehyde. It is noteworthy that, even when an asymmetric autocatalyst with an extremely low ee was used as the initial catalyst, an almost enantiomerically pure product, i.e., asymmetric autocatalysis, could be obtained by consecutive reactions [16]. For example, when pyrimidyl alkanol with ca. 0.00005% ee was used as the initial catalyst, almost enantiomerically pure (> 99.5% ee) product was obtained after three consecutive asymmetric autocatalytic reactions [16]. Moreover, a variety of chiral organic compounds [26, 27] and inorganic crystals including isotopically chiral compounds [28, 29], inorganic crystals such as quartz [30], organic crystals of achiral compounds [31, 32] and even a physical chiral factor, that is, right- or left-handed circularly polarized light [33], can act as chiral initiators to afford 5-pyrimidyl alkanol with a high ee in conjunction with asymmetric autocatalysis, with the product having an absolute configuration corresponding to that of the chiral initiators.

On the other hand, from the standpoint of statistics, small fluctuations in the ratio of the two enantiomers are expected to be present in racemic mixtures of chiral molecules [1, 34, 35]. We envisaged that when the reaction system involves asymmetric autocatalysis with amplification of ee, the initial small imbalance of enantiomers in racemic mixtures that arises from the reaction of achiral reactants becomes overwhelming to afford a highly enantiomerically enriched product [36–44].

We have reported that without adding any chiral substance, enantioenriched (S)- or (R)-pyrimidyl alkanol 2 is generated in an approximately stochastic distribution from the reaction between pyrimidine-5-carbaldehyde 1 and i-Pr2Zn in conjunction with asymmetric autocatalysis [45–48].

Results and Discussion

We previously reported that dialkylzincs are activated by amines to add to aldehydes [49, 50]. Because an amine is a Lewis base, it coordinates to the zinc atom of dialkylzinc [51], and this coordination enhances the nucleophilic character of the dialkylzinc. We reasoned as follows: when achiral amine is added to the reaction between aldehyde 1 and i-Pr2Zn, the achiral amine acts as a catalyst to promote the formation of racemic alkanol 2 with statistical fluctuation of chirality. The initial enantioenrichment would be amplified by the subsequent asymmetric autocatalysis to afford (S)- or (R)-alkanol 2.

Here, we report that the enantioenriched pyrimidyl alkanol 2 is generated from the reaction between pyrimidine-5-carbaldehyde 1 and i-Pr2Zn in conjunction with asymmetric autocatalysis under achiral conditions in the presence of an achiral amine, such as N,N'-dimethylpiperazine 3, N,N'-diethylpiperazine 4 or N-methylmorpholine 5 (Figure 1).

Figure 1
figure 1

Asymmetric synthesis of pyrimidyl alkanol in the presence of achiral amines without the addition of a chiral substance; After the reaction between pyrimidine-5-carbaldehyde 1 and i -Pr 2 Zn in the presence of achiral amines, asymmetric autocatalysis amplified the spontaneously generated small fluctuation of ee to afford the enantiomerically enriched ( S )- or ( R )-5-pyrimidyl alkanol 2.

Full size image

First, reaction of pyrimidine-5-carbaldehyde 1 with i-Pr2Zn in the presence of achiral N,N'-dimethylpiperazine 3 in toluene, followed by one-pot asymmetric autocatalysis with amplification of ee, was examined. The enantioenriched (S)- or (R)-5-pyrimidyl alkanol 2 was obtained. The results are shown in Table 1. To examine the distribution of the absolute configuration of the predominantly formed enantiomer 2, 75 experiments were run under the same reaction conditions. In all cases, enantioenriched 5-pyrimidyl alkanols 2 with either S or R configurations were formed. As shown in Figure 2a, the absolute configurations of the resulting 5-pyrimidyl alkanol 2 exhibited an approximate stochastic distribution (the S form occurred 39 times and the R form occurred 36 times). It should be noted that the ee of the product 2 can be easily amplified significantly by further consecutive asymmetric autocatalytic reactions. That is, by using the alkanol 2 with low to moderate ee obtained in the described method as the asymmetric autocatalyst, additional reactions between pyrimidine-5-carbaldehyde 1 and i-Pr2Zn could afford finally almost enantiomerically pure product 2 with the same absolute configuration as to the submitted asymmetric autocatalyst, in highly reproducible manner [16].

Table 1 Asymmetric synthesis of pyrimidyl alkanol 2 without adding chiral substances by the addition of diisopropylzinc to pyrimidine-5-carbaldehyde 1 in the presence of N,N'-dimethylpiperazine 3.
Full size table
Figure 2
figure 2

Histogram of the absolute configuration and enantiomeric excess of pyrimidyl alkanol 2. The reaction of aldehyde 1 with i-Pr2Zn in the presence of (a) N,N'-dimethylpiperazine 3, (b) N,N'-diethylpiperazine 4, (c). N-methylmorpholine 5, (d) total of (a), (b) and (c); stochastic behavior in the formation of (S)- and (R)-5-pyrimidyl alkanols 2 was observed in the presence of achiral amines 3-5, respectively.

Full size image

Next, the addition of i-Pr2Zn to pyrimidine-5-carbaldehyde 1 in the presence of achiral N,N'-diethylpiperazine 4 was examined. The results are summarized in Table 2 and Figure 2b. The absolute configurations of the pyrimidyl alkanol 2 formed show an approximate stochastic distribution (formation of S 9 times and R 11 times). The reaction in the presence of achiral N-methylmorpholine 5 gave the results of the stochastic formation of (S)- and (R)-alkanol 2 (formation of S 11 times and R 9 times, Table 3 and Figure 2c). The total distribution of alkanol 2 in the presence of achiral amines 3-5 is summarized in Figure 2d. The results of the formation of (S)-2 in 59 times and (R)-2 in 56 times strongly suggest that the reaction is spontaneous absolute asymmetric synthesis.

Table 2 Asymmetric synthesis of pyrimidyl alkanol 2 without adding chiral substances by the addition of diisopropylzinc to pyrimidine-5-carbaldehyde 1 in the presence of N,N'-diethylpiperazine 4.
Full size table
Table 3 Asymmetric synthesis of pyrimidyl alkanol 2 without adding chiral substances by the addition of diisopropylzinc to pyrimidine-5-carbaldehyde 1 in the presence of N-methylmorpholine 5.
Full size table

Experimental

The typical experimental procedure is as follows: The pyrimidine-5-carbaldehyde 1 (37.6 mg, 0.20 mmol) dissolved in 2.0 mL of toluene was added dropwise over a period of 1 h to a mixture of i-Pr2Zn (0.40 mL of 1 M toluene solution, 0.40 mmol) and achiral N,N'-dimethylpiperazine 3 (1.1 mg, 1.0 × 10-2 mmol) in toluene (4.0 mL) at 0°C. After the mixture was stirred for a period of 12 h at 0°C, 6.6 mL of toluene and i-Pr2Zn (0.80 mL of 1 M toluene solution, 0.80 mmol) were added successively, and the mixture was stirred at 0°C for a period of 15 min. The aldehyde 1 (75.3 mg, 0.4 mmol) in 2.0 mL of toluene was added dropwise at 0°C over a period of 40 min. After the mixture was stirred at 0°C for a period of 2 h, the reaction was quenched using 2.4 mL of 1 M hydrochloric acid. Saturated aqueous sodium hydrogen carbonate (7.2 mL) was then added, and the mixture filtered through Celite. The filtrate was extracted using ethyl acetate, dried over anhydrous sodium sulfate, and evaporated. Purification of the residue by silica gel TLC gave the pyrimidyl alkanol 2.

Conclusions

We have demonstrated the stochastic formation of (S)- and (R)-5-pyrimidyl alkanol 2 from pyrimidine-5-carbaldehyde 1 and i-Pr2Zn in the presence of achiral amines without the intervention of a chiral auxiliary. The presence of achiral amines facilitated the initiation of asymmetric autocatalysis by activation of diisopropylzinc. The stochastic behavior of the formation of (S)-and (R)-5-pyrimidyl alkanol 2 was observed in the presence of achiral amines. We believe that the phenomenon reported here constitutes one of the conditions necessary for a spontaneous absolute asymmetric synthesis. In this reaction system involving asymmetric autocatalysis with amplification of ee, the imbalance of enantiomeric purity in the initially forming racemic mixtures that arises from the reaction of achiral reactants becomes overwhelming to afford an enantiomerically enriched product. The mechanism and reaction model for the spontaneous generation of enantiopurity and amplification of ee in asymmetric autocatalysis [22, 35–44, 52–56] are now under investigation.

Methods

All reactions were performed under an argon atmosphere. Toluene was distilled under argon in the presence of sodium benzophenone ketyl before use. Toluene solution of diisopropylzinc (1.0 M) is commercially available. Achiral amines 3-5 are commercial sources and were distilled from potassium hydroxide under reduced pressure before use. Pyrimidine-5-carbaldehyde 1 was synthesized and purified according to a reported procedure and was finally purified by sublimation before use. The ee of 5-pyrimidyl alkanol 2 was determined by HPLC using a chiral stationary phase (Daicel Chiralpak IB, eluent 5% 2-propanol in hexane (v/v), flow rate 1.0 mL min-1, 254 nm UV detector, retention time 11.4 min for (S)-2, 15.9 min for (R)-2).

Abbreviations

S :

sinister

R :

rectus

T :

tertiary

I :

iso

EE:

enantiomeric excess PR: propyl

BU:

butyl

M:

milli

M:

mol/L

G:

gram

L:

liter

ME:

methyl

ET:

ethyl

TLC:

thin-layer chromatography

HPLC:

high performance liquid chromatography

MIN:

minute.

References

  1. Mislow K: Absolute asymmetric synthesis: A commentary. Collect Czechoslov Chem Commun 2003, 68: 849–863. 10.1135/cccc20030849

    Article  CAS  Google Scholar 

  2. Bolli M, Micura R, Eschenmoser A: Pyranosyl-RNA: chiroselective self-assembly of base sequences by ligative oligomerization of tetranucleotide-2',3'-cyclophosphates (with a commentary concerning the origin of biomolecular homochirality). Chem Biol 1997, 4: 309–320. 10.1016/S1074-5521(97)90074-0

    Article  CAS  Google Scholar 

  3. Kondepudi DK, Asakura K: Chiral autocatalysis, spontaneous symmetry breaking, and stochastic behavior. Acc Chem Res 2001, 34: 946–954. 10.1021/ar010089t

    Article  CAS  Google Scholar 

  4. Green MM, Park J-W, Sato T, Teramoto A, Lifson S, Selinger RLB, Selinger JV: The macromolecular route to chiral amplification. Angew Chem Int Ed 1999, 38: 3139–3154.

    CAS  Google Scholar 

  5. Girard C, Kagan HB: Nonlinear effects in asymmetric synthesis and stereoselective reactions: ten years of investigation. Angew Chem Int Ed 1998, 37: 2922–2959. 10.1002/(SICI)1521-3773(19981116)37:21<2922::AID-ANIE2922>3.0.CO;2-1

    Article  Google Scholar 

  6. Zepik H, Shavit E, Tang M, Jensen TR, Kjaer K, Bolbach G, Leiserowitz L, Weissbuch I, Lahav M: Chiral amplification of oligopeptides in two-dimensional crystalline self-assemblies on water. Science 2002, 295: 1266–1269. 10.1126/science.1065625

    Article  CAS  Google Scholar 

  7. Kondepudi DK, Kaufman RJ, Singh N: Chiral symmetry breaking in sodium chlorate crystallization. Science 1990, 250: 975–976. 10.1126/science.250.4983.975

    Article  CAS  Google Scholar 

  8. Pincock RE, Perkins RR, Ma AS, Wilson KR: Probability distribution of enantiomorphous forms in spontaneous generation of optically active substances. Science 1971, 174: 1018–1020. 10.1126/science.174.4013.1018

    Article  CAS  Google Scholar 

  9. Havinga E: Spontaneous formation of optically active substances. Biochim Biophys Acta 1954, 13: 171–174. 10.1016/0006-3002(54)90300-5

    Article  CAS  Google Scholar 

  10. Viedma C: Chiral symmetry breaking during crystallization: complete chiral purity induced by nonlinear autocatalysis and recycling. Phys Rev Lett 2005, 94: 065504. 10.1103/PhysRevLett.94.065504

    Article  Google Scholar 

  11. Frank FC: On spontaneous asymmetric synthesis. Biochim Biophys Acta 1953, 11: 459–463. 10.1016/0006-3002(53)90082-1

    Article  CAS  Google Scholar 

  12. Mangel M: Simple theory of relaxation from instabilities. Phys Rev A 1981, 24: 3226–3238. 10.1103/PhysRevA.24.3226

    Article  CAS  Google Scholar 

  13. Iwamoto K: A reaction model for generation of enantiomers via a stereoselective process by a racemic catalyst. Nippon Kagaku Kaishi 1999, 8: 527–531.

    Article  Google Scholar 

  14. Soai K, Shibata T, Morioka H, Choji K: Asymmetric autocatalysis and amplification of enantiomeric excess of a chiral molecule. Nature 1995, 378: 767–768. 10.1038/378767a0

    Article  CAS  Google Scholar 

  15. Shibata T, Yonekubo S, Soai K: Practically perfect asymmetric autocatalysis using 2-alkynyl-5-pyrimidylalkanol. Angew Chem Int Ed 1999, 38: 659–661. 10.1002/(SICI)1521-3773(19990301)38:5<659::AID-ANIE659>3.0.CO;2-P

    Article  CAS  Google Scholar 

  16. Sato I, Urabe H, Ishiguro S, Shibata T, Soai K: Amplification of chirality from extremely low to greater than 99.5% ee by asymmetric autocatalysis. Angew Chem Int Ed 2003, 42: 315–317. 10.1002/anie.200390105

    Article  CAS  Google Scholar 

  17. Soai K, Shibata T, Sato I: Enantioselective automultiplication of chiral molecules by asymmetric autocatalysis. Acc Chem Res 2000, 33: 382–390. 10.1021/ar9900820

    Article  CAS  Google Scholar 

  18. Soai K, Shibata T, Sato I: Discovery and development of asymmetric autocatalysis. Bull Chem Soc Jpn 2004, 77: 1063–1073. 10.1246/bcsj.77.1063

    Article  CAS  Google Scholar 

  19. Soai K, Kawasaki T: Discovery of asymmetric autocatalysis with amplification of chirality and its implications in chiral homogeneity of biomolecules. Chirality 2006, 18: 469–478. 10.1002/chir.20289

    Article  CAS  Google Scholar 

  20. Soai K, Kawasaki T: Asymmetric autocatalysis with amplification of chirality. Top Curr Chem 2008, 284: 1–33. full_text

    Article  CAS  Google Scholar 

  21. Bolm C, Bienewald F, Seger A: Asymmetric autocatalysis with amplification of chirality. Angew Chem Int Ed 1996, 35: 1657–1659. 10.1002/anie.199616571

    Article  CAS  Google Scholar 

  22. Blackmond DG: Asymmetric autocatalysis and its implications for the origin of homochirality. Proc Natl Acad Sci USA 2004, 101: 5732–5736. 10.1073/pnas.0308363101

    Article  CAS  Google Scholar 

  23. Podlech J, Gehring T: New aspects of Soai's asymmetric autocatalysis. Angew Chem Int Ed 2005, 44: 5776–5777. 10.1002/anie.200501742

    Article  CAS  Google Scholar 

  24. Todd MH: Asymmetric autocatalysis: product recruitment for the increase in the chiral environment (PRICE). Chem Soc Rev 2002, 31: 211–222. 10.1039/b104169j

    Article  CAS  Google Scholar 

  25. Avalos M, Babiano R, Cintas P, Jiménez JL, Palacios JC: Chiral autocatalysis: where stereochemistry meets the origin of life. Chem Commun 2000, 11: 887–892. 10.1039/a908300f

    Article  Google Scholar 

  26. Shibata T, Yamamoto J, Matsumoto N, Yonekubo S, Osanai S, Soai K: Amplification of a slight enantiomeric imbalance in molecules based on asymmetric autocatalysis. The first correlation between high enantiomeric enrichment in a chiral molecule and circularly polarized light. J Am Chem Soc 1998, 120: 12157–12158. 10.1021/ja980815w

    Article  CAS  Google Scholar 

  27. Lutz F, Igarashi T, Kinoshita T, Asahina M, Tsukiyama K, Kawasaki T, Soai K: Mechanistic insights in the reversal of enantioselectivity of chiral catalysts by achiral catalysts in asymmetric autocatalysis. J Am Chem Soc 2008, 130: 2956–2958. 10.1021/ja077156k

    Article  CAS  Google Scholar 

  28. Kawasaki T, Matsumura Y, Tsutsumi T, Suzuki K, Ito M, Soai K: Asymmetric autocatalysis triggered by carbon isotope (13C /12C ) chirality. Science 2009, 324: 492–495. 10.1126/science.1170322

    Article  CAS  Google Scholar 

  29. Kawasaki T, Shimizu M, Nishiyama D, Ito M, Ozawa H, Soai K: Asymmetric autocatalysis induced by meteoritic amino acids with hydrogen isotope chirality. Chem Commun 2009, 29: 4396–4398. 10.1039/b908754k

    Article  Google Scholar 

  30. Soai K, Osanai S, Kadowaki K, Yonekubo S, Shibata T, Sato I: d - and l -Quartz-promoted highly enantioselective synthesis of a chiral compound. J Am Chem Soc 1999, 121: 11235–11236. 10.1021/ja993128t

    Article  CAS  Google Scholar 

  31. Kawasaki T, Jo K, Igarashi H, Sato I, Nagano M, Koshima H, Soai K: Asymmetric amplification using chiral cocrystals formed from achiral organic molecules by asymmetric autocatalysis. Angew Chem Int Ed 2005, 44: 2774–2777. 10.1002/anie.200462963

    Article  CAS  Google Scholar 

  32. Kawasaki T, Suzuki K, Hakoda Y, Soai K: Achiral nucleobase cytosine acts as an origin of homochirality of biomolecules in conjunction with asymmetric autocatalysis. Angew Chem Int Ed 2008, 47: 496–499. 10.1002/anie.200703634

    Article  CAS  Google Scholar 

  33. Kawasaki T, Sato M, Ishiguro I, Saito T, Morishita M, Sato I, Nishino H, Inoue Y, Soai K: Enantioselective synthesis of near enantiopure compound by asymmetric autocatalysis triggered by asymmetric photolysis with circularly polarized light. J Am Chem Soc 2005, 127: 3274–3275. 10.1021/ja0422108

    Article  CAS  Google Scholar 

  34. Mills WH: Some aspects of stereochemistry. Chem and Ind 1932, 51: 750–759. 10.1002/jctb.5000513702

    Article  CAS  Google Scholar 

  35. Pályi G, Micskei K, Zékány L, Zucchi C, Caglioti L: Racemates and the Soai reaction. Magy Kem Lapja 2005, 60: 17–24.

    Google Scholar 

  36. Islas JR, Lavabre D, Grevy J-M, Lamoneda RH, Cabrera HR, Micheau J-C, Buhse T: Mirror-symmetry breaking in the Soai reaction: A kinetic understanding. Proc Natl Acad Sci USA 2005, 102: 13743–13748. 10.1073/pnas.0503171102

    Article  CAS  Google Scholar 

  37. Lavabre D, Micheau JC, Islas JR, Buhse T: Kinetic insight into specific features of the autocatalytic Soai reaction. Top Curr Chem 2008, 284: 67–96. full_text

    Article  CAS  Google Scholar 

  38. Gridnev ID, Serafimov JM, Quiney H, Brown JM: Reflections on spontaneous asymmetric synthesis by amplifying autocatalysis. Org Biomol Chem 2003, 1: 3811–3819. 10.1039/b307382n

    Article  CAS  Google Scholar 

  39. Saito Y, Hyuga H: Rate equation approaches to amplification of enantiomeric excess and chiral symmetry breaking. Top Curr Chem 2008, 284: 97–118. full_text

    Article  CAS  Google Scholar 

  40. Lente G: Stochastic kinetic models of chiral autocatalysis: A general tool for the quantitative interpretation of total asymmetric synthesis. J Phys Chem A 2005, 109: 11058–11063. 10.1021/jp054613f

    Article  CAS  Google Scholar 

  41. Shao J, Liu L: Stochastic fluctuations and chiral symmetry breaking: exact solution of Lente model. J Phys Chem A 2007, 111: 9570–9572. 10.1021/jp0739364

    Article  CAS  Google Scholar 

  42. Micskei K, Rabai G, Gal E, Caglioti L, Pályi G: Oscillatory symmetry breaking in the Soai reaction. J Phys Chem B 2008, 112: 9196–9200. 10.1021/jp803334b

    Article  CAS  Google Scholar 

  43. Crusats J, Hochberg D, Moyano A, Ribó JM: Frank model and spontaneous emergence of chirality in closed systems. Chem Phys Chem 2009, 10: 2123–2131.

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  45. Soai K, Shibata T, Kowata Y: Preparation of optically active pyrimidylalkyl alcohols by spontaneous absolute asymmetric synthesis. Jpn Kokai Tokkyo Koho 1997. JP 09025269 A 19970128.

    Google Scholar 

  46. Soai K, Sato I, Shibata T, Komiya S, Hayashi M, Matsueda Y, Imamura H, Hayase T, Morioka H, Tabira H, Yamamoto J, Kowata Y: Asymmetric synthesis of pyrimidyl alkanol without adding chiral substances by the addition of diisopropylzinc to pyrimidine-5-carbaldehyde in conjunction with asymmetric autocatalysis. Tetrahedron: Asymmetry 2003, 14: 185–188. 10.1016/S0957-4166(02)00791-7

    Article  CAS  Google Scholar 

  47. Kawasaki T, Suzuki K, Shimizu M, Ishikawa K, Soai K: Spontaneous absolute asymmetric synthesis in the presence of achiral silica gel in conjunction with asymmetric autocatalysis. Chirality 2006, 18: 479–482. 10.1002/chir.20273

    Article  CAS  Google Scholar 

  48. Singleton DA, Vo LK: A few molecules can control the enantiomeric outcome. Evidence supporting absolute asymmetric synthesis using the Soai asymmetric autocatalysis. Org Lett 2003, 5: 4337–4339. 10.1021/ol035605p

    Article  CAS  Google Scholar 

  49. Soai K, Watanabe M, Koyano M: Synthesis of hydroxy ketones by chemoselective alkylation of keto aldehydes with dialkylzincs catalyzed by amino alcohol, diamine, or dilithium salt of piperazine. Bull Chem Soc Jpn 1989, 62: 2124–2125. 10.1246/bcsj.62.2124

    Article  CAS  Google Scholar 

  50. Niwa S, Soai K: Asymmetric synthesis using chiral piperazines. Part 3. Enantioselective addition of dialkylzincs to aryl aldehydes catalysed by chiral piperazines. J Chem Soc Perkin Trans 1 1991, 2717–2720. 10.1039/p19910002717

    Google Scholar 

  51. Lennartson A, Hedström A, Håkansson M: Diisopropyl( N , N , N' , N' -tetramethylethylenediamine)zinc(II), the first crystal structure of a diisopropylzinc complex. Acta Cryst 2007, E63: m123-m125.

    Google Scholar 

  52. Sato I, Omiya D, Igarashi H, Kato K, Ogi Y, Tsukiyama K, Soai K: Relationship between the time, yield, and enantiomeric excess of asymmetric autocatalysis of chiral 2-alkynyl-5-pyrimidyl alkanol with amplification of enantiomeric excess. Tetrahedron: Asymmetry 2003, 14: 975–979. 10.1016/S0957-4166(03)00164-2

    Article  CAS  Google Scholar 

  53. Blackmond DG, McMillan CR, Ramdeehul S, Schorm A, Brown JM: Origins of asymmetric amplification in autocatalytic alkylzinc additions. J Am Chem Soc 2001, 123: 10103–10104. 10.1021/ja0165133

    Article  CAS  Google Scholar 

  54. Gridnev ID, Serafimov JM, Brown JM: Solution structure and reagent binding of the zinc alkoxide catalyst in the Soai asymmetric autocatalytic reaction. Angew Chem Int Ed 2004, 43: 4884–4887. 10.1002/anie.200353572

    Article  CAS  Google Scholar 

  55. Klankermayer J, Gridnev ID, Brown JM: Role of the isopropyl group in asymmetric autocatalytic zinc alkylations. Chem Commun 2007, 3151–3153. 10.1039/b705978g

    Google Scholar 

  56. Schiaffino L, Ercolani G: Unraveling the mechanism of the Soai asymmetric autocatalytic reaction by first-principles calculations: induction and amplification of chirality by self-assembly of hexamolecular complexes. Angew Chem Int Ed 2008, 47: 6832–6835. 10.1002/anie.200802450

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science. The authors thank Ms. Sayaka Kamimura for performing some experiments.

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Authors and Affiliations

  1. Department of Applied Chemistry and Research Institute for Science and Technology, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan

    Kenta Suzuki, Kunihiko Hatase, Daisuke Nishiyama, Tsuneomi Kawasaki & Kenso Soai

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  1. Kenta Suzuki
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  4. Tsuneomi Kawasaki
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Correspondence to Kenso Soai.

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Authors' contributions

KSo conceived the research project and obtained the research funding. KSu, KH and DN performed the asymmetric autocatalytic reactions in the presence of achiral amines. TK performed the project and taught how to perform the experiments. KSu, TK and KSo wrote the paper.

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Suzuki, K., Hatase, K., Nishiyama, D. et al. Spontaneous absolute asymmetric synthesis promoted by achiral amines in conjunction with asymmetric autocatalysis. J Syst Chem 1, 5 (2010). https://doi.org/10.1186/1759-2208-1-5

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