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

Kenta Suzuki; Kunihiko Hatase; Daisuke Nishiyama; Tsuneomi Kawasaki; Kenso Soai

doi:10.1186/1759-2208-1-5

Research article
Open Access

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

Kenta Suzuki¹,
Kunihiko Hatase¹,
Daisuke Nishiyama¹,
Tsuneomi Kawasaki¹ and
Kenso Soai¹Email author

Journal of Systems Chemistry20101:5

https://doi.org/10.1186/1759-2208-1-5

Received: 26 February 2010
Accepted: 18 August 2010
Published: 18 August 2010

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.

Keywords

Absolute Configuration
Chiral Compound
Alkanol
Sodium Hydrogen Carbonate
Aqueous Sodium Hydrogen Carbonate

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
**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**.

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.

Run	Pyrimidyl alkanol2		Run	Pyrimidyl alkanol2		Run	Pyrimidyl alkanol2
	ee	Config.		ee	Config.		ee	Config.
1	19	R	26	3	R	52	36	S
2	18	S	27	7	S	53	23	S
3	8	R	28	4	S	54	32	R
4	10	S	29	14	R	55	32	S
5	11	R	30	6	S	56	4	S
6	8	S	31	6	R	57	6	R
7	5	S	32	4	S	58	12	S
8	9	R	33	4	R	59	15	S
9	6	S	34	3	S	60	5	S
10	4	S	35	15	S	61	42	R
11	4	S	36	20	S	62	52	R
12	57	R	37	18	R	63	2	S
13	2	R	38	9	R	64	43	R
14	37	S	39	37	S	65	35	R
15	23	R	40	27	S	66	3	S
16	4	S	41	28	R	67	2	R
17	6	R	42	3	R	68	4	S
18	4	S	43	9	S	69	4	S
19	7	S	44	32	S	70	42	R
20	47	R	45	29	R	71	32	R
21	29	R	46	11	S	72	18	R
22	25	R	47	16	R	73	6	S
23	10	S	48	52	R	74	9	R
24	12	S	49	9	R	75	19	R
25	31	R	50	4	S
26	12	S	51	19	R

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.

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.

Run	Pyrimidyl alkanol 2		Run	Pyrimidyl alkanol 2		Run	Pyrimidyl alkanol 2
	ee	Config.		ee	Config.		ee	Config.
1	50	S	8	53	S	15	36	S
2	57	R	9	39	R	16	24	S
3	47	R	10	40	R	17	22	R
4	55	S	11	37	S	18	5	S
5	14	R	12	20	S	19	35	R
6	27	R	13	47	R	20	11	S
7	10	R	14	47	R

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.

Run	Pyrimidyl alkanol 2		Run	Pyrimidyl alkanol 2		Run	Pyrimidyl alkanol 2
	ee	Config.		ee	Config.		ee	Config.
1	34	S	8	15	R	15	6	S
2	37	R	9	33	S	16	9	R
3	52	S	10	7	R	17	29	R
4	33	S	11	10	S	18	12	S
5	20	R	12	6	S	19	12	R
6	16	R	13	7	R	20	27	S
7	33	S	14	7	S

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.

Declarations

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.

Authors’ Affiliations

(1)

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

References

Mislow K: Absolute asymmetric synthesis: A commentary. Collect Czechoslov Chem Commun 2003, 68: 849–863. 10.1135/cccc20030849View ArticleGoogle Scholar
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)90074-0View ArticleGoogle Scholar
Kondepudi DK, Asakura K: Chiral autocatalysis, spontaneous symmetry breaking, and stochastic behavior. Acc Chem Res 2001, 34: 946–954. 10.1021/ar010089tView ArticleGoogle Scholar
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.Google Scholar
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;2-1View ArticleGoogle Scholar
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.1065625View ArticleGoogle Scholar
Kondepudi DK, Kaufman RJ, Singh N: Chiral symmetry breaking in sodium chlorate crystallization. Science 1990, 250: 975–976. 10.1126/science.250.4983.975View ArticleGoogle Scholar
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.174.4013.1018View ArticleGoogle Scholar
Havinga E: Spontaneous formation of optically active substances. Biochim Biophys Acta 1954, 13: 171–174. 10.1016/0006-3002(54)90300-5View ArticleGoogle Scholar
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.94.065504View ArticleGoogle Scholar
Frank FC: On spontaneous asymmetric synthesis. Biochim Biophys Acta 1953, 11: 459–463. 10.1016/0006-3002(53)90082-1View ArticleGoogle Scholar
Mangel M: Simple theory of relaxation from instabilities. Phys Rev A 1981, 24: 3226–3238. 10.1103/PhysRevA.24.3226View ArticleGoogle Scholar
Iwamoto K: A reaction model for generation of enantiomers via a stereoselective process by a racemic catalyst. Nippon Kagaku Kaishi 1999, 8: 527–531.View ArticleGoogle Scholar
Soai K, Shibata T, Morioka H, Choji K: Asymmetric autocatalysis and amplification of enantiomeric excess of a chiral molecule. Nature 1995, 378: 767–768. 10.1038/378767a0View ArticleGoogle Scholar
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-PView ArticleGoogle Scholar
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.200390105View ArticleGoogle Scholar
Soai K, Shibata T, Sato I: Enantioselective automultiplication of chiral molecules by asymmetric autocatalysis. Acc Chem Res 2000, 33: 382–390. 10.1021/ar9900820View ArticleGoogle Scholar
Soai K, Shibata T, Sato I: Discovery and development of asymmetric autocatalysis. Bull Chem Soc Jpn 2004, 77: 1063–1073. 10.1246/bcsj.77.1063View ArticleGoogle Scholar
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.20289View ArticleGoogle Scholar
Soai K, Kawasaki T: Asymmetric autocatalysis with amplification of chirality. Top Curr Chem 2008, 284: 1–33. full_textView ArticleGoogle Scholar
Bolm C, Bienewald F, Seger A: Asymmetric autocatalysis with amplification of chirality. Angew Chem Int Ed 1996, 35: 1657–1659. 10.1002/anie.199616571View ArticleGoogle Scholar
Blackmond DG: Asymmetric autocatalysis and its implications for the origin of homochirality. Proc Natl Acad Sci USA 2004, 101: 5732–5736. 10.1073/pnas.0308363101View ArticleGoogle Scholar
Podlech J, Gehring T: New aspects of Soai's asymmetric autocatalysis. Angew Chem Int Ed 2005, 44: 5776–5777. 10.1002/anie.200501742View ArticleGoogle Scholar
Todd MH: Asymmetric autocatalysis: product recruitment for the increase in the chiral environment (PRICE). Chem Soc Rev 2002, 31: 211–222. 10.1039/b104169jView ArticleGoogle Scholar
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/a908300fView ArticleGoogle Scholar
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/ja980815wView ArticleGoogle Scholar
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/ja077156kView ArticleGoogle Scholar
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.1170322View ArticleGoogle Scholar
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/b908754kView ArticleGoogle Scholar
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/ja993128tView ArticleGoogle Scholar
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.200462963View ArticleGoogle Scholar
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.200703634View ArticleGoogle Scholar
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/ja0422108View ArticleGoogle Scholar
Mills WH: Some aspects of stereochemistry. Chem and Ind 1932, 51: 750–759. 10.1002/jctb.5000513702View ArticleGoogle Scholar
Pályi G, Micskei K, Zékány L, Zucchi C, Caglioti L: Racemates and the Soai reaction. Magy Kem Lapja 2005, 60: 17–24.Google Scholar
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.0503171102View ArticleGoogle Scholar
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_textView ArticleGoogle Scholar
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/b307382nView ArticleGoogle Scholar
Saito Y, Hyuga H: Rate equation approaches to amplification of enantiomeric excess and chiral symmetry breaking. Top Curr Chem 2008, 284: 97–118. full_textView ArticleGoogle Scholar
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/jp054613fView ArticleGoogle Scholar
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/jp0739364View ArticleGoogle Scholar
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/jp803334bView ArticleGoogle Scholar
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.Google Scholar
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.82.1372View ArticleGoogle Scholar
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
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)00791-7View ArticleGoogle Scholar
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.20273View ArticleGoogle Scholar
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/ol035605pView ArticleGoogle Scholar
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.62.2124View ArticleGoogle Scholar
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/p19910002717Google Scholar
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
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)00164-2View ArticleGoogle Scholar
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/ja0165133View ArticleGoogle Scholar
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.200353572View ArticleGoogle Scholar
Klankermayer J, Gridnev ID, Brown JM: Role of the isopropyl group in asymmetric autocatalytic zinc alkylations. Chem Commun 2007, 3151–3153. 10.1039/b705978gGoogle Scholar
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.200802450View ArticleGoogle Scholar

Copyright

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.