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Cited by 63Origins and Evolution of LifeAsymmetric Synthesis and CatalysisChemistry and Stereochemistry Studies

Asymmetric autocatalysis. Chiral symmetry breaking and the origins of homochirality of organic molecules

Open access
SOAI, Kenso·2019·Proceedings of the Japan Academy Series B
DOI 10.2183/pjab.95.009PMC PMC6541725
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Abstract

Biological homochirality, such as that of l-amino acids, has been a puzzle with regards to the chemical origin of life. Asymmetric autocatalysis is a reaction in which a chiral product acts as an asymmetric catalyst to produce more of itself in the same absolute configuration. 5-Pyrimidyl alkanol was found to act as an asymmetric autocatalyst in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde. Asymmetric autocatalysis of 2-alkynyl-5-pyrimidyl alkanol with an extremely low enantiomeric excess of ca. 0.00005% exhibited significant asymmetric amplification to afford the same pyrimidyl alkanol with >99.5% enantiomeric excess and with an increase in the quantity of the same compound. We have employed asymmetric autocatalysis to examine the origin of homochirality. Asymmetric autocatalysis triggered by circularly polarized light, chiral minerals such as quartz, chiral organic crystals composed of achiral compounds gave highly enantioenriched pyrimidyl alkanol with absolute configurations corresponding with those of the chiral triggers. Absolute asymmetric synthesis without the intervention of any chiral factor was achieved. Chiral isotopomers acted as chiral triggers of asymmetric autocatalysis.

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Crossref · 10.2183/pjab.95.009

Cites

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Statistics

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Claims the paper makes

26 of 152 cited sources checked · 20 supported · 0 flagged · accuracy not yet measured

  • Interpretationreasoning

    An enantiomeric excess amplification process is needed to reach enantiopure organic compounds.

    “Thus, an ee amplification process is needed to reach enantiopure organic compounds (Scheme 1).11–20)”
    Quote in the paperSubstantial claim3 of 10 sources checked
    • cites [11] 11) Kitamura, M., Okada, S., Suga, S. and Noyori, R. (1989) Enantioselective addition of dialkylzincs to aldehydes promoted by chiral amino alcohols. Mechanism and nonlinear effect. J. Am. Chem. Soc. 111, 4028–4036. source
    • cites [12] 12) Satyanarayana, T., Abraham, S. and Kagan, H.B. (2009) Nonlinear effects in asymmetric catalysis. Angew. Chem. Int. Ed. 48, 456–494. source
    • cites [13] 13) Kondepudi, D.K. and Asakura, K. (2001) Chiral autocatalysis, spontaneous symmetry breaking, and stochastic behavior. Acc. Chem. Res. 34, 946–954. source
    • cites [14] 14) Viedma, C. (2005) Chiral symmetry breaking during crystallization: Complete chiral purity induced by nonlinear autocatalysis and recycling. Phys. Rev. Lett. 94, 065504. source
    • cites [15] 15) Soloshonok, V.A., Ueki, H., Yasumoto, M., Mekala, S., Hirschi, J.S. and Singleton, D.A. (2007) Phenomenon of optical self-purification of chiral non-racemic compounds. J. Am. Chem. Soc. 129, 12112–12113. source
    • cites [16] 16) Hayashi, Y., Matsuzawa, M., Yamaguchi, J., Yonehara, S., Matsumoto, Y., Shoji, M. (2006) Large nonlinear effect observed in the enantiomeric excess of proline in solution and that in the solid state. Angew. Chem. Int. Ed. 45, 4593–4597. source

      The paper’s Abstract reports amplification from low-ee proline to a sugar intermediate at 96% ee and proposes this as a possible route to homochiral molecules. It does not say amplification is necessary to obtain enantiopure organic compounds, and 96% ee is not enantiopure. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [17] 17) Córdova, A., Engqvist, M., Ibrahem, I., Casas, J. and Sundén, H. (2005) Plausible origins of homochirality in the amino acid catalyzed neogenesis of carbohydrates. Chem. Commun. (Camb.) 2047–2049. source
    • cites [18] 18) Green, M.M., Park, J.-W., Sato, T., Teramoto, A., Lifson, S., Selinger, R.L.B. (1999) The macromolecular route to chiral amplification. Angew. Chem. Int. Ed. 38, 3138–3154. source
    • cites [19] 19) Noorduin, W.L., Vlieg, E., Kellogg, R.M. and Kaptein, B. (2009) From Ostwald ripening to single chirality. Angew. Chem. Int. Ed. 48, 9600–9606. source

      Section 3 (p. 4) describes an exponential increase in enantiomeric excess that reaches an enantiomerically pure end state, supporting ee amplification as one route. The claim that such a process is needed generally is broader than the paper supports: the Concluding Remarks (p. 6) also identify asymmetric synthesis and classical resolution as routes to homochiral compounds. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [20] 20) Saito, Y. and Hyuga, H. (2013) Colloquium: homochirality: Symmetry breaking in systems driven far from equilibrium. Rev. Mod. Phys. 85, 603–621. source
  • Findingcitation

    The crystal structures of asymmetric autocatalysts 1c are either tetrameric or oligomeric, as determined by X-ray diffraction.

    “We found that the crystal structures of asymmetric autocatalysts 1c are either tetrameric or oligomeric, as determined by X-ray diffraction (Fig. 3).66,67)”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [66] 66) Matsumoto, A., Abe, T., Hara, A., Tobita, T., Sasagawa, T.T., Kawasaki, T. (2015) Crystal structure of isopropylzinc alkoxide of pyrimidyl alkanol: Mechanistic insights for asymmetric autocatalysis with amplification of enantiomeric excess. Angew. Chem. Int. Ed. 54, 15218–15221. source
    • cites [67] 67) Matsumoto, A., Fujiwara, S., Abe, T., Hara, A., Tobita, T., Sasagawa, T. (2016) Elucidation of the structures of asymmetric autocatalyst based on X-ray crystallography. Bull. Chem. Soc. Jpn. 89, 1170–1177. source
  • Findingcitation

    Retgersite acts as a chiral trigger of asymmetric autocatalysis.

    “It was also found that retgersite acts as a chiral trigger of asymmetric autocatalysis.78)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [78] 78) Matsumoto, A., Ozawa, H., Inumaru, A. and Soai, K. (2015) Asymmetric induction by retgersite, nickel sulfate hexahydrate, in conjunction with asymmetric autocatalysis. New J. Chem. 39, 6742–6745. source
  • Findingcitation

    The ee of alkanol 1f from the enantiotopic face reaction was amplified to >99.5% by subsequent asymmetric autocatalyses.

    “The ee of the obtained alkanol was amplified to >99.5% by the subsequent asymmetric autocatalyses.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [93] 93) Kawasaki, T., Kamimura, S., Amihara, A., Suzuki, K. and Soai, K. (2011) Enantioselective C–C bond formation as a result of the oriented prochirality of an achiral aldehyde at the single-crystal face upon treatment with a dialkylzinc vapor. Angew. Chem. Int. Ed. 50, 6796–6798. source
    • Rests on an assumption: Certain achiral organic compounds form achiral crystals with enantiotopic faces.
  • Findingcitation

    Reactions of pyrimidine-5-carbaldehyde with i-Pr2Zn in the presence of achiral amorphous silica gel or achiral amines without chiral factor gave (S)-1c or (R)-1c stochastically.

    “In addition, the reactions between pyrimidine-5-carbaldehyde and i-Pr2Zn in the presence of achiral amorphous silica gel98) and achiral amines99) without using any chiral factor afforded (S)-1c or (R)-1c in a stochastic manner.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [98] 98) Kawasaki, T., Suzuki, K., Shimizu, M., Ishikawa, K. and Soai, K. (2006) Spontaneous absolute asymmetric synthesis in the presence of achiral silica gel in conjunction with asymmetric autocatalysis. Chirality 18, 479–482. source
    • cites [99] 99) Suzuki, K., Hatase, K., Nishiyama, D., Kawasaki, T. and Soai, K. (2010) Spontaneous absolute asymmetric synthesis promoted by achiral amines in conjunction with asymmetric autocatalysis. J. Syst. Chem. 1, 5. source
  • Classified as probably not a substantial claim. 8
  • May combine two claims. 20
  • Not yet classified. 1

  • Classified as probably not a substantial claim.

    Premisecitation

    The linkage between the induced small enantioenrichment and enantiopure compounds has remained a puzzle.

    “The linkage between the induced small enantioenrichment and the enantiopure compounds has thus remained a puzzle.11–20)”
    Quote in the paperSubstantial claim3 of 10 sources checked
    • cites [11] 11) Kitamura, M., Okada, S., Suga, S. and Noyori, R. (1989) Enantioselective addition of dialkylzincs to aldehydes promoted by chiral amino alcohols. Mechanism and nonlinear effect. J. Am. Chem. Soc. 111, 4028–4036. source
    • cites [12] 12) Satyanarayana, T., Abraham, S. and Kagan, H.B. (2009) Nonlinear effects in asymmetric catalysis. Angew. Chem. Int. Ed. 48, 456–494. source
    • cites [13] 13) Kondepudi, D.K. and Asakura, K. (2001) Chiral autocatalysis, spontaneous symmetry breaking, and stochastic behavior. Acc. Chem. Res. 34, 946–954. source
    • cites [14] 14) Viedma, C. (2005) Chiral symmetry breaking during crystallization: Complete chiral purity induced by nonlinear autocatalysis and recycling. Phys. Rev. Lett. 94, 065504. source

      The Introduction (p. 1) says that natural mechanisms generally produce only small enantiomeric excesses and that reaching total chiral purity requires amplification; the discussion (p. 3) calls for a mechanism to explain that transition. But the Conclusion (p. 5) proposes and experimentally supports such a mechanism for sodium chlorate crystallization, so the paper does not support treating the linkage as wholly unexplained. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [15] 15) Soloshonok, V.A., Ueki, H., Yasumoto, M., Mekala, S., Hirschi, J.S. and Singleton, D.A. (2007) Phenomenon of optical self-purification of chiral non-racemic compounds. J. Am. Chem. Soc. 129, 12112–12113. source
    • cites [16] 16) Hayashi, Y., Matsuzawa, M., Yamaguchi, J., Yonehara, S., Matsumoto, Y., Shoji, M. (2006) Large nonlinear effect observed in the enantiomeric excess of proline in solution and that in the solid state. Angew. Chem. Int. Ed. 45, 4593–4597. source
    • cites [17] 17) Córdova, A., Engqvist, M., Ibrahem, I., Casas, J. and Sundén, H. (2005) Plausible origins of homochirality in the amino acid catalyzed neogenesis of carbohydrates. Chem. Commun. (Camb.) 2047–2049. source
    • cites [18] 18) Green, M.M., Park, J.-W., Sato, T., Teramoto, A., Lifson, S., Selinger, R.L.B. (1999) The macromolecular route to chiral amplification. Angew. Chem. Int. Ed. 38, 3138–3154. source
    • cites [19] 19) Noorduin, W.L., Vlieg, E., Kellogg, R.M. and Kaptein, B. (2009) From Ostwald ripening to single chirality. Angew. Chem. Int. Ed. 48, 9600–9606. source

      Section 5, p. 6 says that moving from models of deracemization to observed molecular mechanisms remains a challenge, supporting the idea of an unresolved question. But Section 3, p. 4 reports that a small initial imbalance can direct the outcome to either enantiomer and describes exponential growth of enantiomeric excess to an enantiopure end state. The source therefore does not present the linkage itself as wholly unexplained. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [20] 20) Saito, Y. and Hyuga, H. (2013) Colloquium: homochirality: Symmetry breaking in systems driven far from equilibrium. Rev. Mod. Phys. 85, 603–621. source

  • May combine two claims.

    Findingcitation

    Exposing one enantiotopic face of 2f to i-Pr2Zn vapor caused attack at the Re-face and gave (R)-pyrimidyl alkanol 1f.

    “When one of these faces was exposed to the vapor of i-Pr2Zn, the exposed Re-face of aldehyde was attacked by i-Pr2Zn to afford (R)-pyrimidyl alkanol 1f.93)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [93] 93) Kawasaki, T., Kamimura, S., Amihara, A., Suzuki, K. and Soai, K. (2011) Enantioselective C–C bond formation as a result of the oriented prochirality of an achiral aldehyde at the single-crystal face upon treatment with a dialkylzinc vapor. Angew. Chem. Int. Ed. 50, 6796–6798. source
    • Rests on an assumption: Certain achiral organic compounds form achiral crystals with enantiotopic faces.

  • May combine two claims.

    Findingcitation

    When the initial ee is low, the actual rate of amplification of ee is more significant than that simulated by the dimeric model, suggesting more aggregation than the dimer.

    “However, when the ee of the initial asymmetric autocatalyst is low, the actual rate of amplification of ee was more significant than that simulated by the dimeric model. Thus, more aggregation of the catalyst than the dimer was envisaged.50)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] 50) Sato, I., Omiya, D., Igarashi, H., Kato, K., Ogi, Y., Tsukiyama, 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. Tetrahedron Asymmetry 14, 975–979. source

  • May combine two claims.

    Findingown data

    Asymmetric autocatalysis of 2-alkynyl-5-pyrimidyl alkanol starting from ca. 0.00005% ee amplifies to >99.5% ee and increases the amount of the same compound.

    “Asymmetric autocatalysis of 2-alkynyl-5-pyrimidyl alkanol with an extremely low enantiomeric excess of ca. 0.00005% exhibited significant asymmetric amplification to afford the same pyrimidyl alkanol with >99.5% enantiomeric excess and with an increase in the quantity of the same compound.”
    Quote in the paperSubstantial claim

  • Not yet classified.

    Finding

    (S)-Pyrimidyl alkanol acts as an asymmetric autocatalyst with amplification of ee in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde to produce more of itself with the same absolute configuration.

    “(S)-Pyrimidyl alkanol 1a acts as an asymmetric autocatalyst with amplification of ee in the enantioselective addition of i-Pr2Zn to pyrimidine-5-carbaldehyde 2a to produce more of itself with the same absolute configuration (Scheme 3).22)”
    Quote in the paperNot yet classified0 of 1 sources checked
    • cites [22] 22) Soai, K., Shibata, T., Morioka, H. and Choji, K. (1995) Asymmetric autocatalysis and amplification of enantiomeric excess of a chiral molecule. Nature 378, 767–768. source

  • May combine two claims.

    Findingown data

    Even after the 10th round, the catalytic reactivity (yield >99%) and enantioselectivity (>99.5% ee) of alkanol 1c did not decrease.

    “Even after the 10th round, the catalytic reactivity (yield >99%) and enantioselectivity (>99.5% ee) of alkanol 1c did not decrease.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Starting from an asymmetric autocatalyst 1c with an extremely low ee of ca. 0.00005%, only three consecutive asymmetric autocatalysis reactions amplified the ee to >99.5% and increased the amount of alkanol 1c by a factor of ca. 630,000.

    “When it was started from an asymmetric autocatalyst 1c with an extremely low ee of ca. 0.00005%, only three consecutive asymmetric autocatalysis reactions amplified the ee of the pyrimidyl alkanol 1c to >99.5% and the amount of alkanol 1c by a factor of ca. 630,000 times.25)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] 25) Sato, I., Urabe, H., Ishiguro, S., Shibata, T. and Soai, K. (2003) Amplification of chirality from extremely low to greater than 99.5% ee by asymmetric autocatalysis. Angew. Chem. Int. Ed. 42, 315–317. source

  • May combine two claims.

    Findingown data

    Both enantiopure and racemic pyrimidyl alkanols form tetrameric crystal structures, but their conformations differ.

    “Both enantiopure (Fig. 3a) and racemic (Fig. 3b) pyrimidyl alkanols form the tetrameric crystal structure. However, these conformations differ from each other.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Asymmetric autocatalysis in the presence of d-NaBrO3 affords (R)-1c, while l-NaBrO3 affords (S)-1c.

    “On the other hand, asymmetric autocatalysis in the presence of d-NaBrO3 afforded (R)-1c, while l-NaBrO3 afforded (S)-1c.76)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76] 76) Sato, I., Kadowaki, K., Ohgo, Y. and Soai, K. (2004) Highly enantioselective asymmetric autocatalysis induced by chiral ionic crystals of sodium chlorate and sodium bromate. J. Mol. Catal. A Chem. 216, 209–214. source

  • May combine two claims.

    Findingcitation

    Asymmetric autocatalysis using d-NaClO3 as a chiral trigger affords (S)-alkanol 1c with high ee, while l-NaClO3 affords (R)-1c.

    “Asymmetric autocatalysis using d-NaClO3 as a chiral trigger afforded (S)-alkanol 1c with high ee, while l-NaClO3 afforded (R)-1c.75)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [75] 75) Sato, I., Kadowaki, K. and Soai, K. (2000) Asymmetric synthesis of an organic compound with high enantiomeric excess induced by inorganic ionic sodium chlorate. Angew. Chem. Int. Ed. 39, 1510–1512. source

  • May combine two claims.

    Findingown data

    In the enantiopure tetrameric crystal, two square (Zn2O2) dimers are positioned on the same side of the macrocycle; in the racemic tetramer, they are positioned on opposite sides.

    “In the enantiopure tetrameric crystal, two square (Zn2O2) dimers are positioned on the same side of the macrocycle (Fig. 3a). In the racemic tetramer, by contrast, square dimers (Zn2O2) are positioned on opposite sides (Fig. 3b).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    Chiral inorganic crystals such as quartz and cinnabar can act as chiral triggers.

    “Chiral inorganic crystals such as quartz and cinnabar can act as chiral triggers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Asymmetric autocatalysis of pyrimidyl alkanol 1 was successfully employed in asymmetric synthesis of sec-alkanols and chiral amplification of alkynyl alkanols.

    “Finally, asymmetric autocatalysis of pyrimidyl alkanol 1 was successfully employed in asymmetric synthesis of sec-alkanols122) and chiral amplification of alkynyl alkanols.123)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [122] 122) Sato, I., Urabe, H., Ishii, S., Tanji, S. and Soai, K. (2001) Asymmetric synthesis with a chiral catalyst generated from asymmetric autocatalysis. Org. Lett. 3, 3851–3854. source
    • cites [123] 123) Funes-Maldonado, M., Sieng, B. and Amedjkouh, M. (2016) Asymmetric autocatalysis as a relay for remote amplification of chirality of target molecules used as triggers. Org. Lett. 18, 2536–2539. source

  • May combine two claims.

    Findingown data

    The ee of (S)-2-alkynylpyrimidyl alkanol 1 as low as ca. 0.00005% was amplified to >99.5% during three consecutive asymmetric autocatalytic reactions, with amount multiplied by ca. 630,000 times.

    “The ee of (S)-2-alkynylpyrimidyl alkanol 1 with as low as ca. 0.00005% ee was amplified to >99.5% ee during three consecutive asymmetric autocatalytic reactions, together with multiplication of its amount by ca. 630,000 times.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Biological homochirality is essential for the emergence and function of life.

    “Biological homochirality is not a mere phenomenon; it is an essential prerequisite for the emergence and function of life.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Several proposed mechanisms for the origin of enantioenriched chirality, such as circularly polarized light, quartz, and absolute asymmetric synthesis, typically induce very small enantiomeric excess, and their correlation to highly enantioenriched compounds is unclear.

    “Several theories and mechanisms such as circularly polarized light, quartz, and absolute asymmetric synthesis have been proposed in relation to the origin of the enantioenriched chirality of organic compounds.2–10) However, in most cases, the enantiomeric excess (ee) induced by those mechanisms has been very small, and the correlation to the highly enantioenriched compounds has remained unclear.”
    Quote in the paperSubstantial claim0 of 9 sources checked
    • cites [2] 2) Guijarro, A. and Yus, M. (2009) The Origin of Chirality in the Molecules of Life. The Royal Society of Chemistry, Cambridge. source
    • cites [3] 3) Mislow, K. (2003) Absolute asymmetric synthesis: A commentary. Collect. Czech. Chem. Commun. 68, 849–864. source
    • cites [4] 4) Feringa, B.L. and van Delden, R.A. (1999) Absolute asymmetric synthesis: The origin, control, and amplification of chirality. Angew. Chem. Int. Ed. 38, 3418–3438. source
    • cites [5] 5) Inoue, Y. (1992) Asymmetric photochemical reactions in solution. Chem. Rev. 92, 741–770. source
    • cites [6] 6) Hazen, R.M. and Sholl, D.S. (2003) Chiral selection on inorganic crystalline surfaces. Nat. Mater. 2, 367–374. source
    • cites [7] 7) Bolli, M., Micura, R. and Eschenmoser, A. (1997) 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. 4, 309–320. source
    • cites [8] 8) Ribó, J.M., Crusats, J., Sagués, F., Claret, J. and Rubires, R. (2001) Chiral sign induction by vortices during the formation of mesophases in stirred solutions. Science 292, 2063–2066. source
    • cites [9] 9) Ernst, K.-H. (2012) Molecular chirality at surfaces. Phys. Status Solidi B 249, 2057–2088. source
    • cites [10] 10) Weissbuch, I. and Lahav, M. (2011) Crystalline architectures as templates of relevance to the origins of homochirality. Chem. Rev. 111, 3236–3267. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    DFT calculation studies proposed structures of catalyst aggregates.

    “The DFT calculation study proposed the structure of catalyst aggregates.55–57)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [55] 55) Schiaffino, L. and Ercolani, G. (2008) 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. 47, 6832–6835. source
    • cites [56] 56) Ercolani, G. and Schiaffino, L. (2011) Putting the mechanism of the Soai reaction to the test: DFT study of the role of aldehyde and dialkylzinc structure. J. Org. Chem. 76, 2619–2626. source
    • cites [57] 57) Gridnev, I.D. and Vorobiev, A.K. (2012) Quantification of sophisticated equilibria in the reaction pool and amplifying catalytic cycle of the Soai reaction. ACS Catal. 2, 2137–2149. source

  • May combine two claims.

    Premisecitation

    (S,S)-threo-N-methylphenylprolinol affords (S)-alkanol, while (S,R)-erythro-N-methylphenylprolinol affords (R)-alkanol.

    “The catalyst (S,S)-threo-N-methylphenylprolinol (PMPM) affords (S)-alkanol 9, while (S,R)-erythro-PMPM affords (R)-alkanol 9 (Scheme 5).47)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] 47) Soai, K., Ookawa, A., Kaba, T. and Ogawa, K. (1987) Catalytic asymmetric induction. Highly enantioselective addition of dialkylzincs to aldehydes using chiral pyrrolidinylmethanols and their metal salts. J. Am. Chem. Soc. 109, 7111–7115. source

  • May combine two claims.

    Interpretationreasoning

    In asymmetric autocatalysis, as the reaction proceeds, the concentration of asymmetric autocatalyst increases while the concentrations of i-Pr2Zn and aldehyde decrease, so the aggregation structures are probably not the same between early and final stages.

    “In asymmetric autocatalysis, along with the propagation of the reaction, the concentration of the asymmetric autocatalyst increases and the concentration of i-Pr2Zn and aldehyde decreases. Thus, it is probable that the aggregation structures of the asymmetric autocatalyst are not the same between the early and final stages of the reaction.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Left- and right-circularly polarized light has been proposed as the origin of chirality of organic compounds such as amino acids.

    “Left (l)- and right (r)-circularly polarized light (CPL) has been proposed as the origin of chirality of organic compounds such as amino acids.5)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] 5) Inoue, Y. (1992) Asymmetric photochemical reactions in solution. Chem. Rev. 92, 741–770. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Reaction models of spontaneous symmetry breaking, i.e., absolute asymmetric synthesis, have been proposed, and these approaches also proposed mechanisms of asymmetric autocatalysis of pyrimidyl alkanol.

    “Reaction models of spontaneous symmetry breaking, i.e. absolute asymmetric synthesis, have been proposed. These approaches also proposed the mechanisms of asymmetric autocatalysis of pyrimidyl alkanol.58–65)”
    Quote in the paperNot a substantial claim0 of 8 sources checked
    • cites [58] 58) Barabás, B., Caglioti, L., Micskei, K. and Pályi, G. (2009) Data-based stochastic approach to absolute asymmetric synthesis by autocatalysis. Bull. Chem. Soc. Jpn. 82, 1372–1376. source
    • cites [59] 59) Micheau, J.-C., Cruz, J.-M., Coudret, C. and Buhse, T. (2010) An autocatalytic cycle model of asymmetric amplification and mirror-symmetry breaking in the Soai reaction. ChemPhysChem 11, 3417–3419. source
    • cites [60] 60) Lavabre, D., Micheau, J.-C., Islas, J.R. and Buhse, T. (2008) Kinetic insight into specific features of the Autocatalytic Soai reaction. Top. Curr. Chem. 284, 67–96. source
    • cites [61] 61) Micskei, K., Rábai, G., Gál, E., Caglioti, L. and Pályi, G. (2008) Oscillatory symmetry breaking in the Soai reaction. J. Phys. Chem. B 112, 9196–9200. source
    • cites [62] 62) Maioli, M., Micskei, K., Caglioti, L., Zucchi, C. and Pályi, G. (2008) Evolution of chirality in consecutive asymmetric autocatalytic reaction cycles. J. Math. Chem. 43, 1505–1515. source
    • cites [63] 63) Crusats, J., Hochberg, D., Moyano, A. and Ribó, J.M. (2009) Frank model and spontaneous emergence of chirality in closed systems. ChemPhysChem 10, 2123–2131. source
    • cites [64] 64) Dóka, É. and Lente, G. (2011) Mechanism-based chemical understanding of chiral symmetry breaking in the Soai reaction. A combined probabilistic and deterministic description of chemical reactions. J. Am. Chem. Soc. 133, 17878–17881. source
    • cites [65] 65) Micheau, J.-C., Coudret, C., Cruz, J.-M. and Buhse, T. (2012) Amplification of enantiomeric excess, mirror-image symmetry breaking and kinetic proofreading in Soai reaction models with different oligomeric orders. Phys. Chem. Chem. Phys. 214, 13239–13248. source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisereasoning

    Quartz exhibits enantiomorphism and is a chiral mineral, and has long been discussed as a possible origin of chirality of organic compounds.

    “Quartz exhibits enantiomorphism and is a chiral mineral; therefore, it has long been discussed as the possible origin of chirality of organic compounds.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Quartz has been used to induce enantioenrichment of organic compounds, but no significant asymmetric induction using quartz has been reported.

    “Quartz has been used to induce enantioenrichment of organic compounds, but no significant asymmetric induction using quartz has been reported.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Asymmetric photolysis of racemic leucine and asymmetric photosynthesis of [6]helicene by circularly polarized light induce enantioenrichment with only ca. 2% ee.

    “It is known that the asymmetric photolysis of racemic leucine and asymmetric photosynthesis of [6]helicene by the irradiation of CPL induce enantioenrichment with only ca. 2% ee.5)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] 5) Inoue, Y. (1992) Asymmetric photochemical reactions in solution. Chem. Rev. 92, 741–770. source

  • May combine two claims.

    Premisecitation

    In most proposed theories of the origin of chirality, the induced ee is very low, and in some theories the induced enantioenrichments are below detection level.

    “In most cases, the ee induced by the proposed theories of the origin of chirality has been very low. Moreover, in some of the proposed theories, the induced enantioenrichments are below detection level.”
    Quote in the paperSubstantial claim0 of 9 sources checked
    • cites [2] 2) Guijarro, A. and Yus, M. (2009) The Origin of Chirality in the Molecules of Life. The Royal Society of Chemistry, Cambridge. source
    • cites [3] 3) Mislow, K. (2003) Absolute asymmetric synthesis: A commentary. Collect. Czech. Chem. Commun. 68, 849–864. source
    • cites [4] 4) Feringa, B.L. and van Delden, R.A. (1999) Absolute asymmetric synthesis: The origin, control, and amplification of chirality. Angew. Chem. Int. Ed. 38, 3418–3438. source
    • cites [5] 5) Inoue, Y. (1992) Asymmetric photochemical reactions in solution. Chem. Rev. 92, 741–770. source
    • cites [6] 6) Hazen, R.M. and Sholl, D.S. (2003) Chiral selection on inorganic crystalline surfaces. Nat. Mater. 2, 367–374. source
    • cites [7] 7) Bolli, M., Micura, R. and Eschenmoser, A. (1997) 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. 4, 309–320. source
    • cites [8] 8) Ribó, J.M., Crusats, J., Sagués, F., Claret, J. and Rubires, R. (2001) Chiral sign induction by vortices during the formation of mesophases in stirred solutions. Science 292, 2063–2066. source
    • cites [9] 9) Ernst, K.-H. (2012) Molecular chirality at surfaces. Phys. Status Solidi B 249, 2057–2088. source
    • cites [10] 10) Weissbuch, I. and Lahav, M. (2011) Crystalline architectures as templates of relevance to the origins of homochirality. Chem. Rev. 111, 3236–3267. source

  • May combine two claims.

    Interpretationown data

    With asymmetric autocatalysis, chiral inorganic crystals and enantiotopic faces of achiral inorganic crystals serve as origins of chirality, producing organic compounds with correlated absolute configurations and high ee.

    “As described, in conjunction with asymmetric autocatalysis, chiral inorganic crystals and the enantiotopic face of an achiral inorganic crystal act as the origins of chirality to afford organic compounds with the correlated absolute configurations with high ee.”
    Quote in the paperSubstantial claim
26 of 26

  • The paper relies on this without support.

    When a chiral product forms from achiral reagents without any chiral factor, the product is always a racemic mixture of the two enantiomers.

    “It should be noted that when a chiral product is formed from achiral reagents without the intervention of any chiral factor, the newly formed chiral products are always mixtures of an equimolar amount of two enantiomers, i.e., a racemate.”

  • The paper relies on this without support.

    Crystal structures of asymmetric autocatalysts provide useful insight into their solution structures and mechanism.

    “Although the crystal structures do not display the solution structures directly, structural information on the crystals provides useful insight to assist in better understanding the mechanism of asymmetric autocatalysis with amplification of ee.”

  • The paper relies on this without support.

    The signs of optical activity for NaClO3 and NaBrO3 in the same enantiomorph are opposite.

    “These correlations are in agreement with the fact that the signs of optical activity for NaClO3 and NaBrO3 in the same enantiomorph are opposite.”

  • The paper relies on this without support.

    Gypsum has an achiral crystal structure but exhibits enantiotopic cleavage faces (010) and (0–10) upon slicing.

    “Although the crystal structure of gypsum is achiral, gypsum exhibits the two-dimensional enantiotopic cleavage (010) and (0–10) face that readily appears upon slicing of the crystal.”

  • The paper relies on this without support.

    Certain classes of achiral organic compounds form chiral crystals.

    “Certain classes of achiral organic compounds are known to form chiral crystals.”

  • The paper relies on this without support.

    Chiral organic crystals made of achiral compounds have rarely been used as chiral catalysts or initiators in enantioselective reactions.

    “However, chiral organic crystals consisting of achiral organic compounds have rarely been used as chiral catalysts or initiators in an enantioselective reaction.”

  • The paper relies on this without support.

    Cytosine is an achiral nucleobase formed under prebiotic conditions.

    “Cytosine is an achiral compound and an achiral nucleobase that is formed under prebiotic conditions.”

  • The paper relies on this without support.

    An achiral crystal of cytosine monohydrate forms after cytosine is crystallized from water.

    “The achiral crystal of cytosine monohydride is known to be formed after the crystallization of cytosine from water.”

  • The paper relies on this without support.

    Adenine is an achiral nucleobase.

    “Adenine is an achiral nucleobase.”

  • The paper relies on this without support.

    Certain achiral organic compounds form achiral crystals with enantiotopic faces.

    “There are certain classes of achiral organic compounds that form achiral crystals with enantiotopic faces.”

  • The paper relies on this without support.

    Without any chiral factor, a racemic chiral product is always formed from achiral compounds.

    “However, it is widely accepted that without the intervention of any chiral factor, a racemic chiral product is always formed from achiral compounds (Scheme 13b).”

  • The paper relies on this without support.

    Carbon, nitrogen, and oxygen isotopomers are much harder to discriminate experimentally than H/D isotopomers because their atomic weight differences are smaller.

    “Carbon (13C/12C), nitrogen (15N/14N) and oxygen (18O/16O) isotopomers should be much more difficult to discriminate experimentally than H/D isotopomers because the chirality originates from the much smaller difference in atomic weight between carbon-13/carbon-12, nitrogen-15/nitrogen-14, and oxygen-18/oxygen-16 (Scheme 14).”

  • The paper relies on this without support.

    Detectable enantioenrichment in asymmetric reactions had not been reported earlier for carbon, nitrogen, and oxygen isotopomers.

    “The induction of detectable enantioenrichment in asymmetric reactions by carbon, nitrogen, and oxygen isotopomers has not been reported earlier.”

  • The paper relies on this without support.

    Many apparently achiral organic molecules on Earth may be chiral due to random substitution of naturally abundant 13C for 12C in an enantiotopic moiety.

    “Many apparently achiral organic molecules on Earth may be chiral because of random substitution of the 1.11% naturally abundant 13C for 12C in an enantiotopic moiety within a structure.”

  • The paper relies on this without support.

    Glycine has no asymmetric carbon but becomes chiral when one methylene hydrogen is replaced by deuterium.

    “Glycine does not possess any asymmetric carbon atom. However, the compound becomes chiral when one of the hydrogen atoms of the methylene group of glycine is substituted by deuterium.”

  • The paper relies on this without support.

    meso-N2,N2,N3,N3-Tetramethyl-2,3-butanediamine 14 is achiral but becomes a chiral nitrogen isotopomer when one 14N is replaced by 15N.

    “meso-N2,N2,N3,N3-Tetramethyl-2,3-butanediamine 14 is an achiral compound because, despite the presence of asymmetric carbon atoms, compound 14 is superimposable with its mirror image. However, when one of the nitrogen (14N) atoms is substituted by 15N, the diamine 14 becomes a chiral nitrogen (15N/14N) isotopomer 14.”

  • The paper relies on this without support.

    5-Ethyl-5-propylundecane 17 is a chiral saturated quaternary hydrocarbon with four different substituents on the asymmetric carbon, and its optical rotation is below detection.

    “5-Ethyl-5-propylundecane 17, i.e., (n-butyl)ethyl(n-hexyl)(n-propyl)methane, is a chiral saturated quaternary hydrocarbon possessing four different substituents on the asymmetric carbon atom. Because the differences in the structures of the four substituents are so small (compared with each other), the value of the optical rotation of the compound is below detection level.”

  • The paper relies on this without support.

    Adenine dinitrate forms chiral crystals.

    “Adenine dinitrate forms chiral crystals.”
18 of 18

Cites

Flagged first, then by citations

2 of the 123 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. 2) Guijarro, A. and Yus, M. (2009) The Origin of Chirality in the Molecules of Life. The Royal Society of Chemistry, Cambridge.
  2. 37) Soai, K. and Kawasaki, T. (2012) Asymmetric autocatalysis — Discovery and state of the art —. <i>In</i> The Soai Reaction and Related Topic (eds. Pályi, G., Zucchi, C. and Caglioti, C.). Academia Nationale di Scienze Lettere e Arti Modena, Modena, Edizioni Artestampa, Modena, pp. 9–34.

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Authors
SOAI, K.
Affiliations
Tokyo University of Science (JP)
Corresponding author
SOAI, Kenso
ORCID
SOAI, Kenso
Venue
Proceedings of the Japan Academy Series B
Publisher
Japan Academy
Published
2019-03-11
Volume
95
Issue
3
Pages
89-110
ISSN
  • 0386-2208 (ISSN-L)
  • 1349-2896
DOI
10.2183/pjab.95.009
PMC
PMC6541725
OpenAlex
W2921594458
Semantic Scholar
3b575c6e34cc9e19e902622ee3785374d72a6868
Cited by
63
References
123
Citations by year
2026: 4 · 2025: 5 · 2024: 5 · 2023: 13 · 2022: 18 · 2021: 10 · 2020: 3 · 2019: 5
FWCI
0.80
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the Japan Academy Series B (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology
  • Japan Society for the Promotion of Science
Topics
  • Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
  • Physical Sciences › Chemistry › Organic Chemistry › Asymmetric Synthesis and Catalysis
  • Physical Sciences › Chemistry › Organic Chemistry › Chemistry and Stereochemistry Studies
Keywords
asymmetric autocatalysis, homochirality, origin of homochirality, chiral symmetry breaking, enantioselective addition, diisopropylzinc, pyrimidine-5-carbaldehyde, circularly polarized light, quartz, absolute asymmetric synthesis, enantiomeric excess amplification
MeSH terms
Alcohols, Aldehydes, Alkynes, Catalysis, Pyrimidines, Stereoisomerism, Zinc Compounds

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

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