Soai Reaction Research Articles

A Framework to Identify Supercritical and Subcritical Turing Bifurcations: Case Study of Soai Reaction Featuring Asymmetric Autocatalysis

A Framework to Identify Supercritical and Subcritical Turing Bifurcations: Case Study of Soai Reaction Featuring Asymmetric Autocatalysis

Asymmetric autocatalysis with amplification of enantiomeric excess utilizing chiral crystals of achiral o-terphenyls as chiral triggers

Chiral crystals composed of achiral hydrocarbon o-terphenyl and its dimethoxy derivative, 4′,5′-dimethoxy-o-terphenyl have been successfully employed as chiral triggers in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde. In conjunction with asymmetric autocatalysis, that is, the Soai reaction, 5-pyrimidyl alkanol with remarkably enhanced enantiomeric excess (up to >99.5% ee) has been synthesized. The resulting 5-pyrimidyl alkanols exhibit the absolute configurations corresponding to those of the enantiomorphic o-terphenyls. These current findings highlight the capability of asymmetric autocatalysis to establish a connection between the crystal chirality of achiral hydrocarbon, such as o-terphenyls and the highly enantioenriched organic compounds.

Achiral 2-pyridone and 4-aminopyridine act as chiral inducers of asymmetric autocatalysis with amplification of enantiomeric excess via the formation of chiral crystals.

Enantiomorphous crystals of achiral 2-pyridone and 4-aminopyridine served as sources of chirality, to induce the asymmetric autocatalysis of 5-pyrimidyl alkanol during the asymmetric addition of diisopropylzinc to the corresponding pyrimidine-5-carbaldehyde, that is, the Soai reaction. Following a significant amplification of enantiomeric excess through asymmetric autocatalysis, highly enantioenriched 5-pyrimidyl alkanol could be synthesized with their corresponding absolute configurations to those of chiral crystals of 2-pyridone and 4-aminopyridine.

Reaction of Triazolic Aldehydes with Diisopropyl Zinc: Chirality Dissipation versus Amplification

The phenomenon of amplifying asymmetric autocatalysis (AAA) has recently been restricted to alkylation of several specific substrates with diisopropyl zinc (Soai reaction). Targeting the extension of the scope of this phenomenon, we studied the reaction of triazolic aldehydes with diisopropyl zinc. Experiments demonstrated a diversity of results for the dissipation of chirality, conserving the existent ee and spontaneous chirality generation. Computational analysis showed that depending on the level of oligomerization of the catalyst, one could expect amplification (monomeric catalyst) while maintaining the existing chirality (dimeric catalyst) or dissipation of chirality (tetrameric catalyst). These findings are promising for the elaboration of synthetic protocols controlling chirality generation. In addition, three optically active triazolic alcohols were characterized.

D-RNA selects L-amino acids in a newly characterized aminoacyl-RNA loop ligation.

Biological life adheres to molecular asymmetry to an extent that chirality is considered a requisite for the earliest biochemical systems. Particularly, L-amino acids and D-sugars (in nucleic acids) are almost exclusive throughout biology, while purely chemical synthesis pathways for these molecules (which necessarily predate biological synthesis pathways) yield an even split of both enantiomers. Thus, the origins-of-life field has outstanding interest in physical and chemical mechanisms for symmetry breaking. Numerous investigations on the origins of homochirality have yielded explanations including magnetic fields, spin-polarized electrons, crystallization, and the Soai reaction. However, proposed mechanisms tend to target molecules of a single species or those resulting from a particular synthesis pathway. These mechanisms are significant only because chemical reactions with such enantioenriched species are assumed to propagate asymmetry throughout chiral molecules. We experimentally suggest such proliferation of asymmetry through an enantiopreferential and self-amplifying reaction between amino acids and RNA - loop ligation. The loop ligation reaction takes place with two RNA strands in a nicked stem-loop, in which the 3’ hydroxyl of one strand is aminoacylated by an amino acid chemically activated with imidazole, forming an aminoacyl ester. The amino acid ligates to the imidazole-activated 5’ phosphate of a second RNA strand, forming a phosphoramidate linkage. The final product is a closed stem loop with an amino acid-bridged backbone. Our results demonstrate five-fold preference for incorporation of L-amino acids in a backbone of D-RNA. We determined that enantioselectivity occurs most prominently in the loop-closing step based on experiments which isolated individual kinetic steps of the loop ligation process. Because aminoacylation is the cornerstone of RNA-coded protein synthesis, the enantiopreference observed in prebiotically plausible loop ligation offers a chemical axis for the selection of L-amino acids in a D-RNA world.

Asymmetric Autocatalysis as an Efficient Link Between the Origin of Homochirality and Highly Enantioenriched Compounds.

Biological homochirality of essential components such as L-amino acids and D-sugars is prerequisite for the emergence, evolution and the maintenance of life. Implication of biological homochirality is described. Considerable interest has been focused on the origin and the process leading to the homochirality. Asymmetric autocatalysis with amplification of enantiomeric excess (ee), i.e., the Soai reaction, is capable to link the low ee induced by the proposed origins of chirality such as circularly polarized light and high ee of the organic compound. Absolute asymmetric synthesis without the intervention of any chiral factor was achieved in the Soai reaction.

London Disperse Interactions Assist Chiral Induction in the Soai Autoamplifying Reaction Provoked by 1- and 2-Aza[6]helicenes

In this paper, DFT computations revealed the mechanisms of the asymmetric catalytic reactions of diisopropylzinc with pyrimidylaldehyde catalyzed by 1- and 2-aza[6]helicenes, which make them effective inductors of the autocatalytic chiral amplification Soai reaction. The generation of chirality takes place through the formation of adducts of aldehyde and helicenes stabilized via non-covalent disperse interactions strictly defining the orientation of the aldehyde molecule in the corresponding transition state.

Asymmetric autocatalysis: The Soai reaction

Asymmetric autocatalysis: The Soai reaction

The Soai Reaction: The Origin of Asymmetry-Amplifying Autocatalysis

The Soai Reaction: The Origin of Asymmetry-Amplifying Autocatalysis

One Soai reaction, two mechanisms?

For over 25 years the chemistry community has puzzled over the mechanism of the Soai reaction, a fascinating chemical process which achieves chiral symmetry breaking by combining autocatalysis with asymmetric amplification. In 2020, the groups of Denmark and Trapp each made a proposal, based on extensive experimental work, on what is the catalytic species there: either a tetrameric product alkoxide aggregate ("SMS tetramer") or a product-substrate dimer ("hemiacetal"). These models seemingly oppose and exclude each other; however, they might also be both valid since the studies were conducted on different substrates which are not necessarily equivalent. This is shown in this Viewpoint by an in-depth comparison of the two studies and of data from earlier reports, which opens up to a discussion on this scenario's far-reaching implications on the fundamental understanding of asymmetry-amplifying autocatalysis.

Asymmetric Autocatalysis as a Link Between Crystal Chirality and Highly Enantioenriched Organic Compounds

AbstractThe origin of biological homochirality has attracted much attention. Pyrimidyl alkanols exhibit asymmetric autocatalysis with significant amplification of enantiomeric excess in the reaction between pyrimidine‐5‐carbaldehyde and diisopropyl zinc (the Soai reaction). Chiral inorganic crystals such as quartz, cinnabar and sodium chlorate act as chiral triggers of asymmetric autocatalysis to afford highly enantioenriched pyrimidyl alkanol, with the absolute configurations corresponding to those of the chiral crystals. Chiral organic crystals composed of achiral organic compounds such as cytosine, adenine dinitrate, and γ‐glycine act as the chiral triggers of the Soai reaction to afford pyrimidyl alkanol with high ee that corresponds to the absolute configuration of the chiral trigger. This review describes that chiral minerals and chiral organic crystals act as the chiral triggers of the Soai reaction and that these chiral crystals are correlated to near‐enantiopure chiral organic compounds.

Symmetry Breaking and Autocatalytic Amplification in Soai Reaction Confined within UiO-MOFs under Heterogenous Conditions.

Symmetry breaking is observed in the Soai reaction in a confinement environment provided by zirconium‐based UiO‐MOFs used as crystalline sponges. Subsequent reaction of encapsulated Soai aldehyde with Zn(i‐Pr)2 vapour promoted absolute asymmetric synthesis of the corresponding alkanol. ATR‐IR and NMR confirm integration of aldehyde into the porous material, and a similar localization of newly formed chiral alkanol after reaction. Despite the confinement, the Soai reaction exhibits significant activity and autocatalytic amplification. Comparative catalytic studies with various UiO‐MOFs indicate different outcomes in terms of enantiomeric excess, handedness distribution of the product and reaction rate, when compared to pristine solid Soai aldehyde, while the crystalline MOF remains highly stable to action of Zn(iPr)2 vapour. This is an unprecedented example of absolute asymmetric synthesis using MOFs.

Spontaneous Deracemizations.

Spontaneous deracemizations is a challenging, multidisciplinary subject in current chirality research. In the absence of any chiral inductors, an achiral substance or a racemic composition is driven into an enantioenriched or even homochiral state through a selective energy input, e.g., chemical potential, photoirradiation, mechanical grinding, ultrasound waves, thermal gradients, etc. The most prominent examples of such transformations are the Soai reaction and the Viedma deracemization. In this review, we track the most recent developments in this topic and recall that many other deracemizations have been reported for solutions from mesophases to conglomerate crystallizations. A compiled set of simply available achiral organic, inorganic, organometallic, and MOF compounds, yielding conglomerate crystals, should give the impetus to realize new experiments on spontaneous deracemizations. Taking into account thermodynamic constraints, modeling efforts have shown that structural features alone are not sufficient to describe spontaneous deracemizations. As a guideline of this review, particular attention is paid to the physicochemical origin and symmetry requirements of such processes.

Asymmetric autocatalysis triggered by triglycine sulfate with switchable chirality by altering the direction of the applied electric field.

Triglycine sulfate (TGS) acts as a chiral trigger for asymmetric autocatalysis with amplification of enantiomeric excess, i.e., the Soai reaction. Therefore, molecular chirality of highly enantioenriched organic compounds is controlled by a ferroelectric crystal TGS, whose polarization is altered by an electric field.

In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis.

Chemical reactions that lead to a spontaneous symmetry breaking or amplification of the enantiomeric excess are of fundamental interest in explaining the formation of a homochiral world. An outstanding example is Soai's asymmetric autocatalysis, in which small enantiomeric excesses of the added product alcohol are amplified in the reaction of diisopropylzinc and pyrimidine‐5‐carbaldehydes. The exact mechanism is still in dispute due to complex reaction equilibria and elusive intermediates. In situ high‐resolution mass spectrometric measurements, detailed kinetic analyses and doping with in situ reacting reaction mixtures show the transient formation of hemiacetal complexes, which can establish an autocatalytic cycle. We propose a mechanism that explains the autocatalytic amplification involving these hemiacetal complexes. Comprehensive kinetic experiments and modelling of the hemiacetal formation and the Soai reaction allow the precise prediction of the reaction progress, the enantiomeric excess as well as the enantiomeric excess dependent time shift in the induction period. Experimental structural data give insights into the privileged properties of the pyrimidyl units and the formation of diastereomeric structures leading to an efficient amplification of even minimal enantiomeric excesses, respectively.

Structural Contributions to Autocatalysis and Asymmetric Amplification in the Soai Reaction.

Diisopropylzinc alkylation of pyrimidine aldehydes-the Soai reaction, with its astonishing attribute of amplifying asymmetric autocatalysis-occupies a unique position in organic chemistry and stands as an eminent challenge for mechanistic elucidation. A new paradigm of "mixed catalyst-substrate" experiments with pyrimidine and pyridine systems allows a disconnection of catalysis from autocatalysis, providing insights into the role played by reactant and alkoxide structure. The alkynyl substituent favorably tunes catalyst solubility, aggregation, and conformation while modulating substrate reactivity and selectivity. The alkyl groups and the heteroaromatic core play further complementary roles in catalyst aggregation and substrate binding. In the study of these structure-activity relationships, novel pyridine substrates demonstrating amplifying autocatalysis were identified. Comparison of three autocatalytic systems representing a continuum of nitrogen Lewis basicity strength suggests how the strength of N-Zn binding events is a predominant contributor toward the rate of autocatalytic progression.

Charting the course of the Soai reaction

Autocatalysis The Soai reaction is unusual in its capacity to produce just one of two mirror-image products by amplifying miniscule asymmetries at the outset. The reaction adds an isopropyl group from organozinc to a specific pyrimidine-substituted aldehyde. The product alcohol then appears to coordinate isopropylzinc in a tetrameric arrangement to catalyze subsequent additions. Athavale et al. report kinetic, spectroscopic, and modeling studies with a simplified substrate (pyridine in place of pyrimidine) that still manifests autocatalysis. They conclude that amplification stems from better substrate accommodation by the less stable homochiral tetramer. Nat. Chem. 12 , 412 (2020).

Demystifying the asymmetry-amplifying, autocatalytic behaviour of the Soai reaction through structural, mechanistic and computational studies.

The Soai reaction has profoundly impacted chemists’ perspective of chiral symmetry breaking, absolute asymmetric synthesis and its role in the origin of biological homochirality. Herein, we describe the unprecedented observation of asymmetry amplifying autocatalysis in the alkylation of 5-(trimethylsilylethynyl)pyridine-3-carbaldehyde using diisopropylzinc. Kinetic studies with a surrogate substrate and spectroscopic analysis of a series of zinc-alkoxides that incorporate specific structural mutations reveal a ‘pyridine-assisted cube escape’. The new tetrameric cluster functions as a catalyst that activates the substrate through a two point binding mode and poises a coordinated diisopropylzinc moiety for alkyl group transfer. Transition-state models leading to both the homochiral and heterochiral products were validated by density functional theory calculations. Moreover, experimental and computational analysis of the heterochiral complex provides a definitive explanation for the non-linear behavior of this system. Our deconstruction of the Soai system reveals the structural logic for autocatalyst evolution, function and substrate compatibility – a central mechanistic aspect of this iconic transformation.

Absolute Autocatalytic Amplification under Heterogenous Phase Conditions Involving Subsequent Hydride Transfer and a Hemiacetal Intermediate

AbstractAbstract: In contrast to the homogenous phase, absolute asymmetric amplification of pyridine alkanol is observed under heterogenous conditions. The reaction of iPr2Zn vapor on a solid powder of pyridine carbaldehyde induced autocatalytic amplification of chirality providing the alkanol product with an enantiopurity up to 90 % ee. In this study, side products were identified and their formation is traced back to redox pathways involving hydride transfer, namely a chiral ester resulting most probably from a disproportionation of the starting aldehyde into a hemiacetal and subsequent hydride loss following a Claisen‐Tishchenko mechanism. These observations provide new perspectives in the elucidation of the mechanism of amplification of chirality in the Soai reaction.

Autocatalytic Models for the Origin of Biological Homochirality.

Autocatalytic models for the emergence of homochirality have been of interest for more than half a century. The sole experimental example of such an amplifying autocatalytic reaction is the Soai reaction. In this review, we trace the history of the theoretical models and the experimental work that led up to the discovery of the remarkable, singular Soai reaction. The experimental and computational studies that have helped to delineate the mechanism of this reaction are discussed in detail. Studies of both the concept of chiral symmetry breaking as well as the subsequent chiral amplification process are discussed. Particular attention is paid to flaws in some of the published models, and suggestions are offered for how such issues might be avoided in future work. The outlook in the search for a prebiotically plausible version of such an amplifying autocatalytic system is presented.