Kinetic Evidence for a Tetrameric Transition State in the Asymmetric Autocatalytic Alkylation of Pyrimidyl Aldehydes

Buono, Frédéric G.; Blackmond, Donna G.

doi:10.1021/ja034705n

Cited by 102 publications

(85 citation statements)

References 14 publications

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“…A variation in only one of the fitted parameters in the monomeric mechanism (model 2) leads to a qualitative reproduction of the kinetic results of Blackmond et al (20). Hence arguments that have been previously promoted to exclude monomer catalysis (18,20,22,23) have to be reassessed. In fact, our simulations give slight indication for a monomeric instead of a dimeric catalytic pathway because of the better agreement of model 2 with the experimental kinetic data reported by Gridnev et al (16).…”

Section: Resultsmentioning

confidence: 80%

“…Blackmond and coworkers (20) conducted a series of calorimetrically monitored kinetic studies from which it was first concluded that the catalyst is dimeric, and then later that it is tetrameric (23) or even multimeric. In these experiments no mirror-symmetry breaking has been mentioned.…”

Section: Resultsmentioning

confidence: 99%

“…From the various attempts of kinetic modeling (19)(20)(21)(22)(23), it appears that autocatalysis and mutual inhibition are the necessary ingredients for the Soai reaction to describe the observed chiral amplification. However, reports using these approaches have not discussed the origin of the experimentally observed mirror-symmetry breaking so far.…”

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confidence: 99%

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Mirror-symmetry breaking in the Soai reaction: A kinetic understanding

Islas

Lavabre

Grévy

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

127

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Kinetic modeling using nonlinear differential equations is proposed to analyze the spontaneous generation of enantiomeric excess in the autocatalytic addition of diisopropylzinc to prochiral pyrimidine carbaldehydes (Soai reaction). Our approach reproduces experimentally observed giant chiral amplification from an initial enantiomeric excess of <10 ؊6 % to >60%, high sensitivity and positive response to the presence of minute amounts of chiral initiator at concentrations <10 ؊14 M, and spontaneous absolute asymmetric synthesis from achiral starting conditions. From our numerical simulations using kinetic schemes derived from the Frank model, including stereospecific autocatalysis and mutual inhibition, we have shown that it is possible to reproduce the mirror-symmetry-breaking behavior of the Soai reaction under batch conditions leading to a bimodal enantiomeric product distribution. Mirror-symmetry breaking was found to be resistant to a loss of stereoselectivity up to 30%. While the mutual inhibition between enantiomers seems to originate from the presence of dimerization equilibria, the exact nature of the autocatalytic stereoselective process still remains to be revealed. From the kinetic viewpoint, simple autocatalysis involving monomers as the catalytic species is consistent with all reported experimental effects of the Soai reaction.alkylzinc addition ͉ autocatalysis ͉ chirality A symmetric synthesis usually requires the intervention of chiral chemical reagents or catalysts. Few examples are known in which the generation of enantiomerically enriched products occurs from achiral precursors without the involvement of such auxiliaries. These cases, known as absolute asymmetric synthesis (1, 2), have been mostly observed in the combination of spontaneous resolution and enantioselective catalysis (3) as well as by the influence of external chiral factors such as circularly polarized light (4) or vortex motion (5). Some cases were reported in which no obvious chiral inductor was used and, nevertheless, high enantiomeric excess (ee) has been obtained systematically. These examples display the signature of mirrorsymmetry breaking (6), i.e., a process in which a small random ee is greatly amplified, whereas the chirality sign remains unpredictable for each individual experiment. The generation of small random ee occurs practically in any chiral system for statistical reasons alone in which the ee is inversely proportional to the square root of the number of molecules, ee ϰ n Ϫ1/2 (7). However, this value remains negligible as long as a large number of molecules is involved, so an amplification mechanism is needed to increase such minute ee to a macroscopic level.Mirror-symmetry breaking in chemical systems is typically associated to autocatalytic kinetics, i.e., a feedback mechanism in which one or several reaction products directly increase the overall rate of the chemical reaction. Hence in the specific case of chiral autocatalysis, the enantiomeric product could act as an asymmetric catalyst of its proper forma...

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Section: Resultsmentioning

confidence: 80%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Mirror-symmetry breaking in the Soai reaction: A kinetic understanding

Islas

Lavabre

Grévy

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

127

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show abstract

“…[10][11][12] We developed a modified Kagan ML 2 model 10,13,14 (Scheme 2) for autocatalytic asymmetric amplification in the case of substrate 1 with R=CH 3 , where the reaction product 2' forms dimers 10 (or tetramers 11,[15][16][17][18] ) that serve as the active autocatalytic species. Our work demonstrated that dimers are formed stochastically, with equal probability of forming homo-(D RR and D SS ) and heterochiral (D RS ) species (K dimer = 4).…”

Section: Scheme 1 Soai Autocatalytic Reaction Initiated By An Isotopmentioning

confidence: 99%

Elucidating the Role of Isotopically Chiral Initiators in the Soai Asymmetric Autocatalytic Reaction

Hawbaker¹,

Blackmond²

2018

Preprint

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A mechanistic rationalization is given for how asymmetric amplification is induced with fidelity in the Soai autocatalytic reaction by chiral initiators that are enantiomeric only by virtue of an isotope, e.g. -CH 3 vs. CD 3 . A transient inhibition of the autocatalytic pathway at the outset of the reaction implicates an interaction between initiator and product initially formed in the uncatalyzed background reaction. Selectivity in formation of the product-initiator complex ultimately induces a slight enantioenrichment in the active dimer catalysts that trigger and direct the autocatalytic pathway.

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“…Certain chemical reactions are indeed known to have such properties (Soai et al, 1995, Sato et al 2003, Mathew et al, 2004. It is important to point out that these reactions are only based on dimerization, but they are nevertheless quite valuable in establishing the basic elements of homochiralization in chemical systems (Kitamura et al 1998, Plasson et al 2004, and can lead to quantitative predictions (Blackmond et al 2001, Buono andBlackmond 2003). For a recent review see the paper by Mislow (2003).…”

Section: Introductionmentioning

confidence: 99%

Unidirectional polymerization leading to homochirality in the RNA world

Nilsson

Brandenburg²,

Andersen³

et al. 2005

International Journal of Astrobiology

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The differences between uni-directional and bidirectional polymerization are considered. The unidirectional case is discussed in the framework of the RNA world. Similar to earlier models of this type, where polymerization was assumed to proceed in a bi-directional fashion (presumed to be relevant to peptide nucleic acids), left-handed and right-handed monomers are produced via an autocatalysis from an achiral substrate. The details of the bifurcation from a racemic solution to a homochiral state of either handedness is shown to be remarkably independent of whether the polymerization in uni-directional or bi-directional. Slightly larger differences are seen when dissociation is allowed and the dissociation fragments are being recycled into the achiral substrate.

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Kinetic Evidence for a Tetrameric Transition State in the Asymmetric Autocatalytic Alkylation of Pyrimidyl Aldehydes

Cited by 102 publications

References 14 publications

Mirror-symmetry breaking in the Soai reaction: A kinetic understanding

Mirror-symmetry breaking in the Soai reaction: A kinetic understanding

Elucidating the Role of Isotopically Chiral Initiators in the Soai Asymmetric Autocatalytic Reaction

Unidirectional polymerization leading to homochirality in the RNA world

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