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Emergence of single-molecular chirality from achiral reactants.

Steendam RR, Verkade JM, van Benthem TJ, Meekes H, van Enckevort WJ, Raap J, Rutjes FP, Vlieg E - Nat Commun (2014)

Bottom Line: The synthesis of enantiopure molecules from achiral precursors without the need for pre-existing chirality is a major challenge associated with the origin of life.We here show that an enantiopure product can be obtained from achiral starting materials in a single organic reaction.An essential characteristic of this reaction is that the chiral product precipitates from the solution, introducing a crystal-solution interface which functions as an asymmetric autocatalytic system that provides sufficient chiral amplification to reach an enantiopure end state.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

ABSTRACT
The synthesis of enantiopure molecules from achiral precursors without the need for pre-existing chirality is a major challenge associated with the origin of life. We here show that an enantiopure product can be obtained from achiral starting materials in a single organic reaction. An essential characteristic of this reaction is that the chiral product precipitates from the solution, introducing a crystal-solution interface which functions as an asymmetric autocatalytic system that provides sufficient chiral amplification to reach an enantiopure end state. This approach not only provides more insight into the origin of life but also offers a pathway to acquire enantiopure compounds for industrial applications.

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Product ee of the solid state against time.(a) Four separate experiments under identical conditions starting with an initial concentration of 2.5 M of achiral reactants. (b) At lower concentrations, less crystals have to be deracemized and deracemization thus proceeds faster. The lines are a guide to the eye.
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f4: Product ee of the solid state against time.(a) Four separate experiments under identical conditions starting with an initial concentration of 2.5 M of achiral reactants. (b) At lower concentrations, less crystals have to be deracemized and deracemization thus proceeds faster. The lines are a guide to the eye.

Mentions: The reaction leads to either enantiopure S-1 or enantiopure R-1 crystals. It is evident from Fig. 4a that deracemization towards S-1 is faster than towards R-1. This could be attributed to traces of chiral impurities, which inhibit the crystal growth of R-1 (refs 31, 32). Chiral impurities can also inhibit solution-phase processes33 and possibly the nucleation of the product, since in a few experiments an offset in ee in favour of S-1 was established at the start of the precipitation (Fig. 4a). However, chiral impurities alone cannot be responsible for symmetry breaking in our experiments since deracemization also proceeds towards R-1, albeit less often. The transformation of the achiral reactants into an enantiopure product was successfully reproduced in a series of identical experiments to obtain 39 enantiopure S-1 and 29 enantiopure R-1 end states. Instead of using reactant 3 from a commercial source, we also used freshly prepared starting materials and again found that deracemization proceeds more often towards S-1. The enantiopure product can be obtained at an increased rate by either lowering the initial concentration of reactants (Fig. 4b) or by lowering the catalyst loading (see Supplementary Fig. 3). This, in turn, results in a lower number of crystals which have to undergo deracemization34. As a result, complete transformation of the achiral reactants into an enantiopure product can be realized within 3 days.


Emergence of single-molecular chirality from achiral reactants.

Steendam RR, Verkade JM, van Benthem TJ, Meekes H, van Enckevort WJ, Raap J, Rutjes FP, Vlieg E - Nat Commun (2014)

Product ee of the solid state against time.(a) Four separate experiments under identical conditions starting with an initial concentration of 2.5 M of achiral reactants. (b) At lower concentrations, less crystals have to be deracemized and deracemization thus proceeds faster. The lines are a guide to the eye.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263183&req=5

f4: Product ee of the solid state against time.(a) Four separate experiments under identical conditions starting with an initial concentration of 2.5 M of achiral reactants. (b) At lower concentrations, less crystals have to be deracemized and deracemization thus proceeds faster. The lines are a guide to the eye.
Mentions: The reaction leads to either enantiopure S-1 or enantiopure R-1 crystals. It is evident from Fig. 4a that deracemization towards S-1 is faster than towards R-1. This could be attributed to traces of chiral impurities, which inhibit the crystal growth of R-1 (refs 31, 32). Chiral impurities can also inhibit solution-phase processes33 and possibly the nucleation of the product, since in a few experiments an offset in ee in favour of S-1 was established at the start of the precipitation (Fig. 4a). However, chiral impurities alone cannot be responsible for symmetry breaking in our experiments since deracemization also proceeds towards R-1, albeit less often. The transformation of the achiral reactants into an enantiopure product was successfully reproduced in a series of identical experiments to obtain 39 enantiopure S-1 and 29 enantiopure R-1 end states. Instead of using reactant 3 from a commercial source, we also used freshly prepared starting materials and again found that deracemization proceeds more often towards S-1. The enantiopure product can be obtained at an increased rate by either lowering the initial concentration of reactants (Fig. 4b) or by lowering the catalyst loading (see Supplementary Fig. 3). This, in turn, results in a lower number of crystals which have to undergo deracemization34. As a result, complete transformation of the achiral reactants into an enantiopure product can be realized within 3 days.

Bottom Line: The synthesis of enantiopure molecules from achiral precursors without the need for pre-existing chirality is a major challenge associated with the origin of life.We here show that an enantiopure product can be obtained from achiral starting materials in a single organic reaction.An essential characteristic of this reaction is that the chiral product precipitates from the solution, introducing a crystal-solution interface which functions as an asymmetric autocatalytic system that provides sufficient chiral amplification to reach an enantiopure end state.

View Article: PubMed Central - PubMed

Affiliation: Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

ABSTRACT
The synthesis of enantiopure molecules from achiral precursors without the need for pre-existing chirality is a major challenge associated with the origin of life. We here show that an enantiopure product can be obtained from achiral starting materials in a single organic reaction. An essential characteristic of this reaction is that the chiral product precipitates from the solution, introducing a crystal-solution interface which functions as an asymmetric autocatalytic system that provides sufficient chiral amplification to reach an enantiopure end state. This approach not only provides more insight into the origin of life but also offers a pathway to acquire enantiopure compounds for industrial applications.

Show MeSH