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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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The aza-Michael reaction in a diluted solution (0.025 M).The product cannot catalyse the reaction (pathway a). It was found that DBU catalyses the reaction both ways so that the product racemizes in solution (pathway b).
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f2: The aza-Michael reaction in a diluted solution (0.025 M).The product cannot catalyse the reaction (pathway a). It was found that DBU catalyses the reaction both ways so that the product racemizes in solution (pathway b).

Mentions: In solution, it was found that 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is a suitable catalyst for the forward aza-Michael reaction24 and at the same time also catalyses the retro reaction25 (see Supplementary Fig. 1). Therefore, product 1 racemizes in solution through the reverse reaction as opposed to a typical racemization process (deprotonation—protonation). In solution and under achiral reaction conditions, the synthesis leads to an equal amount of right- (R-1) and left-handed (S-1) versions of the product. Since Mannich bases may catalyse their own formation in solution262728, we also attempted to catalyse the reaction asymmetrically using the enantiopure Mannich product as a catalyst (Fig. 2). However, it was found that the product is not suited to catalyse its own formation in solution. Also in the presence of DBU, the enantiopure product still did not influence the reaction asymmetrically. Instead, a racemic solution was obtained due to the reversible reaction and this shows that there is no chiral amplification in solution.


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)

The aza-Michael reaction in a diluted solution (0.025 M).The product cannot catalyse the reaction (pathway a). It was found that DBU catalyses the reaction both ways so that the product racemizes in solution (pathway b).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: The aza-Michael reaction in a diluted solution (0.025 M).The product cannot catalyse the reaction (pathway a). It was found that DBU catalyses the reaction both ways so that the product racemizes in solution (pathway b).
Mentions: In solution, it was found that 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is a suitable catalyst for the forward aza-Michael reaction24 and at the same time also catalyses the retro reaction25 (see Supplementary Fig. 1). Therefore, product 1 racemizes in solution through the reverse reaction as opposed to a typical racemization process (deprotonation—protonation). In solution and under achiral reaction conditions, the synthesis leads to an equal amount of right- (R-1) and left-handed (S-1) versions of the product. Since Mannich bases may catalyse their own formation in solution262728, we also attempted to catalyse the reaction asymmetrically using the enantiopure Mannich product as a catalyst (Fig. 2). However, it was found that the product is not suited to catalyse its own formation in solution. Also in the presence of DBU, the enantiopure product still did not influence the reaction asymmetrically. Instead, a racemic solution was obtained due to the reversible reaction and this shows that there is no chiral amplification in solution.

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