Catalytic Gels for a Prebiotically Relevant Asymmetric Aldol Reaction in Water: From Organocatalyst Design to Hydrogel Discovery and Back Again

TY - JOUR

T1 - Catalytic Gels for a Prebiotically Relevant Asymmetric Aldol Reaction in Water

T2 - From Organocatalyst Design to Hydrogel Discovery and Back Again

AU - Hawkins, Kirsten

AU - Patterson, Anna

AU - Clarke, Paul Andrew

AU - Smith, David Kelham

N1 - © 2020 American Chemical Society. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

PY - 2020/3/4

Y1 - 2020/3/4

N2 - This paper reports an investigation into organocatalytic hydrogels as prebiotically-relevant systems. Gels are interesting prebiotic reaction media, combining heterogeneous and homogeneous characteristics with a structurally-organised active ‘solid-like’ catalyst separated from the surrounding environment, yet in intimate contact with the solution phase and readily accessible via ‘liquid-like’ diffusion. A simple self-assembling glutamine amide derivative 1 was initially found to catalyse a model aldol reaction between cyclohexanone and 4-nitrobenzaldehyde, but did not maintain its gel structure during reaction. In this study, it was observed that compound 1 could react directly with the benzaldehyde to form a hydrogel in situ based on Schiff base 2 as a low-molecular-weight gelator (LMWG) This new dynamic gel is a rare example of a two-component self-assembled LMWG hydrogel and was fully characterised. It was demonstrated that glutamine amide 1 could select an optimal aldehyde component and preferentially assemble from mixtures. In the hunt for an organocatalyst, reductive conditions were applied to the Schiff base to yield secondary amine 3, which is also a highly effective hydrogelator at very low loadings with a high degree of nanoscale order. Most importantly, the hydrogel based on 3 catalysed the prebiotically-relevant aldol dimerisation of glycolaldehyde to give threose and erythrose. In buffered conditions, this reaction gave excellent conversions, good diastereoselectivity and some enantioselectivity. Catalysis using the hydrogel of 3 was much better than using non-assembled 3 – demonstrating a clear benefit of self-assembly. The results sug-gest hydrogels offer a potential strategy by which prebiotic reactions can be promoted using simple prebiotically-plausible LMWGs, that can selectively assemble from complex mixtures. Such processes may have been of prebiotic im-portance.

AB - This paper reports an investigation into organocatalytic hydrogels as prebiotically-relevant systems. Gels are interesting prebiotic reaction media, combining heterogeneous and homogeneous characteristics with a structurally-organised active ‘solid-like’ catalyst separated from the surrounding environment, yet in intimate contact with the solution phase and readily accessible via ‘liquid-like’ diffusion. A simple self-assembling glutamine amide derivative 1 was initially found to catalyse a model aldol reaction between cyclohexanone and 4-nitrobenzaldehyde, but did not maintain its gel structure during reaction. In this study, it was observed that compound 1 could react directly with the benzaldehyde to form a hydrogel in situ based on Schiff base 2 as a low-molecular-weight gelator (LMWG) This new dynamic gel is a rare example of a two-component self-assembled LMWG hydrogel and was fully characterised. It was demonstrated that glutamine amide 1 could select an optimal aldehyde component and preferentially assemble from mixtures. In the hunt for an organocatalyst, reductive conditions were applied to the Schiff base to yield secondary amine 3, which is also a highly effective hydrogelator at very low loadings with a high degree of nanoscale order. Most importantly, the hydrogel based on 3 catalysed the prebiotically-relevant aldol dimerisation of glycolaldehyde to give threose and erythrose. In buffered conditions, this reaction gave excellent conversions, good diastereoselectivity and some enantioselectivity. Catalysis using the hydrogel of 3 was much better than using non-assembled 3 – demonstrating a clear benefit of self-assembly. The results sug-gest hydrogels offer a potential strategy by which prebiotic reactions can be promoted using simple prebiotically-plausible LMWGs, that can selectively assemble from complex mixtures. Such processes may have been of prebiotic im-portance.

KW - HYDROGELS

KW - Prebiotic chemistry

KW - origin of life

KW - aldol reactions

U2 - 10.1021/jacs.9b13156

DO - 10.1021/jacs.9b13156

M3 - Article

SN - 0002-7863

VL - 142

SP - 4379

EP - 4389

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 9

ER -