Organocatalysis with Endogenous Compounds: Towards Novel Non-enzymatic Reactions

The aldol reaction of the endogeneous compounds acetone and methylglyoxal has been studied using organocatalysis in relation to biologically relevant non-enzymatic reactions. Under preparative conditions, 3-hydroxy-2,5-hexadione, known as Henze’s ketol, is formed in high yield and with enantioselectivities up to 88% ee. Furthermore, Henze’s ketol is also formed under simulated physiological conditions at micromolar scale, indicating that this reaction might take place in living organisms

Mechanistic Insights in the Mode of Action of Bifunctional Pyrrolidine-Squaramide-derived Organocatalysts

The modes of catalytic action of three squaramide-derived bifunctional organocatalysts have been investigated using DFT methods. The [5+2] cycloaddition between oxidopyrilium ylides and enals has been used as model reaction. Two primary modes are possible for the different catalysts studied. The preference for one mode over the other is due to the possibility of additional favourable π,π-interactions between the H-bond activated pyrilium ylide and an electron-deficient aromatic ring bonded to a squaramide NH-group. The model can be extended to other reactions catalyzed by the same catalysts such as formal [2+2] cycloadditions between nitroalkenes and α,β-unsaturated aldehydes. The computational results are in excellent concurrence with the available experimental reports on the observed total enantioselectivity and differences in diastereoselectivity depending on the substrate and the reactionThis work was supported by Spanish MINECO Contracts CTQ2013-44367-C2-1-P (to P.M.) and CTQ2014-52107 (to J.L.V.). We also acknowledge the Government of Aragón (Spain) (Group E-10), the Basque Government (Spain) (IT328-10) and Aarhus University (Denmark) for financial support. We acknowledge the Institute of Biocomputation and Physics of Complex Systems (BIFI) at the University of Zaragoza (Spain) for computer time at clusters Terminus and Memento. D.R.-L. Thanks the Spanish Ministry of Education (MEC) for a predoctoral grant (FPU program)