Dispersion Effects on Reactivity and Chemo-, Regio- and Stereoselectivity in Organocatalysed Domino Reactions: A Joint Experimental and Theoretical Study

SPP 1807: Control of London dispersion interactions in molecular chemistry

This joint experimental and theoretical project aims at the development of facile and environmentally friendly organocatalytic multi-step domino reactions exploiting dispersion interactions in these novel systems. We plan to conduct a series of multi-component domino reactions involving readily available nitroolefins and aldehydes, as well as CH-acidic malononitrile already known for its broad application and its versatile use as an exceptionally reactive compound. We will mainly focus on the following three unprecedented reactions: (i) three-component two-step domino Knoevenagel/vinylogous Michael reaction; (ii) three-component five-step branched domino Knoevenagel/nitro-Michael/nitroalkane-Michael/intramolecular condensation/isomerization; (iii) two-component six-step domino Knoevenagel/dimerisation/ intermolecular condensation/intramolecular aza-Michael/intramolecular condensation/ isomerization reaction. Detailed mechanistic investigations will be performed using conventional density-functional methods in conjunction with semiempirical van der Waals corrections as well as novel highly accurate density-functional methods to shed light on the intriguing differences in chemoselectivity, regioselectivity and stereoselectivity in these organocatalysed domino transformations, and, in particular, to understand and exploit the influence of dispersion interaction in these transformations. Taking the envisioned domino reactions as test cases, computational setups for a density-functional based description of organocatalysis will be developed.