Cationic Iodine(I)-based halogen bond donors in enantioselective organocatalysis

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The use of halogen bonding (XB) in noncovalent organocatalysis can be considered as established by now, however only two examples have so far been published in which enantioselective transformations are based primarily on XB. With a successfully XB-catalyzed asymmetric Mukaiyama aldol reaction as starting point, this field of research will be decisively developed further in this project. In the first subproject, the mechanism of the asymmetric induction will be elucidated in detail via DFT calculations and experimental studies, in order to be able to systematically further optimize the catalysts.In the second subproject, various options to diversify the structure of a bidentate bis(iodoimidazolium)-based catalyst will be realized:a) next to the currently employed 1,3-benzene backbone, a 1,4 substitution pattern will also be utilized which has already been investigated for achiral systems. The thus-extended bite angle should allow access to novel substrates. b) The ring sizes of the rigid chiral sidearms will be systematically varied by using different building blocks (amino alcohols) and synthesis routes. A fundamentally different geometry of the binding pocket can then be expected.c) All core structures generated by these means will be equipped with further substituents. Next to the use of corresponding more complex amino alcohols as starting materials, more importantly a method for late-stage functionalization of the catalyst structure will be developed based on preliminary work already performed in our group. In addition to purely steric modifications, this will also allow access to powerful bifunctional halogen bond donors. In the third subproject, new substrates and reactions will be made accessible to asymmetric XB catalysis via the larger selection of catalysts. Especially the bifunctional catalysts developed in this project should be able to significantly extend the repertoire of reactions that can be catalyzed. Furthermore, the activation of „soft“ substrates (according to the HSAB principle) will be investigated in particular, as XB donors with their similarly „soft“ halogen atoms should be ideally suited for these compounds. A deeper understanding of this asymmetric induction and a significant broadening of the structural basis of the catalysts should thus provide the foundations to establish enantioselective XB catalysis as complementary counterpart to HB catalysis – and, in the long term, to systematically utilize the special features of this interaction.