While the field of organocatalysis underwent fast development in the past decade, many organocatalytic systems still suffer from low activity or selectivity. Whereas one can counterbalance the low activity of a catalyst by increasing the reaction time or the catalyst loading, the impaired selectivity is irreparable. The talk will mainly focus on two case studies of selectivity aspects in reactions promoted by dendritc or branched compounds equipped with an organocatalytically-active unit. In the case of the increasingly popular Baylis-Hillman reaction, we found that homogeneous dendritic imidazole-based catalysts suffer from reduced chemoselectivity, as compared to their polystyrene-supported analogues. Hypothesizing that the superior chemoselectivity of the latter originates from the hydrophobic envelopment of the catalytic sites in the polymer-supported systems, we prepared and examined a series of branched/dendritic N-alkylimidazole-based catalysts with the catalytic site, partially enveloped by flexible hydrophobic tails, which demonstrated a sharp improvement of the chemoselectivity in the model reaction (e.g. catalyst I, Fig. 1a). Alternatively, branched organocatalysts were used in conjunction with Lewis acid additives, inducing almost perfect chemoselectivity (e.g. catalyst II, Fig. 1a). Site-selective catalysis of multisite substrates opens new gateways to natural product modifications and protection-free organic synthesis. Recently, outstanding examples of such selectivity in functionalization of polyalcohol substrates were reported. These were based on inducing specific interactions of the catalyst with the substrate through an intricate network of reversible covalent or supramolecular bonds, or on matching the catalyst reactivity to that of a particular site on the substrate. We hypothesized that a similar differentiation, between chemically similar reactive functionalities within a di- or a multifunctional substrate, could be achieved using compartmentalization and polarity gradient principles in dendritic catalysts. First demonstration of this principle was achieved using internally-functionalized branched and dendritic catalysts and model amphiphilic diol substrates (e.g. Fig. 1b).

Use of branched and dendritic scaffolds for controlling selectivity in organocatalysis

254th National Meeting (2017)

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