Chemoselectivity Improvement via Partial Shielding of an Imidazole Active Site in Branched/Dendritic Homogeneous Catalysts of the Baylis–Hillman Reaction

While comparing analogous polystyrene-supported and homogeneous catalysts for the Baylis–Hillman reaction, we hypothesized that the hydrophobic envelopment of the imidazole catalytic sites of the former is responsible for the significantly better chemoselectivity exhibited by the heterogeneous catalysts compared to their homogeneous counterparts. In order to test this hypothesis, we prepared a series of branched/dendritic homogeneous catalysts, with an imidazole active site near the focal point and flexible tails of various lengths and polarities, capable of providing partial shielding of this site. The design of the catalysts was based on a 5-hydroxyisophthalate scaffold, and they were prepared through a number of multistep synthetic pathways. The comparison of the catalysts under a variety of conditions in a model Baylis–Hillman reaction demonstrated that long hydrophobic tales enhance the chemoselectivity parameter of the catalysis, while reducing the rate of the consumption of the substrates, and that the chemoselectivity is further improved by the presence of a free phenolic moiety in the vicinity of the catalytic imidazole unit. Moreover, in second-generation catalysts, the peripheral long tails could be either hydrophobic or polar, since the dendritic inner backbone itself presumably partially provides the necessary isolation of the catalytic site. Thus, experimental results support our hypothesis. (Figure presented.).