Chemoselective Baylis-Hillman Reaction Catalysis by Lewis Base – Metal Bifunctional System

The Baylis-Hillman reaction is a very useful carbon-carbon bond-forming reaction, which acquired high synthetic popularity due to its operational simplicity and the broad application potential of the Baylis-Hillman products. In the past, it has been observed in our group that, while N-alkylimidazole-based polymer-supported catalyst exhibit outstanding chemoselectivity in this reaction, their homogeneous analogues promote the reaction with poor chemoselectivity (i.e. multiple byproducts are formed along with the Baylis-Hillman adduct).

The combination of organocatalysis and transition metals is an emerging field in organic chemistry. It has been reported that transition metals, functioning as Lewis acids, can be added as co-catalysts to organocatalytic systems. In attempt to enhance this approach, applying it for the model Baylis-Hillman reaction (Figure 1a), we synthesized bifunctional catalysts (Figure 1b and c), which include N-alkylimidazole units as organocatalysts and a pyridine-based chelate as a ligating site for a metal as a co-catalyst.

When various metal salt additives were added to the catalytic system, some of them caused a dramatic improvement in the chemoselectivity of the catalysis (Figure 1d), reaching above 70% selectivity (versus 20-30% without the metal additive). Recently, we succeeded increasing the chemoselectivity even further, up to 95%, by changing the benzyloxy group of the bifunctional catalyst into a hydroxyl group.
Furthermore, we were able to prove that the coordinative site pyridine serves merely as a ligator for the Lewis acid, since being 2,6-disubstituted it lacks the catalytic activity.

This poster describes the effect of various parameters, such as the nature of the metal salt, its concentration, the reaction time, and the structure of the new catalytic systems, on the model Baylis-Hillman reaction.