Investigation of Cocatalysis Conditions Using an Automated Microscale Multireactor Workstation: Synthesis of meso-Tetramesitylporphyrin

Prior manual work has shown that the condensation of mesitaldehyde and pyrrole leading to tetramesitylporphyrin depends sensitively on concentration and requires cocatalysis involving BF3·O(Et)2 and ethanol or other protic species. We have applied an automated microscale chemistry workstation capable of parallel or adaptive experimentation to systematically investigate these cocatalysis conditions. Examination of experimental grids spanning a 1000-fold range of the concentrations of BF3·O(Et)2 and ethanol identified the best cocatalysis conditions for various mesitaldehyde and pyrrole concentrations. As the reaction concentration increased from 10 to 200 mM, the optimal yields were achieved with a parallel increase in BF3·O(Et)2 concentration (from 3.3 to 56 mM), but the amount of ethanol remained relatively constant. Catalysis conditions were identified that afforded ∼30% yields for reactants in the range of 10−73 mM, thereby enabling the reaction to be performed at increased concentration without loss i...