Quantification of Electrophilic Activation by Hydrogen-Bonding Organocatalysts

A spectrophotometric sensor is described that provides a useful assessment of the LUMO-lowering provided by catalysts in DielsAlder and FriedelCrafts reactions. A broad range of 33 hydrogen-bonding catalysts was assessed with the sensor, and the relative rates in the above reactions spanned 5 orders of magnitude as determined via H-1- and H-2 NMR spectroscopic measurements, respectively. The differences between the maximum wavelength shift of the sensor with and without catalyst (Delta lambda max(1)) were found to correlate linearly with ln(k(rel)) values for both reactions, even though the substrate feature that interacts with the catalyst differs significantly (ketone vs nitro). The sensor provides an assessment of both the inherent reactivity of a catalyst architecture as well as the sensitivity of the reaction to changes within an architecture. In contrast, catalyst pK(a) values are a poor measure of reactivity, although correlations have been identified within catalyst classes.