Spectroscopic Study of a Cinchona Alkaloid-Catalyzed Henry Reaction

A spectroscopic study of an organocatalytic Henry reaction between nitroalkanes and aldehydes catalyzed by a quinidine-derived Cinchona alkaloid is described. The binding modes of the reaction substrates are investigated using electronic absorption and fluorescence spectroscopy and further corroborated by nuclear magnetic resonance measurements. Aldehydes are shown to associate with both the 6′-OH group and the basic quinuclidine nitrogen of the catalyst, whereas nitroalkanes do not exhibit a clear binding mode. Reaction progress kinetic analysis reveals that the reaction is first-order in both of the substrates and the catalyst. Second, the reaction proceeds approximately five times faster in the excess of the nitroalkanes than in the excess of the aldehydes, suggesting that binding of the aldehydes results in the inhibition of the catalyst. Aldehydes deactivate the basic quinuclidine site, thus suppressing the deprotonation of the nitroalkanes which is the proposed initial step in the reaction cycle.