1995 Syntex Award Lecture Correlation and prediction of rate constants for organic reactions

Marcus theory provides a framework for correlating rate and equilibrium constants, and thus the possibility of predicting rate from structure. This had been successful for a number of simple reactions, including the addition of hydroxide to carbonyl compounds, enolate formation from carbonyl compounds, and aldol addition and elimination reactions. The theory can be extended, as Multidimensional Marcus Theory, to cover concerted reactions such as E2 eliminations, the water-mediated proton switch, or the breakdown of the tetrahedral intermediate in amide hydrolysis. We have now found that Marcus theory can be applied not only to inter-molecular reactions but also to intra-molecular reactions. This is illustrated for aldol condensation and ester/lactone formation.