Analysis of highly disfavored processes through pathway-specific correlated fluorescence.

A new method is described for the detection of disfavored reaction pathways. The approach combines organic synthesis, to independently prepare reactant and product, with the low detection limits of confocally adjusted fluorescence correlation spectroscopy. Selective detection of disfavored products is achieved by designing a system in which the analyte displays a unique absorption and emission of light. This was accomplished through application of a substance-selective intramolecular charge transfer. The power of this technique was demonstrated by monitoring the progress of the thermal retro-[2+2]-cycloaddition. In conjunction with concurrent 1H-NMR monitoring, the relative abundance of major and disfavored reaction products can be determined and used to calculate the energetics of processes disfavored by more than 5 kcal/mol.