Multistep Transformations

A one-pot reaction in which a starting compound is transformed into a skeletally rearranged product by way of several unremarkable steps may appear to be extraordinary and unexpected. One such example is the conversion of the sesquiterpene santonin into santonic acid on heating with base. From the formulas shown in the following equation, this reaction not only adds one equivalent of water (expected if the lactone is opened), but also creates a new carbonyl group and removes both carbon-carbon double bonds. The nature of the transformation of santonin to santonic acid remained unknown for many years, but was resolved in 1948 by the work of R. B. Woodward and coworkers at Harvard.

The mechanism by which this remarkable change takes place will be displayed above.

Initial hydrolysis of the lactone to santoninic acid is followed by isomerism of the α,β-unsaturation to a β,ν-location and tautomerization. The resulting diketone, in its cis-fused configuration, then undergoes an intramolecular Michael reaction, forming a new five-membered ring (note the colored bond).