Cyclobutane based "overbred intermediates" and their exploration in organic synthesis

"Overbred intermediates" have been used in organic synthesis for a long time, but these intermediates are not categorized as such. This name was given recently in Hoffman's book Elements of Synthesis Planning. These intermediates are very useful to synthesize complex carbocyclic molecules. A number of powerful and efficient strategies have been developed by using overbred intermediates through innovative fragmentative transformations. This review is based on four-member overbred intermediates (cyclobutane based) that have been used in the total synthesis of natural products from 1968 to 2020. In the initial part, we have discussed synthetic methods (photochemical, metal-mediated, and other miscellaneous transformations) for the construction of cyclobutane overbred intermediates. In the later section, we have discussed how the overbred skeleton is cleaved through numerous fragmentation methods to access the desired target structure.