Oxidative Ring Contraction of Cyclobutenes: General Approach to Cyclopropylketones including Mechanistic Insights

An
original oxidative ring contraction of easily accessible cyclobutene
derivatives for the selective formation of cyclopropylketones (CPKs)
under atmospheric conditions is reported. Comprehensive mechanistic
studies are proposed to support this novel, yet unusual, rearrangement.
Insights into the mechanism ultimately led to simplification and generalization
of the ring contraction of cyclobutenes using mCPBA
as an oxidant. This unique and functional group tolerant transformation
proceeds under mild conditions at room temperature, providing access
to a new library of polyfunctionalized motifs. With CPKs being attractive
and privileged pharmacophores, the elaboration of such a simple and
straightforward strategy represents a highly valuable tool for drug
discovery and medicinal chemistry. Additionally, the described method
was employed to generate a pool of bioactive substances and key precursors
in a minimum number of steps.