gamma-Functionalization of Enones and Regioselective Cyclopropylcarbinyl Radical Fragmentations

gamma-Functionalized enones are common core structures in natural products and pharmaceuticals. Existing strategies for gamma-functionalization of carbonyl compounds mainly limit to acyclic substrates, such as enals and alpha,beta-unsaturated carboxylic acids and derivatives. Our group developed a strategy of transition metal-enabled gamma-functionalization of enones via radical addition to silyl dienol ethers, which is applicable to both cyclic and acyclic alpha,beta-unsaturated carbonyls. We reasoned that the radical addition to the gamma-carbon of silylated dienolates would be favored on the basis of the inferred stability of the alkoxyallyl radical intermediate, which is only accessible through the addition to the desired gamma-position. Decomposition of the radical either by homolytic cleavage of the O−Si bond or further formation of an activated enone would subsequently lead to the gamma-substituted enones. Based on this design, a series of new methodologies have been developed for the gamma-functionalization of enones, including Cu-catalyzed gamma-sulfonylation, Cu-catalyzed gamma-alkylation, Mn-mediated gamma-alkylation, Fe-catalyzed gamma-amination, and Ni-catalyzed gamma-arylation. In Part two, the regioselective cyclopropylcarbinyl radical fragmentation was discussed. With the ring strain from the oxygen bridge, the regioselective ring opening was realized, which resulted in the synthetically valuable [3.2.1]-oxabicylic moieties.