Catalytic Synthesis of Zinc Metallacycles

Since their discovery in 1849, organozinc compounds have become integral reagents in organic chemistry due to their relative stability and high functional group tolerance compared to other organometallic reagents. Here we demonstrate the synthesis of zinc metallacycles through a cobalt to zinc transemetalation pathway. This method uses Zn powder and is carried out at room temperature compared to the harsh reaction conditions and activated zinc species typically required. Reductive coupling reactions of alkynes and imines are attractive methods for the synthesis of chiral allylic amines. Mechanistically, these reactions involve oxidative cyclization of the alkyne and the imine to generate a metallacyclic intermediate, which then reacts with H2 or an H2 surrogate to form the product. As an alternative to this hydrogenolysis pathway, here we show that transmetalation to zinc can occur, forming a zinc metallacycle product. Additionally, an acrylate component can be incorporated in a multicomponent reductive coupling reaction to produce a new Zn metallacycle product. After aqueous workup, chiral β2,3 amino acid derivatives are formed. These organozinc products serve as a versatile nucleophiles for carbon−carbon and carbon−heteroatom coupling reactions. Mechanistic studies based on isotopic labeling experiments and DFT calculations suggest that the key transmetalation step occurs between a Co(II) species and ZnCl2.