Rhodium(II)-Catalyzed Synthesis of Polyether Macrocyles

Significance

The ability of diazo compounds to generate electrophilic carbenes was used to synthesize polyether macrocycles. Hence, the rhodium(II)-catalyzed condensation of α-diazo-β-keto esters with cyclic ethers (used as solvent) afforded 16- and 18-membered macrocycles. A number of rhodium(II) catalysts {[Rh₂(esp)₂], [Rh₂(OAc)₄]} were successful for this reaction, but the more ­lipophilic and soluble [Rh₂(Oct)₄] was found to be more practical for isolation. Surprisingly, it was found that the more concentrated the mixture, the more efficient the reaction. The structures of the products were supported by X-ray diffraction analysis. A plausible mechanism was proposed involving the addition of the cyclic ether into the generated electrophilic metal carbenoids affording oxonium ylides. The macrocycle would then be generated by two simultaneous intermolecular nucleophilic attacks of the enolate of each moiety onto the oxonium electrophilic carbon atom of the other.