The reversible Nicholas reaction in the synthesis of highly symmetric natural-product-based macrocycles

Abstract

Two different approaches to highly symmetric macrocycles by reversible Nicholas reactions have been developed. The first sequence uses a bis[Co2(CO)6] complex derived from a double propargylic alcohol supporting two natural product moieties. The reactions with BF3·OEt2 and different benzene dimethanols yielded either (1:1) or (2:2) adducts, depending essentially on the nature of the tether joining both Co clusters. Alternatively, the Nicholas reactions of Co-complexed propargyl alcohol templates with one steroid and one monoterpene fragment as well as one aromatic terminus containing an alcohol moiety yielded the corresponding macrocycles derived from self-dimerization. Both routes to macrocycles are complementary and efficiently produce sophisticated natural-product-containing structures.