The Reversible Nicholas Reaction in the Synthesis of Highly Symmetric Natural‐Product‐Based Macrocycles

Abstract

AbstractTwo 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.