RhCl(PPh3)3-Catalyzed Intramolecular Cycloaddition of Enediynes: The Nature of the Tether and Substituents Controls the Reaction Mechanism

Abstract

In this study we analyze a series of intramolecular [2+2+2] cycloadditions of enediynes catalyzed by the Wilkinson’s complex with the B3LYP method. We are interested in the changes observed in the rate-determining oxidative coupling step of acyclic and cyclic enediynes as a function of the type of enediyne tether and the substituents present in the alkyne moieties in the case of acyclic systems. Our results show that the oxidative coupling step occurs between the two alkyne groups when the active catalyst is the RhClPH3 species, irrespective of the tether, the substituents of the alkyne groups, and the cyclic or acyclic nature of the enediynes. The same alkyne–alkyne coupling is favored in the cycloaddition of cyclic enediynes catalyzed by RhCl(PH3)2 as the active catalyst. With this catalyst, however, the preferred coupling in acyclic enediynes depends on the nature of the tether and substituents. Carbon-, oxygen-, and nitrogen-tethered enediynes with terminal alkynes favor the alkyne–alkyne oxidative coupling, whereas when the alkynes have an alkyl substituent, the enyne coupling is favored.