Influence of the Acetylenic Substituent on the Intramolecular Carbolithiation of Alkynes

Abstract

AbstractThe intramolecular carbolithiation of a series of propargylic ethers has been performed to evaluate the influence of the terminal substituent on the efficiency and the stereochemical outcome of the cyclization. Our results show that only 5‐exo‐dig cyclizations are observed, and dihydrobenzofurans are obtained exclusively. Depending on the nature of the terminal substituent, two cases can be considered. If the terminal substituent carried by the acetylenic carbon atom is itself a carbon atom, the cyclization can occur provided the terminal propargylic position bears a coordinating element and is at least disubstituted. When the cyclization occurs, it follows an anti‐carbolithiation pathway and thus leads to the E isomer of the exocyclic double bond. Only in one case (Ph) was a mixture of the E and Z isomers of the resulting olefin recovered. The cyclization can also take place if the alkyne is directly substituted by S or Si, provided the cyclization conditions are tuned. In the case of the trimethylsilyl substituent, a syn‐carbolithiation was observed. If the double bond is recovered, in most cases, in the exocyclic position, the products can aromatize directly for SPh‐substituted substrate 24. Furthermore, in the two latter cases, when alkylation of the vinyllithium intermediate is performed, isomerization of the double bond seems instantaneous.