Transition-Metal-Free Alkynylation of Aryl Chlorides

Abstract

Two sets of conditions have been developed for a base-mediated, transition-metal-free alkynylation of aryl chlorides that proceeds via benzyne intermediates. The first set of conditions involves the use of TMPLi base in a pentane/THF mixture at 25 °C. The second set involves use of a metal alkoxide base in dioxane at elevated temperature. Reasonable functional group tolerance has been observed. Fluoro, trifluoromethyl, silyl, cyano, and alcohol functionalities are compatible with the reaction conditions.

Hyperconjugation

“…Stabilization of bent alkynes is not limited to cycloadditions—t can be applied to other alkyne‐forming and “alkyne‐consuming” reactions, such as formation and reactivity of o‐benzynes …”

Recent mechanistic developments and next generation catalysts for the Sonogashira coupling reaction

“…In this case no mechanism has been suggested (Scheme 11). 82 The rst set of conditions involves the use of the hindered lithium 2,2,6,6-tetramethylpiperidide (TMPLi) base in a pentane-THF mixture at room temperature. The second set of conditions involves use of a metal alkoxide base in dioxane.…”

The Aryne Ene Reaction

“…A lack of o / p product mixtures and no deuterium incorporation when the reaction was conducted in acetonitrile- d 3 provided additional evidence for a concerted process. Elsewhere, Daugulis and co-workers have described the o -arylation of anilines under strongly basic conditions, 50 analogous to the investigations into phenoxides, 47 which again operates via a non-ene pathway.…”