Gold-Catalyzed Intermolecular Reactions of Alkynes with Alkenes: Novel Reactivities and Global Mechanistic Picture

Gold catalysis is a powerful tool to build C–C bonds and create molecular complexity via selective activation of alkynes. Despite the advances in intramolecular reactions of alkynes with alkenes, the intermolecular version remains challenging and scarce, since the final products are also alkenes which compete with the initial substrates leading to undesired oligomerizations. In this Doctoral Thesis, we explored intermolecular reactions of a wide range of alkynes with alkenes and investigated in detail the reaction mechanisms by both experiments and DFT calculations.

Our group developed the gold(I)-catalyzed [2+2] cycloaddition of arylalkynes with alkenes to furnish regioselectively cyclobutenes. Now we found that ortho-substituted arylalkynes react with alkenes to give 1,3-dienes by a metathesis-type process, whereas less sterically demanding 1,3-butadiynes react with alkenes leading to 1-alkynylcyclobutenes. A comprehensive theoretical study showed that key intermediates in these transformations are cyclopropyl gold(I) carbenes, whose electronic and steric properties determine their evolution through divergent pathways close in energy.

Cyclobutenes are important frameworks in natural and biologically active products as well as versatile synthetic intermediates. Thus, we focused on expanding the scope of the gold(I)-catalyzed [2+2] cycloaddition to access more functionalized 1-vinyl-, 3-vinyl- and 3-alkynylcyclobutenes. Furthermore, we developed one-pot procedures to convert the valuable cyclobutenes into a variety of architectures via cycloaddition, ring opening, expansion or contraction.

Finally, we discovered a novel intermolecular reaction of bromoalkynes with allylsilanes catalyzed by gold(I) which renders a totally different outcome: skipped enynes via a cross-coupling-type process or skipped dienes via allylation/cyclization cascade. Based on experiments and theoretical calculations, the mechanism of these reactions was proposed to proceed via an unprecedented rearrangement.