Indium-Catalyzed Cycloisomerization of 1,6-Cyclohexenylalkynes

Abstract

Efficient four- and five-step routes to access functionalized bicyclo[3.2.1]oct-2-ene and bicyclo[3.3.1]nonadiene via indium-mediated cycloisomerization of 1,6-enynes has been developed. This atom-economical catalytic process was optimized and relied on the efficiency of InCl3 leading to the preparation of functionalized bicyclic adducts in up to 99% isolated yield. The cyclization occurred on two different processes (5-exo versus 6-endo pathway) and were influenced by the substitution of the alkynyl moiety. The exo process was favored for non-substituted alkynes whereas the endo pathway was generally observed for substituted alkynes. Then, the presence of electron-withdrawing groups on the aryl substituted alkyne increased the ratio of the exo isomer. DFT calculations were performed on stability of intermediates and corroborated the intervention of InCl3.

Recent Advances in Organometallic Chemistry and Catalysis

“…Returning to the synthetic utility of gold, Michelet and co-workers recently reported an efficient and mild synthetic route for the preparation of functionalized bicyclo[3.2.1]oct-2-ene and bicyclo[3.3.1]nonadiene derivatives, which represent privileged scaffolds for natural products and biologically active molecules, via gold-catalyzed cycloisomerization of 1,6-cyclohexenylalkynes [20]. These studies are complemented in the present Special Issue with a work demonstrating that the cheaper Lewis acid InCl 3 can alternatively act as an effective catalyst for such cycloisomerization processes [21]. A critical comparison between the indium-and gold-based catalytic systems was made by the authors, and density functional theory (DFT) calculations on the corresponding key intermediates involved in the catalytic cycles were included in the manuscript.…”

Au- and Pd-catalyzed cyclization processes: synthesis of polyfunctionalized cyclopropanes

“…7 The functionalization of di- or tri-substituted cyclopropanes thus remains scarcely reported in the literature. Inspired by the work of Shuto and Cramer, and following our previous work on “escape the flatland”, 8 we wondered if and how cyclopropane derivatives, recently prepared by our group, would react in the presence of a Pd complex. 9 We thought they would be suitable for participating in a Pd-catalyzed C–H activation of the cyclopropane moiety and therefore lead to the construction of a three dimensional oxacyclic compound (Scheme 1d).…”

Characterization of an unanticipated indium-sulfur metallocycle complex

“…Indium compounds such as indium(III) chloride have been used as catalysts for many organic reactions including the hydroarylation of biaryls and cycloisomerization of cyclohexenylalkynes [13].…”

“…Indium compounds such as indium(III) chloride have been used as catalysts for many organic reactions including the hydroarylation of biaryls and cycloisomerization of cyclohexenylalkynes [ 13 ]. Indium(III) fluoride and indium(III) triflate promote the cyanation of aldehydes and Diels–Alder reaction of imines [ 14 , 15 ].…”