Copper‐Catalyzed Allylic C−H Alkynylation by Cross‐Dehydrogenative Coupling

Abstract

C-H bond functionalization is a well-developed concept that has been thoroughly studied and gives entry to rather complex molecules without the need for previous derivatization of the substrates. The use of copper complexes in allylic C-H bond functionalization under oxidative conditions as an alternative to the well-established palladium-based methodologies remains largely underdeveloped. Here, we show for the first time a selective cross-dehydrogenative coupling reaction between underivatized allylic substrates and terminal alkynes to produce 1,4-enynes in high yields in a single step, using an in situ synthesized copper catalyst and an oxidant.

Allylic C–H Alkynylation via Copper-Photocatalyzed Cross-Dehydrogenative Coupling

“…By using the isolated complex [Cu I -L1] (see SI) as catalyst, very similar results were obtained as when it is produced in situ (entry 24, 70%). Interestingly, and contrary to what we observed under thermal conditions, 7 using Cu II instead of Cu I resulted in 30% yield of 3a (entry 25). Importantly, high selectivity towards the allylic alkynylation product was achieved in all cases, in strong contrast to the results under thermal conditions.…”

“…We began our investigation on the photocatalyzed CDC between phenylacetylene (1a) and cyclohexene (2a) as model reactants using white light (xenon lamp,  = 300-700 nm) at room temperature (23-26 °C) (Scheme 2). We employed the reaction conditions from our previous report 7 (except the reaction temperature) using DTBP as oxidant and terpyridine ligand L1 (Table 1). Terpyridines are important chelating ligands in many applications spawning from supramolecular 11 and macromolecular chemistry to luminescent devices 12 and photoelectrical cells.…”

“…Very recently, we reported the alkynylation of underivatized allylic substrates under oxidative conditions using terminal alkynes. 7 This is an example of a thermal crossdehydrogenative coupling (CDC) reaction, which can be described as the coupling of a pre-nucleophile and a preelectrophile, both devoid of leaving groups. 8…”

Recent Advances on Copper-Catalyzed C–C Bond Formation via C–H Functionalization

“…Moreover, cleavage of the alkene C-H bond was shown to be important in the rate-determining step, as revealed by kinetic isotopic effect studies (KIEs). 54…”

“…In a recent improvement of their previous work, 54 Almasalma and Mejía achieved the allylic alkynylation of cyclic alkenes at room temperature by exploiting the photophysical properties of the copper(I) terpyridyl complex that they had initially employed as a CDC catalyst (Scheme 28). This was possible simply by changing the oxidant from DTBP to TBHP.…”