anti-Hydroarylation of Activated Internal Alkynes: Merging Pd and Energy Transfer Catalysis

Abstract

A general catalytic anti-hydroarylation of electron-deficient internal alkynes compatible with both electron-poor and electron-rich aryl reagents is reported. This selectivity is achieved through a sequential syn-carbopalladation of the alkyne by an Ar− Pd species, followed by a tandem, Ir-photocatalyzed, counter-thermodynamic E → Z isomerization. The use of ortho-substituted boronic acids enables direct access to pharmaceutically relevant heterocyclic cores via a cascade process. Mechanistic insight into the involvement of Ar−Pd versus Pd−H as an active species is provided.

Rhodium-Catalyzed Reductive trans-Alkylacylation of Internal Alkynes via a Formal Carborhodation/C–H Carbonylation Cascade

“…A second plausible pathway might include insertion of CO into the vinyl–Rh bond of the intermediate C , followed by the C–H activation of the intermediate F to generate the six-membered cyclorhodation intermediate E (Pathway II) . In the absence of CO or HCO 2 H/Piv 2 O, the nucleophilic addition with MeOH and H 2 O occurs to assemble 3a , which supports the formation of the intermediate C .…”

“…Herein, we report a new rhodium-catalyzed reductive catalysis for trans -alkylacylation of internal alkynes via a formal carborhodation and C–H carbonylation cascade for assembling cyclopenta­[ de ]­quinoline-2,5­(1 H ,3 H )-diones (Scheme B). This method utilizes alkyl bromides as the coupling partners that perform trans -carborhodation with the alkyne moiety and then enables C–H carbonylation as the terminating step. In contrast to the precedent metal hydride catalysis, this method represents a new route that allows carbonylation of aromatic C–H bonds with unsaturated hydrocarbons through the use of a Mn metal reductant to reductively regenerate the active Rh species.…”

“…The possible mechanisms for this alkyne reductive alkylacylation reaction were proposed (Scheme ). − Initially, the active Rh I species is formed by the reduction of the Rh II species and coordination of the phosphorus ligand. , Meanwhile, substrate 1a can undergo homolysis of the C–Br bond to generate the alkyl radical intermediate A . The active Rh I species undergoes single electron oxidation with the intermediate A and/or direct insertion into the C–Br bond of substrate 1a to afford the alkyl C­(sp 3 )-Rh II intermediate B , followed by a formal anti- carborhodation of the CC triple bond in the intermediate B to deliver the vinyl-Rh II intermediate C .…”

Recent Advances in the Functionalization of Terminal and Internal Alkynes

“…In 2020, Carretero and co‐workers developed catalytic formal anti ‐hydroarylation of activated internal alkynes (Scheme 8). [14] The reaction was compatible with both electron rich and electron deficient aryl reagents under the optimum conditions were as follows: Pd(OAc) 2 /dppe (5 mol%), AcOH (20 mol%), Ir(ppy) 3 (1 mol%), THF at room temperature for 24 h under blue light irradiation.…”

Transition-Metal-Catalyzed Functionalization of Alkynes with Organoboron Reagents: New Trends, Mechanistic Insights, and Applications

“…Exploiting the compatibility between both Pd- and Ir-catalytic cycles, Carretero’s group has recently expanded this reactivity to the anti -arylation of internal alkynes activated with electron-deficient substituents (Scheme ). The reaction rendered the corresponding formal anti -arylation product for a diverse array of both electron-poor and electron-rich aryl boronic acids. A variety of electron-withdrawing alkyne substituents were amenable to the reaction, including esters, amides, ketones, aldehydes, sulfones, and phosphonates.…”