The Gold‐Catalyzed Hydroarylation of Alkynes with Electron‐Rich Heteroarenes – A Kinetic Investigation and New Synthetic Possibilities

Abstract

Theg old-catalyzed mono-hydroarylation and two-fold hydroarylation of alkynes with electron-rich heteroarenes was analyzed by a 1 HNMR kinetic study. Theo btainedr ate constants for the decreasing alkyne concentration provide information on the reactivity of this addition reaction. Thee xaminations show the orthogonal reactivity of gold and ap roton for the twor eactions teps.T he first hydroarylation is exclusively promoted by gold(I), whereast he second step is premised on ap roton which will be reversibly derivedf rom the formation of s,p-acetylide complexes from the terminal alkynes or by interaction with solvents.B ased on kinetic data, it was possible to synthesizeal arger ange of mono-adducts in moderate to good yields,f urthermore the synthesiso fh etero-di-adducts,b earing two different substituents,w as explored.

Catalytic Gold Chemistry: From Simple Salts to Complexes for Regioselective C−H Bond Functionalization

“…Instead of Schmidbaur‐Bayler salt, the same group showed that the reaction can be stopped at the monoarylation stage 279 by utilizing IPrAuNTf 2 as catalyst (Scheme 48, Eq. (2)) [249] . On the other hand, the second hydroarylation to generate 280 was shown to be effected by Bronsted catalysis, suggesting the orthogonal reactivity of gold and proton for the two reaction steps.…”

“…(2)). [249] On the other hand, the second hydroarylation to generate 280 was shown to be effected by Bronsted catalysis, suggesting the orthogonal reactivity of gold and proton for the two reaction steps. From 1 H NMR kinetics, it was confirmed that IPrAuNTf 2 promotes the in situ σ,π-acetylide formation from terminal alkynes, which enables the reversibility of protons to favor the crucial second hydroarylation.…”

Gold-Catalyzed Intermolecular Alkyne Hydrofunctionalizations—Mechanistic Insights

“…In all these pathways, the gold center is not directly involved in the second hydroarylation process, but it rather acts indirectly by promoting the generation of protons which in turn catalyze the hydroarylation. A subsequent kinetic study by Hashmi on the Au(I)-catalyzed hydroarylation of phenylacetylene by heterocycles indicated that phenylacetylene served as a source of proton for the second hydroarylation observed in such reactions [121]. In the absence of phenylacetylene as a proton source, Au(I) is unable to catalyze further conversion of the monoarylated product (Scheme 21, reaction (b)); on the other hand, a proton source by itself, such as 5% HNTf 2 (bis(trifluoromethanesulfonyl)imine) proves adequate to catalyze the second hydroarylation in the absence of gold.…”

The preference for dual-gold(i) catalysis in the hydro(alkoxylation vs. phenoxylation) of alkynes

“…The final step corresponds to the dissociation of [Au(IPr)] + from the enol ether intermediate VI to deliver the transhydroalkoxylated product, 73 with a free energy change of -13.7 kcal/mol, overcoming a relatively high energy barrier of 15.2 kcal/mol via a phenol-assisted pathway, even though this protonation step might be assisted by an acid reagent. 74,75 However, it is also possible that this last step is assisted by the alkyne substrate, being just 6.4 kcal/mol higher in energy than the water-assisted pathway, 76 thus releasing the vinyl ether and regenerating complex I. Given that I and [Au(IPr)(OHR)] + are close in energy, they will be in equilibrium under the reaction conditions.…”