Mechanism and reactivity of rhodium-catalyzed intermolecular [5+1] cycloaddition of 3-acyloxy-1,4-enyne (ACE) and CO: A computational study

Abstract

The first theoretical study on the mechanism of [RhCl(CO)2]2-catalyzed [5 + 1] cycloadditions of 3-acyloxy-1,4-enyne (ACE) and CO has been performed using density functional theory (DFT) calculations. The effect of ester on reactivity of this reaction has been investigated. The computational results have revealed that the preferred catalytic cycle involves the sequential steps of 1,2-acyloxy migration, CO insertion, reductive elimination to form ketene intermediate, 6π-electroncyclization, and aromatization to afford the resorcinol product. The 1,2-acyloxy migration is found to be the rate-determining step of the catalytic cycle. The electron-rich p-dimethylaminobenzoate substrate promotes 1,2-acyloxy migration and significantly increases the reactivity by stabilizing the positive charge building up in the oxocyclic transition state.

Rhodium(I)‐Catalyzed Benzannulation of Heteroaryl Propargylic Esters: Synthesis of Indoles and Related Heterocycles

“…[10, 12d, 17] Under our standard conditions, both products 6n and 6o could be prepared in 70% and 66% yields, respectively. Surprisingly, we found that the benzannulation of 5n with an electron-rich ester was completed in less than 1 min at room temperature.…”

“…[17a] The double bond in the aryl group of 15 , however, is unlikely to coordinate to rhodium. A sequence of 1,2-acyloxy migration, carbene formation, and CO insertion may afford ketene 18 .…”

“…This is different from the Rh(I)-catalyzed [5+n] cycloaddition of 3-acyloxy-1,4-enyne with alkyne and CO, where the rhodium binds to both alkyne and alkene simultaneously in the initial π-complex. [17] Promoted by the Rh(I) catalyst, the 1,2-acyloxy migration occurs stepwise with an overall barrier of 21.9 kcal/mol, leading to the formation of zwitterion intermediate 22 , where the positive charge is stabilized by both the alkene and the furan moieties. The 1,2-acyloxy migration requires the highest free energy of activation ( TS1 ), thus being rate determining step, which is consistent with faster reactions for electron-rich esters such as 5n .…”

“…The 1,2-acyloxy migration requires the highest free energy of activation ( TS1 ), thus being rate determining step, which is consistent with faster reactions for electron-rich esters such as 5n . [17] …”

“…In contrast to reactions involving 3-acyloxy-1,4-enynes, where the 1,4-enyne serves as a bidentate ligand, [17] the furan ring does not coordinate to rhodium at any time. The benzannulation involves much higher energy barriers when the furan moiety coordinates to the metal centre to form metallacyles related to 14 or 14 ′ as shown in Figures S1 and S2).…”