Why [4 + 2 + 1] but Not [2 + 2 + 1]? Why Allenes? A Mechanistic Study of the Rhodium-Catalyzed [4 + 2 + 1] Cycloaddition of In Situ Generated Ene–Ene–Allenes and Carbon Monoxide

Abstract

Transition metal-catalyzed [4 + 2 + 1] cycloaddition of in situ generated ene/yne–ene–allenes (from ene/yne–ene propargyl esters) and carbon monoxide (CO) gives the [4 + 2 + 1] cycloadducts rather than [2 + 2 + 1] cycloadducts. Investigating the mechanism of this [4 + 2 + 1] reaction and understanding why the [2 + 2 + 1] reaction does not compete and the role of the allene moiety in the substrates are important. This is also helpful to guide the future design of new [4 + 2 + 1] cycloadditions. Reported here are the kinetic and computed studies of the [4 + 2 + 1] reactions of ene–ene propargyl esters and CO. A quantum chemical study (at the DLPNO-CCSD­(T)//BMK level) revealed that the [4 + 2 + 1] reaction includes four key steps, which are 1,3-acyloxy migration (rate-determining step), oxidative cyclization, CO migratory insertion, and reductive elimination. The allene moiety in the substrates is critical for providing additional coordination to the rhodium center in the final step of the catalytic cycle, which in turn favors the reductive elimination transition state in the [4 + 2 + 1] rather than in the [2 + 2 + 1] pathway. The CO insertion step in the [4 + 2 + 1] reaction, which could occur through either the UP (favored here) or DOWN CO insertion pathway, has also been deeply scrutinized, and some guidance from this analysis has been provided to help the future design of new [4 + 2 + 1] reactions. Quantum chemical calculations have also been applied to explain why [4 + 2] and [4 + 1] cycloadditions do not happen and how trienes as side products for some substrates are generated.

Strain-Release-Controlled [4 + 2 + 1] Reaction of Cyclopropyl-Capped Diene-ynes/Diene-enes and Carbon Monoxide Catalyzed by Rhodium

“…Instead of participating in the [4 + 2] cycloaddition, the 16-electron complex IN4 prefers to be coordinated by a CO molecule to form an 18-electron complex, IN5 , which then easily undergoes CO insertion reaction into the C1–Rh bond via the UP CO pathway, forming intermediate IN6 via TS3 (requiring an activation free energy of 19.2 kcal/mol, from IN6 to TS3 ). In principle, the CO molecule could be inserted into the Rh–C2 bond in IN5 (via the DOWN CO insertion pathway), but this is disfavored and excluded for further consideration (see the SI for the transition state), like that in the [4 + 2 + 1] reaction , in Scheme b. To continue the [4 + 2 + 1] reaction, IN6 then undergoes a reductive elimination (via TS4 ) to give intermediate IN7 , which can be further coordinated by a CO molecule to generate IN7-CO , a complex between the [4 + 2 + 1] product and catalytic species.…”

“…The allene is critical to provide additional coordination to help this [4 + 2 + 1] reaction. 4 We can envision that this intermediate group can be further transformed into other useful groups, which is our ongoing research. Here, we report a serendipitously discovered [4 + 2 + 1] reaction of cyclopropyl-capped diene-ynes/dieneenes with CO, which also belongs to the SDS (Scheme 1c).…”

“…The SDS could be more powerful if a special intermediate group required in the substrates for the [4 + 2 + 1] reaction can have rich chemistry of transformations, which in turn will significantly access many other useful skeletons. For example, our previous [4 + 2 + 1] reaction of in situ generated ene/yne–ene–allenes with CO belongs to the SDS (Scheme b). − In this reaction, the traditional dienes are changed to ene–allenes, where allenes are in situ generated. The allene is critical to provide additional coordination to help this [4 + 2 + 1] reaction .…”

“…We proposed that the catalytic species of this reaction is a monomer of the catalyst, [Rh(CO 2 )Cl], similar to that in the [4 + 2 + 1] and [5 + 2 + 1] reactions. 4,5,16 The reaction starts from generating complex IN1 from the dimeric [Rh(CO) 2 Cl] 2 and model substrate with an oxygen tether. Then, IN1 can dissociate a CO to generate IN2.…”

Insights into the mechanism and selectivity of the Rh(i)-catalyzed cycloisomerization reaction of benzylallene-alkynes involving C–H bond activation

“…3 Rhodium-catalyzed cyclizations of allenes with other multiple bonds have attracted much attention over the last few decades for the construction of complex polycyclic skeletons. 4–6…”