Computational Mechanistic Study of C-C Coupling of Methanol and Allenes Catalyzed by an Iridium Complex

Density functional theory calculations have been performed to understand the mechanism of the C-C couplings of methanol with allenes (e.g., 1,1-dimethylallene (2all)) catalyzed by an iridium complex (1cat). The study leads us to propose the following mechanism for the reaction. The iridium complex first needs to be activated via methanolysis to generate the active catalyst (an iridium alkoxide complex). Starting from the active catalyst, the catalytic cycle for the C-C coupling includes four steps: beta-hydrogen elimination to give formaldehyde and an iridium hydride complex, allene hydrometalation to afford a (eta(7)-pi-allyl)iridium intermediate, addition of formaldehyde to the (eta(3)-pi-allyl)iridium intermediate to produce a homoallylic iridium alkoxide complex, and methanolysis of the formed homoallylic iridium alkoxide complex to deliver the final coupling product 3alc and regenerate the active catalyst. The regioselectivity exclusively producing the alcohol 3alc with an all-carbon quaternary center is due to the Ir-CMe2 bond being weaker than the Ir-CH2 bond and the steric effect between the methyl groups of the allene substrate and the C,O-benzoate ligand of the catalyst. The replacement of the middle hydrogen of the eta(3)-pi-allyl moiety of 1cat with a F, Cl, Me, or OMe group (F and OMe groups in particular) can benefit the catalyst activation both kinetically and thermodynamically. The possibility of using 1cat for the coupling of allene (2all) with amine (CH3NH2) was also explored. The allene coupling with amine is energetically less favorable than the coupling with methanol but could be experimentally achievable. Because the barrier for the activation of 1cat by amine (34.0 kcal/mol) could be too high, we proposed to lower the barrier by replacing the middle hydrogen atom of the eta(3)-pi-allyl moiety in 1cat with a F or OMe group.