The iridium-catalyzed hydroarylation of alkenyl ethers developed by Nishimura and co-workers (Ebe, Y.; Onoda, M.; Nishimura, T.; Yorimitsu, H. Angew. Chem. Int. Ed. 2017, 56, 5607-5611) represents a rare example of regio- and enantioselective hydroarylation of challenging internal alkenes. In the present study, density functional theory calculations were performed in order to investigate the detailed reaction mechanism and the origins of the experimentally observed regio- and enantioselectivities. The computations show that the initial C-H oxidative addition and the isomerization between the allylic ethers and the 1-alkenyl ethers via the migratory insertion into the Ir-H bond/β-hydride elimination are both feasible. The reaction was found to proceed through the modified Chalk-Harrod-type mechanism via the migratory insertion into the Ir-C bond/C-H reductive elimination. The migratory insertion into the Ir-C bond constitutes the rate- and selectivity-determining step of the overall reaction. The calculations reproduced quite well the experimentally observed regio- and enantioselectivities. The enantioselectivity of the reaction was found to arise from the reactions of the (E)- and (Z)-1-alkenyl ethers, which afford the opposite enantiomers of product with the aryl group installed at the α-position to the alkoxy group. It turns out that the strong electron-donating character of the alkoxy group plays an important role in determining the regioselectivity, since it can stabilize the developed positive charge of the α-insertion transition state, leading to the aryl group being selectively installed at the α-position.

Ar ecently reported palladium-catalyzed allylic substitution of vinyl-substituted cyclic carbonates (VCCs) with aryl amines represents ar are example of ar egio-and enantioselective synthesis of a,a-disubstituted allylic N-aryl amines.H owever,t he underlying reasons for this unusual selectivity profile remain elusive.I nt he present work, density functional theory (DFT) calculations in combination with mechanistic control experiments were performed to elucidate in detail this allylic amination manifold and the origin of the regio-and enantioselectivity.T he combined data show that after oxidative addition of the VCC to Pd 0 ,t he nucleophilic attackv ia an originally proposed outer-sphere pathway gives, however,t he opposite regioisomer compared to the experimental results.Instead, nucleophilic attackofthe amine reagent via au nique type of chelation-assisted, inner-sphere pathway accounts for the experimentally observed "branched" regioselectivity and high enantio-control.

Density functional theory calculations were performed to investigate the iridium-catalyzed isomerization of 1-alkenes to trans-2-alkenes. The computations show that the originally proposed π-allyl mechanism is kinetically unfeasible. A metal-ligand cooperative mechanism was suggested to account for the experimental results. The reaction was found to begin with the C(sp)-H oxidative addition of the pyridine ligand to give the Ir(III) hydride intermediate, from which the isomerization further takes place via the insertion/elimination pathway.

Palladium/boron-catalyzed allylic substitution of vinylethylene carbonates with water provides a powerful approach for the enantioselective synthesis of the tertiary C−O bond. Density functional theory calculations in the present work show that the nucleophilic attack via a distinctive type of chelation-assisted inner-sphere pathway is responsible for the experimentally observed regio-and enantioselectivities. The chelation between the hydroxyl group of the boronate moiety and the Pd center in the nucleophilic attack enables the exclusive branched-regioselectivity. The enantioselectivity was rationalized in terms of the lone pair---π repulsive interaction between the O atom of the chelated hydroxyl group and the phenyl ring of the ligand.

A palladium‐catalyzed chemoselective coupling of readily available bicyclo[1.1.1]pentanyl alcohols (BCP−OH) with various halides is reported, which offers expedient approaches to a wide range of cyclobutanone and β,γ‐enone skeletons via single or double C−C activation. The chemistry shows a broad substrate scope in terms of both the range of BCP−OH and halides including a series of natural product derivatives. Moreover, dependency of reaction chemodivergence on base additive has been investigated through experimental and density functional theory (DFT) studies, which is expected to significantly enrich the reaction modes and increase the synthetic potential of BCP−OH in preparing more complex molecules.