Mechanistic Insights into Formation of All-Carbon Quaternary Centers via Scandium-Catalyzed C–H Alkylation of Imidazoles with 1,1-Disubstituted Alkenes

Abstract

This density functional theory (DFT) study reveals a detailed plausible mechanism for the Sc-catalyzed C–H cycloaddition of imidazoles to 1,1-disubstituted alkenes to form all-carbon quaternary stereocenters. The Sc complex binds the imidazole substrate to enable deprotonative C2–H bond activation by the Sc-bound α-carbon to afford the active species. This complex undergoes intramolecular cyclization (CC into Sc–imidazolyl insertion) with exo-selectivity, generating a β-all-carbon-substituted quaternary center in the polycyclic imidazole derivative. The Sc-bound α-carbon deprotonates the imidazole C2–H bond to deliver the product and regenerate the active catalyst, which is the rate-determining step. Calculations illuminate the electronic effect of the ancillary Cp ligand on the catalyst activity and reveal the steric bias caused by using a chiral catalyst that induce the enantioselectivity. The insights can have implications for advancing rare-earth metal-catalyzed C–H functionalization of imidazoles.

Unveiling the Detailed Mechanism and Origins of Chemo-, Regio-, and Stereoselectivity of Rare-Earth Catalyzed Alternating Copolymerization of Polar and Nonpolar Olefins

“…However, when a polar olefin is used, the heteroatom involved in the monomer may participate in coordination to give a σ-complex. As shown in Figure , for the current copolymerization reaction, the representative coordination complexes between the AP or St monomer and the cationic Sc species Cat-Sc-1 , generated by the reaction of Sc-1 with [Ph 3 C]­[B­(C 6 F 5 ) 4 ], were simulated. As illustrated in the figure, four types were displayed as follows: (1) Sc–σ–AP coordination complex 1 ; (2) Sc–π–AP coordination complex 2 ; (3) Sc–σ–π–AP coordination complex 3 ; and (4) Sc–π–St coordination complex 4 .…”

Mechanism and Origin of Site Selectivity and Regioselectivity of Scandium-Catalyzed Benzylic C–H Alkylation of Tertiary Anilines with Alkenes

“…This indicates that 1,2-insertion is preferred from the perspective of steric factors. To be noted, the natural charges distributed on the Sc–C­(vinyl) bond in transition states suggest that the Sc (+1.60) –C 1(−0.85) attractive interaction in TS2 is significantly favored over the Sc (+1.61) –C 2(−0.57) bond in TS2′ . Quantificationally, the distortion/interaction analysis shows that the interaction between the alkene and the catalyst moiety in TS2 (Δ E int = −36.2 kcal/mol) is stronger than that in TS2′ (Δ E int = −34.5 kcal/mol) by 1.7 kcal/mol.…”

Exo-Selective Intramolecular C–H Alkylation with 1,1-Disubstituted Alkenes by Rare-Earth Catalysts: Construction of Indanes and Tetralins with an All-Carbon Quaternary Center

“…In endo-TS2 , there was a large distortion in the core four-membered ring (Sc–C2–C1–C3) as shown by the large distorted dihedral angle D­(Sc–C2–C1–C3) = 44.6°, and the coordination interaction between the Sc atom and the O1 atom in the anisyl unit no longer existed. However, in exo-TS2 , the four-membered ring (Sc–C1–C2–C3) was almost planar (D­(Sc–C1–C2–C3) = 2.2°) without showing significant distortion . The C2–H activation of the coordinated anisole unit by the Sc–C alkyl bond in D could yield E , which upon coordination of another molecule of 1t finally released the exo-annulation product 2t and regenerated the catalytic species C .…”