Mechanism and Origin of MAD‐Induced Ni/N‐Heterocyclic Carbene‐Catalyzed Regio‐ and Enantioselective C−H Cyclization of Pyridines with Alkenes

Abstract

This work presentsaDFT-based computational study on the regio-ande nantioselective CÀHf unctionalization of pyridines with alkenes at the relatively unreactiveC 4position, whichw as successfully achieved by Shi et al. [J. Am. Chem. Soc. 2019, 141,5 628-5634] using Ni 0 /N-heterocyclic carbene( NHC) catalysis undert he assistanceo fa na luminum-based Lewis acid additive (2,6-tBu 2 -4-Me-C 6 H 2 O) 2 AlMe (MAD).T he calculationsi ndicate that the selectivef unctionalizationi nvolves at hree-step mechanism in whichaunique H-migration assisted oxidation metalation( HMAOM) step is identified as the rate-and enantioselectivity-determining step. The newly proposed mechanism can well rationalize the experimental observation that the preferred product is the endo-type (vs. exo-type), R-configuration (vs. S-configuration) product at the C4 (vs. C2) position, and also unveil the reasons that the NHC ligand and the MAD additive can facilitate the reaction.[a] X.Scheme1.Arepresentative example of MAD-induced Ni 0 /NHC-catalyzed regio-and enantioselective CÀHc yclization of alkene-tethered pyridine 1 reported by Shi and co-workers. [29] Scheme2.Proposed reaction pathway by Shi et al. [29] for the Ni 0 -catalyzed regio-a nd enantioselectiveC ÀHa ctivationa tt he C4-positiono falkene-tethered pyridine (1). Figure 7. (a) Geometries and the relativee nergies (in kcal mol À1 )o fkey intermediates and rate-determining transitions tates for the endo-type cyclization at the C4-position in the Ni 0 -catalyzed reaction with and without presence of the NHC ligand, and (b) HOMOs andLUMOso fNi(cod),p yridine-MAD adduct 3, and Ni(NHC).

Insights into the Regioselectivity of Hydroheteroarylation of Allylbenzene with Pyridine Catalyzed by Ni/AlMe3 with N-Heterocyclic Carbene: The Concerted Hydrogen Transfer Mechanism

“…This is mainly due to the difference in the energy of the LLHT transition state and Ni­(NHC)­(alkene) ( 4a or 4b ) (Figures and ). Herein, we carried out the distortion–interaction analysis , to give insights into the regioselectivity for the formation of the linear product P1 (Table ). The distortion energies Δ E dist (Ni­(NHC)­(alkene)) and Δ E dist (pyridine-AlMe 3 ) were calculated from the difference between the energy of the distorted structure of each fragment taken from the LLHT transition state structure and the energy of each optimized structure.…”

“…In combination with the experimental results, density functional calculations have been widely used to elucidate reaction mechanisms of Ni-catalyzed hydroelementation reactions. − In addition to the OA/MI and CMD mechanisms, recent density functional studies showed that hydroarylation and hydroalkenylation of alkenes and alkynes catalyzed by Ni complexes proceed via a ligand-to-ligand H-transfer (LLHT) pathway. − In the LLHT pathway, aromatic C–H bond activation occurs by direct H-transfer from the arene to alkene/alkyne; subsequently, the hydroarylation product is reductively eliminated. The alkene/alkyne plays the role of a hydrogen acceptor in the LLHT mechanism similar to what a Lewis base does in the CMD mechanism.…”

Enantio- and Regioselective Ni-Catalyzed para-C–H Alkylation of Pyridines with Styrenes via Intermolecular Hydroarylation

“…To elucidate the detailed mechanism and origins of the enantioselectivity, we performed DFT-based first-principles calculations for the reaction denoted by entry 7 in Table at the B3LYP-D3­(BJ)/LANL2DZ-6-311+G­(d,p)/SMD­(cyclohexane)//B3LYP-D3­(BJ)/LANL2DZ-6-31G­(d,p)/SMD­(cyclohexane) level. According to the previous reports, , the reaction could follow a ligand-to-ligand hydrogen transfer (LLHT) mechanism. As indicated by calculated Gibbs energy profiles (Figure ), the reaction goes through three stages: substrate coordination, LLHT, and C–C reductive elimination.…”

C–H Functionalization of Arenes via NHC-Supported Ni/Al Bimetallic Catalysis

“…46 DFT calculation was also conducted to further understand the detailed reaction mechanism. 47 C-H activation and alkene insertion proceeded simultaneously in one elementary step, suggesting an LLHT mechanism in the catalytic cycle. And the origin of the preferential R-configuration product was the smaller H-H repulsion effect in the transition state.…”