Theoretical Study For The Transition Metal Promoted C-H Bond Cleavage And Functionalization

Organic synthesis chemistry is always pursuing efficient approaches for the construction of pharmaceutical molecules,natural products,multifunctional materials,and other functional molecules.Transition metal-catalyzed cross-coupling reactions provide practical methods for the formation of new carbon–carbon and carbon–heteroatom bonds.In particular,transition metal-catalyzed C–H functionalization has been widely used in synthetic chemistry due to the good practicality and high atom economy.For a very long time,the research emphasis focused on the development and application of Pd-catalyzed C-H activation.Over the past decades,rhodium and iridium catalyzed transformations have received increasing attentions due to the versatility and wide application of rhodium and iridium catalysis.With the explosive progress in experimental aspect,computational study of Rhand Ir-catalyzed C–H functionalization has also achieved great accomplishment.The advances in computational methods and computing power make theoretical calculation a practical yet powerful tool for mechanistic study.Both the detailed reaction pathway and origin of selectivity in transition metal-catalyzed transformations could be gained through computational study.Furthermore,predictions about the reactivity of new substrates and catalysts are also available for further experimental investigations.Our research mainly focused on the theoretical study of Rh-and Ir-catalyzed C–H functionalization.This paper includes the following four parts:1.DFT calculation was employedto study the mechanism of rhodium(II)-catalyzed chemoselective C(sp~3)-H oxygenation.Theoretical calculations indicated that the mechanism for the rhodium-catalyzed oxidation of toluene included the oxidation of [Rh2(tfa)4] by Selectfluor,deprotonation of toluene,the second deprotonation by fluoride to form carbene–Rh complex,the second oxidation by Selectfluor,carbene insertion,and reductive elimination to release the products regenerate the active catalyst [Rh2(tfa)4].The computational results are also well verified by the further validation experiments.2.Theoretical calculation was used to study Rh(III)-catalyzed C-H alkynylation of arenes under the hypervalent iodine reagents assistance.The catalytic cycleincludeed deprotonation of arenes under chelation assistance,alkyne insertion andα-iodine elimination.Moreover,the origin of selectivity and effects of hypervalent iodine reagents were also illuminated by theoretical calculation.The calculated results are in good agreement with the experimental results.3.DFT method N12 was used to study the mechanism of the [Ir(cod)OH]2/Xyl-MeO-BIPHEP-catalyzed para-selective C-H borylation reaction.The results revealed that the use of a bulky diphosphine ligand such as Xyl-MeO-BIPHEP was unfavorable for the previously proposed iridium(III)/iridium(V)catalytic cycle because it resulted in considerable steric repulsion in the hepta-coordinated iridium(V)intermediate.Inspired by this steric effect,we have proposed a novel iridium(I)/iridium(III)-based catalytic cycle,including:(i)the oxidative addition of the C-H bond of the substrate to an active iridium(I)boryl complex;(ii)the reductive elimination of a C–B bond;(iii)the oxidative addition of B2pin2 to an iridium(I)hydride complex;and(iv)the reductive elimination of a B-H bond.