Theoretical Study On The Mechanism And Selectivity Of Rhodium Catalyzed C-H Bond Reactions

Transition-metal-catalyzed cross-coupling has emerged as an efficient strategy for chemical synthesis.Within this area,direct C–H bond transformation is one of the most efficient and environmentally friendly processes for the construction of new C–C or C–heteroatom bonds.Over past decades,rhodium-catalyzed C–H functionalization has attracted considerable attention because of the versatility and wide application of rhodium catalysis in chemistry.A series of C–X?X=C,N,or O?bond formation reactions could be realized from corresponding C–H bonds using rhodium catalysts.Various experimental studies on rhodium-catalyzed C–H functionalization reactions have been reported and in tandem,computational studies and mechanistic research have also progressed significantly.The research work of this thesis includes two parts.In the first part of this thesis,Our researches fouce on the mechanistic study of rhodium-catalyzed C–H functionalization reactions.The mechanistic study under discussion is divided into three main parts:C–H bond cleavage step,transformation of the C–Rh bond,and regeneration of the active catalyst.In the C–H bond cleavage step,computational results of four possible mechanisms,including concerted metalation deprotonation?CMD?,oxidative addition?OA?,Friedel-Crafts-type?SEAr?,and?-complex assisted metathesis??-CAM?are discussed.Subsequent transformation of the C–Rh bond,for example,via CO insertion,olefin insertion,alkyne insertion,carbene insertion,or nitrene insertion constructed new C–C or C–heteroatom bonds.For the regeneration of the active catalyst,reductive elimination of a high-valent rhodium complex and protonation of the C–Rh bond were emphasized as potential mechanism candidates.In addition to detailing the reaction pathway,we studied the changes in oxidation state of rhodium and compared the Rh?III?/Rh?I?catalytic cycle to the Rh?III?/Rh?V?catalytic cycle using DFT calculation.Firstly,density functional theory?DFT?method has been used to study the mechanism,regio-,and diastereoselectivity of rhodium-catalyzed cyclization C-H bond activation of n-arylnitrones with alkynes.The results elucidated that the reaction pathway for Rh?III?-catalyzed cyclization of N-arylnitrones with alkyne contains a C-H bond activation,an alkyne insertion into Rh-C bond,a reductive elimination to form an Rh?I?complex,an oxidative addition leading to N-O cleavage,an imine insertion into the Rh-C bond and the final protonolysis to regenerate the products and the active catalyst.The regioselectivity of this reaction with asymmetric alkyne is controlled by the electronic effect in alkyne insertion type instead of steric effects.The diastereoselectivity is controlled by the imine insertion step.In this step,the sterically less hindered transition state is favored,leading to stereoselective product formation.Secondly,we combination of theoretical and experimental studies were performed to explore the mechanism of C–H amination under Rhodium?III?catalysis.A tridendate Rh?III?complex has been isolated as the resting state of the catalyst,and DFT studies suggested the interme-diacy of a nitrene species.In addition,experimental and theoretical studies were conducted to elucidate the mechanism of a sequential Cp*Rh?III?-catalyzed C–H activation and Wagner–Meerwein-type rearrangement reaction.How the oxidative O–N bond is cleaved and the role of HOAc were uncovered in this study.Moreover,an unprecedented dearomatized spirocyclopropane intermediate was discovered whereby N-phenoxyacetamide was found to act as a formal one-carbon component in this unexpected Rh?III?-catalyzed[1+2]annulation process.Both experimental and DFT studies suggest that protonation of an olefin-insertion intermediate by HOAc,followed by intramolecular attack,are the key steps to form this intermediate and cleave the O–N bond.DFT calculations also reveal a reasonable energy profile for an acid promoted rearrangement of the key intermediate.Finally,the mechanistic study of the synthesis of substituted pyridines in Rh III-catalyzed C-H activation of?,?-unsaturated oxime and alkenes was carried out by using DFT calculations.Both the Rh?III?/Rh?I?and Rh?III?/Rh?V?catalytic cycles were considered.The theoretical study indicated that the most feasible mechanism involved a Rh?III?/Rh?V?catalytic cycle.The Rh?V?-nitrenoid intermediate could be formed by migration of the pivalate from N to Rh,which much more easily than the C-N bond formation via reductive elimination or?-hydride elimination step.The regioselectivity of substituted pyridines with alkene is controlled by the electronic effect.In the second part,dirhodium catalysts were carefully studied and analyzed for the selectivity of C–H Functionalization.We mainly focused on the selectively of rhodium carbene and nitrenoid insertions into C?sp3?–H bonds.Firstly,we studied the enantioselectivity and site selectivity of the C-H bond functionalization reaction between diazo ester and 2-methylpentane molecules catalyzed by the dirhodium catalyst Rh₂[R-tris?p-tBuC6H4?TPCP]₄.Density functional computations using the ONIOM method enable the study of the conformers of the dirhodium catalyst shown that the C2-symmetric is favored.Computational studies provide further insight into the dirhodium catalysts catalyzed C–H bond selectivity of this reaction.The corresponding selectivity of the reaction is mainly due to the chiral functional group of the catalyst in the C2 symmetric conformation resulting in a steric hindrance effect when R attacks.Computational studies is also to to explain why the the dirhodium catalyst Rh₂[R-tris?p-tBuC6H4?TPCP]₄ is more selective for the primary C-H bond.Structural analysis of the transition states suggested that the steric repulsion accounts for the energy difference.In the nitrenoid insertions into C?sp3?–H bonds part,different dirhodium catalyst can controlled diastereoselective synthesis of cyclic amines via C-H functionalization.We undertook a systematic computational study to address the catalyst effects on diastereoselective of these C-H amination reactions.The diastereoselectivity is mainly controlled by steric hindrance effects.The tran2,5-disubstituted pyrrolidine is favored with the dirhodium catalyst Rh₂?OAc?₄.The2,5-disubstituted pyrrolidine of the cis type has the least steric hindrance with the dirhodium catalyst Rh₂?S-tert-PTTL?₄,the reactivity is higher.