Quantum Chemical Studies On The Mechanisms For Transition Metal-Catalyzed Cross-Coupling Reactions

This dissertation reports a series of mechanistic studies on some representative transition metal-catalyzed cross-coupling reactions by using quantum computational methods. The main contents of this dissertation include the following:Chapter 1 briefly reviews transition metal-catalyzed cross-coupling reactions and relevant primary steps in organometallic chemistry.Chapter 2 aims to give a brief introduction to the category and principles of main quantum computational methods.From Chapter 3 to Chapter 7, five research topics of mechanistic study on cross-coupling reactions, accomplished during my PhD period, have been reported. Chapter 3 describes a study on the mechanism of copper-catalyzed cross-coupling reactions of aryl halides with amides and the impact of ancillary ligands on the catalytic efficiency. Through rough estimate of the relative concentrations of possible catalytic species and examination of oxidative addition of these species with aryl bromide, we suggest that the active copper catalyst is a neutral L2Cu(amidate) species. Oxidative addition of this species with aryl halides constitutes the rate-limiting step of the catalytic cycle. On the basis of the proposed pathway, the effect of several common ligands used in the experiments on the catalytic efficiency is examined, and all the results are in consistent with experimental observations.Chapter 4 reports our study on the mechanism of palladium-catalyzed decarboxylative Heck reactions between carboxylic acids and olefins, and factors controlling the rate-limiting decarboxylation step have been examined. The catalytic cycle is suggested to comprise four steps:decarboxylation, alkene insertion, (3-H elimination and catalyst regeneration. Decarboxylation is the rate-limiting step, in which palladium center dissociates one molecule of neutral DMSO ligand before extruding CO2 to produce an experimentally isolable Pd(II)-Aryl intermediate. The effect of anionic ligands, neutral ligands, carboxylic acids substrate and metal center on the rate-limiting decarboxylation step is examined, providing insightful information for the development of more efficient catalytic decarboxylative reactions.Chapter 5 describes an investigation into the mechanism of a novel copper-catalyzed exclusive meta C-H bond arylation reaction of anilides. A kinetically competent amide-directed carbocupration mechanism, which is distinct from the mechanistic hypothesis in the original report, has been proposed on the basis of examination of several possible reaction pathways. The regioselectivity predicted by this mechanism is in agreement with the experimental observations, favoring meta product exclusively. The critical step of this carbocupration mechanism involves an amide-directed syn addition of Cu(III)-Ph across phenyl C2=C3 bond to generate a C2-cuprated, C3-arylated intermediate. Such reactivity has never been reported in the literature, and thus our results provide the possibility of access of such reactivity experimentally and their application in catalytic reactions.Chapter 6 describes our study on the origin of stereo-and regioselectivity of reaction of organocopper reagents with allylic electrophiles. Our results suggest that the stereo-and regioselectivity of this reaction is controlled by the early oxidative addition step, in contrast to the consensus of related Truji-Trost reaction in which the product regioselectivity is determined by the late-stage reductive elimination step. The regioselectivity of this reaction is caused by different trans effect of the ligands on the copper center.Chapter 7 describes our study on the reaction pathway of a new manganese-catalyzed [2+2+2] annulation reaction of 1,3-dicarbonyl compounds with terminal alkynes, with an emphasis on the origin of the product regioselectivity. A pathway involving carbometalation/alkyne insertion/intramolecular nucleophilic addition sequence has been supported by our results, which can rationally reproduce the stereo-and regioselectivity observed in experiments. The regioselectivity of this reaction is controlled by carbometalation and alkyne insertion step. Electronic and steric factors affecting these two steps have been discussed.The three topics in Chapter 3 to Chapter 5 deal with three new kinds of transition metal-catalyzed cross-coupling reactions; the topic in Chapter 6 represents an old, yet important field of organometallic chemistry and our findings into this topic is also significant; the topic in Chapter 7 demonstrates the ability of theoretical study on the understanding of newly developed transition metal-catalyzed reactions.These studies together demonstrate the powerfulness of quantum computational methods in mechanistic studies of transition metal catalysis. They can provide information that is hard to obtain by experimental means, for example, the structure and energetics of critical intermediates and transition states, and relevant electronic and/or steric effect on the efficiency of the catalytic cycle.