10
1 Theoretical View of Rh-Catalyzed C–H Functionalization
according to certain rules, so as to expound the internal relations of complex reactions and the internal relations between total reactions and elementary reactions. The
rate of chemical reaction is closely related to the specific pathways through which
the reaction takes place.
Although the mechanism details for Rh-catalyzed C–H functionalization reactions
may vary from case to case, the catalytic cycle generally consists of three main
steps: C–H bond cleavage, C–Rh bond transformation, and regeneration of the active
catalyst [133–140].
C–H bond cleavage often occurs as the initial step in rhodium-catalyzed C–H
functionalization reactions. In general, there are four possible reaction modes for
rhodium-mediated C–H bond cleavage (Scheme 1.15): concerted metalation–deprotonation (CMD) [141, 142], oxidative addition (OA) [143], Friedel–Crafts-type electrophilic aromatic substitution [144] (SEAr), and σ-complex assisted metathesis
[145] (σ-CAM). In rhodium-catalyzed C–H functionalization reactions, the C–H
bond cleavage step leads to the construction of a C–Rh bond, which is the precursor
for the following transformation to construct new C–X bonds. This process is often
realized through insertion reactions including CO [123, 146, 147], olefin [98, 148–
150], acetylene [106, 151, 152], and carbene/nitrene [73, 153, 154] insertion. Formation of the final product after C–Rh bond transformation is considered to be a
relatively simple process and could involve C–C/N reductive elimination from the
high-valent rhodium complex or protonation of the newly formed C/N–Rh bond.
In order to study the law of chemical reaction rate and find out the intrinsic
causes of various chemical reaction rates, synthetic chemists must explore the reaction mechanism and find out the key to determine the reaction rate, so as to control
the chemical reaction rate more effectively [104, 106]. Traditional research methods
for reaction mechanism include (1) determining the important intermediate or decisive step of a reaction by isotope tracing, (2) determining the effect of different
factors (e.g. reaction temperature, solvent, substituent effect, etc.) on reaction rate
and selectivity by competitive test, (3) study the relationship between the reaction
rate and the concentration of reactants and catalysts obtaining by kinetic experiments, and (4) characterization and tracking of intermediates by instrumental analysis. However, these methods are often macroscopic observation of the average state
of many molecules, which cannot watch a process of the transformation for one
molecule from a micro perspective. Fortunately, theoretical calculations based on
first principles have become one of the important means to study the reaction mechanism with the development of software and the improvement of hardware computing
capability in recent several decades. Through theoretical calculation and simulation, the transformation of one molecule in the reaction process can be “watched”
more clearly from the microscopic point of view [131, 132]. Actually, theoretical
calculation can be considered to be a special kind of microscope, which can see the
geometrical structure, electronic structure, spectrum, and dynamic process at atomic
level, which is helpful for chemistry to understand the real reaction mechanism.
1 Theoretical View of Rh-Catalyzed C–H Functionalization
according to certain rules, so as to expound the internal relations of complex reactions and the internal relations between total reactions and elementary reactions. The
rate of chemical reaction is closely related to the specific pathways through which
the reaction takes place.
Although the mechanism details for Rh-catalyzed C–H functionalization reactions
may vary from case to case, the catalytic cycle generally consists of three main
steps: C–H bond cleavage, C–Rh bond transformation, and regeneration of the active
catalyst [133–140].
C–H bond cleavage often occurs as the initial step in rhodium-catalyzed C–H
functionalization reactions. In general, there are four possible reaction modes for
rhodium-mediated C–H bond cleavage (Scheme 1.15): concerted metalation–deprotonation (CMD) [141, 142], oxidative addition (OA) [143], Friedel–Crafts-type electrophilic aromatic substitution [144] (SEAr), and σ-complex assisted metathesis
[145] (σ-CAM). In rhodium-catalyzed C–H functionalization reactions, the C–H
bond cleavage step leads to the construction of a C–Rh bond, which is the precursor
for the following transformation to construct new C–X bonds. This process is often
realized through insertion reactions including CO [123, 146, 147], olefin [98, 148–
150], acetylene [106, 151, 152], and carbene/nitrene [73, 153, 154] insertion. Formation of the final product after C–Rh bond transformation is considered to be a
relatively simple process and could involve C–C/N reductive elimination from the
high-valent rhodium complex or protonation of the newly formed C/N–Rh bond.
In order to study the law of chemical reaction rate and find out the intrinsic
causes of various chemical reaction rates, synthetic chemists must explore the reaction mechanism and find out the key to determine the reaction rate, so as to control
the chemical reaction rate more effectively [104, 106]. Traditional research methods
for reaction mechanism include (1) determining the important intermediate or decisive step of a reaction by isotope tracing, (2) determining the effect of different
factors (e.g. reaction temperature, solvent, substituent effect, etc.) on reaction rate
and selectivity by competitive test, (3) study the relationship between the reaction
rate and the concentration of reactants and catalysts obtaining by kinetic experiments, and (4) characterization and tracking of intermediates by instrumental analysis. However, these methods are often macroscopic observation of the average state
of many molecules, which cannot watch a process of the transformation for one
molecule from a micro perspective. Fortunately, theoretical calculations based on
first principles have become one of the important means to study the reaction mechanism with the development of software and the improvement of hardware computing
capability in recent several decades. Through theoretical calculation and simulation, the transformation of one molecule in the reaction process can be “watched”
more clearly from the microscopic point of view [131, 132]. Actually, theoretical
calculation can be considered to be a special kind of microscope, which can see the
geometrical structure, electronic structure, spectrum, and dynamic process at atomic
level, which is helpful for chemistry to understand the real reaction mechanism.