The Essential Role of Bond Energetics in C–H Activation/Functionalization

Abstract

The most fundamental concepts in chemistry are structure, energetics, reactivity and their inter-relationships, which are indispensable for promoting chemistry into a rational science. In this regard, bond energy, the intrinsic determinant directly related to structure and reactivity, should be most essential in serving as a quantitative basis for the design and understanding of organic transformations. Although C-H activation/functionalization have drawn tremendous research attention and flourished during the past decades, understanding the governing rules of bond energetics in these processes is still fragmentary and seems applicable only to limited cases, such as metal-oxo-mediated hydrogen atom abstraction. Despite the complexity of C-H activation/functionalization and the difficulties in measuring bond energies both for the substrates and intermediates, this is definitely a very important issue that should be more generally contemplated. To this end, this review is rooted in the energetic aspects of C-H activation/functionalization, which were previously rarely discussed in detail. Starting with a concise but necessary introduction of various classical methods for measuring heterolytic and homolytic energies for C-H bonds, the present review provides examples that applied the concept and values of C-H bond energy in rationalizing the observations associated with reactivity and/or selectivity in C-H activation/functionalization.

Nonconjugated Hydrocarbons as Rigid‐Linear Motifs: Isosteres for Material Sciences and Bioorganic and Medicinal Chemistry

“…The thermodynamic relationship of the homolytic bond dissociation energy (BDE), gas‐phase acidities (Δ H a ), the ionization energy of hydrogen (IE( H )=313.6 kcal mol −1 ), and the electron affinity (EA) is given by the following equation, representing the thermodynamic cycle [Eq. ] …”

Sequential Cross‐Coupling/Annulation of ortho‐Vinyl Bromobenzenes with Aromatic Bromides for the Synthesis of Polycyclic Aromatic Compounds

“…Zuschriften (3ap), quinoline (3aq, 3au, 3ay), benzo[d]thiazole (3ar), quinoxaline (3at), pyridine (3as, 3ax), thiophene (3aw)a nd benzofuran (3av), were well tolerated in this sequential process.E xcellent regioselectivities were also observed for 3at-3 ay, [13] which is ascribed to the prominent difference between two C À Hb onds for palladium promoted activation in these heteroaromatic system. [14] To illustrate the synthetic scope of this method, several experiments were carried out. First, agram-scale reaction was performed, affording the product 3aa in high yield, consistent with the small-scale trial (Scheme 4a).…”

Nitrene Insertion into Aromatic and Benzylic C−H Bonds Catalyzed by Copper Complexes of Fluorinated Bis‐ and Tris(pyrazolyl)borates

“…The [HB(3,4,5-Br 3 Pz) 3 ]Cu(NCMe) catalyst of Perez et al [32] displayed similar behavior with mesitylene ( Table 1). [48] Products from the toluene reaction show that the reaction is less chemoselective, and the nitrene insertions take place at both arene and benzylic CÀ H sites, with slight preference for benzylic sites (Table 3, entries 1, 2). The [a] All the reactions were performed at room temperature and the yields reported below are isolated yields after separation and purification by column chromatography.…”

“…The calculated singlet-triplet splitting is~13 kcal mol À 1 for both the bis(pyrazolyl)borate and tris(pyrazolyl)borate models. This difference is expected due to the breaking of the stronger arene CÀ H bond [48] and the unfavorable formation of arene radical upon the loss of aromaticity. [51] Significant spin density is found on both the nitrene nitrogen and the copper, Information).…”