Electrochemical Ring Expansion to Synthesize Medium-Sized Lactams Through C–C Bond Cleavage

Abstract

Medium-sized nitrogen heterocycles are prevalent motifs in many kinds of bioactive molecules and natural products. Owing to the unfavorable enthalpic and entropic barriers during the transition states, access to medium-sized rings is challenging. Herein, a general and practical electrochemical ringexpansion protocol has been developed from commercially available benzocyclic ketones and amides. In this regard, a series of highly functionalized eightto eleven-membered lactams could be successfully accessed in high yields and efficiencies. Notably, this transformation features excellent tolerance toward different electronic substituents of benzocyclic ketone and aniline moieties. Furthermore, satisfactory yields for gram-scale and direct one-pot synthesis, as well as the esterification of inert benzylic C-H bond, are additional advantages. Mechanistic studies indicate that this electrochemical dehydrogenative ring expansion proceeds through a unique remote amidyl radical migration-induced C-C bond cleavage and subsequent single-electron oxidation.

Electrophotochemical Ce-Catalyzed Ring-Opening Functionalization of Cycloalkanols under Redox-Neutral Conditions: Scope and Mechanism

“…Because blue light is critical for this transformation, we suspected that it might be involved in the reduction of the Ce­(IV) species, which is light-sensitive. , Herein, an EPR experiment was performed in the presence of DMPO as the spin trap (Figure a). When DMPO was added into the mixture of (Bu 4 N) 2 CeCl 6 , 1 , and 4-( tert -butyl)­pyridine, an alkoxy radical was trapped after photolysis.…”

“…Carbon–carbon (C–C) bonds are the most widespread and fundamental building blocks that make up organic compounds. Selective cleavage and functionalization of these inert bonds is of great importance. , In particular, β-scission of C–C bonds in alcohols, which are abundant in biomass, has attracted extensive attention. − It is well-known that, as a key step of β-scission, the generation of an alkoxy radical from alcohol is often challenging due to the extremely high O–H bond dissociation energy (∼105 kcal/mol). Traditionally, to overcome the energy barrier, strong oxidants such as bromine, hypervalent iodide, − selectfluor, and so forth or high-valent metal salts are inevitable (Scheme a).…”

“…Traditionally, to overcome the energy barrier, strong oxidants such as bromine, hypervalent iodide, − selectfluor, and so forth or high-valent metal salts are inevitable (Scheme a). In recent years, the above-described PCET and LMCT processes have been found to be efficient ways to directly generate alkoxy radicals from alcohol under mild conditions. ,− These discoveries positively impact the development of alkoxy radical chemistry, leading to some significant progress, such as the emergence of a greener redox-neutral catalytic process to regenerate the active catalytic species. However, the redox-neutral methods remain largely underexplored, as the reported relevant systems often rely on applying certain type of in situ -formed radical intermediates as the oxidants (Scheme b). , Thus, a more versatile redox-neutral method which is compatible with a broader substrate scope is anticipated.…”

Catalytic Electrophilic Halogenation of Arenes with Electron-Withdrawing Substituents

“…Fluorinated solvents, such as 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and 2,2,2-trifluoroethanol (TFE), have been known to promote various electrophilic reactions due to their excellent hydrogen bond donating ability. Besides Friedel–Crafts-type reaction, nitrogenation, oxygenation, and dearomative functionalization, fluorinated solvents also show excellent performance in electrophilic halogenation reactions. For example, Gulder and co-workers reported the efficient combination of HFIP and morpholine in haliranium-induced polyene cyclization reactions.…”

Electrochemical Oxidative [4+2] Annulation of Different Styrenes toward the Synthesis of 1,2-Dihydronaphthalenes

“…[25][26][27][28] Recently, electrochemical synthesis attracted more and more attentions due to its simple and mild reaction conditions. [29][30][31][32][33][34] In 2019, Ye and his colleagues reported an electrochemical [4+2] annulation of styrenes to access naphthalene derivatives under mild conditions. 35 The transformation of styrenes, such as difunctionalization, 36-…”