Oxidative coupling of sp 2 and sp 3 carbon–hydrogen bonds to construct dihydrobenzofurans

Abstract

Metal-catalyzed cross-couplings provide powerful, concise, and accurate methods to construct carbon–carbon bonds from organohalides and organometallic reagents. Recent developments extended cross-couplings to reactions where one of the two partners connects with an aryl or alkyl carbon–hydrogen bond. From an economic and environmental point of view, oxidative couplings between two carbon–hydrogen bonds would be ideal. Oxidative coupling between phenyl and “inert” alkyl carbon–hydrogen bonds still awaits realization. It is very difficult to develop successful strategies for oxidative coupling of two carbon–hydrogen bonds owning different chemical properties. This article provides a solution to this challenge in a convenient preparation of dihydrobenzofurans from substituted phenyl alkyl ethers. For the phenyl carbon–hydrogen bond activation, our choice falls on the carboxylic acid fragment to form the palladacycle as a key intermediate. Through careful manipulation of an additional ligand, the second “inert” alkyl carbon–hydrogen bond activation takes place to facilitate the formation of structurally diversified dihydrobenzofurans.

Pd-Catalyzed ipso,meta-Dimethylation of ortho-Substituted Iodoarenes via a Base-Controlled C–H Activation Cascade with Dimethyl Carbonate as the Methyl Source

“…It involves triple C–H activation and threefold C–C bond formation. The reaction also represents an innovative and facile method for the synthesis of 2,3-dihydrobenzofurans, − which are ubiquitous in naturally occurring compounds, pharmaceuticals, and agrochemicals. − Therefore, we set out to study the reaction. Remarkably, 4a was formed as the major product when KOAc was used (entry 4), and the yield was enhanced to 80% by tuning the conditions (entry 5).…”

Fe‐Catalyzed Intramolecular Cross‐Dehydrogenative Arylation (CDA), Efficient Synthesis of 1‐Arylnaphthalenes and 4‐Arylcoumarins

“…[36,[61][62][63][64][65][66][67][68][69][70][71] In 2009, we developed a Fe-catalyzed cross-dehydrogenation coupling reaction of electron-rich aromatic hydrocarbons and diphenylmethane [36] (Scheme 1,b). Based on our continuous research on the field of transition-metalcatalyzed oxidative coupling of unactivated CÀ H bonds, [36,72,73] we here developed an inexpensive, readily available FeCl 3 /DDQ system to efficiently catalyze the tandem cross-dehydrogenative arylation/ oxidation reaction of 1,4-diphenylbutane and (3phenoxypropyl) benzene towards the synthesis of 1arylnaphthalenes and 4-arylcoumarins (Scheme 1,c).…”

Copper-Catalyzed Direct Alkylation of Perfluoroarenes with Hydrocarbons

“…Despite the recent promise, a direct coupling between alkanes and arenes via a twofold oxidative C-H bond activation to yield C(sp 2 )-C(sp 3 ) bonds is largely underdeveloped as a synthetic tool. [14][15][16][17][18][19][20] Indeed, only a few examples have been revealed with limited scope and/or under harsh conditions. For instance, a ruthenium-catalyzed cross-dehydrogenative coupling (CDC) of arenes with cycloalkanes (135 o C) was reported while it requires directing groups to facilitate an ortho-metallacyclic intermediate.…”