Advances in Copper‐Catalyzed CC Coupling Reactions and Related Domino Reactions Based on Active Methylene Compounds

Abstract

Active methylene compounds are a major class of reaction partners for C-C bond formation with sp(2) C-X (X = halide) fragments. As one of the most-classical versions of the Ullmann-type coupling reaction, activated-methylene-based C-C coupling reactions have been efficiently employed in a large number of syntheses. Although this type of reaction has long relied on noble-metal catalysis, the renaissance of copper catalysis at the end of last century has led to dramatic developments in Ullmann C-C coupling reactions. Owing to its low cost, abundance, as well as excellent catalytic activity, the exceptional atom economy of copper catalysis is gaining widespread attention in various organic synthesis. This review summarizes the advances in copper-catalyzed intermolecular and intramolecular C-C coupling reactions that use activated methylene species as well as in tandem reactions that are initiated by this transformation.

A concise and efficient synthesis of benzimidazo[1,2-c]quinazolines through CuI-catalyzed intramolecular N-arylations

“…Other copper salts such as Cu(OTf) 2 , CuBr or CuCl were also able to catalyze the reaction, but they were not as efficient as CuI as the catalyst ( Table 1 , entries 5–9). It is worth mentioning that the imino group (sp 2 ) other than the amino group (sp 3 ) in 3a reacted through the Cu-catalyzed Ullmann reaction [ 18 – 25 ].…”

Synthesis of β-arylated alkylamides via Pd-catalyzed one-pot installation of a directing group and C(sp3)–H arylation

“…Upon this assumption as well as our interest in both domino reactions and C–H functionalization chemistry [ 35 – 40 ], we have executed efforts to the AQ-assisted β-C–H functionalization reactions of alkylamides via activation of the C(sp 3 )–H bond, a classical protocol toward β-arylamide synthesis. While the known examples, including C(sp 3 )–H alkylation, arylation or oxygenation employing different transition metal catalysts such as palladium, nickel, and iron have provided enriched routes for the synthesis of structurally diverse amides, a two step process involving the operation in installing the AQ to the substrate has been required [ 41 – 50 ].…”

Cascade SN2′–SNAr, Elimination, and 1,5‐Hydride Shift Reactions by Acetylacetone/Acetoacetic Esters: Synthesis of 9,10‐Dihydroacridines

“…The importance of active methylene compounds with two electron‐withdrawing groups (EWGs) on the carbon atom is well known. They are highly versatile reagents in synthetic organic chemistry because of their easy conversion into the corresponding enolates They have been employed in a variety of reactions such as condensation, alkylation, cyclization halogenation, acylation, and Michael addition . Recently, their cascade reaction with Morita–Baylis–Hillman (MBH) acetates through successive S N 2′–S N Ar and eliminative aromatization was reported for the synthesis of naphthalene and quinoline derivatives (Figure ) .…”