Dirhodium(II)‐Catalyzed Cyclopropanation of Alkyne‐Containing α‐Diazoacetates for the Synthesis of Cycloalkynes

Abstract

An efficient dirhodium(II)‐catalyzed macrocyclization reaction of alkyne‐containing diazoacetates through intramolecular metal carbene cyclopropanation is described. This method provides a variety of 12‐ to 22‐membered macrocyclic alkynes, which incorporate ortho‐aryl, cyclopropane, and cyclopropene units, in good to excellent yields under mild reaction conditions.magnified image

Divergent, C–C Bond Forming Macrocyclizations Using Modular Sulfonylhydrazone and Derived Substrates

“…Beyond the highly prevalent Huisgen cycloaddition, other variants of Cu-catalyzed alkyne macrocyclizations and cycloadditions , are very commonly utilized, as are a diverse array of intramolecular palladium-catalyzed C–C and C–X couplings . Beyond these prevalent transformations, there are also reported examples of library generation using photocatalyzed macrocyclization, reductive amination, nucleophilic substitution, Friedel–Crafts alkylations, the intramolecular Ullmann reaction, Pauson–Khand reactions, rhodium-catalyzed O–H/N–H insertions, condensation reactions, and cyclopropanations . While many other synthetic methods for macrocyclic ring closure have been utilized in target-oriented syntheses, , these methodologies are often limited by reaction efficiency, substrate scope, and functional group tolerance, thereby presenting a key challenge for DOS …”

“…15 Beyond these prevalent transformations, there are also reported examples of library generation using photocatalyzed macrocyclization, 16 reductive amination, 17 nucleophilic substitution, 18 Friedel−Crafts alkylations, 19 the intramolecular Ullmann reaction, 20 Pauson−Khand reactions, 12d rhodium-catalyzed O−H/N−H insertions, 21 condensation reactions, 22 and cyclopropanations. 23 While many other synthetic methods for macrocyclic ring closure have been utilized in target-oriented syntheses, 5a,24 these methodologies are often limited by reaction efficiency, substrate scope, and functional group tolerance, thereby presenting a key challenge for DOS. 25 Given the limited scope of transformations available for macrocyclic ring closure, we have employed a reaction screening approach to identify new C−C bond forming macrocyclizations that are tolerant of diverse substitutions, ring sizes, and functional groups.…”