Silver-Promoted, Palladium-Catalyzed Direct Arylation of Cyclopropanes: Facile Access to Spiro 3,3′-Cyclopropyl Oxindoles

Abstract

The Pd-catalyzed, Ag(I)-mediated intramolecular direct arylation of cyclopropane C-H bonds is described. Various spiro 3,3'-cyclopropyl oxindoles can be obtained in good to excellent yields from easily accessible 2-bromoanilides. The kinetic isotope effect was determined and epimerization studies were conducted, suggesting that the formation of a putative Pd-enolate is not operative and that the reaction proceeds via a C-H arylation pathway.

Cobalt Catalyzed Reductive Spirocyclopropanation Reactions

“…However, there is evidence to suggest that reliance on cross-coupling as a strategy for fragmentbased drug discovery may be leading to higher rates of failure in clinical development due to the poor physical properties of flat aromatic systems (e. g., low solubility and high melting point). [4] Spirocyclopropanes may be prepared by the addition of a carbene equivalent to a methylenecycloalkane. In this vein, spirocyclopropanes [3] combine a unique three-dimensional architecture with conformational rigidity, thus representing high-value targets for the development of new synthetic methods.…”

“…In this vein, spirocyclopropanes [3] combine a unique three-dimensional architecture with conformational rigidity, thus representing high-value targets for the development of new synthetic methods. [4] Spirocyclopropanes may be prepared by the addition of a carbene equivalent to a methylenecycloalkane. [5,6] An alterna-tive disconnection that could be considered is the addition of a cyclic carbene to an alkene.…”

Catalytic C–H Bond Functionalization of Cyclopropane Derivatives

“…Acetate-mediated CMD (step C) provides a rare seven-membered ring palladacycle which undergoes ring opening (step D), followed by deprotonation/reductive elimination (step E) to provide the desired products. Additionally, Charette and coworkers disclosed the synthesis of biologically active 3,3 0 -cyclopropyl oxindole 44 via a Pd-catalyzed, Ag-promoted C-H functionalization of cyclopropanecarboxamide 43 derived from 2-bromoaniline (Scheme 10) [31]. Substitution on the aryl ring or on the cyclopropane, including heterocycles such as furan or thiophene, was well tolerated.…”

Palladium(0)-Catalyzed Benzylic C(<i>sp</i>³)–H Functionalization for the Concise Synthesis of Heterocycles and Its Applications

“…A variety of different directing groups and reaction conditions involving Pd catalysts have been developed for extending the substrate scope of C-H functionalization reactions. [21][22][23][24][25][26][27][28][29] However, very little progress has been made towards controlling the selectivity of C(sp Review Chem. Pharm.…”