Palladium-Catalyzed Cyclocoupling of 2-Halobiaryls with Isocyanides via the Cleavage of Carbon−Hydrogen Bonds

Abstract

To demonstrate the utility of isocyanides in catalytic C−H bond functionalization reactions, a palladium-catalyzed cyclocoupling reaction of 2-halobiaryls with isocyanides was developed. The reaction afforded an array of fluorenone imine derivatives via the cleavage of a C−H bond at the 2′-position of 2-halobiaryls. The use of 2,6-disubstituted phenyl isocyanide was crucial for this catalytic cyclocoupling reaction to proceed. The reaction was applicable to heterocyclic and vinylic substrates, allowing the construction of a wide range of ring system. The large kinetic isotope effect observed (k H/k D = 5.3) indicates that C−H bond activation was the turnover-limiting step in this catalysis.

Renaissance of Organic Synthesis Using Isocyanides

“…35 To our delight, the desired cyclocoupling of 2-halobiphenyl and isocyanide proceeded under conditions almost identical to those of Larock's cyclocarbonylation (eq 10). 36 A minor difference from Larock's conditions was the effect of the ligand: PPh 3 , in place of bulky electron-rich PCy 3 , promoted the reaction effectively. The use of 2,6-disubstituted aryl isocyanides was essential for an efficient reaction.…”

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

“…Several other groups had previously reported concise methods for the synthesis of carbo-and heterocyclic systems through isocyanide insertion and C(sp 2 )-H activation steps. [87][88][89] While there have been several reports describing the formation of indoles via the Ru-catalyzed C(sp 3 )-H activation of 2,6-disubstituted isocyanides, 90,91) there have been no reports pertaining to the synthesis of heterocycles through Pd-catalyzed isocyanide insertion and C(sp 3 )-H functionalization steps. We envisioned that the reaction of o-methylphenyl isocyanide 38 with aryl halide 39 in the presence of a palladium catalyst would give 2-arylindole 40 through a cascade process consisting of the oxidative addition of Pd(0) to the aryl halide, isocyanide insertion, benzylic C(sp 3 )-H functionalization, and reductive elimination (Chart 11).…”

Catalytic Isonitrile Insertions and Condensations Initiated by RNC–X Complexation

“…(54)]. [89] The optimal isonitrile proved to be 2,6-diisopropylphenyl isocyanide ( 233 ); aliphatic isonitriles are unsuitable reaction partners. A wide range of biaryls, electron-deficient pyridines, and similar substrates, effectively participate in the coupling.…”