Nickel catalysis for biaryl coupling reactions has received significant attention as a less expensive and less toxic alternative to “standard” palladium catalysis. Here we describe recent developments in nickel-catalyzed biaryl coupling methodology, along with mechanistic studies and applications. In particular we focus on nickel-catalyzed coupling reactions in which “unreactive” bonds such as C–H, C–O, and C–C bonds are converted into biaryl moieties.

Direct C–H bond arylation in the α- and β-positions of spirocyclic thiophenes containing various functional groups (amine, ether, acetal, lactone) was accomplished. Selective phenylation in the α-position of the thiophene ring was achieved by using the catalytic system PdCl₂/bipy/Ag₂CO₃. The introduction of phenyl moieties to the β-position was performed with the catalytic system PdCl₂/P[OCH(CF₃)₂]₃/Ag₂CO₃. Even the five-membered lactone 10 with an electron-withdrawing carbonyl moiety directly attached to the thiophene ring was arylated. Spirocyclic thiophenes substituted with a phenyl moiety in position A (top position) or B (left position) display low nanomolar σ₁ affinities (e.g., 4a: K_i = 1.6 nM; 5a: K_i = 2.4 nM), indicating an additional hydrophobic pocket on the complementary σ₁ receptor protein. A phenyl moiety in position C (at the bottom position) is not tolerated by the σ₁ receptor (e.g., 12: K_i = 483 nM). However, an additional phenyl moiety in position A is able to compensate at least partially the unfavorable effects of the phenyl moiety in position C.

The direct functionalization of CH bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon–carbon and carbon–heteroatom bonds. This Review provides an overview of CH bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

This account highlights elements of our efforts to explore new functionalization chemistry of fullerenes using molecular catalysts since 2006. These endeavors have led to the development of new reactions such as (i) organoboron addition to fullerenes, (ii) CH bond allylation and arylation of organo(hydro)fullerenes, (iii) CH/CC bond cleavage of alkynyl(hydro)fullerenes, (iv) regioselective tetraallylation of fullerenes, (v) double nucleophilic substitution of aziridinofullerene, and (vi) [2 + 2] cycloaddition of aziridinofullerene with alkynes. These works not only highlight the potential of molecular catalysis for fullerene functionalization, but also unlock opportunities for markedly different strategies in nanocarbon synthesis. DOI 10.1002/tcr.201100022

Novel nickel-based catalytic systems for the CH arylation of azoles with haloarenes and aryl triflates have been developed. We have established that Ni(OAc)₂/bipy/LiOtBu serves as a general catalytic system for the coupling with aryl bromides and iodides as aryl electrophiles. For couplings with more challenging electrophiles, such as aryl chlorides and triflates, the Ni(OAc)₂/dppf (dppf=1,1′-bis(diphenylphosphino)ferrocene) system was found to be effective. Thiazoles, benzothiazoles, oxazoles, benzoxazoles, and benzimidazoles can be used as the heteroarene coupling partner. Upon further investigation, we discovered a new protocol for the present coupling using Mg(OtBu)₂ as a milder and less expensive alternative to LiOtBu. Attempts to reveal the mechanism of this nickel-catalyzed heterobiaryl coupling are also described. This newly developed methodology has been successfully applied to the syntheses of febuxostat (a xanthine oxidase inhibitor that is effective for the treatment of gout and hyperuricemia), tafamidis (effective for the treatment of TTR amyloid polyneuropathy), and texaline (a natural product having antitubercular activity).