Nickel-catalyzed alkyne annulation by anilines: versatile indole synthesis by C–H/N–H functionalization

Abstract

Versatile nickel catalysts enabled the step-economical synthesis of decorated indoles through alkyne annulations with anilines bearing removable directing groups. The C-H/N-H activation strategy efficiently occurred in the absence of any metal oxidants and with excellent selectivities.

Nickel Catalysts/N,N′-Bidentate Directing Groups: An Excellent Partnership in Directed C–H Activation Reactions

“…19 In this system, the alkyne also has a double role, functioning as both a coupling partner and a hydrogen acceptor; therefore Ackermann's method also does not require the addition of sacrificial metal oxidants. Several electrophilic functional groups, including OMe, F, Cl, Ac, and CN groups are well tolerated in this system.…”

“…Coordination of amide 267 to the Ni(II) center gives the complex 293, which undergoes a reversible CH bond cleavage to give nickellacycle 294. Base-promoted single-electron transfer (SET) of R f I followed by the abstraction of a benzylic hydrogen generates a benzyl radical (ArCH 2 •) and R f H (detected by 19 F NMR). The complex 294 accepts the benzyl radical to produce Ni(III) species 295, which undergoes reductive elimination followed by protonation to give the final product 296 and a Ni(I) complex.…”

Dehydrogenative Heck Annelations of Internal Alkynes

“…The term 'direct dehydrogenative anulation' has been proposed by Jiao and co-workers to designate these reactions, 11 but has also been used for annelations involving the elimination of only one hydrogen atom. 11 Moreover, annelations of internal alkynes with loss of two hydrogens have also been performed under rhodium, 12,13 ruthenium, 14 copper 15 and nickel 16 catalysis. Thus, we suggest the term 'dehydrogenative Heck annelation' (DHA), such a name recalling the seminal report from Heck's team 1 and the DHR.…”

“…With 2-aryl-1-methylindole (Equation 16), 3-aryl-1-methylindole (Equation 17) or 2,2′-bis(N-methylindolyl) (Equation 18) as the substrate, the DHA implies one molecule of the alkyne. 36 After screening of different parameters, Jiao and co-workers performed these domino reactions in N,N-dimethylformamide, as above in the presence of an organic acid, but with addition of substoichiometric amounts of both tetrabutylammonium bromide and potassium carbonate.…”

Mechanistic insight into conjugated N–N bond cleavage by Rh(iii)-catalyzed redox-neutral C–H activation of pyrazolones

“…16 A large number of DG-assisted oxidative couplings, [17][18][19][20] especially, the redox-neutral couplings containing an oxidizing directing group 21 (DG ox ) as an internal oxidant have attracted great attention due to improved reactiv-ity, selectivity and substrate scope as compared with those utilizing external oxidants. 16 A large number of DG-assisted oxidative couplings, [17][18][19][20] especially, the redox-neutral couplings containing an oxidizing directing group 21 (DG ox ) as an internal oxidant have attracted great attention due to improved reactiv-ity, selectivity and substrate scope as compared with those utilizing external oxidants.…”