Direct Ortho Arylation of 9-(Pyridin-2-yl)-9H-carbazoles Bearing a Removable Directing Group via Palladium(II)-Catalyzed C–H Bond Activation

Abstract

A one-pot synthesis of ortho-arylated 9-(pyridin-2-yl)-9H-carbazoles via C–H bond activation is presented. Silver nitrate and tert-butyl alcohol were found to be the best oxidant and solvent for the process, respectively. The product yields are from modest to excellent, and the reaction showed sufficient functional group tolerance. p-Benzoquinone served as an important ligand for the transmetalation and reductive elimination steps in the catalytic process. The key intermediate of the reaction, a 9-(pyridin-2-yl)-9H-carbazole palladacycle, was isolated, and its structure was unequivocally confirmed by X-ray crystallography. No kinetic isotope effect (k H/k D = 1.00 ± 0.17) for the C–H bond activation step was observed. In addition, a Hammett experiment gave a negative ρ value, −2.16 ± 0.02. The directing group, pyridinyl, was demonstrated to be a removable functional group. Finally, a rational catalytic mechanism is presented on the basis of all experimental evidence.

ChemInform Abstract: Rhodium‐Catalyzed/Copper‐Mediated Selective C2 Alkynylation of Indoles and C1 Alkynylation of Carbazoles with γ‐Substituted tert‐Propargyl Alcohols.

“…The only one example prior to our study was reported by Zhou andL iv ery recently,i nt hat the Ir-catalyzed C1 alkynylation of N-pyrimidyl-carbazole was achievedb yu sing the hypervalent iodine alkynylating reagent TIPS-EBX. [28] Pleasingly, it was found that C1-selective alkynylation of N-pyridyl-carbazole 4 [26] with g-substituted tert-propargyl alcohols could be realized under our conditions for the alkynylation of indoles. As shown in Scheme 3, tert-propargyl alcohols with various electron-withdrawing or -donatings ubstituents including H, Cl, Ph, Et, CO 2 Et, and OMe at the para position of the phenylr ing all workedw ell to afford the C1 alkynylated carbazoles in good to excellent yields (5a-5d, 5f,a nd 5g).…”

“…In addition, given the importance of carbazole derivatives in variousb iologically active compounds and materials science, [25] we were also intrigued to extendt his CÀHa lkynylation reaction to carbazole substrates. To the best of our knowledge,t he CÀHf unctionalization of carbazoles is much less developed than other heteroareneso wing to their intrinsic inertness, [26,27] in which direct and specific C1 alkynylation is especially challenging. The only one example prior to our study was reported by Zhou andL iv ery recently,i nt hat the Ir-catalyzed C1 alkynylation of N-pyrimidyl-carbazole was achievedb yu sing the hypervalent iodine alkynylating reagent TIPS-EBX.…”

“…[30] Unfortunately,o ur effortst or emove the pyridyl directing group of the alkynylated carbazole 5a under similarc onditions were unsuccessful, although there has been ar eport on the cleavage of the pyridyl group of 1-aryl-9-(pyridin-2-yl)-9H-carbazoles under similar N-methylation/hydrolysisconditions. [26] Our previouss tudies on the rhodium/copper-catalyzed synthesis of pyrido[2,1-a]indoles have showedt hat no appreciable reactionc ould be observed if the stoichiometric reaction of [RhCl(cod)] 2 with pyridyli ndole was performed in the absence of Cu(OAc) 2 ·H 2 O, however,t he biscyclometalated Rh III complex was obtained in the presence of Cu(OAc) 2 ·H 2 O, which clearly indicated that the cyclometalation of the pyridyl indolew as enforcedw ith the Rh III species. In addition, we have demonstrated that Cu(OAc) 2 ·H 2 Oi sn ot only an oxidantb ut also responsible fort he CÀCb ond cleavage of tert-propargyl alcohols to generate the alkynylcopper species.…”

Silver(I)‐ or Copper(II)‐Mediated Dearomatization of Aromatic Ynones: Direct Access to Spirocyclic Scaffolds

“…[13] Thei mportance of the ynone carbonyl group is noteworthy,asdemonstrated by the contrasting reactivity of propargyl alcohol 7 (Table 1, compare entries 6a nd 8);t reatment of compound 7 with 0.1 equivalents of AgOTf for 1h at room temperature resulted in its complete conversion into known carbazole 8, [14] presumably through an initial spirocyclization, followed by 1,2 migration (compare 4a to 4b,F igure 1b)a nd dehydration. [13] Thei mportance of the ynone carbonyl group is noteworthy,asdemonstrated by the contrasting reactivity of propargyl alcohol 7 (Table 1, compare entries 6a nd 8);t reatment of compound 7 with 0.1 equivalents of AgOTf for 1h at room temperature resulted in its complete conversion into known carbazole 8, [14] presumably through an initial spirocyclization, followed by 1,2 migration (compare 4a to 4b,F igure 1b)a nd dehydration.…”

“…Zuschriften temperature being optimal, furnishing spirocyclic indolenine 6a in quantitative yield (entry 7, for X-ray crystallographic data see the Supporting Information). [13] Thei mportance of the ynone carbonyl group is noteworthy,asdemonstrated by the contrasting reactivity of propargyl alcohol 7 ( Table 1, compare entries 6a nd 8);t reatment of compound 7 with 0.1 equivalents of AgOTf for 1h at room temperature resulted in its complete conversion into known carbazole 8, [14] presumably through an initial spirocyclization, followed by 1,2 migration (compare 4a to 4b,F igure 1b)a nd dehydration. [8] Therelative ease of the migration in the conversion of 7 into 8 is presumably driven by the higher migratory aptitude of the more electron-rich alkene.…”