Cp*Co^III-Catalyzed Branch-Selective Hydroarylation of Alkynes via C–H Activation: Efficient Access to α-gem-Vinylindoles

Abstract

An efficient, atom-economical, and regioselective insertion of indoles into terminal alkynes has been realized via cobalt­(III)-catalyzed C–H activation under mild conditions, leading to efficient synthesis of α-gem-vinylindoles. The insertion of the alkynes follows a rare 1,2-selectivity, and silyl alkynes, alkyl alkynes, propargyl alcohols, and protected propargyl amines are all applicable. The mechanism of this hydroarylation system has been studied in detail by a combination of experimental and computational approaches. In the reaction of silyl terminal alkynes, the regioselectivity is dictated by the steric effects of the alkyne substituent, especially in the protonolysis stage. However, for protected propargyl amines, the selectivity results from electronic effects during the insertion step, with protonolysis being insignificant in the determination of selectivity. An internal alkyne also coupled in high efficiency but with low regioselectivity. Comparisons of cobalt, rhodium, and iridium catalysts have also been made in terms of regioselectivity and reactivity, and both are high for cobalt catalysts.

Cobalt‐Catalyzed Direct C(sp2)–H Alkylation with Unactivated Alkenes

“…On the basis of these control experiments and previous reports,[2g], [7a], [7d], , the plausible catalytic cycle is shown in Scheme . The active cationic species I is generated in the presence of Cp*Co(CO)I 2 , AgSbF 6 , and pivOH, which then undergoes electrophilic metalation with 1a in a reversible manner to form cobaltacycle II upon the release of pivOH.…”

“…While the desired product was not detected without an acidic additive (entries 1–3), product 3aa was obtained in a 16 % yield with AcOH (2 equiv.) (entry 4), The C(sp 2 )–H alkenylation product 4aa (11 % yield), which is synthesized through the β‐hydride elimination after migratory insertion into alkenes, was also isolated. In the presence of the AgSbF 6 additive, other acids were screened (entries 5–7), and pivOH (pivalic acid) was identified to be the most powerful for linear‐selective C–H alkylation (entry 5).…”

C−H Functionalization of Indoles by 3d Transition‐Metal Catalysis

“…This protocol has significantly broadened the scope of the indole C‐2 alkenylation. Inspired by this report, Li group has demonstrated the regioselective insertion of indoles into terminal alkynes using a Co(III) catalyst . The addition of alkynes followed a rare 1,2‐selectivity leading to α‐gem‐ vinylindoles.…”

“…Inspired by this report, Li group has demonstrated the regioselective insertion of indoles into terminal alkynes using a Co(III) catalyst. [38] The addition of alkynes followed a rare 1,2-selectivity leading to α-gem-vinylindoles. This method applies to silyl alkynes, alkyl alkynes, propargyl alcohols and protected amines.A comprehensive mechanistic study by the authors suggests that the steric or electronics on the alkynes are responsible for the observed selectivity depending upon the substrates.…”

Developments in Cp*CoIII‐Catalyzed C−H Bond Functionalizations

“…An uncommon regioselective 1,2‐insertion reaction of indole with wide range of alkyne was achieved by Li/Lan and co‐workers in the presence of Cp*Co(III)‐catalyst (Scheme ). A series of experimental and theoretical investigations were performed to understand insight the mechanism of the reaction.…”