Direct C-Arylation of Free (NH)-Indoles and Pyrroles Catalyzed by Ar−Rh(III) Complexes Assembled In Situ

Abstract

Ar-Rh(III) pivalate complexes assembled in situ from the reaction of [RhCl(coe)2]2 (coe = cis-cyclooctene), [p-(CF3)C6H4]3P, and CsOPiv effectively catalyzed the direct C-arylation of free (NH)-indoles and (NH)-pyrroles in good yields and with high regioselectivity. The reaction displayed excellent functional group compatibility and low moisture sensitivity. Kinetics studies support a mechanism involving phosphine displacement by indole in complex 2 (resting state of the catalyst), followed by a rate-limiting C-H bond metalation.

Overview of the Mechanistic Work on the Concerted Metallation–Deprotonation Pathway

“…Larock and Sames had used stoichiometric amounts of pivalate salts in palladium and rhodium systems. 45,46 Fagnou first used pivalic acid (PivOH) as a co-catalyst in a palladium-catalyzed direct arylation reaction in order to efficiently functionalize benzene and other simple arenes. 47 The pivalate anion is believed to act as a catalytic proton shuttle from benzene to the stoichiometric carbonate base.…”

C-2/C-3 Annulation and C-2 Alkylation of Indoles with 2-Alkoxycyclopropanoate Esters

“…Recent examples of indole functionalization include asymmetric C-3 Friedel-Craft reactions, 1,2,3 allylations, 4,5 radical couplings, 6 arylations, 7,8,9 Michael-additions, 10 C-H activation, 11 and N-arylations. 12 Indoles containing a fused 5-membered ring at the C-2 and C-3 positions are well represented in nature, and include the penitrems 13 and kopsane 14 alkaloids.…”

The synthesis of 1,2,3,6,6a,7-hexahydro-7-methyl-5-imino-1H-pyrrolo[1,2-c]imidazolo[5,4-b]indole

“…Such processes may be related to the palladium-and rhodium-catalyzed direct intermolecular arylations of indoles, which proceed via electrophilic metallation and involve C2/C3 equilibration. 8,9 Finally, the mechanism could involve a nitrene formed from the primary amino group engaging in a cycloaddition with the indole double bond forming an aziridine 20. Intramolecular nucleophilic ring opening, as indicated in Scheme 11 would complete the process.…”