Modular synthesis of indoles from imines and o-dihaloarenes or o-chlorosulfonates by a Pd-catalyzed cascade process.
A detailed study of the scope of a new Pd-catalyzed synthesis of indoles from 1,2-dihaloarenes and o-halobenzene sulfonates and imines is described. The cascade reaction comprises an imine alpha-arylation followed by an intramolecular C-N bond-forming reaction promoted by the same Pd catalyst. The reaction with 1,2-dibromobenzene shows wide scope and allows the introduction of aryl, alkyl, and vinyl substituents at different positions of the five-membered ring of the indole. The regioselective synthesis of indoles substituted in the six-membered ring can be carried out by employing o-dihalobenzene derivatives with two different halogens, taking advantage of the different reactivities of I, Br, and Cl in oxidative addition reactions. This paper also introduces a method for the efficient cleavage of the N-t-butyl group, thus allowing for the preparation of N-H indoles through the same methodology. Finally, the reaction with o-halosulfonates has been studied. The best substrates are o-chlorononaflates, which lead to indoles in very high yield. The reaction is particularly appropriate for the synthesis of the challenging 6-substituted indoles. In view of the availability of o-chlorophenols, which are direct precursors of the chlorononaflates, this reaction represents an efficient entry into indoles substituted in the six-membered ring. The concept is illustrated by the preparation of a 4,6-disubstituted indole from naturally occurring anethole.
Barluenga
José
J
Instituto Universitario de Quimica Organometalica Enrique Moles, Unidad Asociada al CSIC, Universidad de Oviedo, c/ Julian Claveria 8, 33006 Oviedo, Spain.
Jiménez-Aquino
Agustín
A
Aznar
Fernando
F
Valdés
Carlos
C
D002384:Catalysis; D006846:Hydrocarbons, Halogenated; D007097:Imines / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis*; D010165:Palladium; D013451:Sulfonic Acids
D006846:Hydrocarbons, Halogenated; D007097:Imines; D007211:Indoles; D013451:Sulfonic Acids; C013880:chlorosulfonic acid; D010165:Palladium