Palladium(II)/Polyoxometalate‐Catalyzed Direct C‐3 Alkenylation of Indoles using Dioxygen as the Terminal Oxidant

Abstract

An efficient and practical synthetic method has been developed for the preparation of 3-vinylindoles by the direct C À H olefination of indoles with alkenes. The transformation is catalyzed by palladium acetate combined with 12-molybdophosphoric acid and uses oxygen as the terminal oxidant. 4-Dimethylaminopyridine (DMAP) was observed to be an effective additive for the olefination reaction. Functional groups such as methoxy, benzylA C H T U N G T R E N N U N G oxy, fluoro, bromo, ester, phenyl, and methyl were tolerated under the reaction conditions.

Pd(ii)/Lewis acid catalyzed regioselective olefination of indole with dioxygen

“…To date, versatile protocols have been explored for the syntheses of 3-vinylindole and its derivatives through olefination. 28–38 However, the challenge is that in these redox metal ion mediated indole olefinations through C–H activation, stoichiometric amounts of oxidants such as Cu( ii ) salts, Ag( i ) salts and MnO 2 have been popularly employed to accomplish efficient Pd( ii )/Pd(0) cycle in catalysis with limited examples of using dioxygen as the oxidant (Scheme 1). 30,32,34,36 In these studies, Wang and Noël conducted the olefination in DMSO with TFA as the additives (Scheme 1a), Lin employed polyoxometalate (Scheme 1b) and Das employed Cu( ii ) (Scheme 1c) to promote the reoxidation of the Pd(0) species back to the active Pd( ii ) in catalysis.…”

Regioselective Direct C‐Alkenylation of Indoles

“…[18] Addition of 2mol %o fpolyoxometalates such as H 3 PMo 12 O 40 can have ab eneficial effect in the reaction of indoles with a,b-unsaturated esters using 10 mol %o f Pd(OAc) 2 . [19] The reaction conditions are less mild than those previously described (5 atm O 2 ,D MF/DMSO,8 08C) and the utilization of methylm ethacrylate as ar eagent affords ar egioisomeric mixture of adducts.S imilarly,ahetero-bimetallic Pd/Cu catalystc an be employed for the FM reactionu nder air with satisfactory results. [20] Alkenylation of 7-azaindoles can be carried out with C-3 regiocontroli ntroducing Cu(OTf) 2 as co-oxidant together with molecular oxygen (Scheme 5).…”

“…Various metal salts are often used in catalytic amount as co‐oxidants when oxygen is used as terminal reagent, although their positive effect is still debatable . Addition of 2 mol % of polyoxometalates such as H 3 PMo 12 O 40 can have a beneficial effect in the reaction of indoles with α,β‐unsaturated esters using 10 mol % of Pd(OAc) 2 . The reaction conditions are less mild than those previously described (5 atm O 2 , DMF/DMSO, 80 °C) and the utilization of methyl methacrylate as a reagent affords a regioisomeric mixture of adducts.…”

Aerobic Oxidative Functionalization of Indoles

“…And 4dimethylaminopyridine (DMAP) was found to be an effective additive (Scheme 7, conditions B). [17] In 2016, Das group further modified the palladium(II)catalyzed aerobic systems by the use of copper(II)/O 2 co-oxidant, which enabled efficient site-selective intermolecular oxidative C3 alkenylation of 7-azaindoles at room temperature (Scheme 7, conditions C). [18] In the studies on the thioether ligand-promoted CÀ H alkenylation of heteroarenes, Carrow and co-workers also disclosed feasible aerobic examples of indole functionalization (Scheme 7, conditions D).…”