Additive-Controlled Divergent Synthesis of Indole and 4H-Benzo[d][1,3]oxazine Derivatives: Palladium-Catalyzed Carbonylative Cyclization of 2-Alkynylanilines and Benzyl Chlorides

Abstract

A palladium-catalyzed divergent carbonylative synthesis of indoles and 4H-benzo­[d]­[1,3]­oxazines from 2-alkynylanilines and benzyl chlorides with benzene-1,3,5-triyl triformate (TFBen) as the CO source has been developed. The reaction using AlCl3 as the additive produced various indoles in high yields, while a series of 4H-benzo­[d]­[1,3]­oxazines was achieved in moderate yields with AcOH as the additive.

Carbonylative synthesis and functionalization of indoles

“…Another example was published by Wu's group, who carried out the synthesis of 1-(1 H -indol-1-yl)-2-arylethan-1-one derivatives by promoting the formation of amides from 2-alkynylanilines by using TFBen (benzene-1,3,5-triyl triformate) as a CO source, Pd(OAc) 2 , DPEPhos (bis[(2-diphenylphosphino)phenyl] ether), and DIPEA ( N , N -diisopropylethylamine) in MeCN. After 24 h, Pd(OAc) 2 and AlCl 3 were added to promote a selective cyclization reaction [ 14 ]. The reaction mechanism proceeds with an initial reduction of Pd(II) to Pd(0) followed by oxidative addition on the ArCH 2 –Cl bond to form the ArCH 2 –Pd II –Cl complex.…”

“…Pd(OAc) 2 and AlCl 3 were added to promote a selective cyclization reaction [14]. The reaction mechanism proceeds with an initial reduction of Pd(II) to Pd(0) followed by oxidative addition on the ArCH 2 -Cl bond to form the ArCH 2 -Pd II -Cl complex.…”

Recent Advances in the Synthesis of Five‐membered Nitrogen Heterocycles Induced by Palladium Ions and Complexes

“…The use of TFBen, mentioned above, has also been explored by Wu and co-workers in the carbonylative cyclization of 2alkynylanilines and benzyl chlorides carried out in the presence of DPEPhos [(oxydi-2,1-phenylene)bis(diphenylphosphane)] li-gand L21. [76] In this case, both Pd(OAc) 2 and DIPEA (N,Ndiisopropylethylamine) were needed to complete the reactions providing the required indole derivatives in medium to high yields (Scheme 50). In mechanistic interpretation, L21 was suggested to induce the formation of the active Pd 0 catalytic species, whereas AlCl 3 acted as a Lewis acid promoting the activation of the alkyne.…”