In the presence of catalytic amount of copper iodide, a remote amide-assisted intramolecular arylation followed by alkylation leads to a general and flexible synthetic method toward the synthesis of medicinally interesting hexahydropyrroloindole alkaloids.

Cyclodipeptide 2,5-diketopiperazines (DKP)a re privileged structuralu nits presenti nd rugs and natural alkaloids.T his work reports an ew method for the synthesis of biologically important DKP scaffoldsb ased on an intramolecular nucleophilic a-addition of generala midest owards an alkynamide system. The utility of this umpolung cyclization mediated by trimethyl phosphine and l-glutamic acid is highlighted by its application to the concise total syntheseso f6 -methoxyspirotryprostatin B( the first total synthesis), spirotryprostatinA,a nd spirotryprostatin B.

In this paper, we report a full account of the synthesis of dimeric hexahydropyrroloindole alkaloids and its analogues. The key feature of our new strategy is the novel catalytic copper (10 %) mediated intramolecular arylations of o-haloanilides followed by intermolecular oxidative dimerization of the resulting oxindoles in one pot. This sequential reaction leads to the key intermediates for the synthesis of (+)-chimonanthine, (+)-folicanthine, (−)-calycanthine and (−)-ditryptophenaline.Graphical Abstract In the presence of catalytic amount of cuprous iodide (10 %), an intramolecular arylation of o-haloanilides followed by an intermolecular oxidative dimerization of the resulting oxindoles leads to a common intermediate for the synthesis of (+)-chimonanthine, (+)-folicanthine and (−)-calycanthine. Based on this cascade sequence, we also developed a flexible strategy towards the asymmetric syntheses of dimeric HPI alkaloids (−)-ditryptophenaline and its analogues.Electronic supplementary materialThe online version of this article (doi:10.1007/s13659-016-0092-8) contains supplementary material, which is available to authorized users.

In this paper, we report an enantioselective total synthesis of (+)-nocardioazine B, a prenylated hexahydropyrrolo­[2,3-b]­indole (HPI) alkaloid with a central 2,5-diketopiperazine (DKP) ring. The key step in our synthetic route is a copper-catalyzed sequential arylation–alkylation of o-haloanilide derivatives. Based on this transformation, the construction of C3 all-carbon quaternary stereocenters presented in the HPI systems was achieved with high yields and excellent diastereoselectivity.

In this communication, we report a copper catalyzed sequential arylation-oxidative dimerization reaction as the key step for the synthesis of hexahydropyrroloindole alkaloids (+)-chimonanthine, (+)-folicanthine and (-)-calycanthine.