Total Synthesis of Dimeric HPI Alkaloids

ABSTRACT: 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. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13659-016-0092-8) contains supplementary material, which is available to authorized users.