General access to the vinca and tacaman alkaloids using a Rh(II)-catalyzed cyclization/cycloaddition cascade

The total synthesis of several members of the vinca and tacaman classes of indole alkaloids has been accomplished. The central step in the synthesis consists of an intramolecular [3+2]-cycloaddition reaction of an alpha-diazo indoloamide which delivers the pentacyclic skeleton of the natural product in excellent yield. The acid lability of the oxabicyclic structure was exploited to establish the trans-DIE ring fusion of (+/-)-3H-epivincamine (3). Finally, a base induced keto-amide ring contraction was utilized to generate the E-ring of the natural product. A variation of the cascade sequence of reactions used to synthesize (+/-)-3H-epivincamine was also employed for the synthesis of the tacaman alkaloids (+/-)-tacamonine and (+/-)-apotacamine.