Palladium-catalysed [2+3] cycloaddition routes to the tricyclic core of the stenine group of Stemona alkaloids

The stemona alkaloids have generated considerable interest in recent years. They are from the Stemonaceae family, which has two genera, Stemona and Croomia and are a structurally interesting class of alkaloids isolated from the roots and rhizomes of the Stemonaceae plant family. Common to all of the Stemona alkaloids is the central azapinoindole, (B, C, D system) shown in stenine below. [Illustration omitted.] The route to the stenine core which we wished to look at, envisaged using a Pd(0) catalysed [2+3] cycloaddition between an activated vinylcyclopropane substrate and a suitable imine to give the hydro indole core. A subsequent intramolecular Heck reaction could then be carried out to construct the seven-membered azepine ring of the tricylic core. [Illustration omitted.] We have already established Pd(0) catalysed [2+3] cycloaddition routes to five-membered heterocylces via the trapping of various imines with vinylcyclopropanes and we hope that using this methodology we can access the tricyclic core of stenine. [Illustration omitted.]