Second-Generation Synthesis of (+)-Fastigiatine Inspired by Conformational Studies.

(+)-Fastigiatine is a complex alkaloid isolated from the alpine club moss Lycopodium fastigatum, most commonly found in New Zealand. It has been the subject of two successful synthetic campaigns. A second-generation route toward fastigiatine was developed to resolve two problematic steps from our initial synthesis.

A phosphate tether-mediated, one-pot, sequential ring-closing metathesis/cross-metathesis/chemoselective hydrogenation protocol.

A versatile three-step, one-pot, sequential reaction protocol involving ring-closing metathesis, cross-metathesis, and chemoselective hydrogenation is reported. This phosphate tether-mediated process occurs without intermediate isolation, is chemoselective, and is governed by stereoelectronic properties innate to phosphate tethers, which ultimately act to preserve the integrity of the bisallylic, bicyclic phosphate for subsequent nucleophilic additions. Overall, this process can be used to efficiently generate advanced polyol synthons.