Total Synthesis of (−)-Blepharocalyxin D and Analogues

An efficient strategy for the total synthesis of (−)-blepharocalyxin D and an analogue is described. The key step involves an acid-mediated cascade process in which reaction of methyl 3,3-dimethoxypropanoate with γ,δ-unsaturated alcohols possessing diastereotopic styrenyl groups gives <i>trans</i>-fused bicyclic lactones with the creation of two rings and four stereocenters in one pot

Alkene 1,3-Difluorination via Transient Oxonium Intermediates

The 1,3-difunctionalization of unactivated alkenes is an under-explored transformation that leads to moieties that are otherwise challenging to prepare. Herein, we report a hypervalent iodine-mediated 1,3-difluorination of homoallylic (aryl) ethers to give unreported 1,3-difluoro-4-oxy groups with moderate to excellent diastereoselectivity. The transformation proceeds through a different mode of reactivity for 1,3-difunctionalization, in which a regioselective addition of fluoride opens a transiently formed oxonium intermediate to rearrange an alkyl chain. The optimized protocol is scalable and shown to proceed well with a variety of functional groups and substitution on the alkenyl chain, hence providing ready access to this fluorinated, conformationally controlled moiety