Reiterative epoxide-based strategies for the synthesis of stereo-n-ads and application to polypropionate synthesis. A personal account

[Display omitted] •Stereoselective synthesis of stereo-n-ads using epoxide cleavage strategy.•Termini-differentiated methodology allows for a linear or convergent synthesis.•Diastereoselective approach for the reiterative construction of polypropionates.•Organometallic reagent aids in assembling different structural variations within the target. The enantioselective synthesis of polypropionates continues to be an attractive realm for the synthetic chemists, mostly due to the challenges presented by the number of consecutive stereogenic centers contained within the aliphatic chain. Over the years, our laboratory has developed a reiterative epoxide-based methodology for the construction of these targets, with the ultimate goal that the approach could be extended to the synthesis of polypropionate-containing natural products. The key steps include the diastereoselective epoxidation of allylic and homoallylic alcohols, and the regioselective cleavage of 2-methyl-3,4-epoxy alcohols. The choice of the organometallic reagent, and the cis/trans geometry of the chiral epoxide are used to control both the relative and absolute configuration of the resulting propionate unit, allowing our approach to be applied in the synthesis of advanced fragments. Additionally, the combination of our first- and second-generation methodologies permits the incorporation of different variations at the methyl moiety.