Iterative Synthesis of 1,3-Polyboronic Esters with High Stereocontrol: Applications to Bahamaolide A and Polyfunctionalised Hydrocarbons

Polyketide natural products often contain common repeat motifs, e.g., propionate, acetate and deoxypropionate, and so can be synthesized by using iterative processes. We report a highly efficient iterative strategy for the synthesis of polyacetates based on boronic ester homologation that does not require functional group manipulation between iterations. This process involves sequential asymmetric diboration of a terminal alkene, forming a 1,2-bis(boronic ester), followed by regio- and stereoselective homologation of the primary boronic ester with a butenyl metallated carbenoid to generate a 1,3-bis(boronic ester). Each transformation independently controls stereochemical configuration, making the process highly versatile, and the sequence can be iterated prior to stereospecific oxidation of the 1,3-poly(boronic ester) to reveal the 1,3-polyol. The methodology was applied to a 14-step synthesis of the oxopolyene macrolide bahamaolide A, and the versatility of the 1,3-polyboronic esters was demonstrated in various stereospecific transformations, leading to poly-alkenes, -alkynes, -ketones, and -aromatics with full stereocontrol.