Abstract
Abstract1,2‐Bis(boronic esters), derived from the enantioselective diboration of terminal alkenes, can be selectively homologated at the primary boronic ester by using enantioenriched primary/secondary lithiated carbamates or benzoates to give 1,3‐bis(boronic esters), which can be subsequently oxidized to the corresponding secondary‐secondary and secondary‐tertiary 1,3‐diols with full stereocontrol. The transformation was applied to a concise total synthesis of the 14‐membered macrolactone, Sch 725674. The nine‐step synthetic route also features a novel desymmetrizing enantioselective diboration of a divinyl carbinol derivative and high‐yielding late‐stage cross‐metathesis and Yamaguchi macrolactonization reactions.
Highlights
Developments in the homologation of boronic esters has continued unabated for almost 40 years, reaching a point where iterative homologation (“one pot”) of a simple boronic ester into a molecule bearing 10 contiguous methyl substituents with full stereocontrol was recently demonstrated.[1]
By combining Morken/Nishiyama diboration with lithiation–borylation we show that powerful new methodology can be generated, enabling incorporation of the 1,3diol motif through boronic ester homologation
We demonstrate its application in the concise total synthesis of the 14-membered macrolactone, Sch 725674
Summary
Developments in the homologation of boronic esters has continued unabated for almost 40 years, reaching a point where iterative homologation (“one pot”) of a simple boronic ester into a molecule bearing 10 contiguous methyl substituents with full stereocontrol was recently demonstrated.[1]. Subsequent heating at 35 8C for 16 h, followed by oxidation (H2O2/NaOH/H2O), gave the desired 1,3-diol (S,S)3 (66 % yield) together with only trace amounts of the doubleaddition product, that is, that derived from homologation of both the primary and secondary boronic esters (Scheme 2 a, entry 1).
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