HFIP‐Promoted <i>E</i> ‐selective Asymmetric Crotylboration of Quaternary α‐Silyl Crotylboronate with Aldehydes

Abstract Polyketide synthesis consistently requires the development of linchpin‐type allylboron reagents, such as α‐silyl crotylboronates. Traditionally, these reagents feature α‐tertiary substitution and are used in aprotic solvents, typically yielding homoallylic alcohols with disubstituted ( Z )‐vinylsilanes. Here, we report the asymmetric synthesis of enantioenriched quaternary α‐silyl crotylboronates via stereospecific allylic Matteson homologation. We further demonstrate that hexafluoroisopropanol (HFIP)—a polar alcoholic solvent that has been underutilized in allylboration—not only enhances reaction reactivity but also overrides the typical ( Z )‐selectivity, enabling access to the otherwise challenging ( E )‐selective products. The method enables the rapid construction of ( E )‐anti‐2,4‐dimethylpent‐3‐en‐1‐oxy motif, a structural unit frequently found in polyketides, and allows the protecting‐group‐free synthesis of PM050463. DFT calculations suggest that HFIP's strong hydrogen bonding effect increases the Lewis acidity of the boron center and the steric effect of Bpin, resulting in high yields and ( E )‐selectivity.