Cornforth–evans transition states in stereocontrolled allylborations of epoxy aldehydes

Allylboration reactions rank among the most reliable tools in organic synthesis. Herein, we report a general synthesis of trifunctionalized allylboronates and systematic investigations of their stereocontrolled transformations with substituted aldehyde substrates, in order to efficiently access diverse, highly substituted target substrates. A peculiar transition in stereocontrol was observed from the polar Felkin–Anh (PFA) to the Cornforth–Evans (CE) model for alkoxy‐ and epoxy‐substituted aldehydes. CE‐type transition states were uniformly identified as minima in advanced, DFT‐based computational studies of allylboration reactions of epoxy aldehydes, conforming well to the experimental data, and highlighting the underestimated relevance of this model. Furthermore, a mechanism‐based rationale for the substitution pattern of the epoxide was delineated that ensures high levels of stereocontrol and renders α,β‐epoxy aldehydes generally applicable substrates for target synthesis.Felkin–Anh or Cornforth–Evans? The allylboration of epoxy aldehydes provides a stereoselective access to contiguously functionalized alkyl chains as found in a myriad of natural products. Studying this transformation in experiment and in silico disclosed high stereoselectivities, the mode of asymmetric induction, and enabled the predictable application for stereocontrolled synthesis of complex molecules. imag