Cu-Catalyzed Hydroboration of Benzylidenecyclopropanes: Reaction Optimization, (Hetero)Aryl Scope, and Origins of Pathway Selectivity

The
copper-catalyzed hydroboration of benzylidenecyclopropanes,
conveniently accessed in one step from readily available benzaldehydes,
is reported. Under otherwise identical reaction conditions, two distinct
phosphine ligands grant access to different products by either suppressing
or promoting the cyclopropane opening via β-carbon elimination.
Computational studies provide insight into how the rigidity and steric
environment of these different bis-phosphine ligands influence the
relative activation energies of β-carbon elimination versus
protodecupration from the key benzylcopper intermediate. The method
tolerates a wide variety of heterocycles prevalent in clinical and
preclinical drug development, giving access to valuable synthetic
intermediates. The versatility of the tertiary cyclopropylboronic
ester products is demonstrated through several derivatization reactions.