Copper- and Palladium-Cocatalyzed Chemo‑, Regio‑, Stereo‑, and Atroposelective Arylboration of 1,3-Enynes

Catalytic
enantioselective borylation reactions of unsaturated
bonds as powerful tools for the synthesis of diverse chiral organoboron
compounds have gained much attention and have wide applications in
various fields. However, the atroposelective arylboration reaction
with carbon–carbon triple bonds of 1,3-enynes to obtain axially
chiral 1,3-dienylboronates remains an elusive and significant challenge.
Hence, we develop a cooperative copper- and palladium-catalyzed arylboration
reaction to assemble plentiful function enriched axially chiral 1,3-dienylboronates
in a single step from easily available 1,3-enynes, B2pin2, and aryl bromides with high levels of chemo-, regio-, stereo-,
and atroposelectivity. The mild reaction conditions lead to good functional
group tolerance, which is proven by the broad substrate scope and
late-stage functionalizations of bioactive compounds or drug molecules.
Moreover, the reaction can be easily scaled up, and a series of further
transformations can be achieved. It is worth emphasizing that several
olefin catalysts and ligands with axial chirality can also be synthesized
through the corresponding elaborations of such products, which further
explains the powerful transformative ability and application potential
of such axially chiral 1,3-dienylboronates. The mechanism experiment
and density functional theory (DFT) calculations revealed the cooperative
process of copper and palladium catalysis, indicating that the chemoselectivity
and regioselectivity of boration are determined by the enyne insertion
step on copper, and the atroposelectivity is controlled by the further
reductive elimination on the palladium center. Meanwhile, the calculation
also demonstrated that the distinct interactions between the PO
and CO groups with the Pd or Bpin center in the key transition
state lead to the formation of products with varying configurations
while employing identical configuration ligands.