1 research outputs found
Nickel-Catalyzed Enantioselective Coupling of Acid Chlorides with α‑Bromobenzoates: An Asymmetric Acyloin Synthesis
The
reaction of common acyl-metal species (acyl anion) with aldehydes
to furnish acyloins has received much less attention and specifically
was restricted to using preformed stoichiometric acyl-metal reagents.
Moreover, the (catalytic) enantioselective variants remain unexplored,
and the asymmetric synthesis of chiral acyloins has met significant
challenges in organic synthesis. Here, we uncover the highly enantioselective
coupling of acid chlorides with α-bromobenzoates by nickel catalysis
for producing enantioenriched protected α-hydroxy ketones (acyloins,
>60 examples) with high enantioselectivities (up to 99% ee). The
successful
execution of this enantioselective coupling protocol enables the formation
of a key ketyl radical from α-bromoalkyl benzoate in situ generated
from corresponding aldehyde and acyl bromide, which finally is captured
by chiral acyl-Ni species catalytically in situ formed from acyl chlorides,
thus avoiding the use of preformed acyl-metal reagents. The synthetic
utility of this chemistry is demonstrated in the downstream synthetic
elaboration toward a diverse set of synthetically valuable chiral
building blocks and biologically active compounds