Nickel(0)-Catalyzed Enantio- and Diastereoselective Synthesis of Benzoxasiloles: Ligand-Controlled Switching from Inter- to Intramolecular Aryl-Transfer Process

A highly enantioselective synthesis
of 3-aryl-, vinyl-, and alkynyl-2,1-benzoxasiloles
(up to 99.9% ee and 99% yield) was achieved via the sequential activation
of an aldehyde and a silane by nickel(0). This strategy was applied
to a simultaneous generation of carbon- and silicon-stereogenic centers
with excellent selectivity (dr = 99:1) via diastereotopic aryl transfer.
Initial mechanistic studies revealed the complete switching of an
aryl-transfer process from an intermolecular (racemic synthesis in
the presence of IPr) to an intramolecular (enantioselective synthesis
using chiral NHC, L5) fashion. A plausible rationale
for the switching of the aryl-transfer process is given by a preliminary
DFT calculation, which suggests that the coordination of 1 to the nickel(0)/L5 fragment in an η2-arene:η2-aldehyde fashion would be a key to the
intramolecular process, while the formation of the corresponding intermediate
is not possible in the presence of IPr. Owing to the chemically labile
nature of its C–Si and O–Si bonds, enantioenriched benzoxasiloles
are utilized for the synthesis of chiral building blocks and antihistaminic
and anticholinergic drug molecules such as (R)-orphenadrine
and (S)-neobenodine with no erosion of the enantiomeric
excess.