Asymmetric catalytic multicomponent cascade reactions have become indispensable tools for enantioselective construction of spirooxindoles. In recent years, a number of successful strategies have been developed for the synthesis of enantioenriched...
We report a scandium-catalyzed
[3 + 2] annulation of alkylideneoxindoles
with allenylsilanes for the enantioselective formation of cyclopentene-spirooxindoles
containing vinylsilanes. Using a Sc(OTf)2/PyBOX/BArF complex,
the spiroannulation of allenylsilanes affords products with >94:6
dr and >90:10 er. The effect of the counterion and ligand to control
selectivity is discussed. The transformation of the vinylsilane is
demonstrated using cross-coupling, epoxidation, and Tamao–Fleming
oxidation reactions. A series of competition experiments provide a
comparison of nucleophilicity between allyl- and allenylsilanes.
A mechanism
for the scandium-catalyzed asymmetric allylsilane annulation
reaction is proposed and supported by reaction heat flow calorimetry,
NMR, and in situ infrared spectroscopy. The nature of a scandium(III)–PyBox/BArF
catalyst is probed using reaction calorimetric analysis, which reveals
a complex interplay between in-solution and precipitated catalyst
species. The scandium(III)–PyBox/BArF catalyst is minimally
soluble until the addition of a bidentate electrophile. The optimal
reaction rate is dependent on precomplexation of the catalyst, order
of complexation of the catalyst components, and delayed addition of
nucleophile. The formation of the active catalyst proceeds through
a bimolecular combination of scandium(III) with a BArF anion, followed
by complexation with PyBox ligand, where the ligand-dependent rate
and selectivity are observed. Notably, ligand-accelerated catalysis
is observed, attributed to the ligand reducing off-cycle oligomerization
of allylsilane. The role of BArF is discussed with a specific focus
on the source of counterion in the reaction rate and enantioselectivity.
We also report the formation of a mechanistically relevant fused tetrahydropyranindole
produced upon the reaction of an allylsilane with alkylidene oxindole.
In situ infrared spectroscopy demonstrates ligand-dependent acceleration
where sterically demanding ligands perform with a faster relative
reaction rate.
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