Benzylic stereocenters are found
in bioactive and drug molecules,
as enantiopure benzylic alcohols have been used to build such a stereogenic
center, but are limited to the construction of a C–C bond.
Silylation of alkyl alcohols has the potential to build bioactive
molecules and building blocks; however, the development of such a
process is challenging and unknown. Herein, we describe an unprecedented
AgF-assisted nickel catalysis in the enantiospecific silylation of
benzylic ethers.
In nickel-mediated Kumada cross-coupling reactions, low valent active nickel complexes are often generated in situ and the ligands usually govern the reactivity or stability of these complexes. However, the decomposition of active nickel complexes is inevitable if the subsequent reaction is sluggish. While we recently developed AgF-assisted nickel catalysis to cross-couple methyl ethers and silylmagnesium reagents, the intriguing catalytic role of AgF and the actual active nickel species remains elusive. Recently, both Ni(0) and Ni(I) intermediate complexes are identified as active species in Kumada cross-coupling reactions. Control experiments in combination with 31 P nuclear magnetic resonance (NMR) suggest that AgF attenuates the decomposition of in situ generated Ni(0) species. The plausible Ni(0) and Ni(I) intermediate complexes were synthesized, and experimental findings are consistent with the actual catalytic cycle being Ni(0)/Ni(II) rather than Ni(I)/Ni(III).
The
hydrogen borrowing strategy is an economical method for the
α-functionalization of ketones. While this strategy is extremely
advantageous, it does not lend itself to the synthesis of β,β-disubstituted
ketones. This can be achieved, if the in situ generated metal hydride
can be intercepted with a nucleophilic coupling partner. We present
a multicomponent strategy for the coupling of alcohols, ketones, and
boronic acids using only 1 mol % nickel catalyst and without the need
for added ligands.
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