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.

Catalyst controlled site-selective C−H functionalization is a challenging but powerful tool in organic synthesis. Polarity-matched and sterically controlled hydrogen atom transfer (HAT) provides an excellent opportunity for site-selective functionalization. As such, the dual Ni/photoredox system was successfully employed to generate acyl radicals from aldehydes via selective formyl C−H activation and subsequently cross-coupled to generate ketones, a ubiquitous structural motif present in the vast majority of natural and bioactive molecules. However, only a handful of examples that are constrained to the use of aryl halides are developed. Given the wide availability of amines, we developed a cross-coupling reaction via C−N bond cleavage using the economic nickel and TBADT catalyst for the first time. A range of alkyl and aryl aldehydes were cross-coupled with benzylic and allylic pyridinium salts to afford ketones with a broad spectrum of functional group tolerance. High regioselectivity toward formyl C−H bonds even in the presence of α-methylene carbonyl or αamino/oxy methylene was obtained.

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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).

Hydroacylation of alkynes is undoubtedly the simplest and most atom-efficient approach for the synthesis of enones with diverse synthetic applications. Despite significant progress in hydroacylations, no hydroacylations exist that make use of aldehydes without a chelating group, especially when combined with terminal alkynes. Here we report a synergistic nickel− photocatalytic system that allows for the highly regio-and stereoselective hydroacylation of unactivated aldehydes and alkynes in milder conditions without the use of chelating groups.