Nickel‐ and Photoredox‐Catalyzed Cross‐Coupling Reactions of Aryl Halides with 4‐Alkyl‐1,4‐dihydropyridines as Formal Nucleophilic Alkylation Reagents

Abstract

A combination of nickel and photoredox catalysts promoted novel cross-coupling reactions of aryl halides with 4-alkyl-1,4-dihydropyridines. 4-Alkyl-1,4-dihydropyridines act as formal nucleophilic alkylation reagents through a photoredox-catalyzed carbon-carbon (C-C) bond-cleavage process. The present strategy provides an alternative to classical carbon-centered nucleophiles, such as organometallic reagents.

Visible‐Light Photocatalysis as an Enabling Tool for the Functionalization of Unactivated C(sp3)‐Substrates

“…In the space of only a few years, significant progress in this area has been made, and elegant protocols for the efficient generation of alkyl radicals from a wide range of precursors are now available. Indeed, during the preparation of this manuscript, the groups of Molander [95] and Nishibayashi [96] reported 1,4-dihydropyridines as a new class of radical precursors in C(sp 3 )-C(sp 2 ) cross-coupling reactions. Despite these advances a number of challenges still remain, including the development of enantioselective procedures, atomefficient precursors, and sustainable photocatalysts.…”

Synthesis of Non‐Classical Arylated C‐Saccharides through Nickel/Photoredox Dual Catalysis

“…[12] With the goal of accessing glycosyl radicals that could be engaged in such dual catalytic processes,w et urned our attention to 4-alkyl-1,4-dihydropyridine derivatives (DHPs). [16] These species have been shown to afford C(sp 3 )centered alkyl radicals efficiently upon single-electron transfer (SET) oxidation. In addition to being bench stable and easy to handle,these compounds tolerate high functionalization levels owing to the mild reaction conditions required for their preparation from the corresponding aldehyde.Awide range of 4-glycosyl-1,4-DHPs was accessed from commercially available pentose and hexose derivatives through deprotection and oxidation chemistry to form the aldehyde.…”

Photoredox/Nickel‐Catalyzed Single‐Electron Tsuji–Trost Reaction: Development and Mechanistic Insights

“…In particular, numerous radical precursors (e.g., alkyltrifluoroborates, carboxylates, alkylsilicates, and 1,4-dihydropyridines) derived from diverse commodity chemicals have been developed. 15 Although such reagents have been extensively utilized in conjunction with photoredox/Ni dual cross-coupling with aryl- 16 and alkenyl 17 electrophiles, we have also begun to expand the scope of electrophilic partners for such transformations (e.g., using isocyanate, 18 acyl chloride, 19 carboxylic acid, 20 and acyl imide electrophiles 21 ). In a continuation of that effort, the cost-effective nature of Ni-based catalysts and the slow α-hydride elimination of alkylnickel species relative to that of palladium was considered to investigate how this approach could be applied to the Tsuji-Trost reaction.…”