Non-activated Alkyl Bromides Research Articles

Nickel-Catalyzed Photoredox Allenylation of Alkyl Halides.

We report a dual Ni/photoredox-catalyzed cross-coupling method for propargyl carbonates and nonactivated alkyl bromides, facilitating the synthesis of a variety of substituted allenes under mild and practical conditions. Mechanistically, the reaction integrates Ni-catalyzed activation of the propargyl electrophile via SN2' oxidative addition at Ni(I) with silyl radical-induced activation of the alkyl halide through halogen-atom transfer. This methodology provides a gentle approach for introducing allenyl groups into complex halogenated aliphatic molecules, offering further opportunities for derivatization.

Copper-catalysed bromine atom transfer cyclisation in SDS micelles.

The atom transfer radical cyclisation (ATRC) of non-activated alkyl bromides was realized under blue light irradiation in carbonate-buffered aqueous SDS solution using a catalytic system of CuBr2, Me6-TREN and ascorbic acid. The beneficial effect of SDS micelles can be accounted for by the activation of the C-Br bond as well as by the suppression of competitive reductive cyclisation.

Minisci C-H Alkylation of Heteroarenes Enabled by Dual Photoredox/Bromide Catalysis in Micellar Solutions*.

Aromatic heterocycles are omnipresent structural motifs in various natural products, pharmaceuticals and agrochemicals. This work describes a photocatalytic Minisci-type C-H functionalization of heteroarenes with non-activated alkyl bromides. The reaction avoids stoichiometric radical-promoters, oxidants, or acids, and is conducted using blue LEDs as the light source. The reactive carbon-centered alkyl radicals are generated by merging the photoredox approach with bromide anion co-catalysis and spatial pre-aggregation of reacting species in the micellar aqueous solutions. The obtained data highlight the critical importance of microstructuring and organization of the components in the reaction mixture.

Photochemical Nickel-Catalyzed Reductive Migratory Cross-Coupling of Alkyl Bromides with Aryl Bromides.

A novel method to access 1,1-diarylalkanes from readily available, nonactivated alkyl bromides and aryl bromides via visible-light-driven nickel and iridium dual catalysis, wherein diisopropylamine ( iPr2NH) is used as the terminal stoichiometric reductant, is reported. Both primary and secondary alkyl bromides can be successfully transformed into the migratory benzylic arylation products with good selectivity. Additionally, this method showcases tolerance toward a wide array of functional groups and the presence of bases.

Silyl-mediated photoredox-catalyzed Giese reaction: addition of non-activated alkyl bromides.

The emergence of photoredox catalysis has enabled the discovery of mild and efficient conditions for the generation of a variety of radical reaction platforms. Herein is disclosed the development of a conjugate addition reaction of non-activated alkyl bromides to Michael acceptors under visible-light photoredox catalysis. Optimization of the reaction was achieved using high-throughput experimentation (HTE) tools to enable the identification of mild, general and practical reaction conditions. A diverse set of alkyl bromides was successfully added to cyclic or acyclic α,β-unsaturated esters and amides. The features of this transformation allowed also access to a key intermediate of Vorinostat®, an HDAC inhibitor used to fight cancer and HIV.

Stereospecific Cross-Coupling between Alkenylboronates and Alkyl Halides Catalyzed by Iron–Bisphosphine Complexes

A stereospecific and high-yielding cross-coupling reaction between alkenylboron reagents and alkyl halides is described. The reaction has been achieved by using well-defined iron-bisphosphine complexes such as 1b FeCl(2)(3,5-t-Bu(2)-SciOPP), which was recently developed by the authors' group. Various nonactivated alkyl bromides and chlorides possessing a base/nucleophile-sensitive functional group can participate in the cross-coupling, demonstrating its utility for stereoselective synthesis of functional molecules bearing a carbon-carbon double bond.