Stereospecific Nickel‐Catalyzed Cross‐Coupling Reactions of Alkyl Grignard Reagents and Identification of Selective Anti‐Breast‐Cancer Agents

Abstract

β-Hydrogen-containing alkyl Grignard reagents were used in a stereospecific nickel-catalyzed cross-coupling reaction to form sp3–sp3 carbon–carbon bonds. Aryl Grignard reagents were also utilized to synthesize 1,1-diarylalkanes. Several compounds synthesized by this method exhibited selective inhibition of proliferation of MCF-7 breast cancer cells.

Enantioselective α‐Benzylation of Acyclic Esters Using π‐Extended Electrophiles

“…[6] Although few in number, these remain the most effective Pd-catalyzed benzylic alkylation methods available. [7] Thus far, the use of acyclic ester nucleophiles has not been described despite the clear utility of the products (Figure 1 c). …”

Nickel-Catalyzed Alkylative Cross-Coupling of Anisoles with Grignard Reagents via C–O Bond Activation

“…[2][3][4] The reactivity of Grignard reagents is affected by many factors, including the Lewis basicity and steric properties of the solvent 2-4 as well as external metal salt additives. [9][10][11] Here, we report nickelcatalyzed cross-coupling of anisole derivatives with Grignard reagents, with reactivity being largely dependent on the halogen atom in the Grignard reagent being used. However, the choice of halide is predominantly determined by its reactivity in the halogen-magnesium exchange reaction (R-I > R-Br > R-Cl), 4 and the impact of the halide on the reactivity of Grignard reagents remains underappreciated for most reactions using them.…”

“…For example, simple anisole (17) did not generate the alkylated product at all under the standard conditions. Substrates containing heteroaromatic moieties such as indoles and pyridines (10,11,(22)(23)(24) could also undergo this alkylative cross-coupling. Under these modified conditions, anisole derivatives 17-21 can be alkylated successfully.…”

Novel conformationally constrained pyrazole derivatives as potential anti-cancer agents

“…Indicatively, carbazoles possessing a unique tricyclic ring system have been permitted for the treatment of cancer [5], while phenazines [6] and several piperazines [7] have been found to display IC 50 values in the nanomolar range against quinone reductase inhibitors. Recently, azoaryl sulfides were proved as selective antibreast cancer agents with IC 50 values in the low micromolar range [8,9]. In this respect, pyrazoles that constitute a prominent family among azaheterocycles comprise a class of molecules with a prominent position in the anticancer portfolio as having been evidenced in numerous publications [10].…”