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

Abstract

Abstractβ-Hydrogen-containing alkyl Grignard reagents were used in a stereospecific nickel-catalyzed cross-coupling reaction to form sp 3 -sp 3 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.

Well-defined nickel and palladium precatalysts for cross-coupling

“…The [(dppe)NiCl 2 ] precatalyst has also been extensively used in Kumada couplings. Jarvo and co-workers reported the alkylation of secondary ethers 127 and the ring opening of oxygen-containing heterocycles with alkyl Grignard reagents 128 . The alkylation of allylic alcohols and ethers has also been reported with methylmagnesium iodide and [(dppe)NiCl 2 ] as a precatalyst 129,130 .…”

Enantiospecific sp2–sp3 coupling of secondary and tertiary boronic esters

“…[20][21][22] and the stereospecific cross-coupling of chiral secondary benzylethers. 23,24 Our alternative strategy has centred on utilizing the readily accessible, stereo-defined, secondary boronic esters. We reasoned that addition of an electron rich aryl lithium reagent (e.g.…”

Palladium‐Catalyzed Asymmetric Benzylic Alkylation of Active Methylene Compounds with α‐Naphthylbenzyl Carbonates and Pivalates

“…[1] In contrast, the asymmetric benzylic alkylation with benzylic electrophiles via p-benzylpalladium intermediates has been less developed despite its isoelectronic character to the p-allylpalladium. [5] The groups of Jarvo [6] and Watson [7] independently developed the nickel-catalyzed, condition-controlled enantiodivergent cross-coupling of secondary benzyl alcohol derivatives,b ut enantioenriched starting substrates are still required for the synthesis of optically active coupling products.O nly limited successful examples include the nickel-catalyzed DY KATof the secondary benzylic (pseudo)halides with organozinc reagents via radical intermediates,w hich is reported by Fu. Fiaud, Legros,and co-workers reported the seminal work on the palladium-catalyzed asymmetric nucleophilic substitution of racemic 1-(2-naphthyl)ethyl acetate with malonate anions.…”

“…However,t he yield and enantiomeric ratio were moderate, and ap artial kinetic resolution was finally proposed. [5] The groups of Jarvo [6] and Watson [7] independently developed the nickel-catalyzed, condition-controlled enantiodivergent cross-coupling of secondary benzyl alcohol derivatives,b ut enantioenriched starting substrates are still required for the synthesis of optically active coupling products.O nly limited successful examples include the nickel-catalyzed DY KATof the secondary benzylic (pseudo)halides with organozinc reagents via radical intermediates,w hich is reported by Fu. [8] Thus,f urther development of DY KATw ith racemic benzyl electrophiles is strongly desired.…”