Reductive cross-electrophile coupling reactions have recently been developed to a versatile and sustainable synthetic tool for selective C-C bond formation. The employment of cheap and abundant electrophiles avoids the pre-formation and handling of organometallic reagents. In situ reductive coupling is effected in the presence of a transition-metal catalyst (Ni, Co, Pd, Fe) and a suitable metallic reductant (Mn, Zn, Mg). This Concept article assesses the current state of the art and summarizes recent protocols with various combinations of alkyl, alkenyl, allyl, and aryl reagents and highlights key mechanistic studies.

Stable C-O linkages are generally unreactive in cross-coupling reactions which mostly employ more electrophilic halides or activated esters (triflates, tosylates). Acetates are cheap and easily accessible electrophiles but have not been used in cross-couplings because the strong C-O bond and high propensity to engage in unwanted acetylation and deprotonation. Reported herein is a selective iron-catalyzed cross-coupling of diverse alkenyl acetates, and it operates under mild reaction conditions (0 °C, 2 h) with a ligand-free catalyst (1-2 mol%).

An operationally simple iron-catalyzed hydrodehalogenation of aryl halides has been developed with 1 mol% Fe(acac)(3) and commercial t-BuMgCl as reductant. The mild reaction conditions (THF, 0 degrees C, 1.5 h) effect rapid chemoselective dehalogenation of (hetero)aryl halides (I, Br, Cl) and tolerate F, Cl, OR, SR, CN, CO(2)R, and vinyl groups.

A new methodology for the direct cross-coupling reaction between aryl halides and alkyl halides under iron catalysis is described. Unlike conventional protocols, the direct cross-coupling obviates the need for the preformation of stoichiometric amounts of Grignard species and thus exhibits a reduced hazard potential. The underlying one-pot reaction involves iron-catalyzed Grignard formation followed by a rapid cross-coupling step. Mechanistic data on the role of N,N,N',N'-tetramethylethylenediamine (TMEDA) as additive, the concentration of intermediates, and the nature of the catalyst species are discussed.

Dedicated to Professor Manfred Scheer on the occasion of his 60th birthday.Abstract: Stable CÀOl inkages are generally unreactive in cross-coupling reactions which mostly employm ore electrophilic halides or activated esters (triflates,t osylates). Acetates are cheapand easily accessible electrophiles but have not been used in cross-couplings because the strong C À Obond and high propensity to engage in unwanted acetylation and deprotonation. Reported herein is as elective iron-catalyzed crosscoupling of diverse alkenyl acetates,a nd it operates under mild reaction conditions (0 8 8C, 2h)w ith al igand-free catalyst (1-2 mol %).The recent developments of selective iron-catalyzed crosscoupling reactions rival their conventional palladium-and nickel-catalyzed counterparts in terms of reactivity and scope while displaying higher sustainability and operational simplicity.[1] However,t he use of non-activated halide-free electrophiles remains at rue challenge for all cross-coupling methods (Scheme 1).[2] Oxygen-based electrophiles are especially attractive starting materials because of their ubiquitous occurrence in biomass-derived chemicals and facile preparation from alcohols or carbonyl compounds.H owever,t he general stability of CÀObonds has limited the scope of most cross-coupling methods to activated esters (triflate,t osylate or in benzyl/allyl position). There are very few nickel-or rhodium-catalyzed protocols which employ non-activated ester derivatives at elevated temperatures.[3]Iron-catalyzed cross-coupling was reported with alkenyl pivalates and aryl carbamates/sulfamates (Scheme 2) where the undesired carbonyl/sulfonyl attack is suppressed by steric shielding (tert-butyl) or electronic deactivation (OR, NR 2 ). [4] To the best of our knowledge,t here are no reports of ironcatalyzed cross-coupling reactions of simple unbiased esters. Among them, organic acetates are an especially attractive class of cheap,halide-free CÀOelectrophiles bearing asmall, nonhazardous leaving group,a nd is easily accessible by various acetylation protocols.[5] However,t he considerable electrophilicity and acidity (pK a 24), and low bond dissociation energy of the acetyl À Ob ond appear to prohibit, on thermodynamic grounds,t he use of acetates in coupling reactions with highly basic/nucleophilic organometallic reagents.C onsistently,a ll known cross-coupling protocols involve mild organoboron/zinc species.[3] Thus,iron-catalyzed cross-couplings between organic acetates and Grignard reagents requires an especially active catalyst which operates under kinetic control where the competing deprotonation and acetylation pathways are suppressed. We envisioned capitalizing on the combination of a) al igand-free,l ow-valent iron catalyst which favors rapid oxidative addition of the nonactivated electrophile,b )Grignard reagents as good nucleophiles which exhibit rapid transmetalation, and c) low temperatures/short reaction times to achieve selective crosscoupling of alkenyl acetates.Similar reaction conditions have been reported for t...