Palladium-catalyzed cross-coupling reaction of phenyl fluoroalkanesulfonates with organometallics

The palladium-catalyzed cross-coupling reaction of phenyl fluoroalkanesulfonates with organozinc, organotin and organoaluminum reagents in the presence of lithium chloride takes place to afford alkylbenzenes in good yields. However, the coupling reaction with organolithium and Grignard reagents proceeds unsatisfactorily with poor regioselectivity. On the basis of the isolation of an oxidative addition product of phenyl fluoroalkanesulfonate to palladium, a catalytic cycle in the reaction is suggested.     

Oxidative addition of heteroaromatic halides to Negishi reagent and subsequent cross-coupling reactions

Heteroarylzirconocene halides were prepared via the oxidative addition of heteroaryl halides to the Negishi reagent ‘Cp₂ZrBu₂’. The palladium-catalyzed cross-coupling of the in situ generated organozirconium reagents with functionalized aryl and heteroaryl halides proceeded smoothly in the presence of CuCl to produce the cross-coupling products in high yields.     

An unprecedented iron-catalyzed cross-coupling of primary and secondary alkyl Grignard reagents with non-activated aryl chlorides

The use of N-heterocyclic carbene ligands in the iron-catalyzed cross-coupling of alkyl Grignards has allowed, for the first time, coupling of non-activated, electron rich aryl chlorides. Surprisingly, the tetrahydrate of FeCl₂ was found to be a better pre-catalyst than anhydrous FeCl₂. Primary Grignard reagents coupled in excellent yields while secondary Grignard reagents coupled in modest yields. The use of acyclic secondary Grignard reagents resulted in the formation of isomers in addition to the desired product. These isomeric products were formed via reversible β-hydrogen elimination, indicating that the cross-coupling proceeds through an ionic pathway.     

Enantioselective nickel-catalyzed cross-coupling reactions of trialkynylindium reagents with racemic secondary benzyl bromides

The first enantioselective sp-sp3 cross-coupling reaction between alkynyl organometals and racemic benzyl bromides is reported. The coupling is performed at room temperature by using NiBr2diglyme and (S)-(iPr)-Pybox as the catalytic system and trialkynylindium reagents as nucleophiles. The reaction is stereoconvergent, both enantiomers of the racemic benzyl bromide are converted into one enantiomer of the product, and stereospecific. The reaction takes place efficiently in good yields and with high atom economy, as the triorganoindium reagents transfer the three organic groups attached to indium (only 40 mol % of R3In is used).     

Ni- or Cu-catalyzed cross-coupling reaction of alkyl fluorides with Grignard reagents

n-Octyl fluoride underwent a cross-coupling reaction with n-propylmagnesium bromide in the presence of 1,3-butadiene using NiCl2 as a catalyst at room temperature to give undecane in moderate yields. This alkyl-alkyl cross-coupling proceeded more efficiently when CuCl2 was employed instead of NiCl2. Addition of 1,3-butadiene dramatically improved the yields of the coupling products from primary alkyl Grignard reagents in both Ni- and Cu-catalyzed reactions. Alkyl fluorides efficiently reacted with tertiary alkyl and phenyl Grignard reagents using CuCl2 in the absence of 1,3-butadiene to afford the coupling products in high yields. The competitive reaction of a mixture of alkyl halides (R-X; X = F, Cl, Br) with nC5H11MgBr showed that the reactivities of the halides increase in the order R-Cl < R-F < R-Br. In contrast, in the Cu-catalyzed reaction with PhMgBr, the reactivities increase in the order R-Cl < R-Br < R-F.     

Palladium-catalyzed aryl-aryl cross-coupling reaction using ortho-substituted arylindium reagents

A range of biaryl compounds (aryl-aryl, aryl-heteroaryl, and heteroaryl-heteroaryl) can be efficiently prepared by a palladium-catalyzed cross-coupling reaction between ortho-substituted triarylindium reagents and aryl halides. The triarylindium reagents are prepared by directed ortho-lithiation and transmetallation to indium from the corresponding benzene derivatives using various directed metallation groups (DMGs). The reaction proceeds smoothly in high yields and short reaction times with high atom economy (the three aryl groups attached to indium are efficiently transferred).     

Silver-catalyzed cross-coupling reactions of alkyl bromides with alkyl or aryl Grignard reagents

Treatment of secondary or tertiary alkyl bromides with alkyl Grignard reagents in the presence of catalytic amounts of silver bromide and potassium fluoride in CH₂Cl₂ afforded the corresponding cross-coupling products in reasonable yields. Moreover, silver showed catalytic activity for the cross-coupling reactions of alkyl bromides with aryl Grignard reagents.     

Iron-catalyzed cross-coupling of imidoyl chlorides with Grignard reagents

[reaction: see text] A general, high yielding rapid iron-catalyzed cross-coupling reaction between Grignard reagents and imidoyl chlorides is described. These reactions are typically completed within 5 min, resulting in high yields of 71-96% using 5% iron catalyst in a THF-NMP solvent mixture. Functionalized imidoyl chlorides (e.g., R = CO(2)Me) gave excellent yields (89%).     

Manganese-catalyzed cross-coupling reaction between aryl Grignard reagents and alkenyl halides

Aryl Grignard reagents react stereospecifically with alkenyl halides in the presence of manganese chloride (10%) to afford good yields of cross-coupling products.     

Unprecedented palladium-catalyzed cross-coupling reaction of alpha-bromo sulfoxides with boronic acids

[reaction: see text] A new Suzuki-type palladium-catalyzed reaction of boronic acids with alpha-bromo sulfoxides has been developed using a protocol similar to the well-documented reaction of boronic acids with aryl halides. Both cross-coupling and homocoupling processes were observed. The best yields in cross-coupling products were obtained when the presence of oxygen was carefully excluded using degassed solvents. The oxidative addition palladium complex intermediate could be isolated and characterized by X-ray single-crystal diffraction.     

Novel cross-coupling reactions between organotellurides and Grignard reagents employing a MnCl2/CuI catalytic system

We present a general protocol for the cross-coupling reaction of Grignard reagents and organic tellurides. Aryl Grignard reagents react stereospecifically with vinyl tellurides in the presence of a catalytic amount of manganese (II) chloride and copper (I) iodide to produce good yields of the corresponding cross-coupling products.     

Iron-catalyzed aryl-aryl cross-coupling reaction tolerating amides and unprotected quinolinones

The iron(III)-catalyzed cross-coupling reaction between functionalized arylcopper reagents and aromatic iodides bearing an amide function or an unprotected quinolinone leads smoothly to polyfunctionalized biphenyls in excellent yields due to an intramolecular chelating effect of the amide group.     

Nickel-mediated decarbonylative cross-coupling of phthalimides with in situ generated diorganozinc reagents

The nickel-mediated cross-coupling of phthalimides with diorganozinc reagents proceeds via a decarbonylative process to produce ortho-substituted benzamides in high yields. In addition to tolerating diverse phthalimide functionality, including alkyl, aryl, and heteroatom containing substituents, this methodology proceeds smoothly with diorganozinc reagents prepared from aryl bromides and utilized without purification.     

Palladium-catalyzed cross-coupling of benzylzinc reagents with 2-bromo-3,3,3-trifluoropropene

α-Trifluoromethyl alkenes can be used as peptide isosteres, moreover, the pre-installed vinyl group make it possible that transformation to diverse fluorine-containing unities. However, the cross-coupling of benzyl group with α-trifluoromethyl alkenes has yet to be developed. In this report, we describe a general method for the cross-coupling of benzylzinc reagents with 2-bromo-3,3,3-trifluoropropene (BTP) to afford diverse α-trifluoromethylalkene derivatives by using Pd(TFA)₂ as catalyst. This method takes advantage of cheap industrial available fluorine building blocks and easily prepared benzylzinc reagents to generate α-trifluoromethylalkene derivatives, which features with mild reaction conditions, wide substrate scope and feasibility of product transformations.     

One-pot Negishi cross-coupling reactions of in situ generated zinc reagents with aryl chlorides, bromides, and triflates

In situ generated aryl, heteroaryl, alkyl, or benzylic polyfunctional zinc reagents obtained by the addition of zinc and LiCl to the corresponding organic iodides undergo smooth Pd(0)-catalyzed cross-coupling reactions with aryl bromides, chlorides, and triflates in the presence of PEPPSI as a catalyst. This procedure avoids the manipulation of water and air-sensitive organozinc reagents and produces cross-coupling products in high yields.     

A mild Negishi cross-coupling of 2-heterocyclic organozinc reagents and aryl chlorides

A mild Negishi cross-coupling of 2-heterocyclic organozinc reagents and aryl chlorides is described. The use of Pd(2)(dba)(3) and X-Phos as a ligand provides high yields for many examples. An efficient method to generate the organozinc reagents at room temperature is also demonstrated.     

An efficient route to heteroarene-substituted vinyl- and allyl-silanes via palladium-phosphine complex catalyzed cross-coupling

Heteroarene-substituted vinyl- and allyl-silanes were obtained in good yields by the cross-coupling reaction of either heteroaryl Grignard reagents with halovinyl- and haloallyl-silanes or, alternatively, silyl- and silylmethyl-substituted vinylmetallic reagents with heteroaryl halides in the presence of PdCl₂(dppb) as a catalyst.     

Iron-catalyzed cross-coupling reactions between a bicyclic alkenyl triflate and Grignard reagents

Fe-catalyzed cross-coupling reactions between a bicyclic alkenyl triflate and Grignard reagents were investigated. Under the optimized reaction conditions, various 2-substituted bicyclic alkenes were synthesized in moderate to excellent yields (52-93%). This method provided an efficient route for the synthesis of 2-substituted bicyclic alkenes with secondary alkyl groups which cannot be synthesized using previous methods such as Pd-catalyzed coupling reactions and lithium-halide exchange reactions.     

Anti-Markovnikov hydroalkylation of allylic amine derivatives via a palladium-catalyzed reductive cross-coupling reaction

Palladium-catalyzed hydroalkylation of allylic amine derivatives by alkylzinc reagents is reported. This reductive cross-coupling reaction yields anti-Markovnikov products using a variety of allylic amine protecting groups. Preliminary mechanistic studies suggest that a reversible β-hydride elimination/hydride insertion process furnishes the primary Pd-alkyl intermediate, which then undergoes transmetalation followed by reductive elimination to form a new sp(3)-sp(3) carbon-carbon bond.     

Unexpected cross-coupling reaction between o-chloroaryl ketones and organomanganese reagents

Alkyl- and arylmanganese reagents react with o-chloro or o-bromoaryl ketones to give the substituted ketones in high yields. The cross-coupling reaction is performed under mild conditions (-60 to +40 degrees C, 30 min to 4 h) and takes place with excellent chemoselectivity. [reaction: see text]