Copper-Catalyzed Difluoromethylation of Aryl Iodides with (Difluoromethyl)zinc Reagent.

Reactivity of mixed organozinc and mixed organocopper reagents: 14. Phosphine-nickel catalyzed aryl-allyl coupling of (n-butyl)(aryl)zincs. Ligand and substrate control on the group selectivity and regioselectivity

Ethyl 3-bromo-3, 3-difluoropropionate (1) was prepared in an overall yield of 75% from the radical addition of dibromodifluoromethane to ethyl vinyl ether under Na2S2O4 initiation, followed by oxidation of the acetal with Caro acid. The treatment of 1 with active zinc dust in anhydrous DMF at room temperature produced the zinc reagent ZnBrCF2CH2CO2C2H5 (2). The cross coupling of the zinc reagent 2 with aryl (alkenyl) halides (R−X) in DMF using Pd(0)−Cu(I) as cocatalyst stereoselectively provided the β-fluoro-α,β-unsaturated esters (RCFCHCO2C2H5 4) directly and in moderate yields. An E/Z ratio ranging from 3:2 to 1:0 was observed. This is the first example that Cu(I) can improve the selectivity of the cross-coupling reaction. Mechanistic studies revealed that zinc reagent 2 underwent stereoselective elimination to produce (Z)-1-fluoro-2-(ethoxycarbonyl)ethenylzinc reagent 6, and then the cross-coupling of 6 with aryl(alkenyl) halides under palladium(0) catalysis afforded the β-fluoro-α,β-unsaturated esters 4.

The treatment of various allylic chlorides or bromides with zinc dust in the presence of lithium chloride and magnesium pivalate (Mg(OCOtBu)2) in THF affords allylic zinc reagents which, after evaporation of the solvent, produce solid zinc reagents that display excellent thermal stability. These allylic reagents undergo Pd-catalyzed cross-coupling reactions with PEPPSI-IPent, as well as highly regioselective and diastereoselective additions to aryl ketones and aldehydes. Acylation with various acid chlorides regioselectively produces the corresponding homoallylic ketones, with the new C-C bond always being formed on the most hindered carbon of the allylic system.

A novel Zn-mediated preparation of propiolonitriles using electrophilic cyanation of alkynyl bromides with N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) has been achieved here. The zinc dust was firstly used to activate the C(sp)–Br bond in the presence of tetrabutylammonium iodide (TBAI) to form an alkynyl zinc reagent in situ, which would undergo a nucleophilic addition with NCTS at the cyano group to afford an imine. Finally the propiolonitrile product was obtained after the elimination of the zinc complex. According to this new protocol, various phenylpropiolonitriles have been prepared from alkynyl bromides in moderate to excellent yields (51–95%), and could also be generated from the combination of inactive alkynyl chlorides with tetrabutylammonium bromide (TBAB) in lower yields (23–70%).

The palladium-catalyzed Negishi cross-coupling reaction of aryl iodides and bromides with (difluoromethyl)zinc reagent bearing a diamine such as TMEDA is achieved to provide the difluoromethylated aromatic compounds in good to excellent yields. The advantages of (difluoromethyl)zinc reagent are that (1) the derivatives, which possess different stability and reactivity, can be readily prepared via ligand screening and (2) transmetalation of a difluoromethyl group from the zinc reagent to palladium catalyst efficiently proceeds without an activator.

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A novel procedure for the preparation of zinc reagents: a practical synthesis of (+)-biotin

Pincer thioamide Pd(II) complex 2 was prepared, and its reaction with cyclohexylzinc chloride yielded novel pincer thioimide Pd(II) complex 3 besides Pd(0) species. The structures of complexes 2 and 3 were confirmed by X-ray analysis. Both complexes are efficient catalysts for Negishi couplings involving primary and secondary alkyl zinc reagents bearing beta-hydrogen atoms. At a concentration of 0.1-0.5 mol % both catalysts readily promoted reactions at room temperature or even at 0 degrees C. The operational simplicity of these processes, in conjunction with the easy accessibility of both catalysts and substrates, promises synthetic utility of this new methodology. An experiment on a scale of 19.35 g carried out at very low catalyst loading of 2 (turnover number: 6,100,000) highlighted the potential application of the catalytic system. Monoalkyl and dialkyl zinc reagents displayed different reactivities and selectivities in reactions with aryl iodides catalyzed by complexes 2 or 3, and isomerization in reactions involving acyclic secondary alkyl zinc derivatives was suppressed by using appropriate amounts of dialkyl zinc reagents. Based on preliminary kinetic profiles and reaction evidence, three possible pathways are proposed for the reactions involving acyclic secondary alkyl zinc reagents to rationalize the difference between mono-alkyl and dialkyl zinc derivatives.

The preparation of HCF 2CdX and HCF 2ZnX via direct insertion into the carbon halogen bond of CF 2HY (Y = Br, I)

Catalytic asymmetric cross-coupling

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Fluorinated stannanes: Part 1. The stereospecific synthesis of fluorinated stannanes via a novel transmetalation of fluorinated zinc and cadmium reagents

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The stereospecific preparation of fluorinated vinyl zinc reagents from polyfluorinated vinyl iodides or bromides and zinc metal

Group selectivity in the allylation of mixed (n‐butyl)(phenyl)zinc reagent can be controlled by changing reaction parameters. CuCN‐catalyzed allylation in tetrahydrofuran (THF)–hexamethylphosphoric triamide is n‐butyl selective and also γ‐selective in the presence of MgCl2, whereas CuI‐catalyzed allylation in THF in the presence of n‐Bu3P takes place with a n‐butyl transfer:phenyl transfer ratio of 23:77 and an α:γ transfer ratio of phenyl of 76:24. NiCl2(Ph3P)2‐catalyzed allylation in the presence of LiCl is phenyl selective with an α:γ ratio of 65:35. The reaction of methyl‐ or n‐butyl(aryl)zinc reagents with an allylic electrophile in THF at room temperature in the presence of NiCl2(Ph3P)2 catalyst and LiCl as an additive provides an atom‐economic alternative to aryl–allyl coupling using diarylzincs. Copyright © 2014 John Wiley & Sons, Ltd.