The presence of LiCl considerably facilitates the insertion of magnesium into various aromatic and heterocyclic bromides. Several functional groups, such as -OBoc, -OTs, -Cl, -F, -CF(3), -OMe, -NMe(2), and -N(2)NR(2), are well tolerated. The presence of a cyano group leads in some cases to competitive reduction of the organic halide to the corresponding ArH compound. The presence of sensitive groups such as methyl or ethyl ester is tolerated upon in situ trapping of the intermediate magnesium reagent with ZnCl(2). This method can also be applied to the preparation of functionalized benzylic zinc reagents from benzylic chlorides. In the case of di- or tribromoaryl derivatives, directing groups such as -OPiv, -OTs, -N(2)NR(2), or -OAc orient the zinc insertion (Zn/LiCl) to the ortho-position, while the reaction with Mg/LiCl or Mg/LiCl/ZnCl(2) leads to regioselective insertion into the para-carbon-bromine bond. Large-scale experiments (20-100 mmol) for all of the metalation procedures are described.

In the presence of zinc dust (1.5-2.0 equiv) and LiCl (1.5-2.0 equiv), various benzylic chlorides bearing functional groups (iodide, cyanide, ester, ketone) are smoothly converted at 25 degrees C to the corresponding zinc reagents without homo-coupling (<5%). The utility of these benzylic zinc reagents is demonstrated by a short synthesis of papaverine.

[reaction: see text] Organocopper compounds prepared by the transmetalation of functionalized arylmagnesium halides with CuCN.2LiCl undergo smooth cross-coupling reactions with aryl fluorides and tosylates bearing a carbonyl function in the ortho position in the presence of Co(acac)(2) (7.5 mol %), Bu(4)NI (1 equiv), and 4-fluorostyrene (20 mol %) as promoters in DME/THF/DMPU leading to polyfunctional aromatics or heterocycles.

A wide range of polyfunctional aryl, heteroaryl, alkyl, and benzylic zinc reagents were coupled with unsaturated halides bearing an acidic NH or OH function, using Pd(OAc)(2) (1 mol %) and S-Phos (2 mol %) as catalyst without the need of protecting groups.

Organic iodides bearing a cationic quaternary ammonium group at a remote position react with zerovalent Pd complexes, Zn, or In leading to a C-I bond insertion. The resulting charge-tagged organometallics can be detected by electrospray-ionization mass spectrometry, which provides detailed information on their stoichiometry, oxidation state, and coordination sphere. The properties of the observed organopalladium and -zinc intermediates largely agree with previous findings, whereas the organoindium species show a surprisingly high tendency to form ate complexes. Magnesium also undergoes insertion into the C-I bond of the charge-tagged organic iodides, but instead of the expected organomagnesium intermediates only the corresponding hydrolysis products could be detected in the diluted solutions. Electrospray-ionization mass spectrometry can also be used to study the reactivity of the charge-tagged species, as was demonstrated for a Pd-catalyzed Negishi cross-coupling reaction. The presented approach permits a straightforward identification of the rate-limiting step and the determination of the corresponding second-order rate constant.