Synthesis of solid 2-pyridylzinc reagents and their application in Negishi reactions.

In search of alternatives to unstable or unreliable 2-pyridylboron reagents, we have explored two new varieties of solid, moderately air-stable 2-pyridylzinc reagents. Both reagents can be manipulated in air and are competent nucleophiles in Negishi cross-coupling reactions.

Preparation of functionalized organoindium reagents by means of magnesium insertion into organic halides in the presence of InCl3 at room temperature.

Magnesium, indium, palladium: An efficient one-pot procedure for the direct preparation of triorganoindium reagents from organic halides by means of magnesium insertion in the presence of InCl(3) and LiCl is reported (see scheme). The organoindium reagents are obtained in good yields from functionalized aryl, heteroaryl, and alkyl bromides and benzyl chlorides at 25 °C in THF within 4 h. Moreover, the resulting organoindium reagents could be efficiently used as reagents in Pd-catalyzed cross-coupling reactions with a wide functional group tolerance.

Cyclohexylcarbonitriles: diastereoselective arylations with TMPZnCl·LiCl.

Deprotonating substituted cyclohexanecarbonitriles with TMPZnCl·LiCl affords zincated nitriles that diastereoselectively couple with aryl bromides in the presence of catalytic Pd(OAc)(2) and S-Phos. Steric and electronic effects influence the diastereoselectivity; 4-t-butyl-, 4-TBSO-, and 2-Me-cyclohexanecarbonitriles exert virtually complete diastereocontrol whereas modest diastereoselectivity is observed with 4-i-Pr-, 4-Me-, and 3-Me-cyclohexanecarbonitriles. The unusual diastereoselectivity trends should prove useful for synthesizing substituted cyclohexanecarbonitrile-containing pharmaceuticals.

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents.

In this review we summarize the most important procedures for the preparation of functionalized organzinc and organomagnesium reagents. In addition, new methods for the preparation of polyfunctional aryl- and heteroaryl zinc- and magnesium compounds, as well as new Pd-catalyzed cross-coupling reactions, are reported herein. Experimental details are given for the most important reactions in the Supporting Information File 1 of this article.

Pd-catalyzed α-arylation of nitriles and esters and γ-arylation of unsaturated nitriles with TMPZnCl·LiCl.

Using TMPZnCl·LiCl as a kinetically highly active base, nitriles and esters undergo a Pd-catalyzed α-arylation under mild conditions. Remarkably, in the case of α,β- or β,γ-unsaturated nitriles, a regioselective γ-arylation or a γ-alkenylation is observed.

Reactions of nitroheteroarenes with carbanions: bridging aromatic, heteroaromatic, and vinylic electrophilicity.

The relative rate constants for the vicarious nucleophilic substitution (VNS) of the anion of chloromethyl phenyl sulfone (1-) with a variety of nitroheteroarenes, for example, nitropyridines, nitropyrroles, nitroimidazoles, 2-nitrothiophene, and 4-nitropyrazole, have been determined by competition experiments. It was shown that nitropyridines are approximately four orders of magnitude more reactive than nitrobenzene. Among the five-membered heterocycles 2-nitrothiophene is the most active followed by nitroimidazoles and 4-nitropyrazole.