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.

A wide range of polyfunctional aryl, heteroaryl, alkyl, and benzylic zinc reagents were coupled with unsaturated aryl halides bearing an acidic NH or OH proton, using Pd(OAc)2 (1 mol %) and S-Phos (2 mol %) as catalyst without the need of protecting groups. A similar nickel-catalyzed reaction is described. The relative kinetic basicity of organozinc compounds as well as their stability toward acidic protons is also described.

Significance: Alkyl-or arylzinc halides are believed to be incompatible with the presence of acidic protons like free OH or NH 2 groups. However, in many cases the rate of their protonation allows performing the Negishi cross-coupling even in the presence of such acidic groups. The organozinc compounds are readily available directly from the corresponding halides. This method allows a simple one-pot reaction leading to a new C-C bond formation.Comment: The rate of the protonation of organozinc species decreases in the row aryl > alkyl > benzyl. Benzylzinc is quenched by aniline at 25 °C only within several hours. In most of the reactions, Pd(OAc) 2 /S-Phos catalytic system was used. However, cheaper Ni(II)/Ph 3 P is almost equally useful, at least for the coupling of aryl-and benzylic zinc halides. Slow addition of the zinc reagent with a syringe pump is always advantageous in this reaction.

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2008 C-C bond formation O 0282 Negishi Cross-Couplings of Unsaturated Halides Bearing Relatively Acidic Hydrogen Atoms with Organozinc Reagents. -The Pd-catalyzed cross coupling of organozinc reagents (I) with aromatic halides bearing unprotected acidic NH or OH groups (II) is smoothly achieved in the presence of S-Phos ligand. -(MANOLIKAKES, G.; SCHADE, M. A.; MUNOZ HERNANDEZ, C.; MAYR, H.; KNOCHEL*, P.; Org. Lett. 10 (2008) 13, 2765-2768; Fachbereich Chem. Biochem.,