Negishi Cross-Coupling of Substrates Bearing Relatively Acidic Protons

Abstract

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.