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Synfacts 2009(3): 0307-0307  
DOI: 10.1055/s-0028-1087703
Metal-Mediated Synthesis
© Georg Thieme Verlag Stuttgart ˙ New York

Negishi Cross-Coupling of Substrates Bearing Relatively Acidic Protons

Contributor(s):Paul Knochel, Andrei Gavryushin
G. Manolikakes, C. M. Hernandez, M. A. Schade, A. Metzger, P. Knochel*
Ludwig-Maximilians-Universität München, Germany and Universidad de Malaga, Spain
Palladium- and Nickel-Catalyzed Cross-Couplings of Unsaturated Halides Bearing Relatively Acidic Protons with Organozinc Reagents
J. Org. Chem.  2008,  73:  8422-8436  
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Publication History

Publication Date:
19 February 2009 (online)

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Key words

organozinc reagents - cross-coupling - aryl halides

Significance

Alkyl- or arylzinc halides are believed to be incompatible with the presence of acidic protons like free OH or NH2 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 organo-zinc 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)/Ph3P 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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