Continuous Synthesis of Organozinc Halides Coupled to Negishi Reactions

Continuous Synthesis of Organozinc Halides Coupled to Negishi Reactions  Article first published online: 20 JUN 2014 DOI: 10.1002/adsc.201400243   Advanced Synthesis & Catalysis Volume 356, Issue 18, pages 3737–3741, December 15, 2014

Nerea Alonso2,3, L. Zane Miller1, Juan de M. Muñoz2, Jesus Alcázar2,* D. Tyler McQuade1,*

1Department of Chemistry and Biochemistry, Florida State University, USA 2Janssen Research and Development, Janssen-Cilag, Toledo, Spain 3Facultad de Química, Universidad de Castilla-La Mancha, Spain   The Negishi cross-coupling is a powerful CC bond forming reaction. The method is less commonly used relative to other cross-coupling methods in part due to lack of availability of organozinc species. While organozinc species can be prepared, problems with reproducibility and handling of these sensitive species can complicate these reactions. Herein, we describe the continuous formation, using an activated packed-bed of metallic zinc, and subsequent use of organozinc halides. We demonstrate that a single column of zinc can provide excellent yields of organozinc halides and that they can be used downstream in subsequent Negishi cross-couplings. The preparation of the zinc column and the scope of the reaction are discussed.

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