CrossRef enabled

PAC Archives

Archive →

Pure Appl. Chem., 2008, Vol. 80, No. 5, pp. 1025-1037

Copper-catalyzed asymmetric allylic substitution reactions with organozinc and Grignard reagents

Koen Geurts, Stephen P. Fletcher, Anthoni W. van Zijl, Adriaan J. Minnaard and Ben L. Feringa

Department of Organic Chemistry and Molecular Inorganic Chemistry,Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands

Abstract: Asymmetric allylic alkylations (AAAs) are among the most powerful C-C bond-forming reactions. We present a brief overview of copper-catalyzed AAAs with organometallic reagents and discuss our own contributions to this field. Work with zinc reagents and phosphoramidite ligands provided a framework for later developments which employ Grignard reagents and ferrocenyl ligands. High yields and excellent regioselectivities and enantioselectivities are achieved. The AAAs may be more general than previously envisioned, in terms of using substrates functionalized with heteroatoms at various positions; heteroatom substituents at the γ-position provide densely functionalized building blocks. These h-AAA reactions rely on the design of appropriate substrates containing heteroatoms and have allowed us to demonstrate viable new approaches toward the synthesis of versatile organic building blocks. We illustrate that the chiral secondary allylic alcohols, primary homo-allylic alcohols and amines can readily be obtained in high enantiomeric purity in a catalytic asymmetric fashion by copper-catalyzed AAAs. Furthermore, we show that manipulation of the terminal olefin provides chiral building blocks where the ee of the starting materials is preserved.