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

Abstract

Copper-catalyzed asymmetric allylic substitution reactions with organozinc and Grignard reagents Geurts, Koen; Fletcher, Stephen P.; van Zijl, Anthoni W.; Minnaard, Adriaan J.; Feringa, Ben L.; Bignall, H. E.; Jauncey, D. L.; Lovell, J. E. J.; Tzioumis, A. K.; Kedziora-Chudczer, L. L. Abstract: Asymmetric allylic alkylations (AAAs) are among the most powerful C-C bondforming 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 homoallylic 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.

Enantioselective and Enantiospecific Transition-Metal-Catalyzed Cross-Coupling Reactions of Organometallic Reagents To Construct C–C Bonds

“… 257 Subsequent developments have expanded the scope of leaving groups and the degree of enantioinduction to prepare both tertiary and quaternary centers, primarily using Cu catalysts. 4 − 6 , 218 …”

Phosphoramidites: Privileged Ligands in Asymmetric Catalysis

“…Even though enantioselective conjugate additions of Grignard reagents have been studied extensively in the past years, [111,115,[208][209][210][211] there have been few reports on the application of monodentate phosphoramidite ligands for this transformation. In 2005, the ring opening of oxabenzonorbornadienes 100 (Scheme 32) with spiro-phosphoramidite ligands L11 (see Figure 2) and various Grignard reagents was reported.…”

Phosphoramidite: privilegierte Liganden in der asymmetrischen Katalyse

“…Obwohl enantioselektive konjugierte Additionen von Grignard-Reagentien in den vergangenen Jahren eingehend untersucht wurden, [111,115,[208][209][210][211] gibt es nur wenige Arbeiten über die Verwendung einzähniger Phosphoramidit-Liganden in dieser Reaktion. 2005 wurde die Ringöffnung der Oxabenzonorbornadiene 100 (Schema 32) mit den Spirophosphoramidit-Liganden L11 (siehe Abbildung 2) und verschiedenen Grignard-Reagentien beschrieben, die in 54-90 % Ausbeute und mit 42-88 % ee zu den substituierten Dihydronaphtholen 101 führte.…”