The Copper-Catalyzed Asymmetric Allylic Substitution

Abstract

This mini-review discusses the rapidly growing field of asymmetric copper-catalyzed chemistry. Although the allylic substitution has been less studied than the conjugate addition, recent breakthroughs have made this methodology a very valuable synthetic tool. Thus, a primary allylic halide or phosphate reacts with Grignard or diorganozinc reagents to afford the S N ' product (or γ-product) in high regio-and enantioselectivities. Besides the results of the authors, we present also other, different approaches to this reaction, with emphasis on the organometallic and the type of chiral ligand used.

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

“…The development of highly enantioselective transition-metal-catalyzed allylic alkylation reactions has enjoyed widespread attention the past decades [1,5,6,8,9]. The palladium-catalyzed substitution reactions using soft nucleophiles are well understood.…”

“…A brief survey of the contributions of several groups to copper-catalyzed AAA reactions, subject of recent reviews [5,6], is presented in Fig. 1.…”

“…Much of our effort has focused on copper-catalyzed additions of hard nucleophiles to electrophiles, especially C-C bond formation using asymmetric 1,4-additions to prochiral α,β-unsaturated carbonyl compounds [1−4]. This paper presents a brief overview of a related transformation -copper-catalyzed asymmetric allylic alkylations (AAAs) with organometallic reagents [1,5,6] followed by a discussion of our own contributions to this emerging field. These powerful reactions have been the subject of extensive studies and allow access to valuable synthons that are often used in the synthesis of complex natural products and molecules of pharmaceutical interest.…”

Copper‐Catalyzed Asymmetric Allylic Alkylation

“…Complementary to it, copper tolerates the use of hard non-stabilized nucleophiles, such as small alkyl groups in the form of organometallic species, including organolithium, magnesium or zinc reagents. [3] One key feature of allylic substitution is controlling the regiochemistry. The displacement of an allylic leaving group can involve two distinct pathways: one resulting from a di-rect attack on the carbon bearing the leaving group at α-position, formally known as S N 2 reaction, and the second γ-substitution, also referred to as S N 2Ј, displaces the leaving group whilst involving an allylic shift of the double bond (Scheme 1).…”

Enyne Chlorides: Substrates for Copper‐Catalyzed Asymmetric Allylic Alkylation

“…[1] Owing to the properties of copper, this transformation allows the use of nonstabilized carbon nucleophiles, namely alkyl or aryl groups in the form of organometallic species. After the pioneering work of van Koten, Bäckvall, and co-workers on copper-catalyzed AAA using Grignard reagents, [2] much attention has focused on this field.…”