Progress in Enantioselective Cu(I)-catalyzed Formation of Stereogenic Centers

Table of Contents

1. Frontmatter

2. Asymmetric Allylic Substitutions Using Organometallic Reagents

   Valentín Hornillos, Jean-Baptiste Gualtierotti, Ben L. Feringa

   Abstract

   This chapter summarises recent progress in Cu-catalysed asymmetric allylic alkylation (AAA) with organometallic compounds, including Grignard, organolithium, organoaluminium, organozinc and organozirconium reagents. New reaction conditions and chiral ligands that improve these transformations or allow to overcome previous limitations associated with chemo-, regio- and enantioselectivities will be described. Moreover, a description of new ligands and conditions for the introduction of previously elusive nucleophiles, such as highly reactive organolithium compounds, is included together with a brief mechanistic discussion. Additionally, new challenging substrates which provide densely functionalised building blocks, as well as new synthetic applications that take advantage of the terminal olefin formed in these reactions, will be described.

3. Formation of Quaternary Stereocentres by Copper-Catalysed Enantioselective Conjugate Addition Reaction

   Beatriz Maciá

   Abstract

   Remarkable progress in copper-catalysed enantioselective conjugate addition (ECA) reactions has been made over the past decade. This enantioselective transformation now allows the challenging formation of chiral quaternary centres by addition of different nucleophiles to trisubstituted α,β-unsaturated systems. This chapter summarises the developments in the area.

4. 1,2- Versus 1,4-Asymmetric Addition of Grignard Reagents to Carbonyl Compounds

   Pablo Ortiz, Francesco Lanza, Syuzanna R. Harutyunyan

   Abstract

   The first copper(I)-catalysed conjugate addition of Grignard reagents to α,β-unsaturated carbonyl compounds was reported in 1941. Impressive developments have been made since then, with catalytic asymmetric additions representing the most remarkable achievement. The recent discovery that copper(I) is able to catalyse the asymmetric 1,2-addition of Grignard reagents to α,β-unsaturated, as well as aromatic ketones, was a true revelation. Recent progress in copper(I)-catalysed addition of Grignard reagents is reviewed throughout this chapter, comparing and contrasting the well-established 1,4-selectivity of Cu(I)-ligand complexes with the newly introduced 1,2-selectivity. Mechanistic insights towards the better understanding of the regiodivergence are also discussed.

5. Asymmetric Addition of Boron and Silicon Nucleophiles

   Alexander Hensel, Martin Oestreich

   Abstract

   The recent progress in catalytic asymmetric carbon–boron and carbon–silicon bond formation catalyzed by chiral copper(I) complexes is tremendous. Within less than a decade, the majority of fundamental bond-forming reactions in this arena, that is, conjugate addition, 1,2-addition and allylic substitution, were accomplished. These enantioselective transformations had been either elusive or not even known before. This chapter summarizes these fascinating developments together with a brief mechanistic discussion as these copper(I) catalyses share transmetalation of interelement bonds such as B–B and Si–B as a common feature.

6. Catalytic Asymmetric Addition Reactions of Cu(I)-Conjugated Soft Carbon Nucleophiles

   Xiaofeng Wei, Yohei Shimizu, Motomu Kanai

   Abstract

   Copper is a ubiquitous element on the earth. Copper catalysts promote a wide variety of reaction types by acting as a Lewis acid, a π acid, a Brønsted base, or an electron mediator. These features make copper catalysts particularly attractive in modern organic chemistry. In this review, we discuss examples of recent copper(I)-catalyzed asymmetric C–C bond-forming reactions via the addition of soft copper(I)-conjugated carbon nucleophiles to carbonyl electrophiles. Specifically, we focus on the unique orthogonal reactivity of soft copper(I)-conjugated carbon nucleophiles to hard protic functional groups, which would allow for protecting group-minimized molecular synthesis.

7. Asymmetric Cycloaddition and Cascade Addition–Cyclization Reactions

   Xin Fang, Jia-Wei Zhang, Chun-Jiang Wang

   Abstract

   The copper(I) catalysis has found a wide range of applications in the field of organic chemistry, due to its ability to promote various organic reactions and more notably in enantioselective transformations. Cu(I)-catalyzed asymmetric cycloaddition and cascade addition–cyclization reactions have proven to be one of the most efficient approaches for the stereoselective construction of diverse biologically important heterocycles. In this chapter, we will discuss the recent developments that have been reported in this area since 2010.

8. 1,2- Versus 1,4-Asymmetric Reduction of Ketones

   Andrei V. Malkov, Kurt Lawson

   Abstract

   Reduction of α,β-unsaturated ketones generally can give rise to a variety of products, of which chiral allylic alcohols (1,2-reduction) and saturated ketones (1,4-reduction) are the most useful from the synthetic point of view. With the appropriate substitution pattern these processes generate new stereogenic centres, where copper hydride coordinated to chiral ligand provided useful level of enantioselectivity. Attractiveness of the catalytic systems based on Cu(I) owes it to their high catalytic activity, low cost and ability to employ hydrogen or ubiquitous hydrosilanes as stoichiometric reducing reagents. This overview is focused on the efforts directed at developing and refining practical methods to tackle the issues of regio- and enantioselectivity with a particular focus on selective 1,2- and 1,4-manifolds, it mostly covers research published in 2010–2015 referring to earlier works for maintaining continuity.

9. Backmatter