Advances in Transition-Metal Mediated Heterocyclic Synthesis

Daniel Sole, Israel Fernandez

• Publisher: Academic Press
• Year: 2018
• Print ISBN: 9780128116517
• eBook ISBN: 9780128116524
• Topic: Physical Sciences
• Subtopic: Organic Chemistry

Advances in Transition-Metal Mediated Heterocyclic Synthesis provides an overview of recent catalytic reactions involving transition metalsto produce heterocyclic compounds. The book is organized according to the type of transformation used to achieve the synthesis of the heterocyclic systems (mainly aza- and oxa-heterocycles). As such, it covers recent applications on the synthesis of heterocycles, also describing the details of the novel transformations in a didactic manner to motivate readers in search of new catalytic processes. The editors have included state-of-the-art strategies, including transition-metal reactions involving unsaturated systems (reactions of allenes, new gold(I)-catalyzed reactions, and Prins reaction).Chapters highlight the versatility of organopalladium chemistry dealing with carbonylative transformations, C-H activation reactions, coupling processes, and the control of the ambiphilic character of organopalladium species. Finally, the book discusses new reactions leading to heterocycles based on C-H activation processes catalyzed by other metals (Rh, Ru, Co).Written by an outstanding team of authors who are leading experts in organometallic chemistry and organic synthesis, this book is a valuable resource not only for chemists mainly focused on synthesis, but also for those interested in reaction mechanisms involving transition metals.- Helpfully organized by transformation type to stimulate the search for new synthetic processes- Completely illustrated and written by global experts- Includes thoughtfully selected strategies chosen by the editors to exemplify the state-of-the-art of the subject, including transition-metal reactions involving unsaturated systems, organopalladium chemistry, and metal-catalyzed C-H activation

Chapter 1

Metal-Mediated Synthesis of Nonaromatic Oxacycles From Allenols

Benito Alcaide¹, Pedro Almendros² and Teresa Martínez del Campo¹, ¹Universidad Complutense de Madrid, Madrid, Spain, ²Instituto de Química Orgánica General-CSIC, Madrid, Spain

Abstract

The allene moiety represents an excellent building block for metal-mediated cyclization reactions, affording heterocyclic skeletons in a single step. The aim of this chapter is to present regiocontrolled metal-mediated preparations of nonaromatic oxacycles starting from allenols through intramolecular reactions. This chapter summarizes recent applications toward the synthesis of oxacycles taking into account the nature of the metal catalyst. This manuscript provides a personal overview on some of the topics that, from our viewpoint, are the most relevant.

Keywords

Allenols; gold; silver; platinum; cyclization; palladium; oxacycles

1.1 Introduction

Nonaromatic oxacycles are ubiquitous structural units that are extensively encountered in a number of biologically active natural products and functional molecules, and therefore their stereocontrolled synthesis remains an intensive research area.^1–7 Transition-metal catalyzed nucleophile addition to allenes is a very powerful tool for the synthesis of functionalized molecules containing heteroatoms in an atom efficient manner.^8–13 The reaction on allenic systems has an added value as the regiochemistry can be controlled by using different metals or by changing the substituents or the length of the chain between the allene and the heteroatom in the intramolecular case. The mechanisms for the cyclization of allenols in the presence of transition metal complexes are summarized in Scheme 1.1. The metal can coordinate to one or the other double bonds of the allene in a Z2-coordination mode, promoting the exo- or endo-attack to the terminal or internal carbon atoms to form different-sized heterocycles. Five- and six-membered rings are often preferred, but larger rings have been obtained by modulating the substitution in the starting material and the metal employed. The purpose of this chapter is to highlight the metal-mediated processes leading to the formation of at least one C–O bond through an intramolecular reaction with an allenyl unit to obtain nonaromatic oxacycles. This chapter has been organized taking into account the nature of the metal catalyst.

Scheme 1.1 Possible paths for the metal-catalyzed cyclization of allenols.

1.2 Silver-Catalyzed Reactions

Olsson and Claesson reported in 1979 the first reaction of α-allenols in the presence of catalytic amounts of silver salts to give dihydrofurans¹⁴ (Scheme 1.2).

Scheme 1.2 First reported silver-catalyzed reaction of α-allenols.

Silver nitrate has been the salt of choice in many transformations of α-allenols, but stoichiometric amounts have to be used in some challenging cases. Alcaide, Almendros, et al. reported the synthesis of spirocyclic dihydrofuran derivatives in the presence of 1 equivalent of AgNO₃^15,16 (Scheme 1.3).

Scheme 1.3 Stoichiometric silver-promoted formation of spirocyclic dihydrofurans.

The catalytic version of this reaction has been carried out by Marshall et al.^17–19 They reported that the reaction with enantioenriched α-allenols with AgNO₃ (20 mol%) led to stereospecific cyclization to the corresponding dihydrofurans, with a presumed attack on the allenic double bond syn to the side chain containing the OH group (Scheme 1.4).

Scheme 1.4 AgNO₃-catalyzed cyclization of enantioenriched α-allenols.

The reaction also seems to be chemoselective. Ma et al. reported that bis-allyl substituted α-allenols can be converted to the 2,5-dihydrofuran derivatives by the attack of the oxygen atom onto the allene, without the involvement of the extra double bonds in the reaction²⁰ (Scheme 1.5).

Scheme 1.5 Preferred mode of cyclization of dienyl α-allenols: allene versus alkene attack.

However, Lee et al. found that when an alkyne is present, the silver salt tends to be more alkynophilic than allenophilic, and nucleophilic attack of the alcohol occurs onto the activated triple bond to give substituted furans²¹ (Scheme 1.6).

Scheme 1.6 Preferred mode of cyclization of alkynyl α-allenols: alkyne versus allene.

The regioselectivity of the reaction has been studied by Marshall and Aurrecoechea with α,α′-allendiols and Krause with bis(α-alle...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Foreword
• Chapter 1. Metal-Mediated Synthesis of Nonaromatic Oxacycles From Allenols
• Chapter 2. Intramolecular Diamination of Alkenes
• Chapter 3. Synthesis of Heterocycles by Palladium-Catalyzed Carbonylative Reactions
• Chapter 4. Synthesis of Heterocyclic Compounds Based on Transition-Metal-Catalyzed Carbene Coupling Reactions
• Chapter 5. Synthesis of Heterocycles With Iron Salts as Sustainable Metal Catalysts
• Chapter 6. Allene Aziridination as a Tool for the Synthesis of Complex Amines
• Chapter 7. Zinc-Mediated Synthesis of Heterocycles
• Chapter 8. Controlling Selectivities in Palladium-Catalyzed Cyclization Reactions Leading to Heterocycles: From Ambiphilic Reactions of Arylpalladium Species to Carbene Insertions
• Index