The Design and Application of Free Radical Chain Reactions in Organic Synthesis. Part 1

Abstract

The successful application of free radical transformations in organic synthesis requires a basic knowledge of elementary radical reactions and an understanding of the principles of free radical chain reactions. Using illustrative examples from the recent literature as a framework, this review provides an introduction to the design and application of free radical reactions for use in organic synthesis. While a few nonchain reactions are discussed, the primary focus is on four of the most important and versatile methods to conduct radical chain reactions. These are: the tin hydride method, the fragmentation method, the thiohydroxamate ester method (the Barton method), and the atom-transfer method. Particular emphasis is placed on the selectivity requirements which must be met for the design of sequences of radical reactions. The review appears in two parts in consecutive issues. Part 1 contains Sections 1 (Introduction) and 2 (The Tin Hydride Method), and Part 2 contains Sections 3 (The Fragmentation Method), 4 (The Thiohydroxamate Ester Method), 5 (The Atom-Transfer Method), and 6 (Non-Chain Methods). Part 1 1.Introduction 1.1.Chain Reactions and Synthetic Planning 2.The Tin Hydride Method 2.1.Intramolecular Cyclizations 2.2.Intermolecular Additions 2.3.Combination Sequences Part 2 3.The Fragmentation Method 4.The Thiohydroxamate Ester Method 5.The Atom-Transfer Method 5.1.Hydrogen Atom Transfer Addition and Cyclization 5.2.Halogen Atom Transfer 5.2.1. Halogen Atom Transfer Addition 5.2.2. Halogen Atom Transfer Cyclization 5.3.3. Halogen Atom Transfer Annulation 5.3.Heteroatom-Halogen Donors 5.4.Organocobalt Group Transfer 6. Non-Chain Methods 7.Summary and Conclusions