Some aspects of radical cascade and relay reactions

Abstract

The ability to create carbon-carbon bonds is at the heart of organic synthesis. Radical processes are particularly apt at creating such bonds, especially in cascade or relay sequences where more than one bond is formed, allowing for a rapid assembly of complex structures. In the present brief overview, examples taken from the authors' laboratory will serve to illustrate the strategic impact of radical-based approaches on synthetic planning. Transformations involving nitrogen-centred radicals, electron transfer from metallic nickel and the reversible degenerative exchange of xanthates will be presented and discussed. The last method has proved to be a particularly powerful tool for the intermolecular creation of carbon-carbon bonds by radical additions even to unactivated alkenes. Various functional groups can be brought into the same molecule in a convergent manner and made to react together in order to further increase the structural complexity. One important benefit of this chemistry is the so-called RAFT/MADIX technology for the manufacture of block copolymers of almost any desired architecture.

Radical Arene Addition vs Radical Reduction: Why Organometal Hydride Chain Reactions Stop and How To Make Them Go

“…From these findings for stannane synthesis reactions, it is clear that the success of a radical-chain method relies largely on the reagent’s capacity to reduce not just the propagating radicals but also any delocalized radicals from chain-transfer side reactions of the substrate, reagent, solvent, initiator, impurities, and products. The combination of the weak tin hydride bond, strong tin halide bonds, , selective halide abstraction, and (less obviously) weakness of Sn –C bonds has for decades made stannane reduction the go-to method (the blade in the Swiss Army knife) of radical synthesis. − Yet, in spite of its most excellent chain, the Holy Grail for free-radical synthesis has long been to replace the organotin hydride with more benign and scalable radical-chain reagents. The biggest stumbling block in this quest for tin-free solutions − has been the short chain or, judging from initiator requirements (eq ), the absence of chain.…”

“…They are pointedly excluded from the experimental model the presence of olefins, benzophenone (or similar photoinitiators), as well as aromatic substrates and solvents, because these produced “extensive first-order radical termination” or second-order “retardation” in the reaction rate. Somewhat perversely, then, in free-radical synthesis, − stannane reductions are routinely performed with benzene solvent on substrates containing allylic, aromatic, and/or conjugated carbonyl groups, all of which inhibit or retard the chain . Even so, in spite of sluggish reduction rates, it has been tacitly assumed Sn • and R • radicals remain the only major radicals in the reduction mixture.…”

Cathodic electroorganic reaction on silicon oxide dielectric electrode

“…Concerning the experimental evidence of the proposed mechanism, 2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), a renowned known radical capture agent ( 31 , 32 ), was used to capture the neutral charge radical intermediate ( SI Appendix , Fig. S7 ).…”

Iron-Catalyzed Oxyalkylation of Terminal Alkynes with Alkyl Iodides

“…1 Radical relay is a useful strategy that employs a precursor to generate a new radical species, with more general and useful functionalities from readily available chemicals via a relay process. 2 Many efforts have been dedicated to developing methods for new bond formation enabled by radical relay process. 3 To date, two types of radical relay precursors, nonoxidative 4 and oxidative radical relay precursors, 5 have been published.…”