Taming the free radical shrew ? learning to control homolytic reactions at higher heteroatoms

Abstract

Free radical chemistry has come a long way in a relatively short period of time. Armed with mechanistic and rate constant data, the synthetic practitioner can now apply free radical chemistry to the synthesis of many different classes of target molecule with confidence. This Feature Article highlights progress made in the understanding and application of free radical reactions at main group higher heteroatoms and demonstrates how this knowledge can be used to construct interesting higher heterocycles, many of which exhibit biological activity, through the use of intramolecular homolytic substitution chemistry.

Radical Cyclizations of Cyclic Ene Sulfonamides Occur with β-Elimination of Sulfonyl Radicals to Form Polycyclic Imines

“…In contrast, homolytic substitutions at sulfur atoms in lower oxidation states (for example, ArSR and ArS(O)R) with carbon, tin and other radicals are common. 32 …”

Intramolecular Homolytic Substitutions in Synthesis

“…As was observed for the chalcogens, rate constants for cyclization at silicon are strongly dependent on the leaving group. Not unexpectedly, increases in rate constant are observed as the leaving radical stability improves: SnMe 3 > GeMe 3 > SiMe 3 . With values of k c in excess of 10 5 s −1 at 80…”

“…3,17,[32][33][34][35] In the case of selenium, the benzyl radical has generally been the leaving group of choice, and its use in selenium chemistry is not complicated by competing 1,n-hydrogen transfer chemistry because the substitution process is some 2 to 3 orders of magnitude faster than that for the similar reaction involving sulfur. 20 However, because of the increased reactivity of the selenium atom toward radicals, that include chain-carrying radicals such as n-tributylstannyl, 2 synthetically useful homolytic chemistry carried out at selenium has utilized the (more reactive) iodide (over the bromide) as radical precursor, or has made use of precursors that do not require chain-carriers.…”

“…One of us contributed to a comprehensive review on homolytic substitution chemistry some 15 years ago, 2 and more recently, presented a feature article, 3 while other reviews have been written on the topic since then. 4,5 The purpose of this article is to provide a practical guide to intramolecular homolytic substitution chemistry, focusing primarily on chemistry developed over the past decade.…”

7-Selenabicyclo[2.2.1]heptane

“…16 With an inherent interest in homolytic substitution reactions involving selenium and their further development, 17 we chose …”