Radical Chemistry with Azides

Abstract

Organic azides represent a very interesting class of compounds since they are precursor of a wide range of nitrogen containing organic molecules. 1 Moreover, they possess a unique reactivity pattern orthogonal to many other organic functional groups. This assessment is also true in the fi eld of radical chemistry. For instance, azides can be considered as protected amino groups that are perfectly tolerated in C -C bond forming reactions. This is illustrated by the synthesis of ( − ) -batzelladine D recently disclosed by P.A. Evans. 2 In this synthesis, a pyrrolo[1,2f]pyrimidine is built via a 5exo trig radical cyclization. The two azido substituents present in the molecule are not reduced under the reaction conditions used to run the cyclization (tributyltin hydride and triethylborane in the presence of air at room temperature) (Scheme 8.1 ).The stability of azides in radical reactions is further illustrated by the radical fragmentation of carbohydrate anomeric alkoxyl radicals bearing an azido substituent at position 3 reported by Suarez (Scheme 8.2 ). 3,4 After fragmentation, the 2 -azido -substituted radical is iodinated and no β -fragmentation of the azide is observed.However, under suitable conditions, azides react with a variety of radicals and this is the basis of several useful synthetic procedures for the formation of carbon -nitrogen bonds. For instance, synthesis of azides by radical addition of an azidyl radical to alkenes (Scheme 8.3 a) and by reaction of an alkyl radical with an azidating reagent (Scheme 8.3 b) will be presented. The reduction of azides leading to aminyl radicals (Scheme 8.3 c) and the addition of alkyl radicals to alkyl azides (Scheme 8.3 d) will also be discussed.

Employing exchange reactions involving hypervalent iodine compounds for the direct synthesis of azide-containing linear and branched polymers

“…The azide radical 46,47 is a particularly interesting functional radical because it can initiate the polymerization of vinyl monomers, [48][49][50][51][52] yielding azide-capped polymers, and can serve as a precursor of numerous organic azides, which are attractive because of their ability to undergo a vast range of chemical transformations, [53][54][55][56][57][58] including azide-alkyne ("click") cycloadditions. [59][60][61][62][63][64][65][66][67] Azide radicals can be generated either in homogeneous systems or electrochemically (on the surface of an electrode 68,69 ) via oxidation of azide anions.…”

Two-Step Azidoalkenylation of Terminal Alkenes Using Iodomethyl Sulfones

“…For tertiary alkyl azides, the nucleophilic substitution approach is often difficult, and free radical processes have proven to be a very convenient alternative. Radical azidation reactions are run under mild conditions, and they are compatible with a broad range of functional groups [19,20,21]. The carboazidation of alkenes represents a particularly attractive method to transform terminal alkenes into functionalized alkyl azides [22].…”

Radical azidation reactions and their application in the synthesis of alkaloids

“…Tertiary alkyl azides are often difficult to generate via substitution reactions, and free radical processes proved to be particularly efficient for their synthesis [6]. Free radical reactions not only allow the mild introduction of azides, but are also compatible with a large number of functional groups and offer unique possibilities to perform sequential transformations.…”