Radical Azidation

In an early experiment, Abramovitch and Breslow observed the formation of traces of alkyl azides during Curtius-type rearrangement of sulfonyl azides. This formation was rationalized by a direct reaction between alkyl radicals and sulfonyl azides. Roberts examined the reaction of aryl and alkyl sulfonyl azides with allylstarmanes in order to 

Radical Chemistry with Azides 253 PhSOjNa (Bu3Sn)2 O 

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The radical carboazidation of alkenes has been achieved in water using triethylborane as initiator [118]. This efficient process is complete in one hour at room temperature in an open to air reaction vessel (Scheme 54, Eq. 54a). These new tin-free carboazidation conditions are environmentally friendly and allow to run reactions with an excess of either the alkene or the radical precursor. They are also suitable for simple radical azidation of alkyl iodides as well as for more complex cascade reactions involving annulation processes (Eq. 54b). In both reactions (Eq. 54a and 54b), an excess of triethylborane (3 equivalents) is required to obtain a good yield. This may be an indication that the chain process, more precisely the reaction between the phenylsul-fonyl radical and Et3B, is not efficient. 

Azide ions are oxidised at low positive potentials and generate azide radicals. Azide radicals will add to an alkene. Thus the anodic oxidation of enol ethers in... 

Ollivier and Renaud built on his new ditin-mediated radical azidation with benzenesulfonyl azide [125] to introduce tandem intramolecular cyclization-azidation processes [126]. For example, iodoacetal 131 provides the corresponding tertiary azide 132 in high yield as a 3 2 mixture of endolexo diastereoisomers (Scheme 41). The necessify of using ditin reagents still constitutes a drawback in this method, as DLP-mediated tin-free reaction conditions failed due to an inefficient chain process. 

Azidobenziodoxoles can be used as efficient radical azidating reagents toward various organic substrates [251,293]. 

The simplest neutral polynitrogen, the N3 radical (azide radical), has been generated as a fleeting molecule by flash photolysis of HN3 (hydrazoic acid) [1] and by reaction of HN3 with fluorine atoms [2], Being a simple free radical, there appears to be no question of its isolation as a stable substance. 

Nitroxide radical spin labels can be used to measure inter-spin distances by pulsed electron paramagnetic resonance (EPR) spectroscopy, and to allow study of structure and folding of DNA and RNA ohgonucleotides [27-30]. Spin-labeling of nucleobases by (TuAAC in solution has first been demonstrated using the radical azide 4-azido-2,2,6,6-tetramethylpiperidine 1-oxyl (4-azido-TEMPO) [31], Alkyne modifications at position 7 of 7-deazapurines and C5-modified pyrimidines allowed attachment of the spin label in the major groove of duplex DNA [31]. In the same year, click chemistry on solid support to introduce spin labels into DNA was reported [32]. 

Benzylic ethers can also easily have a hydrogen atom abstracted to form a benzylic radical. Through ligand exchange and homolysis, phenyliodine(III) diacetate and TMSN3 generate azide radicals. The azide radical abstracts the benzylic hydrogen atom to form the benzylic radical. Azide abstraction from a molecule of PhI(N3)2 forms the product 16. ... 

Chlorine azide is used for the radical azidation of glycals under UV radiation, whereas an ionic mechanism operates in the dark. As for the NaNs/CAN system, high equatorial selectivity for the azide at C2 is obtained, whereas the selectivity at the anomeric carbon was poorer (Scheme 8.14). 

Scheme 6.30 Decarboxylative radical azidation using PTOC, MPDOC or MMODC esters...

Scheme 6.32 Silver(I)-catalyzed decaiboxylative radical azidation of aliphatic carboxylic acids...

Lapointe G, Kapat A, Weidner K, Renaud P (2012) Radical azidation reactions and their application in the synthesis of alkaloids. Pure Appl Chem 84(7) 1633-1641... 

Nyfeler E, Renaud P (2008) Decarboxylative radical azidation using MPDOC and MMDOC... 

Liu C, Wang X, Li Z, Cui L, Li C (2015) Silver-catalyzed decarboxylative radical azidation of aliphatic carboxylic acids in aqueous solution. J Am Chem Soc 137(31) 9820-9823... 

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