Carboazidation

Azides are also involved in other procedures in order to obtain the indolizidinone skeleton where the azido group acts only as a precursor of a primary amine group. The radical carboazidation process described in Scheme 9 allowed the easy assembly of the precursor 31 which upon reduction of the azido group afforded the indolizinones 32 in good overall yield <2004JOC2755>. 

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. 

The azide polymers can be divided into the two subclasses the aromatic azides and the acid azides, such as carboazides and sulfoazides. 

In 2(X)5, Renaud and Landais reported the first enantioselective synthesis of hyacinthacine Ai and its epimer at the C-3 position using as a key step a stereocontrolled free-radical carboazidation of a chiral allylsilane XI (Scheme 15) [22]. Tamao-Fleming C—Si bond oxidation and reduction of the azide, with ring-closure achieved the total synthesis. 

Direct introduction of HN3, or its equivalents, onto olefins constitutes an efficient and straightforward approach. Unfortunately, the most efficient reactions are multi-step sequences, such as epoxidation followed by opening with azide ions or hydroboration followed by iodination and snbstitution. Several one-step methods, such as halo-azidation, diazidation, seleno-azidation, nitrato-azidation, ° formation of a-azido ketones," and carboazidation, have also been reported, bnt the conceptually simplest reaction, the hydroazidation reaction, has been much less developed (Figure 4.1). 

The intermolecular addition of carbon-centered radicals to unactivated alkenes followed by azidation (a formal carboazidation of alkenes) has been reported. A one-pot procedure similar to the one used for intramolecular reactions gives good results (Scheme 8.28). Slow addition of benzenesulfonyl azide is not necessary because this electrophilic reagent does not react with the initial electrophilic or ambiphilic radicals. Excellent results are obtained with a-iodo and -xanthate esters. a-Bromoacetates give also satisfactory results. The carboazidation process allows to prepare pyrroUdinone derivatives in a straightforward manner (Scheme 8.28, bottom example). A tin-free version of this reaction using triethylborane instead of hexabutylditin has also been reported. ... 

The carboazidation has been applied in nalnral product synthesis. For instance, lepadi-formine (Scheme 8.29) and hyacinthacine Aj (Scheme 8.30) have been prepared via carboazidation of a methylenecyclohexane derivative and a chiral aUylsilane, respectively (Scheme 8.29 and 8.30). hi this last case, a remarkable diastereoselectivity was observed in the carboazidation process. Both reactions are based on the use of 3-pyridylsulfonyl azide instead of benzenesulfonylazide to facilitate the purification of the intermediate azides. ... 

Sdiar, P. and Renaud, P. (2006) Total synthesis of the marine alkaloid ( )-lepadiformine via a radical carboazidation. Org. Lett., 8,1569-1571. 

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