Azides by Olefin Hydroazidation Reactions

Organic Azides Syntheses and Applications Edited by Stefan Erase and Klaus Banert e 2010 John Wiley Sons, Ltd. ISBN 978-0-470-51998-1 

In this chapter, we first describe the successful methods for the hydroazidation of a,P-unsaturated carbonyl compounds. The classic approach for the addition of hydrazoic acid and its derivatives onto non-activated double bonds is then examined. In the last section, we present our own work in this area and our progress towards a general method for the hydroazidation of olefins. 

The conjugate addition of hydrazoic acid is of considerable interest, as the azides obtained are easily reduced, for example, to the corresponding jS-amino acid derivatives. The importance of )3-amino acids resides in their special conformational preferences in peptides, and their presence in many natural products and bioactive compounds.  

In 1915, Oliveri-Mandala first reported on the conjugate addition of hydrazoic acid onto a quinone derivative, but the product obtained was an aromatic azide. The first real hydroazidation reaction of electron-deficient double bond was then reported 

In 1999, Jacobsen reported on a catalytic asymmetric conjugated addition of hydrazoic acid to unsaturated imide derivatives (Equation 4.1). This breakthrough was possible through the use of aluminium salen azide complex 1 as catalyst. The reaction proceeded in excellent yields and enantioselectivities for alkyl substituted acceptors. Two mechanisms were proposed for this reaction activation of the azide as an aluminium azide as shown by Chung and co-workers or Lewis acid activation of the imide. The first-order dependence of the rate law on catalyst 1 indicated that dual activation was improbable. In 2005, Jacobsen reported on the extension of this methodology to ,j8-unsaturated ketones. 

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Azides by Olefin Hydroazidation Reactions 103 Table 4.2 The hydroazidation of monosubstituted olefins... 

Azides by Olefin Hydroazidation Reactions 105 Table 4.4 Comparison of TsN (17), azide 49 and azide 50 in the hydroazidation reaction... 

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 structural features of 11b are noteworthy even in the presence of excess amino acid, only the 1 1 complex of 12 and Co was detected by NMR spectroscopy in sharp contrast to complex 4 (Fignre 4.4). This is probably due to the steric bulk of ligand 12 and explains its increased reactivity and lower stability. Unfortunately, we were unable to obtain reproducible results using complex 11b, as yields (40-70%) and reaction time (8 8 h) were batch-dependent. In many cases, an initiation time was observed before the reaction started. Mukaiyama and co-workers used ferf-butyl hydroperoxide as a cobalt-catalyst for the hydration of certain olefins when initiation of the reaction was difficult. A similar effect was observed in the hydroazidation reaction when using catalyst 11 with ethanesulfonyl azide (7) for the hydroazidation of 4-phenylbut-l-ene (3), complete conversion was observed after 2-8 h using 30% of ferf-butyl hydroperoxide. In situ formation of complex 11b in the reaction mixture leads to reproducible reaction times (2h) and yields (70%). Co(BF4)2-6H20 was the best Co salt for this procedure, as complex formation was faster than with other salts and quick oxidation to the Co(III) complex occurred in the presence of tert-butyl hydroperoxide. 

The first successful approach was reported by Heathcock in 1969 using mercury(ll) salts. The reaction proceeds via an olefin azidomercuration followed by a reductive demercuration in the work-up. The azides derived from terminal olefins were obtained in 50-88% yield with good Markovnikov selectivity, while non-terminal olefins gave lower yields (Figure 4.2). An obvious drawback of this procedure is the use of a stoichiometric amount of mercury salts. This procedure also leads to the formation of potentially explosive Hg(N3)2. Nevertheless, this method is unique and reliable for the hydroazidation of monosubstituted non-activated olefins. 

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