Ethers, a-azido

Addition to alkenes. Hydrazoic acid ados readily to cnol ethers to give a-azido ethers. Addition to styrenes and 1,1 -disubstituted or trisubstituted alkenes requires a Lewis acid catalyst (TiC or AlCl,). Benzylic, allylk. and tertiary alcohols react with HN, TiCl4 to form azides. 

The photoreactions of azides can in most cases be rationalized in terms of the initial formation of nitrenes which then undergo rearrangement, insertion or addition reactions. Nitrene rearrangement is thought to be responsible for the conversion of the a-azido ethers (81) into the imino ethers (82), and the first silanediimine (83) to be described has been prepared in a similar fashion from the diazide (84) as shown in Scheme 4. Intramolecular nitrene addition to suitably aligned nitrogen-nitrogen double bonds has been employed in the synthesis of triaziridines. 

The report by Lieber and co-workers discusses such diverse classes of azides as acyl azides, carbamyl azides, vinyl azides, and a-azido ethers, thioethers and amines. None of these violates the limits of the asymmetric stretching frequency cited earlier. 

T. L. Amyes and W. P. Jencks, Lifetimes of oxocarbenium ions in aqueous solution from common ion inhibition of the solvolysis of a-azido ethers by added azide ion,./. Am. Chem. Soc., Ill (1989) 7888-7900. 

On a related note, Taguchi et al. made use of In(OTf)3 to catalyze the azidation of acetals in their study on the tandem azidation and 1,3-dipolar cycloaddition reaction for the synthesis of fused triazole derivatives [151] (Figure 8.64). Note that the a-azido ether could be isolated and coaxed into forming the cyclized product without the presence of In(OTf)3, clarifying that In(OTf)3 is only required for the initial substitution step. 

The reactions of HN3 with cyclic alcohols to yield mixtures of ketones, amines, and products with an enlarged ring are catalyzed by H2SO4 [1]. Tertiary alcohols are converted to azides in the presence of acid [12] or TiCU [13]. Aldehydes and ketones with HN3 undergo a Schmidt-type reaction by liberating N2 and inserting NH In the presence of H or Lewis acids [14]. Ketones yield secondary amides and, in the case of cyclic ketones, lactames. Aldehydes are converted to nitriles or N-formylamines. Tetrazole derivatives result with excess HN3 [1, 15]. However, a-azido ethers are obtained from aldehydes and HN3 in the presence of alcohols by catalysis of TiC [16]. Carboxylic acids and anhydrides form amines, N2, and CO2 in Schmidt reactions with HN3. Intermediates are carbamic acids which form by insertion of NH into the R-COOH bond [1, 14]. High yields result for acids of arenes [17]. 

Using the above procedures, allyl a-azido alkyl ethers of type 281 were prepared by employing an unsaturated alcohol such as allyl alcohol [76] (Scheme 32). The reaction of an aldehyde with allyl alcohol and HN3 in a ratio of 1 3 9 carried out in the presence of TiCl4 as catalyst provided azido ethers 281, 283, and 285 in 70-90% yield. The ratio of reagents is critical to ensure a high yield of azido ether and to prevent formation of acetal and diazide side products [75]. Thermolysis of azido alkenes 281, 283, and 285 in benzene (the solvent of choice) for 6-20 h led to 2,5-dihydrooxazoles 282,284, and 286, respectively, in 66-90% yield. 

The overall pathway for the conversion of the unsaturated azido ether 281 to 2,5-dihydrooxazoles 282 involves first formation of the dipolar cycloaddition product 287, which thermolyzes to oxazoline 282 or is converted by silica gel to oxazolinoaziridine 288. While thermolysis or acid-catalyzed decomposition of triazolines to a mixture of imine and aziridine is well-documented [71,73], this chemoselective decomposition, depending on whether thermolysis or exposure to silica gel is used, is unprecedented. It is postulated that acidic surface sites on silica catalyze the triazoline decomposition via an intermediate resembling 289, which prefers to close to an aziridine 288. On the other hand, thermolysis of 287 may proceed via 290 (or the corresponding diradical) in which hydrogen migration is favored over ring closure. 

Conversion of Carbonyl Croups and their 0,0- or 0,(V-Acetals into a-Halo, a-Azido, a-Alkinyl, and a-Phosphono Ethers... 

Chiral silyl ether 210 was prepared and subjected to azidonation with trimethylsilyl azide (TMSN3) and iodoben-zene diacetate [PhI(OAc)2], which served as a substitute of IN3, to give a-azido-dioxasilepine 211 as a colorless oil, in diastereoselective ratio 1 3 (Equation 40) <20050BC816>. 

Treatment of triisopropylsilyl enol ethers of cyclic ketones with ammonium cerium nitrate (3 equiv) and sodium azide (4.5 equiv) in acetonitrile at — 20 °C gave a-azido ketones in good yields124. By varying the ratio of the reagents the yields were lower or the formation of byproducts, difficult to separate, increased. Mixture of diastereomers (ratio not reported) were generally obtained from substituted substrates, except from the bicyclic ketones 16. 

Trimethylsilyl enol ethers proved to be unsuitable substrates due to the ease of hydrolysis to the ketone. Presumably, for the same reason, the yield of the a-azido ketone prepared from 17 dropped to less than 50% on reaction scales larger than 100 mg125. 

The a-azido-sulphide (145), which was generated in situ from the thioacetal (144), was reported122 to undergo SnCl4-catalysed rearrangement to the cyclic imino-thiomethyl ethers (146) and (147). 

In 1989, Amyes and Jencks reported a study of azide common ion inhibition for solvolysis of a series of ot-azido ethers (Fig. I).23 The rate constants A Hoh for addition of water to the oxocarbenium ions were determined with an assumed diffusion controlled second-order rate constant /caz of 5.0 x 109 M-1 s 1 for attack on the oxocarbenium ion by azide and the observed rate suppression by varying concentrations of added azide, as determined from Equation (1). With Hoh in hand, the lifetime of the oxocarbenium ion was taken as hoh... 

Sodium Azide/Ammonium Cerium(IV) Nitrate. Silyl enol ethers give a-azido ketones on treament with sodium azide and anhydrous ammonium cerium(IV) nitrate in anhydrous acetonitrile (see Eq. 97).297 325 33i With a glycal, the 2-azido-1-hydroxy nitrate derivative is formed.332 Low yields due to hydrolysis of the silyl enol ether may be improved by use of the triisopropylsilyl (TIPS) derivatives,331 although with a sterically encumbered taxane-derived enol ether the TMS derivative gives higher yields than the TIPS derivative.325 The mechanism is believed to involve addition of an azide radical to the double bond. 

A synthesis of a-azido ketones consists of the oxidation of triisopropylsilyl enol ethers in the presence of NaNj. Nitroalkanes act as aldol acceptors when their anions are exposed to CAN in the presence of silyl enol ethers. Conjugated ketones are obtained on subsequent treatment with triethylamine. 

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