Azides, reaction with epoxides

Alkali metal azides react with epoxides in a appropriate solvent to give vicinal azidohydrins. Phase-transfer reagents may be used. The reactions usually require high temperatures and/or long reaction times. 

Reaction with epoxides. Vanderwerf and co-workers added a saturated aqueous solution of sodium azide (in slight excess) to a refluxing solution of propylene oxide in dioxane and established that the main product is l-azido-2-propanol. Cyclopentene oxide reacts to give /ran.s-2-azidocyclopentanol. 

Azides react with epoxides too. This epoxide is one diastereoisomer (trans) but racemic and the symbol ( ) under each structure reminds you of this (Chapter 14). Azide attacks at either end of the three-membered ring (the two ends are the same) to give the hydroxy-azide. The reaction is carried out in a mixture of water and an organic solvent with ammonium chloride as buffer to provide a proton for the intermediate. Triphenylphosphine in water is used for reduction to the primary amine. 

The azidohydrins obtained by azide ion opening of epoxides, except for those possessing a tertiary hydroxy group, can be readily converted to azido mesylates on treatment with pyridine/methanesulfonyl chloride. Reduction and subsequent aziridine formation results upon reaction with hydrazine/ Raney nickel, lithium aluminum hydride, or sodium borohydride/cobalt(II)... 

Detailed investigations indicated an interesting mechanism for azide openings catalyzed by 2 [6]. Chloride-epoxide addition products were observed in the initial stages of the ARO reaction with 2 in amounts commensurate with the catalyst loading. Azide complex 3, characterized as the TH F adduct, was isolated from the reaction mixture and proved to be an active and recyclable catalyst for the ARO, pointing to the role of 2 as that of a precatalyst. Kinetic experiments revealed a second-order dependence on the concentration of 3, a zero-order dependence on azide source, and inverse-order dependence on epoxide concentration. The sue-... 

Although several interesting nitrogen-centered nucleophiles have been developed with ARO reactions of epoxides (vide supra), kinetic resolutions with such reagents are unlikely to be of practical value for the recovery of enantioenriched terminal epoxides. This is due to the fact that these nucleophiles are too valuable to be discarded in a by-product of the resolution, are generally not atom-economical, and, particularly in the case of azide, may represent safety hazards. 

The cleavage of epoxides by water is a classical reaction. Such epoxide cleavage can be catalyzed by both acids and bases in aqueous media. In the presence of other nucleophiles, the corresponding nucleophilic ringopening products are obtained with the nucleophiles being incorporated into the products.68 Examples include azides, iodides, and thiols in the presence or absence of metal salts in aqueous media. The pH of the reaction medium controls the reactivity and regioselectivity of the... 

By combining several click reactions, click chemistry allows for the rapid synthesis of useful new compounds of high complexity and combinatorial libraries. The 2-type reaction of the azide ion with a variety of epoxides to give azido alcohols has been exploited extensively in click chemistry. First of all, azido alcohols can be converted into amino alcohols upon reduction.70 On the other hand, aliphatic azides are quite stable toward a number of other standard organic synthesis conditions (orthogonality), but readily undergo 1,3-dipolar cycloaddition with alkynes. An example of the sequential reactions of... 

A rather complex microwave-assisted ring-opening of chiral difluorinated epoxy-cyclooctenones has been studied by Percy and coworkers (Scheme 6.131) [265]. The epoxide resisted conventional hydrolysis, but reacted smoothly in basic aqueous media (ammonia or N-methylimidazole) under microwave irradiation at 100 °C for 10 min to afford unique hemiacetals and hemiaminals in good yields. Other nitrogen nucleophiles, such as sodium azide or imidazole, failed to trigger the reaction. The reaction with sodium hydroxide led to much poorer conversion of the starting material. 

The importance of reactions with complex, metal hydrides in carbohydrate chemistry is well documented by a vast number of publications that deal mainly with reduction of carbonyl groups, N- and O-acyl functions, lactones, azides, and epoxides, as well as with reactions of sulfonic esters. With rare exceptions, lithium aluminum hydride and lithium, sodium, or potassium borohydride are the... 

One can easily envisage the formation of stereochemically enriched materials by an asymmetric version if the methodology developed by Jacobsen et al. <2000ACR421> of epoxide ring-opening reactions with azides is applied in the reaction sequence. 

Alkyl azides have been involved in the synthesis of indolizidinone derivatives in several ways. One example (Scheme 7) is the intramolecular Schmidt reaction between alkyl azides and ketones which can be used to transform azidoketone 24 into the corresponding indolizidinones 26 through intermediate 25 <2001JOC886> or with epoxides to obtain the indolizidine 27 <2004JOC3093>. 

Asymmetric Ring Opening Reaction of Epoxides with Trimethylsilyl Azide (TMSN3)... 

Sodium azide reacts with various epoxides at 25°-30°C at pH 6-7 to give azido alcohols [57-59]. The use of harsh conditions as earlier employed by Van der Werf et al. [59] (16-40 hr reflux in dioxane) led to the production of 1,3-diazidopropanol instead of l-azido-3-chloro-2-propanol when starting with epichlorohydrin. Several representative examples of the conditions and products of the reaction of azides with epoxides are shown in Table V. 

Preparation of Organic Azide Compounds by the Reaction of Sodium Azide with Epoxides in Aqueous Solution [60]... 

Azidohydrins. Epoxides are converted to trans-siloxy azides by reaction with N3Si(CH3)3 (1.5 equiv.) and aluminum isopropoxide (1 equiv.) in CH2C12. The reaction involves selective attack of azide on the less-substituted carbon of the epoxide. 

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