Azide, as nucleophile

Scheme 4.15 Ring opening of epoxides with azide as nucleophile.

Alkyl azides prepared by nucleophilic substitution of alkyl halides by sodium azide as shown m the first entry of Table 22 3 are reduced to alkylammes by a variety of reagents including lithium aluminum hydride... 

Bartoli recently discovered that by switching from azide to p-anisidine as nucleophile, the ARO of racemic trans- 3-substituted styrene oxides could be catalyzed by the (salen)Cr-Cl complex 2 with complete regioselectivity and moderate selectivity factors (Scheme 7.36) [14]. The ability to access anti-P-amino alcohols nicely complements the existing methods for the preparation of syn-aryl isoserines and related compounds [67] by asymmetric oxidation of trans-cinnamate derivatives [68]. 

Additions of oxygen and nitrogen nucleophiles to vinyloxiranes can be achieved with Pd(0) catalysis [103, 104]. Acetate, silanols, amines, sulfonamides, and azide have been used as nucleophiles, and the stereochemical outcome of these additions, where applicable, is normally the result of two consecutive SN2 reactions. This is demonstrated by the additions of NaNHTs to vinylepoxides 29 and 30, affording syn- and anti-amino alcohols 31 and 32, respectively, in good yields and with high diastereoselectivities (Scheme 9.22) [105]. 

Morpholine, pyrrolidine and sodium azide can also be also used as nucleophiles in the synthesis of 3-substitututed A3-cephems 515 via the conjugate addition of the 2,3-allenoate moiety in 513 [233]. 

The high nitrogen content and the endothermic nature of the tetrazole ring lends itself to the synthesis of energetic materials. Compounds such as -H tetrazole and 5-aminotetrazole can be used as nucleophiles to incorporate the tetrazole ring into other molecules. 5-Aminotetrazole is synthesized from the reaction of dicyandiamide with sodium azide in hydrochloric acid. 

Alkyl azides. Sodium azide as such is of little use for preparation of alkyl azides by nucleophilic substitution reactions because of solubility problems. The reaction can be carried out under phase-transfer conditions with methyltrioctylam-monium chloride/NaN3.3 An even more effective polymeric reagent can be obtained by reaction of NaN3 with Amberlite IR-400.4 This reagent converts alkyl bromides, iodides, or tosylates into azides at 20° in essentially quantitative yield. The solvents of choice are CH3CN, CHC13, ether, or DMF. 

In order to simplify these preparations, Boivin et al. [52] made use of the allylic rearrangement reaction (Ferrier type) which was one of the first accesses to 3-amino glycals. By use of azide as the nucleophile, the L-arabino configurated glycal 78... 

Surprisingly, when the cyclic sulfamidate derived from iV-acetyl-D-allosamine 126 was treated with different nucleophiles, three types of products were formed by nucleophilic displacement of sulfamide at C-3 and proton abstraction at C-2 or C-4 (Scheme 18) <1997T5863>. Potassium acetate and sodium azide effectively provide regioselective ring opening to afford thio and azido derivatives 127. When oxy-anions were used as nucleophiles, elimination was the main pathway (sugars 128 and 129). 

Demko and Sharpless proved the efficiency of this version of the click chemistry approach by successful syntheses of 5-acyltetrazoles from azides and acyl cyanides followed by their further functionalization. They used />-nitrophenyl cyanoformate to bring together an azide and nucleophiles in a one-pot process to give in high yield disubstituted acyltetrazoles, such as 544 and 545, via 1-substituted 5-acyltetrazole 543 (Scheme 79) <2002AGE2113>. 

Azide ions are by far the most common nucleophilic species employed in substitution reactions for the preparation of amino sugars. An azido moiety is stable under many reaction conditions but can be reduced to an amino group by a variety of reagents. The nucleophilicity of azido ions can be increased by the addition of a suitable crown ether to complex the counterion.36c,63b In the past, ammonia and hydrazine were used as nucleophiles to overcome unfavourable dipolar interactions that arise when charged nucleophiles were used. However, a drawback of the use of these nucleophiles is that the product is still nucleophilic and can perform a second displacement. Phthalimide ions have successfully been applied in displacement reactions to yield a protected amino sugar derivative.58 63f... 

In the palladium-catalyzed allylic amination reaction, primary and secondary amines can be used as nucleophiles, whereas ammonia does not react. Therefore, many ammonia synthons have been developed, and a variety of protected primary allyl amines can now be prepared using azide, sulphonamide, phthalimide, di-f-butyl iminocarbonate ((Boc)2NLi), and dialkyl A-(rerr-butoxycarbonyl)phosphoramide anions as the nucleophile [20], An example of the use of ((Boc)2NLi) 30 as the amine nucleophile in the palladium-catalyzed allylic amination reaction is shown in Eq. (9). This reaction also illustrates the problem with the regioselectivity in the reaction as a mixture of the products 31-33 are obtained [21]. 

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