Azidolysis

Azide is widely useful as a surrogate for ammonia in nucleophilic substitution reactions, due to its high nucleophilicity, low basicity, and stability towards a variety of conditions for subsequent transformations. In particular, the azidolysis of... 

Jacobsen demonstrated that the (salen)Cr system used to effect intermolecular, cooperative asymmetric azidolysis of meso-epoxides (Schemes 7.3 and 7.5) could be applied to sulfur-centered nucleophiles (Scheme 7.13). In order to overcome moderate enantioselectivity (<60% ee), a dithiol nucleophile was employed as part of a double resolution strategy in which the minor enantiomer of the monoaddition product reacts preferentially to form the meso- bis-addition product, thereby increasing the ee of the C2-symmetric bis-addition product. Enantiopure 1,2-mer-capto alcohols (>99% ee) were obtained from the meso-epoxide in ca. 50% overall yield by a burdensome (though effective) multistep sequence, [23]. 

In contrast, Cozzi and Umani-Ronchi found the (salen)Cr-Cl complex 2 to be very effective for the desymmetrization of meso-slilbene oxide with use of substituted indoles as nucleophiles (Scheme 7.25) [49]. The reaction is high-yielding, highly enantioselective, and takes place exclusively at sp2-hybridized C3, independently of the indole substitution pattern at positions 1 and 2. The successful use of N-alkyl substrates (Scheme 7.25, entries 2 and 4) suggests that nucleophile activation does not occur in this reaction, in stark contrast with the highly enantioselective cooperative bimetallic mechanism of the (salen)Cr-Cl-catalyzed asymmetric azidolysis reaction (Scheme 7.5). However, no kinetic studies on this reaction were reported. 

Scheme 10.34 HheC-catalyzed azidolysis of an epoxystyrene derivative.

Preparation. All recently used routes to azidoquinoxalines have been covered already by azidolysis of halogenoquinoxalines (Sections 3.2.4 and 3.4.5), by azidolysis of alkylsulfonylquinoxalines (Section 5.4), by diazotization and subsequent azidolysis of quinoxalinamines (Section 6.3.2.3), and by treatment of hydrazinoquinoxalines with nitrous acid (Section 6.4.2.1). 

The 4-0- (282) and 4,7-di-O-methanesulfonates (283) of a-DL-carba-galactopyranose obtained from 258 produced, after azidolysis in DMF, hydrogenolysis, and acetylation, penta-A, 0-acetyl-4-amino- (284) and 4,7-diamino-4,7-dideoxy-o -DL-carba-glucopyranose (285). 

Scheme 13. Enzyme-catalyzed aminolysis and azidolysis of epoxides...

Ring opening of meso aziridines has also been investigated. Jacobsen and coworkers found that tridentate Schiff base Cr(III) complex 62 is efficient at inducing good levels of enantioselectivity in the azidolysis of aziridines 60 [Eq. (10.15)]. Alkyl-substituted aziridines were found to work best with the electron-deficient dinitrophenylmethyl providing optimal results ... 

Treatment of 2-(aroylamino)pyrimidines (18), prepared from 15 and aroyl chlorides with PC15 followed by azidolysis in aqueous acetone, gave the tetrazoles 19, whose subsequent pyrolysis afforded 2-aryl-l,2,4-... 

X. Wu, F. Kong, D. Lu, and G. Li, Synthesis, crystalline structure, conformational analysis, and azidolysis of methyl 2,3-anhydro-a-D-manno- and allo-pyranoside p-bromobenzyl ethers, Carbohydr. Res., 235 (1994) 163-178. 

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