Epoxides azidolysis

Feringa and coworkers [59] in 2010 developed another interesting one-pot transformation involving a CuAAC process. Halohydrin dehalogenase (HheC) was used for an enantioselective epoxide azidolysis to 1,2-azido alcohols, which were subsequently transformed to chiral hydroxyl triazoles with excellent enantioselectivities (Scheme 9.21). 

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]. 

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

Schneider, C. Quaternary ammonium salt catalyzed azidolysis of epoxides with Me3SiN3. Synlett 2000, 1840-1842. 

Yamamoto has reported that ytterbium triisopropoxide, prepared in situ from Yb(OTf)3 and LiOPr in THF, can be used in a very mild, highly efficient, and widely applicable procedure for the azidolysis of epoxides. In every case except styrene oxide, products are derived from the attack of azide at the less hindered carbon atom. The method appears to be quite tolerant of functionality, leaving preexisting tosyl, acyl, and siloxy groups intact (e.g.,... 

A total synthesis of 5-ep/-trehazolin (trehalostatin, 3) was accomplished starting with D-glucose (Scheme 13).71 Thus, benzylation of the allyl alcohol 83, prepared from d-glucose in 10 steps,70 gave 95, and cleavage of the silyl group afforded 96. Sharpless epoxidation of 96 by l-DIPT or d-DIPT furnished the two stereoisomers of 97 and 98. Benzylation of the epoxide 98 afforded 99, which upon azidolysis afforded the... 

The methanolysis, azidolysis, and aminolysis of epoxy benzyl ethers and epoxy alcohols have been reported <93JOCl22l>. All the epoxides studied showed a tendency toward C-3 selectivity when a Lewis-acidic metal cation (Li+, Mg2+, or Zn2+) was added to the reaction mixture, suggesting that the nucleophilic attack in these instances is chelation-controlled (Equation (11), and see Table 2). 

Indium trichloride induces rearrangement of aryl-substituted epoxides to the respective aryl-substituted acetaldehydes via an exclusive hydride shift As phenyl group migration occurs more readily than hydride migration, stilbene oxide is converted to diphenylacetaldehyde (Scheme 8.140) [184]. N-Tosyl aziridines react smoothly with carboxylic acids in the presence of a catalytic amount of indium triflate to afford the corresponding -aminoacetates and benzoates (Scheme 8.141) [185]. Indium trichloride and indium bromide catalyze regio- and diastereoselective azidolysis, bromolysis, and iodolysis of a, -epoxycarboxylates in water (Scheme 8.142) [186]. 

When racemic aryl glycidyl ethers were subjected to aminolysis in aqueous buffer catalyzed by hepatic microsomal epoxide hydrolase from rat, the corresponding (S)-configurated amino-alcohols were obtained in 51-88% ee 131. On the other hand, when azide was employed as nucleophile for the asymmetric opening of 2-methyl-1,2-epoxyheptane in the presence of an immobilized crude enzyme preparation derived from Rhodococcus sp., which contains an epoxide hydrolase activity, the reaction revealed a complex picture 1321. The (S)-epoxide from the racemate was hydrolyzed (as in the absence of azide), and the less readily accepted (i )-enantiomer was transformed into the corresponding azido-alcohol (ee >60%). Although at present only speculations can be made about the actual mechanism of both the aminolysis and azidolysis reaction, in both cases it was proven that the reaction was catalyzed by a protein and that no reaction was observed in the absence of biocatalyst... 

Experimental studies show that HheC mediates attack at the less substituted carbon of various epoxides with the nucleophiles azide, cyanide, and nitrite. " For azidolysis of styrene oxide, the observed regioselectivity is different from that in solution. While chemical conversion of styrene oxide with azide results in 2% attack at the terminal carbon (C/3), HheC-mediated azidolysis increases this value to 79%. This observation made us interested in studying the regioselectivity of HheC-mediated epoxide opening and to investigate the factors controlling it. 

Azidolysis of glycidic acids. In the presence of copper(II) nitrate trihydrate, regioselective ring opening of the epoxide by sodium azide in water (pH 4) to provide 3-azido-2-hydroxy carboxylic acids is observed. 

Azidolysis of epoxides. The opening of epoxide to give 2-azido alcohols may... 

Lutje Spelberg, J.H., van Hylckama Vlieg, J.E.T., Tang, L, Janssen, D.B., and Kellogg, R.M. (2000) Highly enantioselective and regioselec-tive biocatalytic azidolysis of aromatic epoxides. Org. Lett., 3 (1), 41—43. 

Acetylated positional isomers (473)—(477) of deoxystreptamine have been synthesized from cyclohexanepentaol tosylates and related epoxides by conventional displacement and ring-opening reactions, respectively. The triaminocyclo-hexanediol penta-acetates (478) and (479) were also prepared by way of azidolysis of l,2,5-tri-0-methanesulphonyl-l,3,4/2,5-cyclohexanepentaol. 

Azidolysis of Epoxides. A simple, efficient, and stereoselective method for the synthesis of /3-azido alcohols by the direct opening of 1,2-epoxides with 1,1,3,3-tetramethylguanidinium azide (TMGA) in CH3CN, catalyzed by Hf(OTf)4 was described (eq 33). ... 

Various V-substituted 6-amino-6-deoxy-D-glucose derivatives, e.g. 6-8, were synthesized by reaction of the corresponding 5,6-anhydro-D-glucose derivative with secondary amines, and shown to be useful as non-ionic surfactants capable of forming reverse micelles for solubilization of amino acids in hexane. Reaction of such tertiary amines with methyl iodide provided quaternary ammonium-sugar derivatives. The 6-amino-2,5-anhydro-6-deoxy-D-gluconate derivative 10, a potential dipeptide isostere, was obtained from the C2-symmetric, D-mannitol derived bis-epoxide 9 following silica-assisted azidolysis (Scheme 3). Its enantiomer was obtained similarly from an L-iditol bis-epoxide. ... 

After 18 rounds of evolution and the introduction of at least 35 mutations, the volumetric activity of the mutant was increased 4000-fold and this allowed a process having a space-time yield greater than 360 gp, d L/d. The optical purity of the desired product was higher than 99.5%. As a result of this extensive protein engineering study, several new and usefiil HHDHs became commercially accessible. The synthetic applicability of these HHDHs was demonstrated on several examples in the past [30,82-85]. Kosjek and coworkers published the resolution of 2,2-disubstituted epoxides 50 via biocatalytic azidolysis and subsequent synthesis of chiral amino alcohols 52 and aziridines 53 containing a tertiary center (Scheme 9.17) [86]. 

C. Molinaro, A.-A. Cuilbault, B. Kosjek, Resolution of 2,2-disubstituted epoxides via biocata-lytic azidolysis, Org. Lett. 12 (2010) 3772-3775. 

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