Epoxides azide

A one-pot epoxidation/azide-opening sequence has been developed <05JA2147>. A samarium-BINOL-PhjAsO complex is used as a catalyst for enantioselective epoxidations of a,p-unsaturated amides. Upon addition of TMSN, a new samarium azide complex is generated which regioselectively opens the epoxide to form 120. This method has also been extended to thiols and cyanide. 

The third compound contains a 1,2,3-trifunctionahzed arrangement that should prompt you to think of asymmetric epoxidation. Azide is a good nucleophile for opening epoxides, so we can start with the allyhc alcohol shown here, carry out an asymmetric epoxidation, and convert to the target with inversion of configuration. 

Synthesis of Triazoles A number of MCRs that use an epoxide-azide-alkyne Cu(I)-catalyzed cycloaddition sequence to provide substituted p-hydroxy-l,2,3-triazoles 70 (Scheme 3.36) have been recently developed. The azida-tion of an epoxide with sodium azide to give 2-azidoalcohols and subsequent reaction with a terminal alkyne have been carried out under mild conditions in environmentally friendly solvents, such as water, using the catalytic system CuSO sodium ascorbate [65] (see the example depicted in Scheme 3.36) [65a] or a porphyrinatocopper(II) complex... 

Scheme 9.21 One-pot epoxide azidation/CuAAC click-chemistry route to hydroxy-1,2,3-triazoles, as described by Feringa and coworkers [59].

A variety of racemic aminodideoxypentopyranoses have been synthesised from 2-methoxy-5,6-dihydro-2H-pyran (85), primarily by manipulating the known products of epoxidation - azide ring opening as exemplified in Scheme 24 for the synthesis of the 2-amino-2.4-dideoxv-DL-threo-Dentoside (86). These amino-sugars... 

Nucleophilic ring opening of epoxides by ammonia (Section 16 12) The strained ring of an epoxide is opened on nucleo philic attack by ammonia and amines to give 3 ammo alcohols Azide ion also re acts with epoxides the products are p azido alcohols... 

Both saturated (50) and unsaturated derivatives (51) are easily accepted by lipases and esterases. Lipase P from Amano resolves azide (52) or naphthyl (53) derivatives with good yields and excellent selectivity. PPL-catalyzed resolution of glycidyl esters (54) is of great synthetic utiUty because it provides an alternative to the Sharpless epoxidation route for the synthesis of P-blockers. The optical purity of glycidyl esters strongly depends on the stmcture of the acyl moiety the hydrolysis of propyl and butyl derivatives of epoxy alcohols results ia esters with ee > 95% (30). 

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)... 

A mixture of the epoxide ca. 5 mmol), sodium azide (6 g, activated by the method of Smith) and 0.25 ml of concentrated sulfuric acid in 70 ml of dimethyl sulfoxide is heated in a flask fitted with a reflux condenser and a drierite tube on a steam bath for 30-40 hr. (Caution carry out reaction in a hood.) The dark reaction mixture is poured into 500 ml of ice water and the product may be filtered, if solid, and washed well with water or extracted with ether and washed with sodium bicarbonate and the water. The crude azido alcohols are usually recrystallized from methanol. 

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-... 

Despite these significant results in azide additions, only limited success has been obtained in enantioselective addition of other sp2-hybridized nitrogen-centered nucleophiles to meso-epoxides. Bartoli et al. demonstrated that aniline was a... 

Figure 7.2 Biologically interesting molecules prepared by (salen)chromium-catalyzed ARO of epoxides with azide.

Subsequent to the development of the (salen)Cr-catalyzed desymmetrization of meso-epoxides with azide (Scheme 7.3), Jacobsen discovered that the analogous (salen)Co(n) complex 6 promoted the enantioselective addition of benzoic acids to meso-epoxides to afford valuable monoprotected C2-symmetric diols (Scheme 7.15) [26], Under the reaction conditions, complex 6 served as a precatalyst for the (salen) Co(iii)-OBz complex, which was fonned in situ by aerobic oxidation. While the enantioselectivity was moderate for certain substrates, the high crystallinity of the products allowed access to enantiopure materials by simple recrystallization. 

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. 

A novel approach to azabicyclic ring systems, based on an epoxide-initiated electrophilic cyclization of an alkyl azide, has been developed by Baskaran. A new stereo- and enantioselective synthesis of the 5-hydroxymethyl azabicyclic framework 91a, present in (+)- and (-)-indolizidines 167B and 209D, for example, was... 

Scheme 8.24 Epoxide-initiated electrophilic cyclization of azides.

The analogous chromium complex was used in the asymmetric ring opening of meso epoxides with trimethylsilyl azide [15] (Scheme 4). In this case a strong dependence on the anion of the ionic hquid was observed. Anions leading to hydrophobic ionic hquids, such as PFe" and SbFe", led to high... 

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