Azido-epoxides

Scheme 10. Asymmetric synthesis of azido epoxide 43 and epoxide 38.

Treatment of the steroid (146 Scheme 48) with LTA and TMS-N3 gives the 5,6-seco-5-oxo-7-carboni-trile steroid (147) useful for the synthesis of ring b homoazasteroids. ZbiraF explains the mechanism as an aza analog of the Eschenmoser fragmentation via formation of the azido epoxide. 

Intramolecular tandem Michael addition-amide formation in the intermediate (291) afforded an epilupinine precursor (Scheme 60) <89H(29)1209>. Another quinolizidine synthesis forming two a bonds in its key step is the reductive double alkylation of azido epoxides with an (o leaving group (292). This strategy has been applied to the synthesis of ring-expanded analogues of indolizidine alkaloids (e.g. (293)) from D-arabinose (Scheme 61) <93TL822l>. 

Methyl isoricinoleate also furnished A-heterocycles via its azido epoxide through reaction with Mel, Nal, and DMF. After 20 h, the product was a mixture of pyrrole and pyridines formed via the two possible keto intermediates. After only 15 min reaction time, the keto azides were isolated and subsequently converted to a dihydropyrrole and a tetrahydropyridine through reaction with PI1P3 (40) (Scheme 20). 

Epoxides are another viable electrophilic partner for alkyl azides. Baskaran and coworkers found that azido-tethered epoxides afforded bicyclic, tertiary amines bearing a hydroxymethyl substituent upon treatment with a Lewis acid followed by reduction. This one-pot procedure was applicable to bicyclic azido epoxides with varying ring sizes, affording the corresponding bicyclic amines in preparatively useful yields (Table 7.8). These reactions probably involve the initial Lewis acid-assisted formation of a cation followed by azide attack. Migration and concomitant loss of N2 then generates an iminium ion, which persists until stereoselective reduction by hydride (Schane 7.32). 

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... 

Synthesis of azindines Irom epoxides via amino alcohols or azido alcohols and reaction with phosphines or phosphites... 

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. 

Paulsen and his coworkers first synthesized (-f-)-203 from L-quebrachitol (286) by a 21-step reaction as follows. The di-O-isopropylidene derivative was oxidized to the ketone (287), and then epoxidized with dimethyl sulfox-onium-methylide to give 288, which was subjected to benzoylation, mesyla-tion, and demethylation, followed by benzylation, to afford 289. Introduction of unsaturation was accomplished by epoxidation of 289 with sodium methoxide to 290 and 291, and deoxygenation to 292. The azido group was introduced with azobis(dicarboxylate) to give 293, which was hydrogeno-lyzed, followed by deprotection to afford 203. 

Similarly, diethylaluminum azide gives (3-azido alcohols. The epoxide of 1-methylcyclohexene gives the tertiary azide, indicating that the regiochemistry is controlled by bond cleavage, but with diaxial stereoselectivity. 

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... 

The synthesis of a,a-disubstituted amino acids is a difficult task and continues to attract attention. An efficient route that utilizes the ring-opening of an epoxide with azide has been reported <06TL9268>. Treatment of the sulfoxide substituted epoxide 23 with NaN3 provides intermediate azido aldehyde 24. This aldehyde was not isolated but oxidized to the acid and then the azide reduced to provide the a,a-disubstituted amino acid 25. The regioselectivity of this reaction was impressive with only one product reported. 

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