Epoxide opening, azide

An explosion was experienced dining work up of an epoxide opening reaction involving acidified sodium azide in a dichloromethane/dimethyl sulfoxide solvent. The author ascribes this to diazidomethane formation from dichloromethane [1]. A second report of an analoguous accident, also attributed to diazidomethane, almost certainly involved hydrogen azide for the cold traps of a vacuum pump on a rotary evaporator were involved this implies an explosive more volatile than dichloromethane. It is recommended that halogenated solvents be not used for azide reactions [2]. 

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. 

Scheme 6.132 Ring-opening of epoxides with azide ions.

P-Aminoalcohols may be generated from (3-azidoalcohols, which are commonly made from the opening of epoxides with azide ion as shown in Scheme 13 (91TL2533). After conversion of the alcohol... 

The enantioselective synthesis (51) of the side chain 30 of taxol had been achieved by way of stereospecific Sharpless epoxidation of cij-cinnamyl alcohol (29a), giving 29b (see Scheme 6). Following oxidation of the alcohol group, protection of the resulting carboxylic acid, regioselective opening of the epoxide with azide, benzoylation, and reduction, a suitably substituted moiety (28) was available which, after protection and deprotection of the acid function to form 30, was coupled to baccatin III. 

An indirect method for generating an amino alcohol (124) is to open an epoxide with azide to give the azido-alcohol 123, and subsequent reduction (19-50) gives the amine group.Sodium azide and Oxone react with epoxides to give an azi-do-alcohol. Under Mitsunobu conditions (10-17), epoxides are converted to 1,2-diazides with The reaction of trimethylsilyl azide and an epoxide was... 

It is apparent, then, that precursors for terminal vinyl azides are obtained following iodine azide addition to olefins only when rather unusual steric or electronic factors are operating. A number of other reaction sequences have been investigated in the search for a general approach to the terminal compounds. The opening of a terminal epoxide by azide ion leads to an azidohydrin which can be readily dehydrated (equation 4). Unfortunately, this reaction sequence... 

Opening of epoxides with azide ions represents a very interesting route to azidocarbinols. The large number of examples quoted in the literature proves the broad scope of this technique." " On treatment of nonsymmetrically substituted oxiranes, the products expected from an 5n2 process are usually obtained. In boiling aqueous dioxane, cyclohexene oxide gives rise to 61% of rrans-2-azidocyclohexa-nol. The reported formation of (35 Scheme 46) with styrene oxide is unexpected, particularly if the formation of (36) from the analogous diphenyl precursor is considered. ... 

Epoxide-opening with sodium azide and a weakly acidic catalyst is increasingly used as a route to hydroxy-azides, and thence to hydroxy-amines [e.g. 16a, 17a-epoxyandrostane — 16 -azido-17a-ol" " 6o,7a-epoxy-4-en-3-one — 6 -azido-... 

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. 

Azido alcohols. The regioselectivity for unsymmetrical epoxide opening with aqueous sodium azide is influenced by pH. 

In 1992, Nugent [12] reported a significant advance in the Lewis acid-promoted opening of meso epoxides (Scheme 2). A novel chiral zirconium complex catalyses epoxide opening with hindered silyl azides iii excellent ee. The catalyst is derived from zirconium tert-h xi-oxide and the tetradentate C3-symmetric ligand 1, available by combination of (5)-pro-pene oxide with (S)-l-aminopropan-2-ol. Al-... 

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