Azidation, cyclic ether

The use of heteroatom nucleophiles is a very popular variation of the Nicholas reaction. Alcohols and amines are most prevalent, while examples of azides, thiols,carboxylic acids, epoxides, hydrides, and fluorides are known. Isobe has made extensive use of alcohol nucleophiles in the preparation of various sized cyclic ethers. In studies directed toward the synthesis of ciguatoxin, Isobe converted alcohol 15 into eight-membered ring cyclic ether 16 using the Nicholas reaction. 

The determination of the lifetime of the ionic intermediates using the azide-clock method has been however useful in showing that electrophilic addition of Br2 can occur, even through a fully concerted mechanism, definable as SN2-like. Bromination of cyclic enol ethers (glycals) 8-10 in methanol in the presence of... 

Kamal A, Prasad BR, Khan MNA (2007) TMSCl-Nal-mediated reaction of aryl azides with cyclic enol ethers an efficient one-pot synthesis of 1,2,3,4-tetrahydroquinolines. J Mol Catal A Che 274 133-136... 

Organic azides combine with open-chain and cyclic eno) ethers to give A -triazolines in high yield. The addition is stereospecific cis and the orientation process is determined by electronic effects.145-160 The triazolines are unstable above 100° and can decompose in mainly two ways. 44 Triazolines from the open-chain enol ethers, vinyl butyl ether, /S-ethoxypropene, and a- and /3-methoxystyrene, eliminate alcohol thermally and are converted into 1,2,3-triazoles. For example, the triazoline 67 from /J-ethoxypropene 66 and p-nitrophenyl azide decomposes quantitatively at 150° into l-(p-nitrophenyl)-5-methyl-1,2,3-triazole (68). 

Triazolines from the cyclic enol ethers, dihydrofuran and dihydropyran, decompose at 100-130° into anils and nitrogen. Thus p-bromophenyl azide reacts with dihydropyran (69) to give triazoline 70 which decomposes thermally into the aryl-inline of 5-valerolactone (71). Photochemical decomposition of 70, on the contrary, yields 7-p-bromophenyl-7-aza-2-oxabi-cyclo[4.1.Q]heptane (72) in 67% yield. Scheiner has shown that aziridine 72 is stable at the decomposition temperature of 70, proving that it is not an intermediate in the thermal conversion of 70 to 71. 51... 

Organic azides combine with open-chain and cyclic enol ethers to give AMriazolines in high yield. The addition is stereospecific cis and the orientation process is determined by electronic effects.196 266 The triazolines are unstable above 100° and can decompose in mainly two ways.260... 

The reactions of cyclic TIPS enol ethers with PhIO/TMSN3 (1 2) have been examined in detail [12 -14]. Two primary modes of reactivity have been identified, one leading to vicinal-diazides (a-pathway) and the other leading to allylic azides (/1-pathway) (Scheme 3). 

The diols (97) from asymmetric dil droxylation are easily converted to cyclic sii e esters (98) and thence to cyclic sulfate esters (99).This two-step process, reaction of the diol (97) with thionyl chloride followed by ruthenium tetroxide catalyzed oxidation, can be done in one pot if desired and transforms the relatively unreactive diol into an epoxide mimic, ue. the 1,2-cyclic sulfate (99), which is an excellent electrophile. A survey of reactions shows that cyclic sulfates can be opened by hydride, azide, fluoride, thiocyanide, carboxylate and nitrate ions. Benzylmagnesium chloride and thie anion of dimethyl malonate can also be used to open the cyclic sulfates. Opening by a nucleophile leads to formation of an intermediate 3-sidfate aiuon (100) which is easily hydrolyzed to a -hydroxy compound (101). Conditions for cat ytic acid hydrolysis have been developed that allow for selective removal of the sulfate ester in the presence of other acid sensitive groups such as acetals, ketals and silyl ethers. 

Cyclic enol ethers are cleaved by bu l nitrite in acidic ethand, providing a useful synthesis of oxim-inomacrolides (Scheme 99). 1,2-Dichloroazides, from addition of chlorine azide to 1,2-dichloroal-... 

Allylic azides, e.g., 1, were produced by treatment of the triisopropylsilyl enol ethers of cyclic ketones with azidotrimethylsilane and iodosobenzene78, but by lowering the temperature and in the presence of the stable radical 2,2,6,6-tetramethylpiperidine-/V-oxyl (TEMPO), 1-triso-propylsilyloxy-l,2-diazides, e.g., 2, became the predominant product79. The radical mechanism of the reaction was demonstrated. A number of 1,2-diazides (Table 4) were produced in the determined optimum conditions (Method B 16h). The simple diastereoselectivity (trans addition) was complete only with the enol ethers of unsubstituted cycloalkanones or 4-tert-butylcy-clohexanone. This 1,2-bis-azidonation procedure has not been exploited to prepare a-azide ketones, which should be available by simple hydrolysis of the adducts. Instead, the cis-l-triiso-propylsilyloxy-1,2-diazides were applied to the preparation of cw-2-azido tertiary cyclohexanols by selective substitution of the C-l azide group by nucleophiles in the presence of Lewis acids. 

Treatment of triisopropylsilyl enol ethers of cyclic ketones with ammonium cerium nitrate (3 equiv) and sodium azide (4.5 equiv) in acetonitrile at — 20 °C gave a-azido ketones in good yields124. By varying the ratio of the reagents the yields were lower or the formation of byproducts, difficult to separate, increased. Mixture of diastereomers (ratio not reported) were generally obtained from substituted substrates, except from the bicyclic ketones 16. 

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