Epoxide intramolecular attack

The suggested reaction mechanism involves a nucleophilic attack of the imine nitrogen at the activated triple bond, followed by a proton exchange, to give a benzimidazolinium system which, by intramolecular attack at the carbonyl group, leads to an epoxide that ring opens to the observed product. For the ethyl derivative (R = Et) a tub conformation could be established by X-ray crystallographic analysis.33... 

Intramolecular attack of the tertiary amide anion 73 on the epoxide yielded a p-lactam <00T3209>. 

The analogous process involving allylic epoxides is more complex, as issues such as the stereochemistry of substituents on the ring and on the alkene play major roles in determining the course of the reaction [38]. Addition of the Schwartz reagent to the alkene only occurs when an unsubstituted vinyl moiety is present and, in the absence of a Lewis acid, intramolecular attack in an anti fashion leads to cyclopropane formation as the major pathway (Scheme 4.10). cis-Epoxides 13 afford cis-cyclopropyl carbinols, while trans-oxiranes 14 give mixtures of anti-trans and anti-cis isomers. The product of (S-elimi-... 

The behavior of 7-bromo-2,3,7-trideoxy-D-amfe/ o-heptono- 1,4-lactone (205) and 7-bromo-2,7-dideoxy- (208) and 7-bromo-3,7-dideoxy-D-g/Mco-heptono-1,4-lactone (211) toward aqueous base has also been studied (229). The 6,7-epoxide is formed by potassium carbonate treatment of each bro-modeoxy heptonolactone. With potassium hydroxide, epoxide migration occurs giving mixtures of epoxides that undergo intramolecular attack by the... 

Acid-catalyzed intramolecular attack of nucleophilic hydroperoxide function on an oxirane ring results in formation of 3-(l-hydroxyalkyl)endoperoxides. For example, epoxidation of unsaturated hydroperoxide 320 affords oxirane-hydroperoxide 321 (66%), which through acid-catalyzed regioselective cyclization gives 1,2-dioxolane 322 (70%) (Scheme 79) . This type of reaction is applicable also to a more complex epoxide-hydroperoxide such as 323, which cyclizes to polyfunctionalized 5-membered cyclic... 

With sodium hydroxide, methyl 2,3-anhydro-a-D-allopyranoside yields methyl 3,6-anhydro-a-D-glucopyranoside by intramolecular attack on the epoxide ring by the 6-hydroxyl group.72 Methyl 2,3-anhydro-a-D-gulopyranoside behaves similarly, and its intermediacy accounts for the conversion of methyl 3,4-anhydro-a-D-galactopyrano-side into methyl 3,6-anhydro-a-D-galactopyranoside on treatment with alkali.67... 

Many newer methods for generating cyclohexane derivatives from carbohydrates still depend on the intramolecular attack of nucleophilic carbon species at electrophilic centers, and the range of options is now extensive. Thus, the nucleophiles may be carb-anions stabilized by carbonyl, phosphonate, nitro, or dithio groups, and they may bond to carbonyl carbon atoms, or to those that carry appropriate leaving groups or are contained in epoxide rings, or as jj-centers of a,p-unsaturated carbonyl systems. Otherwise, the nucleophilic activity at the 7-centers of allylsilanes or a-positions of vinyl silanes may be used to react with electrophilic carbon atoms. 

Nazarov and co-workers1814 have noted intramolecular attack 1-y a carboxyl function on an epoxide ring in the case of the bicyclul. .--) I heptene derivative shown m Eq. (757), Other work of a similar char-... 

Certain uneaturated fatty acids give lactone esters on treatment with peracetic acid, presumably by intramolecular attack of the carboxyl function on the initially-formed epoxide ring. Thus, 4,8-cpnxypentanoic acid generated by peracetic add oxidation of 4 pentenoie acid undergoes cleavage to give a five-membered lactone as... 

The first cyclisations to be put to synthetic use were those of aryl lithiums onto carbonyl compounds, imines and epoxides. These are known as Parham cyclisations , and the method for transforming an aryl bromide to an aryllithium the Parham protocol , after W. E. Parham, who developed the reaction. We will survey the use of Parham cyclisations in synthesis, before assessing intramolecular attack of other electrophiles. The most important of these are the alkenes, and the usefulness of anionic cyclisations onto unactivated double bonds compares very favourably with radical cyclisations, particularly with regard to stereochemical control. 

The answer must be a mechanism related to the one we have just seen for epichlorohydrin. Attack by hydroxide on CCI3 is almost unknown and it is much more likely that intramolecular attack by alkoxide to give an epoxide should occur. The carboxylate anion can then invert the stereogenic centre by intramolecular S>j2 displacement at the central carbon atom. Notice that the tether ensures attack at the central atom. The second four-membered lactone also hydrolyses by attack at the carbonyl group. 

In 1997, Taguchi, Hanzawa and coworkers described the formation of cyclopropyl carbinols from alkenyl oxiranes through chemoselective hydrozirconation followed by intramolecular attack of the generated alkylzirconocene on the epoxide ring (Scheme 18) [27]. Both the reactivity and the selectivity patterns are worthy of note. The sequence was made possible owing to the chemoselective hydrozirconation of the alkene in the presence of oxirane. Despite the poor nu-... 

The presence of donors which can occupy the alkene coordination site slows down the reaction. A kinetic analysis of the epoxidation of a number of alkenes has shown that the coordinating power of the olefin, and its tendency to undergo the intramolecular attack, increase with substitution of the alkene with electron donor groups provided they are not too bulky ° ... 

Jamison, following the precedent of Hudrlik, has used a trimethylsilyl substituent on a polyepoxide that enables both a highly stereoselective epoxidation process, but also directs intramolecular attack (Equation 13). Conveniently, the silyl substituents are cleaved under the reaction conditions <2003OL2339, 2006JA1056>. 

Tandem Vasella-type elimination can be followed by intramolecular attack on a nearby epoxide to form 2,5-disubstituted tetrahydrofurans (Equation 14) <20030L1931>. Substituent effects on epoxide cyclizations have been examined <1996JOC2075>. 

An intramolecular reaction of epoxides promoted by a titanium halide which is somewhat different from simple opening of an epoxide with a nucleophile is shown in Eq. (290) [654]. The starting epoxide was first attacked by a bromide ligand of TiBr4, in an intermolecular manner, and this was followed by the intramolecular attack of... 

Ionization methods leading to unstabilized cations can give pieparatively useful yields when the center is tertiary. In Scheme 17 a variety of examples is shown. Cyclohexene epoxides (example 2, Scheme 17) are generally useful initiators for monocyclizations. The cyclopropyl ketone is effective with aryl termination (example 4, Scheme 17), but in example 5 (Scheme 17) the ion obtained on cyclization is quenched by intramolecular attack of the enol. 

A number of bromocyclopropanes which also contain an electrophilic center in the molecule, undergo intramolecular substitution under the right conditions. When l-bromo-7-(3-chloro-propyl)tricyclo[4.1.0.0 ]heptane was reacted with butyllithium, tetracyclo[5.3.0.0 .0 ]de-cane (10) was obtained in 52% yield.Under similar conditions several substituted 7-bromo-bicyclo[4.1.0]heptene anti-epoxides and other epoxides were converted to polycyclic alcohols which result from intramolecular attack of the cyclopropyl anion on the oxirane ring. ... 

Racemic hydroxy ester 225 was converted, via a Sharpless kinetic resolution, to the enantiomerically pure epoxide 226. This epoxide was then converted to the diol "/-lactone by intramolecular attack of the ester, assisted by nucleophilic dealkylation with iodide ion. Deprotonation and methylation anti to the alkoxide followed by acetonide formation afforded 227 in 56% yield. Dibal reduction, protection of the resulting aldehyde as the terminal olefin, silylation of the tertiary alcohol, and liberation of the aldehyde via ozonolysis provided a 45% yield of the C-9 to C-15 fragment 228. 

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