Epoxides nucleophilic attack

Epoxides, like cyclic halonium ions, undergo ring opening through rearside attack of nucleophiles (see Section 6.3.2). Two mechanisms are shown, for both basic and acidic conditions. Under acidic conditions, protonation of the epoxide oxygen occurs first. The epoxidation-nucleophilic attack sequence also adds substituents to the double bond in an anti sense. 

With unsymmetrical epoxides, nucleophilic attack occurs at the more substituted carbon atom. 

The reaction follows the same two-step process as the opening of epoxide rings with other negatively charged nucleophiles— that is, nucleophilic attack from the back side of the epoxide ring, followed by protonation of the resulting alkoxide. In unsymmetrical epoxides, nucleophilic attack occurs at the less substituted carbon atom. 

For substituted epoxides, nucleophilic attack generally takes place at the less sterically hindered side of the epoxide. Using this type of reaction, show how you might prepare the following compound from benzene, ammonia, and any other reagents of your choice. 

The experimental observations combine with the principles of nucleophilic substi tution to give the picture of epoxide ring opening shown m Figure 16 5 The nucleophile attacks the less crowded carbon from the side opposite the carbon-oxygen bond Bond... 

As we ve just seen nucleophilic ring opening of ethylene oxide yields 2 substituted derivatives of ethanol Those reactions involved nucleophilic attack on the carbon of the ring under neutral or basic conditions Other nucleophilic ring openings of epoxides like wise give 2 substituted derivatives of ethanol but either involve an acid as a reactant or occur under conditions of acid catalysis... 

Predict which carbon undergoes nucleophilic attack on acid catalyzed ring opening of cis 3 3 3 tnfluoro 2 3 epoxybutane Examine the C—O bond distances of the protonated form of the epoxide on Learning By Modeling How do these bond distances compare with your prediction" ... 

Nucleophilic Reactions. The strong electronegativity of fluorine results in the facile reaction of perfluoroepoxides with nucleophiles. These reactions comprise the majority of the reported reactions of this class of compounds. Nucleophilic attack on the epoxide ring takes place at the more highly substituted carbon atom to give ring-opened products. Fluorinated alkoxides are intermediates in these reactions and are in equiUbrium with fluoride ion and a perfluorocarbonyl compound. The process is illustrated by the reaction of methanol and HFPO to form methyl 2,3,3,3-tetrafluoro-2-methoxypropanoate (eq. 4). 

The reactions are highly exothermic. Under Uquid-phase conditions at about 200°C, the overall heat of reaction is —83.7 to —104.6 kJ/mol (—20 to —25 kcal/mol) ethylene oxide reacting (324). The opening of the oxide ring is considered to occur by an ionic mechanism with a nucleophilic attack on one of the epoxide carbon atoms (325). Both acidic and basic catalysts accelerate the reactions, as does elevated temperature. The reaction kinetics and product distribution have been studied by a number of workers (326,327). 

The most important oxirane syntheses are by addition of an oxygen atom to a carbon-carbon double bond, i.e. by the epoxidation of alkenes, and these are considered in Section 5.05.4.2.2. The closing, by nucleophilic attack of oxygen on carbon, of an OCCX moiety is dealt with in Section 5.05.4.2.1 (this approach often uses alkenes as starting materials). Finally, oxirane synthesis from heterocycles is considered in Section 5.05.4.3 one of these methods, thermal rearrangement of 1,4-peroxides (Section 5.05.4.3.2), has assumed some importance in recent years. The synthesis of oxiranes is reviewed in (B-73MI50500) and (64HC(19-1U). 

Double bonds in a,/3-unsaturated keto steroids can be selectively oxidized with alkaline hydrogen peroxide to yield epoxy ketones. In contrast to the electrophilic addition mechanism of peracids, the mechanism of alkaline epoxidation involves nucleophilic attack of hydroperoxide ion on the con-... 

In general, thiocyanate salts are used for the epoxide-thiirane conversions. The reaction proceeds by nucleophilic attack on the epoxide by thiocyanate ion followed by cyclization as shown for (121) (125). The formation of a... 

Polyfluoroalkyl- andperfluoroalkyl-substituted CO and CN multiple bonds as dipolarophiles. Dmzo alkanes are well known to react with carbonyl compounds, usually under very mild conditions, to give oxiranes and ketones The reaction has been interpreted as a nucleophilic attack of the diazo alkane on the carbonyl group to yield diazonium betaines or 1,2,3 oxadiazol 2 ines as reaction intermediates, which generally are too unstable to be isolated Aromatic diazo compounds react readily with partially fluorinated and perfluorinated ketones to give l,3,4-oxadiazol-3-ines m high yield At 25 °C and above, the aryloxa-diazolines lose nitrogen to give epoxides [111]... 

Nucleophilic ring opening of epoxides by ammonia (Section 16.12) The strained ring of an epoxide is opened on nucleophilic attack by ammonia and amines to give p-amino alcohols. Azide ion also reacts with epoxides the products are p-azido alcohols. 

The cleavage reaction occurs in three steps O protonation of the epoxide, Sn2 nucleophilic attack on the protonated epoxide, and deprotonation of the ring-opened product. Draw the complete mechanism. How many intermediates are there Which step determines diol stereochemistry ... 

The product of nucleophilic attack can be anticipated by examining the lowest-unoccupied molecular orbital (LUMO) on protonated cyclopentene oxide. From which direction (top or bottom) would a nucleophile be more likely to approach each epoxide carbon in order to transfer electrons into this orbital Explain. Does one carbon contribute more to the LUMO, or is the orbital evenly spread out over both epoxide carbons Assuming that LUMO shape dictates product stereochemistry, predict which stereoisomers will be obtained, and their approximate relative amounts. Is the anticipated kinetic product also the thermodynamic product (Compare energies of 1,2-cyclopentanediol stereoisomers to tell.)... 

Epoxides, in contrast to ethers, readily undergo nucleophilic attack, resulting in ring opening and relief of strain. Ring opening proceeds by a different mechanism, and may lead to different products, depending on reaction conditions. 

With weak nucleophiles such as methanol, and in the presence of acid, the reaction proceeds via nucleophilic attack on the protonated epoxide. Examine the LUMO of protonatedpropylene oxide. Does this properly identify the site for nucleophilic attack which will lead to the observed product (Hint The most accessible parts of the LUMO are best identified by simultaneously displaying the molecule as a space-filling model and the LUMO as a mesh surface.)... 

In general, 2-substituted allylic alcohols are epoxidized in good enantioselectivity. Like glycidol, however, the product epoxides are susceptible to ring opening via nucleophilic attack at the C-3 position. Results of the AE reaction on 2-methyl-2-propene-l-ol followed by derivatization of the resulting epoxy alcohol are shown in Table 1.6.1. Other examples are shown below. 

Grignard reagents do react with epoxides 24 by an SN2-mechanism, resulting in a ring-opening reaction. An epoxide carbon bearing no additional substituent—i.e. a methylene group—is more reactive towards nucleophilic attack than a substituted one ... 

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... 

O Brien et al. provided the first examples of olefin formation by reductive alkylation of aziridines [97]. Treatment of aziridine 267 with s-BuLi gave olefin 270 in 76% yield (Scheme 5.68). For the formation of olefin 270 they suggest a reaction pathway that proceeds in a manner analogous to that proposed for epoxides [36] namely, nucleophilic attack of s-BuLi on lithiated aziridine 268 to form dilithiated species 269, which eliminates Li2NTs (TsNH2 was observed as a product of this reaction) to yield olefin 270. 

The procedure is outlined in Scheme 8.33, starting from the generic allylic alcohol 125. SAE on 125 would provide epoxide 126, which could easily be transformed into the unsaturated epoxy ester 127 by oxidation/Horner-Emmonds olefmation (two-carbon extension). This operation makes the oxirane carbon adjacent to the double bond more susceptible to nucleophilic attack by a hydride, so reductive opening (DIBAL) of 127 provides, with concomitant ester reduction, diol 128. Pro-... 

Cyclic acid anhydrides are highly reactive not only to electrophilic attack but also to nucleophilic attack. Alternating copolyesters were obtained from cyclic acid anhydrides and epoxides at high temperatures261-263. ... 

The corresponding reactions of transient Co(OEP)H with alkyl halides and epoxides in DMF has been proposed to proceed by an ionic rather than a radical mechanism, with loss of from Co(OEP)H to give [Co(TAP), and products arising from nucleophilic attack on the substrates. " " Overall, a general kinetic model for the reaction of cobalt porphyrins with alkenes under free radical conditions has been developed." Cobalt porphyrin hydride complexes are also important as intermediates in the cobalt porphyrin-catalyzed chain transfer polymerization of alkenes (see below). 

Vflth MeO as nucleophile, attack occurs cleanly ai the right atom in the epoxide,the bromide is made ith PBrg and the synthesis finished according to plan. 

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