Epoxides nucleophilic substitution reactions

Overall the stereospecificity of this method is the same as that observed m per oxy acid oxidation of alkenes Substituents that are cis to each other m the alkene remain CIS m the epoxide This is because formation of the bromohydrm involves anti addition and the ensuing intramolecular nucleophilic substitution reaction takes place with mver Sion of configuration at the carbon that bears the halide leaving group... 

An a ,/3-epoxycarboxylic ester (also called glycidic ester) 3 is formed upon reaction of a a-halo ester 2 with an aldehyde or ketone 1 in the presence of a base such as sodium ethoxide or sodium amide. Mechanistically it is a Knoevenagel-type reaction of the aldehyde or ketone 1 with the deprotonated a-halo ester to the a-halo alkoxide 4, followed by an intramolecular nucleophilic substitution reaction to give the epoxide 3 ... 

The normal pathway toward excretion of foreign molecules like aflatoxin Bi and dibenzo [a,/]pyrene, however, also involves nucleophilic substitution reactions of their epoxides. 

The arene oxide valence tautomer of oxepins in principle should undergo nucleophilic substitution reactions (Sn2) which are characteristic of simple epoxides. In reality oxepin-benzene oxide (7) is resistant to attack by hard nucleophiles such as OH-, H20, NH2- and RNH2. Attempts to obtain quantitative data on the relative rates of attack of nucleophiles on (7) in aqueous solution hqye been thwarted by competition from the dominant aromatization reaction. 

Epoxides are much more reactive than simple ethers due to ring strain, and are useful intermediates because of their chemical versatility. They undergo nucleophilic substitution reactions with both acids and bases to produce alcohols (see Sections 4.3.7 and 5.5.4). 

A nucleophile is an electron rich species that reacts with an electrophile. The term electrophile literally means electron-loving , and is an electron-deficient species that can accept an electron pair. A number of nucleophilic substitution reactions can occur with alkyl halides, alcohols and epoxides. However, it can also take place with carboxylic acid derivatives, and is called nucleophilic acyl substitution. 

Nucleophilic addition of sulfur ylides to C=0 double bonds is an important means of synthesis of epoxides [198], Because optically active epoxides are widely applied as versatile intermediates in the preparation of, e.g., pharmaceuticals, the asymmetric design of this sulfur ylide-based reaction has attracted much interest [199, 200, 212, 213], One aspect of this asymmetric organocatalytic process which has been realized by several groups is shown in Scheme 6.87A. In the first step a chiral sulfur ylide of type 204 is formed in a nucleophilic substitution reaction starting from a halogenated alkane, a base, and a chiral sulfide of type 203 as organocata-... 

Epoxides are important intermediates in many industrial processes. For example, the reaction of the simplest epoxide, ethylene oxide, with water is employed to produce ethylene glycol, which is used in antifreeze and to prepare polymers such as Dacron. One method for the preparation of ethylene oxide employs an intramolecular nucleophilic substitution reaction of ethylene chlorohydrin ... 

Using retrosynthetic analysis, we recognize that the c/.v-epoxide can be prepared from the c/s-alkene. The m-alkene can be prepared by catalytic hydrogenation of an alkyne. Finally, substituted alkynes can be prepared by nucleophilic substitution reactions using acetylide ion nucleophiles (see Section 10.8). On the basis of this analysis, the synthesis reported in the literature was accomplished as shown in Figure 23.3. 

Although they really belong in Chapter 17 with other nucleophilic substitution reactions, we included the last few examples of epoxide-opening reactions here because they have many things in common with the reactions of bromonium ions. Now we are going to make the analogy work the other way when we look at the stereochemistry of the reactions of bromonium ions, and hence at the stereoselectivity of electrophilic additions to alkenes. We shall first remind you of an epoxide reaction from Chapter 17, where you saw this. 

Terminal epoxides of high enantiopurity are among the most important chiral building blocks in enantioselective synthesis, because they are easily opened through nucleophilic substitution reactions. Furthermore, this procedure can be scaled to industrial levels with low catalyst loading. Chiral metal salen complexes have also been successfully applied to the asymmetric hydroxylation of C H bonds, asymmetric oxidation of sulfides, asymmetric aziridination of alkenes, and the asymmetric alkylation of keto esters to name a few. 

Table 2. Azides obtained by nucleophilic substitution reactions between azide ion and epoxides...

Palladium-catalyzed nucleophilic substitution reactions of allylic substrates have become useful in organic synthesis. As allylic substrates, allyl alcohols, halides, carboxylates, phosphates or vinyl epoxides can be utilized. 

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