Ring-opening of epoxides

Acid sensitive epoxides can be reacted with a nucleophile pre-adsorbed on dried alumina [70]. The reaction is carried out in diethyl ether at ambient temperature in 10 to 60 min (e.g. equation 4.9). 

Neutral alumina catalyses the nucleophilic attack of alcohols, thiols, acetic acid and benzeneselenol on a diverse range of epoxides under mild conditions (e.g. equation 4.10) [71]. 

This reaction requires more vigorous conditions than the reaction of alcohols, resulting in low yields in many cases. For this reason the reaction is not commonly used in synthesis. An epoxide (also known as an oxirane) is a three-membered cyclic ether  

Like cyclopropane, epoxides have a large amount of ring strain and are much more reactive than normal ethers. Because of this ring strain, one carbon-oxygen bond of an 

Both of the carbons of the epoxide ring are electrophilic, so at first glance, either might be expected to react with the nucleophile, methoxide ion. However, reactions of epoxides under basic or neutral conditions, as in this case, usually follow an SN2 mechanism. Therefore, the nucleophile reacts at the less hindered secondary carbon, with inversion of configuration. 

Another example, in which it can be seen that the reaction proceeds with inversion of configuration, is provided in the following reaction  

Because such reactions have features of both the SN2 mechanism (stereochemistry) and the SN1 mechanism (regiochemistry), they are said to follow a borderline SN2 mechanism. The transition state geometry resembles that for an SN2 reaction, but the bond to the leaving group is broken to a greater extent than the bond to the nucleophile is formed, resulting in considerable positive charge buildup on the carbon. Therefore, the transition state that has 

The regioselective ring opening of 2,3-epoxy acids can also be achieved (Eqs 269 and 270) [616]. The titanium-promoted reaction always favors C3 opening of the epoxides whereas in the absence of Ti(0-i-Pr)4 the same reaction proceeds with much lower or even reversed regioselectivity. The same tendency was observed for the reaction of 2,3-epoxy amides [616]. 

Opening of an enyne monoepoxide with an amine took place regio- and stereose-lectively (Eq. 271) [636], showing that the rule of C3 opening of 2,3-epoxyalcohols is still valid for substrates of this type. 

TiCU plays a dual role in effecting epoxide opening and subsequent deoxygenation with allylsilane as depicted in Eq. (277) [641]. The reaction is highly stereospecific. 

Epoxide opening accompanied by the pinacol-type rearrangement of a carbon framework in the presence of a titanium Lewis acid has been used for the stereoselective synthesis of acyclic compounds [642,643], Equations (278) and (279) illustrate this transformation and exemplify the dependence of stereospecificity on the geometry of the epoxide 

The methylenecyclopropane oxide — cyclobutanone rearrangement has been coupled with asymmetric epoxidation to give optically active cyclobutanones, a versatile synthetic intermediate, without loss of the original enantiopurity of the epoxides (Eq. 282) [646]. Both processes occurring in this transformation are promoted by the same titanium species. Representative results are shown in Eqs 283 [646] and 284 [647]. The versatility of these transformations obviously relies on the facile accessibility of optically active epoxides. 

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We saw an example of nucleophilic ring opening of epoxides in Section 15 4 where the reaction of Grignard reagents with ethylene oxide was described as a synthetic route to primary alcohols... 

Nucleophilic ring opening of epoxides has many of the features of an 8 2 reac tion Inversion of configuration is observed at the carbon at which substitution occurs... 

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... 

Nucleophilic ring opening of epoxides by ammonia (Section 16 12) The strained ring of an epoxide is opened on nucleo philic attack by ammonia and amines to give 3 ammo alcohols Azide ion also re acts with epoxides the products are p azido alcohols... 

CRV737) A critical discussion of the mechanisms of ring-opening of epoxides by nucleophiles. 

Acid-catalyzed ring opening of epoxides is discussed in Section 16.13. 

Reductive ring opening of epoxides in radical reactions in presence of titanocenes as electron transfer catalysts 98SL801. 

Ring opening of epoxides and some other transformations of heterocycles on aluminum oxide 97T7999. 

The first example of asymmetric catalytic ring-opening of epoxides with sp2-hybridized carbon-centered nucleophiles was reported by Oguni, who demonstrated that phenyllithium and a chiral Schiff base ligand undergo reaction to form a stable system that can be used to catalyze the enantioselective addition of phenyllithium to meso-epoxides (Scheme 7.24) [48]. Oguni proposed that phenyllithium... 

Synthesis of Complex Molecules by Intramolecular Ring-opening of Epoxides with Heteronucleophiles... 

Ring opening of epoxides with nucleophiles other than water (Cl, BrT I, NOz , CN ) can also be catalyzed by halohydrin dehalogenase enzymes (EC 3.8.1.5, also named haloalkane dehalogenase or haloalcohd dehalogenase) (Figure 6.74) [197]. 

Scheme 12.15 gives some examples of both acid-catalyzed and nucleophilic ring openings of epoxides. Entries 1 and 2 are cases in which epoxidation and solvolysis are carried out without isolation of the epoxide. Both cases also illustrate the preference for anti stereochemistry. The regioselectivity in Entry 3 is indicative of dominant bond cleavage in the TS. The reaction in Entry 4 was studied in a number of solvents. The product results from net syn addition as a result of phenonium ion participation. The ds-epoxide also gives mainly the syn product, presumably via isomerization to the... 

Scheme 12.15. Nucleophilic and Solvolytic Ring Opening of Epoxides...

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