Nucleophilic Ring-Opening Reactions of Epoxides

There is an important difference in the regiochemistry of ring-opening reactions of epoxides depending on the reaction conditions. Unsynunetrically substituted epoxides tend to react with anionic nucleophiles at the less hindered carbon of the ring. Under conditions of acid catalysis, however, the more highly substituted carbon is attacked. 

Nucleophiles attack here when reaction is -catalyzed by acids. 

The underlying reasons for this difference in regioselectivity will be explained in Section 16.13. 

Ethylene oxide is a very reactive substance. It reacts rapidly and exothermically with anionic nucleophiles to yield 2-substituted derivatives of ethanol by cleaving the carbon-oxygen bond of the ring  

PROBLEM 16.12 What is the principal organic product formed in the reaction of ethylene oxide with each of the following  

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Wordy Over the past few years, we have encountered numerous examples of water as the perfect solvent. We observed this first in osmium-catalyzed dihydroxylation reactions and also in nucleophilic ring-opening reactions of epoxides. We also observed this in cycloaddition reactions and in most oxime ether, hydrazone, and aromatic heterocycle condensation processes.Finally, we observed it in formation reactions of an amide from a primary amine and an acid chloride using aqueous Schotten-Baumann conditions. ... 

Potassium hydrogen fluoride or sodium hydrogen fluoride may serve as a fluoride ion source for the nucleophilic ring-opening reaction of epoxides. Attack of fluoride occurs predominantly at the less-hindered, i.e. least-substituted, site in the epoxide, as discussed in the following examples. 

Nucleophilic ring-opening reactions of epoxides may also occur under conditions of acid catalysis. Here the nucleophile is not an anion but rather a solvent molecule. 

Sobhani S, Vafaee A. Efficient one-pot synthesis of P-hydrox3fphosphonates regioselective nucleophilic ring opening reaction of epoxides with triethyl phosphite catalyzed by Al(OTf)3. Tetrahedron 2009 65 7691-7695. 

Click chemistry is a chemical concept enunciated by Barry Sharpless, Scripps Research Institute, USA, in 2001, which highlights the importance of using a set of powerful, highly reliable, selective reactions under simple reaction conditions to join small molecular units together quickly for the rapid synthesis of new compounds via heteroatom links and create molecular diversity. Several types of reactions have been identified that fulfill the criteria- thermodynamically favored reactions that lead specifically to one product such as nucleophilic ring opening reactions of epoxides and aziridines, nonaldol type carbonyl reactions, additions to carbon-carbon multiple bonds, Michael additions, and cycloaddition reactions. The best-known cHck reactions are the copper-catalyzed reaction of azides and alkynes or the so-called CuAAC reaction and the thiol-ene reaction. 

The primary type of epoxide reaction remains the nucleophilic ring-opening reaction. The ring opening reactions of epoxides with oxygen nucleophiles represents an important method for the synthesis of differentially O-substituted 1,2-diols. The ring opening of epoxides with... 

This chapter is concerned with the reactions of epoxides with Lewis acids in the absence of nucleophilic substances. These reactions can lead to a wide variety of rearranged structures depending upon the environment of the epoxide system. The ring-opening reactions of epoxides involving external nucleophiles are discussed in Chapter 3. 

The turn of the millenium will see the 20th anniversary of the seminal discovery of the asymmetric epoxidation [1, 2] of ally lie alcohols catalysed by titanium(IV) isopropoxide and tartrate esters. The utility of this transformation largely results from the regio- and stereocontrol possible in subsequent nucleophilic ring opening reactions of the derived epoxy alcohols. Thus, a sequence of asymmetric epoxidation, epoxide opening and further functionalisation leads to a diverse array of molecules in enantiomerically pure form. In comparision, asymmetric epoxidation of unfunctionalised alkenes [3] has yet to match the enantioselectivities which the Ti-tartrate system can deliver with allylic alcohols. The recent discovery of other asymmetric epoxidation reactions [4] suggests that a number of practical options may eventually become available. 

Nucleophilic ring-opening reactions of strained heterocycHc electrophiles (epoxides, aziridines, and aziridinium ions). 

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