Reactions of Epoxides Ring-Opening

Epoxides can also be opened by reaction with acids other than H30+. For example, if anhydrous HX is used, an epoxide is converted into a trans halohydrin  

The regiochemistry of acid-catalyzed ring opening depends on the epoxide s structure, and a mixture of products is usually formed. When both epoxide carbon atoms are either primary or secondary, attack of the nucleophile occurs primarily at the less highly substituted site. When one of the epoxide carbon atoms is tertiary, however, nucleophilic attack occurs primarily at the more highly substituted site. Thus, 1,2-epoxypropane reacts with HC1 to give primarily l-chloro-2-propanol, but 2-methyl-l,2-epoxypropane gives 2-chloro-2-methyl-l-propanol as the major product. 

Acid-induced ring opening of 1,2-epoxy-l-methylcydohexarte with HBr. There is a high degree of SN1-llke carbocation character in the transition state, which leads to back-side attack of the nucleophile at the tertiary center and to formation of the isomer of 2-bromo-2-methylcyclohexanol that has -Br and -OH groups trans. 

Evidently, the transition state for acid-catalyzed epoxide opening tj an SN2-like geometry but also has a large amount of Spjl-like carboeata character, Since the positive charge in the protonated epoxide is shared the more highly substituted carbon atom, back-side attack of Br- occurs the more highly substituted site, 

Identify the substitution pattern of the two epoxide carbon atoms—in tl case, one carbon is secondary and one is primary, Then recall the guideline for epoxide cleavages. An epoxide with only primary and secondary carbon usually undergoes cleavage by SN2 attack of a nucleophile on the leas h dered carbon, but an epoxide with a tertiary carbon atom usually unded goes cleavage by an SN1 mechanism. In this case, an Ss 2 cleavage of tlwl primary C-0 epoxide bond will occur. 

Epoxides have significant ring strain, and as a result, they exhibit unique reactivity. Specifically, epoxides undergo reactions in which the ring is opened, which alleviates the strain. In this section, we will see that epoxides can be opened under conditions involving a strong nucleophile or under acid-catalyzed conditions. 

When an epoxide is subjected to attack by a strong nucleophile, a ring-opening reaction occurs. For example, consider the opening of ethylene oxide by a hydroxide ion. 

MECHANISM 14.5 EPOXIDE RING OPENING WITH A STRONG NUCLEOPHILE 

In the first step, hydroxide functions as a nucieophiie and opens the ring in an S vj2 process 

Many strong nucleophiles can be used to open an epoxide. 

Acid-catalyzed epoxide cleavage takes place by back-side attack of] nucleophile on the protonated epoxide in a manner analogous to the fn step of alkene bromination, in which a cyclic bromonium ion is opened 1 nucleophilic attack (Section 7.2). When an epoxycycloalkane is opened 1 aqueous acid, a rans-1,2-diol results, just as a rans-1,2-dibromide res from cycloalkene bromination. 

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There is an important difference in the regiochemistry of ring opening reactions of epoxides depending on the reaction conditions Unsymmetncally 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... 

Rearrangement of fluorine with concomitant ring opening takes place in fluorinated epoxides Hexafluoroacetone can be prepared easily from perfluo-ropropylene oxide by isomerization with a fluorinated catalyst like alumina pre treated with hydrogen fluoride [26, 27, 28] In ring-opening reactions of epoxides, the distribution of products, ketone versus acyl fluoride, depends on the catalyst [29] (equation 7) When cesium, potassium, or silver fluoride are used as catalysts, dimenc products also are formed [29]... 

The enantioselectivity was significantly influenced by the steric factor of the thiols employed. When p-MeC6H4SH and PhSH were used, the optical yields decreased to 69% and 3%, respectively. Shibasaki et al. have reported that gallium-lithium-bi-naphthoxide (GLB) 51 became a good catalyst for the enantioselective ring opening reaction of epoxide for the production of 52 (Eq. 7.39) [46]. 

Figure 15. Epoxide ring opening reactions of epoxides and diol epoxides from benzo[a]pyrene, 4-azabenzo[a]pyrene and 10-azabenzo [a]pyrene.

Scheme 4.43 Ring-opening reaction of epoxides prepared by Shi s asymmetric epoxidation.

Asymmetric Ring Opening Reaction of Epoxides with Trimethylsilyl Azide (TMSN3)... 

Dioos, B. M. L. Geiutsa W. A. Jacobs, P. A. (2004) Coordination of Crlll(salen) on fimctionalised silica for asymmetric ring opening reactions of epoxides.. Catalysis Lett., 97 125-129. 

Song, C. E. Oh, C. R. Rob, E. J. Choo, D. J. (2000) Cr(salen) catalysed asymmetric ring opening reactions of epoxides in room temperature ionic liquids., Chem. Commun., 1743-1744. 

Schneider, C. (2006) Synthesis of 1,2-difunctionalized fine chemicals through catalytic, enantioselective ring-opening reactions of epoxides., Synthesis, 3919-3944. 

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. ... 

Some examples for the application of such immobilization strategies and the application of the immobilized complexes to asymmetric hydrogenation and epoxidation as well as to ring-opening reactions of epoxides will be presented in this chapter. 

Novel Heterogenized Catalysts for Asymmetric Ring-Opening Reactions of Epoxides... 

Different immobilization methods were employed, and the new heterogenized catalysts were applied in asymmetric hydrogenation and epoxidation of olefins, as well as in ring-opening reactions of epoxides. In some cases, the typical catalytic properties of homogeneous catalysts could be transferred to the heterogeneous systems. The immobilization of complexes on solid supports facilitated recovery and recycling of the catalysts. 

The chemoselectivity, regioselectivity, diastereoselectivity, and enantioselectivity of heteroatom oxidations, epoxidations and CH insertions by dioxiranes have been reviewed.26 The selective ring-opening reactions of epoxides at high pressures have been reviewed (in Japanese).27... 

The ring-opening reactions of epoxides has been an especially active area of research. 

Until now, three main F-C transformations have been used for catalytic stereoselective formation of benzylic carbon stereocenters - 1,2-addition of arenes to carbonyl (C=X, X O, NR) moieties, 1,4-addition of arenes to electron-deficient C-C double bonds, and ring-opening reaction of epoxides. 

Fig. 98 Ti(III)-Rh(I)-catalyzed reductive ring opening reactions of epoxides (for simplicity Cp2TiCl 359a is depicted as a monomer)...

The above type of reaction is characteristic of the so-called polymer reactions . The rate itself and the activation parameters may be quite different from those of the conventional anionic ring-opening reaction of epoxides. In the above reaction of a polymeric epoxide, a polymer consisting of 77% THF. diyl units and 16% epoxide units was isolated in a soluble form. If the opening of the epoxide ring by an alkoxide group had occurred in a random fashion, cross-linking would have taken place to produce an insoluble polymer. 

When BusSnSePh is allowed to react with epoxides in the presence of BF3-OEt2, the ring-opening reaction of epoxides proceeds with complete regioselectivity to afford the /3-hydroxy phenylselenides (Equation (99)). 

Figure 3.1 Ring opening reactions of epoxides in the presence of active hydrogen compounds.

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... 

Further examples of fluorinating ring-opening reactions of epoxides with the boron trifluoridc-diethyl ether complex are given by the formation of 6. 7, 8, 9. and 10. ... 

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