Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 1223 125

II. INTRODUCTION

Epoxidation of CDX double bonds is a very active field in organic chemistry. It seems that for almost every type of double bond a special epoxidation reagent has been developed.

One can find quite a few cases of peroxy acids reacting for hours at elevated temperatures with simple alkenes in order to form regular epoxides. More deactivated olefins require lengthy treatment with strongly basic hydrogen peroxide solution.

There are many other reactions devised for oxygen transfer such as various oxidants combined with transition metals with or without macrocyclic hosts and industrial specific epoxidations using oxygen, to name just a few.

Because of the large number of literature data on epoxidations, we cannot hope to give a full review of all publications that have appeared. We shall therefore restrict ourselves to a brief survey of the still continuing research that has led to the currently accepted interpretation of epoxidations. Using earlier reviews1 10 as a starting point, we shall mainly discuss the results achieved in the last years. Here recent developments are described by presenting some characteristic new examples.

III.EPOXIDATION OF THE C=C BOND

A.Epoxidation by Peroxy Acids

The epoxidation of olefins by peroxycarboxylic acids is quite important and has been reviewed repeatedly2,6,9. The two characteristic features of epoxidations with peroxycarboxylic acids are such that the epoxidations are accelerated by both increasing electron density of the carbon carbon double bond and electron-attracting groups on the peroxycarboxylic acid.

In coordinating solvents, peroxycarboxylic acids form a complex with the solvent through intermolecular hydrogen bonding11. Thus, a well-known cyclic transition state has been widely accepted (equation 1).

Solvent effects in the peroxycarboxylic acid epoxidations are significant. The epoxidation rates in ether or ethyl acetate are approximately one-tenth of those in benzene or chloroform. The much slower epoxidation with peroxycarboxylic acids with intermolecular hydrogen bonding is indicative of the development of a cyclic transition state.

It is known that peroxycarboxylic acids exist in an intramolecular hydrogen-bonded form in noncoordinating solvents and in an intermolecular hydrogen-bonded form in coordinating solvents such as ether12,13. When a coordinating group is present in an olefin, a directed epoxidation could be attained. A typical example is the syn epoxidation of acyclic and cyclic allyl alcohols14 17. It was postulated that a hydrogen bond formed

process is directed by other functionalities22 26 (e.g. equation 4).

(i-Pr)3 Si O

MCPBA

(4)

O

(i-Pr)3 Si O

For selective epoxidation Rebek and coworkers synthesized highly crowded peroxyacids

(1) and their naphthalene and acridine homologues and compared their epoxidation rates27.

The resulting cis/trans ratios for the epoxidation of 2-octenes were 1.2, 5.6 and 7.7 for MCPBA, 1a and 1b, respectively, suggesting a high ratio for the U-shaped peroxy acid

(1). These results indicate that a stereoselective epoxidation is possible by using highly crowded peroxy acids.

The ability of other peracids28, sodium perborate and sodium percarbonate29, to release oxidative species in an organic medium has made them useful reagents in organic synthesis. The oldest organic reaction reported with sodium perborate concerns the formation of peracids (equation 5).

The formation of peracids as the effective oxidizing species has often been proposed for oxidations with sodium percarbonate in the presence of organic acids or acid anhydrides30 32. It was observed that at room temperature and in dichloromethane as solvent, the addition of acetic anhydride induced the epoxidation by sodium perborate of mono-, diand trisubstituted alkenes, including ˛,ˇ-unsaturated ketones in a slightly exothermic reaction33 (equation 6).

O

sodium perborate

(6)

CH2 Cl2 /A c2 O

New epoxidation methods have been developed by the utilization of alkanesulfonic peracids and peroxymonosulfate34,35.

B. Metal-catalyzed Epoxidations

1. Epoxidation by hydrogen peroxide

Hydrogen peroxide is a mild oxidant and its use in olefin epoxidations requires the application of appropriate catalysts. The oxidation with aqueous hydrogen peroxide in the presence of tungstic acid yields the corresponding epoxides (equation 7)9.

The catalytic epoxidation proceeds via the formation of peroxytungstic acid. Similarly, other metal catalysts are effective in the H2O2 oxidation. Aqueous conditions are not appropriate for epoxidations since epoxides are prone to undergo acid-catalyzed hydrolysis36. Polymer-anchored catalysts are conveniently separated from the reaction mixture after catalyzed H2O2 epoxidations (equation 8)9.

In the last decade, transition metal complexes (e.g. metalloporphyrins) have been used to catalyze epoxidation. These entities can reproduce and mimic all reactions catalyzed by heme-enzymes (cytochromes P-450)54. Synthetic metalloporphyrins are analogous to the prosthetic group of heme-containing enzymes which selectively catalyze various oxidation reactions. The metallo complexes of Fe, Co, Cr, Mn, Al, Zn, Ru, etc. possessing porphyrin ligands have been mostly studied55 57. Porphyrin ligands (4) are planar and can possess several redox states of the central metallic ions and hence they can exist as oxo metals.

iodosylarenes58 62, peracids63,64, hypochlorites65 70, alkylhydroperoxides71,72, hydrogen peroxide73 75, amine N-oxide76 and ozone77 has been described. The mechanism consists of an oxygen atom transfer from oxometalloporphyrins to alkenes with the ratedetermining step of the formation of a charge-transfer complex64 (Scheme 3).

The reactions following the rate-determining step (epoxidation vs rearrangement) were proposed to be dependent on a number of factors that included the oxidation potentials of the alkenes and the active oxidant, the steric and electronic structures of the reactants (steric bulk and geometry of both species and the metal axial ligand of the metalloporphyrins) as well as the properties of various substrates to undergo rearrangements. Examination of the metal and ligands revealed various features of metalloporphyrincatalyzed epoxidations. Sometimes, the epoxidation was accompanied by rearrangements and isomerizations indicative of a one-electron transfer from olefin to oxo metals78 80. cis-Olefins are more reactive than trans-olefins in porphyrin-catalyzed epoxidation by iodosylbenzene. For example, cis-stilbene is epoxidized by tetraarylporphyrin [Fe(TPP)Cl] (4c,d) in 77% yield whereas trans-stilbene does not react under the same conditions. In contrast, the use of Mn porphyrin yields a mixture of cis and trans isomers81. High selectivity is induced by sufficient noncovalent interactions between the substrate and the metalloporphyrin. The use of NaOCl as oxidant promotes epoxidation in good yields and with high regioand stereoselectivities for terpenes and steroids82. Dienes can selectively be transformed to monoepoxide83.

3. Asymmetric epoxidation

Chiral porphyrins, prepared in different ways84,85 (chiral units attached to preformed porphyrins84, chiral substituents introduced during the synthesis of porphyrins86 or chiral porphyrins synthesized without the introduction of chiral groups69,87 90), proved to be effective as asymmetric epoxidation catalysts.

O

+

MV

rate-limiting step

MV

Prochiral olefins, such as ˇ-methylstyrene, can be epoxidized with 72% enantiomeric excess, either with ‘picket’ metalloporphyrins (‘basket handle’ iron-porphyrin)91,92 or with bulky ligand porphyrins93 96. Chiral binaphthyl bridges give a rigid conformation and a chiral environment to the metallic center, which recognizes the substrate84. A serious weak point for the metalloporphyrin-catalyzed epoxidation is the oxidation of the porphyrin rings themselves, resulting in low turnover9. The rings may be moderately stabilized by introducing sterically bulky groups or electron-withdrawing groups97 99.

At present, the best enantiomeric excess with different olefins is achieved by chiral salen ligands100 108. Contrary to the porphyrin systems, salen complexes (5) [i.e. N,N0 - ethylene-bis(salicylidene-aminate) ligands] bear tetravalent and potentially stereogenic carbon centers in the vicinity of the metal binding site.

The reaction of cyclohexene with Mn(III)(salen)/t-BuOOH afforded cyclohexene oxide as the single product in the presence of radical inhibitors. When PhIO was used as the terminal oxidant, stereospecific epoxidation could be attained. Similar results were obtained with Co(II)(salen) (5); stereospecific epoxidation took place with PhIO as the