Peroxy acids epoxidations

Alkene Peroxy acid Epoxide Carboxylic acid... 

Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves, or with peroxy acids. Epoxidation of allylic alcohols can also be done with high enantioselectivity. In the Sharpless asymmetric epoxidation,allylic alcohols are converted to optically active epoxides in better than 90% ee, by treatment with r-BuOOH, titanium tetraisopropoxide and optically active diethyl tartrate. The Ti(OCHMe2)4 and diethyl tartrate can be present in catalytic amounts (15-lOmol %) if molecular sieves are present. Polymer-supported catalysts have also been reported. Since both (-t-) and ( —) diethyl tartrate are readily available, and the reaction is stereospecific, either enantiomer of the product can be prepared. The method has been successful for a wide range of primary allylic alcohols, where the double bond is mono-, di-, tri-, and tetrasubstituted. This procedure, in which an optically active catalyst is used to induce asymmetry, has proved to be one of the most important methods of asymmetric synthesis, and has been used to prepare a large number of optically active natural products and other compounds. The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound formed from the titanium alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the r-BuOOH. ... 

Familiar instances of the conversion of terpenea into epoxides include oamphepe, 1 cor-3-wie,3 and a- and jB-pinwne.1 m Examples of peroxy acid epoxidation are even more plentiful among the higher terpenes,1111 particularly in the field of steroids. . Epoxide I unctions have now been introduced in virtually every conceivable site of the cyclopentaperhydrophenanthrene skeleton, aa indicated in Table 4. 

The carbonyl oxygens are responsible for the stereo-directing effects of peroxy acids on the epoxidation of allylic and homoallylic carbamoyloxyalkenes (188 —> 189)298. For other mechanistic investigations of the peroxy acid epoxidations of alkenes, see elsewhere299-301. 

Stabilizing the transition state when the epoxidation is occurring syn. This hydrogen bond means that peroxy-acid epoxidations of alkenes with adjacent hydroxyl groups are much faster than epoxidations of simple alkenes, even when no stereochemistry is involved. 

Alkenes conjugated with CbbO are electron-deficient and hence do not react readily with organic peroxy acids. The observation that the stereochemistry of the pyrazolinone (109) is not retained in the epoxidation product (110) is interesting (equation 38). The epoxide (110) is not formed directly from (109). Since the double bond in (109) is electron-deficient its peroxy acid epoxidation to furnish (111) is a slow process. The isomerization of the (Z)-pyrazolinone (109) to the corresponding ( )-isomer is a comparatively fast process. MCPBA epoxidation of the ( )-isomer derived from (109) furnishes (110). 

Dienones with extended conjugation undergo peroxy acid epoxidation regioselectively at the yiS-double bond, even if it is less substituted than the a,p-double bond. The epoxidation of (112) is regio-and stereo-selective (equation 39). Attempted epoxidation of (113a) using nucleophilic reagents furnishes polymeric materials. The epoxidation has been carried out with MCPBA (equation 40). 2a... 

Oxirane synthesis from [2+1] fragments 1.03.4.2.3(0 Peroxy acid epoxidation... 

You may notice additives in peroxy-acid epoxidations, such as sodium carbonate/sodium acetate here. These are buffers, added to prevent the reaction mixture becoming too acidic— remember, the carboxyiic acid is a by-product of the epoxidation. Some epoxides are unstabie in acid, as we shaii see shortiy. 

Attempted peroxy acid epoxidation of the bicyclic ketone (31 equation 13) gave the lactone (33), instead of several possible rational alternatives. The epoxide (32) was implicated as an intermediate when it was independently synthesized from the epoxy alcohol, and shown to give (33) on treatment with aqueous acid.- A mechanism involving scission of the acyl bridgehead bond via the hydrated 1,1 -diol form of the ketone was proposed to account for the formation of this unexpected product. The rearrangement of the isolongifolene derivative (34 equation 14) appears to be mechanistically related. The product (35) is formed by brief treatment with dilute HCIO4 in dioxane as a mixture of isomers believed to arise by acid-catalyzed epimerization of the carbinol center. ... 

On the other hand, no epoxide has been reported to be immune to reaction with BF3, although an interesting example of inertness was noted by Crandall and Machleder. Allene epoxides are usually too sensitive to acids to be isolable from peroxy acid epoxidations, but the bulky r-butyl groups on (70 equation 30) make it exceptionally unreactive. Several hours of reflux with BF3 in ether were required to effect the conversion to (71). 

Oxirane Synthesis from 2 + 1] Fragments 1.03.4.4.1 Peroxy acid epoxidation... 

Alkenes can be epoxidized with a variety of peroxy acids benzoic acid (MCPBA) is the most commonly used. Woods and Beak have provided experimental evidence for the butterfly transition state (A) in Scheme 61 (Bartlett mechanism <50RCP47 involved in peroxy acid epoxidations <9iJA628i>. 

Directing effects of various functional groups on the stereoselectivities of peroxy acid epoxidations have been studied in detail. In the case of allylic alcohols, the weak directing effect of the hydroxy... 

In ketone-directed peroxy acid epoxidations of cyclic alkenes the actual epoxidizing agent has been shown by 180-labeling not to involve a dioxirane <94TL6155>. Instead, an a-hydroxy-benzoylperoxide or a carbonyl oxide is believed to be responsible for observed stereoselectivities in the intramolecular epoxidations. The extent of syn-selectivity is greater for ketones than with esters the syn/anti ratios increase when ether is used as solvent rather than CH2C12, the reverse situation for hydroxyl-directed epoxidations. Fused-ring oxiranes can also be prepared from acyclic precursors. Four different approaches are discussed below. 

Stereoselectivity has been observed during the peroxy acid epoxidation of some homoallylic and bishomoaUylic alcohols, and the epoxidation of the allylic carbamate (24) is syn stereoselective (eq 7). ... 

The peroxy-acid epoxidation of olefins in the presence of base may prevent further reaction of acid-sensitive epoxides. Thus when protoadamantene is epoxidized with MCPBA in the presence of sodium carbonate the endo-epoxide (347) is isolable but the ex [Pg.59]

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