Hydroxy epoxides rearrangement

Scheme 1.49. Cationic domino rearrangement/reduction sequence of a-hydroxy epoxides.

Scheme 1.52. Proposed catalytic cycle for the cationic domino rearrangement/hetero-Tishchenko reduction process of secondary a-hydroxy epoxides in the presence of Sml2.

Rearrangement of epoxy silyl ethers. When treated with 1 equiv. of TiCl4, a-silyloxy epoxides rearrange to p-hydroxy carbonyl compounds. 

Oxidation of organic substrates. This hydroperoxide converts 2,3-dimethyl-2-butcne into tetramethylethylene oxide with simultaneous formation of 3-bromo-4,5-dihydro-5-hydroxy-4,4-dimethyl-3,5-diphenyl-3H-pyrazole (2). Dialkyl olefins, however, are not epoxidized by I. Enol ethers are converted to a variety of epoxide rearrangement products.2... 

Ozone adds directly to double bonds in fatty acids to form ozonides (183-185). These decompose to lipid alkoxyl and peroxyl radicals that abstract hydrogens to initiate radical chains (186). In the process, internal rearrangements within the original lipid molecule(s) yield hydroxy epoxides and hydroxy epidioxides with 1,3- and 1,4-cyclic hydroperoxides ... 

Pan, C.-A., Wang, B.-M., Tu, Y.-Q., Song, Z.-L. Samarium-catalyzed tandem semipinacol rearrangement/Tishchenko reaction of a-hydroxy epoxides a novel approach to highly stereoselective construction of 2-quaternary 1,3-diol units. Angew. Chem., Int. Ed. Engl. 2001,40, 3877-3880. 

Rearrangements. a-Hydroxy epoxides undergo 1,2-rearrangement to give enones... 

Recent advances in the semi-pinacol rearrangement of a-hydroxy epoxides and related compounds 07CSR1823. 

SCHEME 9. Rearrangement of hydroxy epoxides. Epoxidation MCPBA or HCO3H rearrangement BF3 etherate/dioxan. 

This reaction has been extensively modified by the application of different initiation systems, including a variety of Brpnsted and Lewis acids, photochemical irradiation, and supercritical CO2. In addition, this rearrangement has been successfully extended to a-halohydrin, aziridines, and of-hydroxy epoxides, as noted in Section A. 

Petuniasterones with side chains bearing functionalities other than orthoesters also occur. The important PS-B and PS-C series (Figure 2) have epoxy groups at the 24,25-position and hydroxy or acyloxy groups at position-22. We have shown (12) that 22-acyloxy epoxides easily rearrange to the bicyclic orthoesters, and also that a 22-hydroxy epoxide yields the isomeric 5-membered cyclic ether as well as a mixture of side chain triols under mild acid treatment. 

A large family of semipinacol rearrangements have been developed for the stereoselective transformation of non-racemic a-hydroxy epoxides. These reactions are usually Lewis acid-promoted, as in the case of the... 

A Lewis acid-promoted tandem rearrangement/reduction of non-racemic a-hydroxy epoxides yields 2-quartemary-l,3-diols. This reaction also successfully transforms a-hydroxy-A-tosyl aziridines into A-tosy 1-1,3-amino alcohols. 

Many additional applications of semipinacol rearrangements on a-hydroxy epoxides have been developed,and these reactions have found use in complex molecule synthesis. For example, a-hydroxy epoxide 47 underwent a Lewis acid-mediated semipinacol ring expansion to set the challenging in-out intrabridgehead stereochemistry of the ingenol core. ... 

When, however, the Sharpless oxidation became such an efficient and reliable source for homochiral hydroxy-epoxides, this rearrangement was recognized as a very useful tool in predictable stereoselective synthesis. 

Micouin et al. found that the nucleophilic substitution of bicycUc hydrazine-epoxide 7 using alkynylaluminum reagent led to the formation of hydroxy group-rearranged product 8 (Scheme 6) [20]. The plausible mechanism of this unique reaction involves (1) the initial formation of aziridinium cation intermediate catalyzed by aluminum Lewis acid and (2) the intramolecular nucleophilic migration of alkynyl group, as in transition state 9. 

The metabolism of 12(S)-HPETE, illustrated in Figure 4.21, yields two main classes of compounds. The enzymatic reduction of 12(S)-HPETE by glutathione peroxidases gives rise to 12(S)-HETE, a signaling molecule involved in cell proliferation and adhesion. Alternatively, structural rearrangements of the hydroperoxy moiety of 12(S)-HPETE produce two distinct hydroxy-epoxides, hepoxilin A3... 

In some cases products of rearrangement are obtained either partially or exclusively on treatment of Grignard reagents with epoxides. Thus, reaction of the 2/ ,3/ -epoxide (14) with methyl Grignard reagent affords a mixture of two epimeric secondary A-nor alcohols (15) in 80% yield and the tertiary hydroxy compound, 2a-methyl-5a-cholestan-2/f-ol (16) in 15 % yield. ... 

High yields of A-homo-B-norsteroids are also obtained on rearrangement of the 5a,6a-epoxides from 3)3-hydroxy-6-methylandrost-5-en-17-one and Sp, 17)5-diacetoxy-6-methylandrost-5-ene. 

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