A-Hydroxy epoxides

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

Scheme 1.51. Samarium-catalyzed domino reaction of secondary 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.

The stereospecific isomerization of 3,4-epoxyalcohols under acidic or basic conditions <2002T6199, 1998TL8259> has been the method of choice for the final step in syntheses of merrilactone (Equation 48) <2006AGE4843>. An analogous acid-promoted closure of benzyl ethers of epoxy alcohols has also been observed <2000H(52)171>. An unusual 4-/ro/o-isomerization of a hydroxy epoxide apparently reflects the inability of a primary alcohol to cyclize via 4-exo- or 5-endo-modes transesterification liberates the secondary alcohol, which undergoes a 4-< //6>-cyclization (Equation 49). An X-ray structure of the product has been reported <2003JOC4422>. Section... 

Reaction with a-hydroxy epoxides. This regioselective reaction provides a key step in a synthesis of a unique furyl sesquiterpene, pleraplysillin-l (5), isolated from a marine sponge. Thus treatment of 1 with TifO-i-Pr), results in the enediol 2. which is converted... 

Perbenzoic acid In chloroform solution reacts with propylvinylcarblnol to give a hydroxy epoxide, l,2-epoxy-3-hydroxyhexane (50%). ... 

However, the unsaturated epoxide shown below reacts with cyanocuprates via an anti-S l -type mechanism. Directed epoxidation of the resultant ally lie alcoholate produces a hydroxy epoxide containing four stereodefined carbon centers. 

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. 

Epoxides — chlorohydrins This reagent converts epoxides into chlorohydrins. The same cleavage of a-hydroxy epoxides results in antt-chlorohydrins. 

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

Hydroxy-4,6-diphenyl-2-pyridone, 456 a-Hydroxy enones, 100, 101 a-Hydroxy epoxides, 60-61 3-Hydroxy esters, 164, 536 Hydroxyindolines, 99... 

In addition, r-butyl dilithioacetoacetate opens rra/ j-a-hydroxy epoxides regio-sclcctively (equation IV). 

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

Without doubt the most general method for the synthesis of chiral epoxides to date is that of Sharpless and co-workers such that the stereochemical outcome of the epoxidation of the allylie alcohol (6) holds true almost no matter the nature of to R. However, recent studies have shown that if t-butyl groups are incorporated at either the carbinol carbon or at the P- -position then the e.e.s of the a-hydroxy-epoxides are much reduced. The synthesis of a-keto-epoxides by the Darzens condensation is well known, but this year has seen the first example of chiral, aqueous-catalysed Darzens condensation to give the epoxy-ketones (7) albeit in only moderate optical and chemical yields (2-62% and 5- 3% respectively). ... 

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. 

A related reaction transforms non-racemic a-hydroxy epoxides (43) into 2-quartemary-1,3-diol monoesters (44) under the influence of samarium iodide and an aldehyde. Though 43 was used as a mixture of diastereomers, only one product diastereomer was observed. 

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. ... 

In a very similar marmer, the corresponding a-hydroxy epoxides 30 and 31 were prepared from the anti-epoxide 25 via 27. 

Further work by Schlessinger s group on approaches to vernolepin has revealed that t-butyl dilithioacetoacetate is a preferable reagent to dilithioacetate for the stereoselective synthesis of fused butyrolactones, originally developed by Danishefsky, from a-hydroxy-epoxides. The greater stereoselectivity of this reagent allows the preparation of pure c/s-fused lactones from /ran -a-hydroxy-epoxides (Scheme 10). 

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