Epoxidation, hydroxyl-directed

A hydroxyalkyl substituent on the internal carbon atom of the allene can also be used to direct the epoxidation reaction (Eq. 13.22) [26]. In the case of vinylallene 70, hydroxyl-directed epoxidation, followed by cyclization of the allene oxide, leads to cyclopentenone 71 in 60% yield, along with 20% of epoxide 72. The greater reactivity of the allene ensures that the epoxidation step will be selective however, in this case the selectivity is not complete. 

This strong directing effect can exert stereochemical control even when opposed by steric effects. Several examples of epoxidation reactions are given in Scheme 12.11. Entries 4 and 5 illustrate the hydroxyl directing effect. Other substituents capable of hydrogen bonding, in particular amides, also can exert a yyu-directing effect.67... 

In 1957, Henbest and Wilson reported hydroxyl-directed epoxidation using m-chloroperoxybenzoic acid (mCPBA) [3]. In the synthetic studies of juvenile... 

Hydroxyl-Directed Epoxidation with Peroxy Acids ° ... 

The hydroxyl-directed epoxidation of alkenes using peroxy acids is sensitive to the nature of the solvent. In the example below, alkene epoxidation occurs on the more accessible a-face when Et20 is used as solvent, whereas the use of CH2CI2 promotes hydroxyl-directed epoxidation on the p-face of the alkene. 

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. 

Reduction of 68a with L-selectride gave a 6 1 mixture of cyclopropyl carbinols in 92% with the (R)-alcohol predominating. Highly stereoselective hydroxyl-directed epoxidation from the a-face of the cyclopentane ring followed by silylation of the alcohol gave 69 (contaminated with a small amount of the product derived from the S-alcohol) in 84% yield. This intermediate was then coupled with the allenyl iodide 63 via the cuprate of 69 to afford an 86% yield of the diyne 70. Partial reduction of the alkynes followed by desilylation and chromatography afforded 71a and 71b in 79% and 13% yields, respectively. Conversion of the undesired major (R)-isomer 71a into the minor (5)-compound was accomplished via an oxidation-reduction sequence to provide 71b in 75% yield contaminated with 16% of the (R)-71a. Orthoester 71b was then cleaved... 

These include a variety of reactions including epoxidation, hydroxylation, and stereospecific synthesis either directly or by degradation of the alternative enantiomer. 

The next stage of the synthesis was ring oxygenation, to convert 8 into 13. The key to this tr ansformation was the observation that the amide oxygen of 8 participated in the solvolysis of the allylic bromide, setting, after hydrolysis, the new secondary stereocenter of 9. Hydroxyl-directed epoxidation gave 10, which was rearranged with Ti(0-i-C,H,) to 11. After some experimentation, it was found that the derived dione 12 could be reduced to the desired cis diol 13 with LiBr and LiAlH(0-t-CjH,),followed by NaBH /CeCl,. 

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