Directed epoxidation, stereoselective

A fully stereocontrolled preparation of 499 has recently been completed by Paquette and coworkers When triene 508 was treated with /7-toluenesulfonyl-acetylene, highly stereoselective addition from the endo surface occurred to deliver an adduct which was directly epoxidized (Scheme XLI). The proximity of the two jc bonds in 509 allows for ready photocyclization. Oxidative cleavage of 510 afforded... 

Allyl- and vinylsilane chemistry was one of the first areas of reagent synthesis impacted by CM methodology. Allylsilanes are commonly employed in nucleophilic additions to carbonyl compounds, epoxides, and Michael acceptors (the Sakurai reaction) vinylsilanes are useful reagents for palladium-coupling reactions. As the ubiquitous application of CM to this substrate class has recently been described in several excellent reviews, this topic will not be discussed in detail, with the exception of the use of silane moieties to direct CM stereoselectivity (previously discussed in Section 11.06.3.2). 

The presence of the substrate of functional groups capable of interacting with the metal directs the stereoselectivity of the epoxidation, as shown by the comparative reactivity of (82) towards TAHP/Mo(CO)6 and peroxybenzoic acid (PBA).241... 

The stereoselectivities of the epoxidations of the htMnoallylic alcohols (104) and (105) and their benzoates (106) and (107) have been studied. The amide-directed epoxidation of the cis-disubstituted al-kene (108) is stereoselective (equation 37). ... 

The most important hydrogen bond donating group in directed epoxidations is the hydroxy group. For allylic or homoallylic alcohols, peracids or tert-butyl hydroperoxide/vanadylbis[2,4-pentanedionate] (see Houben-Weyl, Vol. IV/la, p 231) are generally the most efficient reagent systems less common catalysts are tri-te/ f-butoxyaluminum, dibutyltin oxide, and molybdenum- and titanium-based systems (see Houben-Weyl, Vol. IV/la, p 227, Vol. E13/2, p 1176). The two classes of reactions show distinct differences in their stereoselectivity patterns. 

This procedure is primarily of industrial importance. It is sufficient to point out that oxirane, which is of great importance in industrial syntheses, is produced entirely by direct catalytic oxidation from ethylene. In the organic preparative laboratory, the direct epoxidation of olefins is carried out in the liquid phase. Independently of the reaction conditions employed, the reaction proceeds via a radical mechanism, generally with a poor yield, with low selectivity, and only rarely stereoselectively. 

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. 

The use of a dihydroxylation procedure can provide high stereoselectivity compared to a direct epoxidation method. The conditions for the dihydroxylation of 5 had to be modified due to the low solubility of the substrate and the base sensitivity of the product (Scheme 3.6). The result was a more efficient process for scale-up compared to an epoxidation [163]. 

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... 

Now the time has come to react one of the alkenes and not the other. The reaction chosen was epoxidation as we could expect only the more nucleophilic non-conjugated alkene to be attacked by mCPBA. Direct epoxidation of the lactone 155 gave only the epoxide 164 with the correct chemoselectivity but the wrong stereoselectivity. The lactone bridge directs the peracid to the top face of the alkene. 

Another modification of Route B requires enantioselective reduction of ketones (E)-27 or stereoselective carbon-carbon bond formation at C-1 of (E)-27 (R = H) with appropriate organometallic species in the presence of chiral additives, both of which successfully supply the optically active (E)-26. The resulting chiral allylic alcohols (E)-26 are subjected to hydrogen bond-directed epoxidation with mCPBA, leading to the diastereoselective formation of syn-epoxy alcohols. In conplementary fashion, antz-selective epoxidation is possible using the Sharpless protocol. ... 

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