Selenoxides alcohol synthesis

Certain chiral epoxides can be prepared from fl-hydroxyselenides (e.g., 43), typically intermediates for allylic alcohol synthesis. The novel reactivity of these substrates seems to be restricted to those cyclic compounds in which the hydroxy and the selenoxide groups can achieve an antiperiplanar disposition [95TL5079],... 

However, the regioselectivity is also affected by statistical factors and if these two effects are in opposition, then the regioselectivity may not be very great, e.g. Scheme 22. However, one extremely useful aspect of the regioselectivity of selenoxide elimination is the marked preference for elimination to take place away from an electronegative atom. P-Oxygen substituents in particular are very effective at directing the elimination away from themselves, as indicated in equations (41) and (42), and this forms the basis of a very useful allylic alcohol synthesis (Section 5.3.4.2.2). ... 

Phenylselenoetherification (8, 26-28). This cyclization has been described in detail.6 The 16 examples reported indicate that the reaction is applicable to unsaturated primary, secondary, and tertiary alcohols as well as to phenols. The most important use is for synthesis of allylic ethers by syn-selenoxide elimination, which proceeds selectively away from the oxygen. The value of this methodology for synthesis of natural products is illustrated by a synthesis of a muscarine analog (1), outlined in equation (I). 

Iodine-catalysed hydroperoxidation of cyclic and acyclic ketones with aqueous hydrogen peroxide in acetonitrile is an efficient and eco-friendly method for the synthesis of gem -dihydroperoxides and the reaction is conducted in a neutral medium with a readily available low-cost oxidant and catalyst.218 Aryl benzyl selenoxides, particularly benzyl 3,5-bis(trifluoromethyl)phenyl selenoxide, are excellent catalysts for the epoxidation of alkenes and Baeyer-Villiger oxidation of aldehydes and ketones with hydrogen peroxide.219 Efficient, eco-friendly, and selective oxidation of secondary alcohols is achieved with hydrogen peroxide using aqueous hydrogen bromide as a catalyst. Other peroxides such as i-butyl hydroperoxide (TBHP), sodium... 

The use of allylic selenides 166 in oxidation reaction leads to intermediate selenoxides 167, which can undergo [2,3]sigmatropic rearrangements to the corresponding allylic selenenates 168. These componds will lead to allylic alcohols 169 after hydrolysis (Scheme 48). This is also a versatile procedure for the synthesis of optically active allylic alcohols, provided that either an asymmetric oxidation or an optically active selenide is used for the rearrangement. Detailed kinetic and thermodynamic studies of [2,3]sigmatropic rearrangements of allylic selenoxides have also been reported.290-294... 

The first synthesis of (R)-4,5-dihydro-37/-dinaphtho[2,l-f l, 2 -i ]selenepin oxide 110 has been achieved from (R)-(+)-l,l -bi-2-naphthol, which in turn was obtained by resolution of raol,l -bi-2-naphthol. Palladium-catalyzed alkoxy carbonylation of the alcohol 108 gave a dimethyl ester which was then reduced by LiAlfLi, and the resultant diol converted to key intermediate chloride 109. Cyclization with sodium selenide gave a novel enantiomerically pure selenide, which upon oxidation yielded the desired selenoxide 110 <2000SC2975>. 

This reaction allows the synthesis of (i) p,p -dienols by oxidation of p-hydroxy-y-alkenyl sel-enides or more conveniently from a-lithioalkyl selenoxides and enones (Scheme 136 and 166) (ii) p,5-dienols from l-lithio-3-alkenyl phenyl selenoxides and carbonyl compounds (Scheme 177) and (iii) 2-(r-hydroxyalkyl)-1,3-butadienes from 1-methylselenocyclobutyllithium and carbonyl compounds (Scheme 178). a,p-Unsaturated alcohols bearing a methylselenoxy or a phenylselenoxy group at the a-position do not lead on thermolysis to propargyl alcohols however, those be ng a (trifluoro-methylphenyl)selenoxy moiety at the a-position are valuable precursors of such con unds (Scheme 179). ... 

Selenoxide elimination is now widely used for the synthesis of a,p-unsaturated carbonyl compounds, allyl alcohols and terminal alkenes since it proceeds under milder conditions than those required for sulfoxide or any of the other eliminations discussed in this chapter. The selenoxides are usually generated by oxidation of the parent selenide using hydrogen peroxide, sodium periodide, a peroxy acid or ozone, and are not usually isolated, the selenoxide fragmenting in situ. The other product of the elimination, the selenenic acid, needs to be removed from the reaction mixture as efficiently as possible. It can disproportionate with any remaining selenoxide to form the conesponding selenide and seleninic acid, or undergo electrophilic addition to the alkene to form a -hydroxy selenide, as shown in... 

The selenoxide elimination of -hydroxy selenoxides, which takes place regioselectively away from the hydroxy group, e.g. as in equation (41), has been developed into a useful synthesis of allylic alcohols. Similar regioselective elimination is also observed for p-acyloxy selenoxides, as shown in equations (39) and (42), and for P-acylamino selenoxides e.g. 115 equation 46). However, the regioselectivity of elimination is less useful for P-chloro and P-amino selenoxides. -" ... 

Although the preference for selenoxide elimination to take place away from a 3-oxygen substituent is very marked, the elimination will still occur towards the oxygen substituent if there is no alternative. This has been used in elegant syntheses of ketene acetals derived from allylic alcohols, which are useful Claisen rearrangement precursors (Scheme 36)" and for the synthesis of phenylseleno methyl ketones. ... 

The oxidative elimination of primary selenides, readily available from the corresponding alcohol by treatment with an arylselenocyanate and tributylphosphine, is an attractive approach to the synthesis of terminal alkenes." However these reactions are relatively slow when compared with other selenoxide eliminations allowing side reactions, in particular the addition of the areneselenenic acid to the newly formed double bond (Scheme 23), to compete. It has been found that arylselenides with electron-withdrawing substituents fragment more readily, giving improved yields of products, in particular the use of o-nitrophenyl and 2-pyridyl selenides has been recommended (Scheme 37). Often for the elimina-... 

Allylic alcohols. Two laboratories have reported a novel synthesis of allyUc alcohols from two carbonyl compounds. One carbonyl compound (1) is treated with benzeneselenol (2 eq.) under acid catalysis to give a selenoacetal (2). This product can be cleaved to the carbanion (a) by n-butyllithium in THE at -78. The carbanion reacts with a second aldehyde or ketone to form a /3-hydroxyselenide (3). The final step involves oxidation and selenoxide fragmentation to the aUyUc alcohol (4). j3-Hydroxyselenides have been obtained by... 

A similar variant of the Claisen rearrangement reacts allyl alcohols such as 600 with 3-bromoselenides (601) to give 602. Oxidation to the transient selenoxide (603) and in situ syn-elimination (sec. 2.9.C.vi) gave 604. This ether possessed the proper functionality for Claisen rearrangement to the final product, ester 605.450 Petrzilka used a variation of this method for the synthesis of phoracantholide J.451... 

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