Allyl selenoxide elimination

Allylic alcohols can also be obtained from epoxides by ring opening with a selenide anion followed by elimination via the selenoxide (see Section 6.8.3 for discussion of selenoxide elimination). The elimination occurs regiospecifically away from the hydroxy group.116 117 118... 

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). 

A number of useful enantioselective syntheses can be performed by attaching a chiral auxihary group to the selenium atom of an appropriate reagent. Examples of such chiral auxiliaries include (49-53). Most of the asymmetric selenium reactions reported to date have involved inter- or intramolecular electrophilic additions to alkenes (i.e. enantioselective variations of processes such as shown in equations (23) and (15), respectively) but others include the desymmefrization of epoxides by ringopening with chiral selenolates, asymmetric selenoxide eliminations to afford chiral allenes or cyclohexenes, and the enantioselective formation of allylic alcohols by [2,3]sigmafropic rearrangement of allylic selenoxides or related species. 

Asymmetric selenoxide elimination of the optically active vinyl selenoxides affords optically active allenes and cyclohexylidenes. On the other hand, asymmetric [2,3]sigmatropic rearrangement of allylic selenoxides, selenimides, and selenium ylides leads to the formation of the corresponding optically active allylic alcohols, amines, and homoallylic selenides, respectively. 

Oxyselenenylation-oxidative deselenenylation (oxyselenenylation-selenoxide elimination) sequence provides the double-bond transpositioned allylic alcohols and ethers from alkenes. Oxyselenenylation of alkenes and its asymmetric... 

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 regioselectivity of selenoxide elimination is similar to that observed for sulfoxides in that it takes place preferentially towards allylic, propargylic and benzylic hydrogens to form conjugated alkenes with CH3 > CH2 CH, e.g. the conjugated diene (103) was obtained from selenoxide (102 equation 40). ... 

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). ... 

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. ... 

There are also stereochemical considerations here and Holmes used the Evans asymmetric aldol reaction (chapter 27) to make the starting material 174 R=Bn. The formation of any allyl vinyl ether reagent involves no change in the stereochemistry of the allyl alcohol - this is acetal exchange at the vinyl ether or acetal centre. The enol ether was added in masked form as a selenium compound 175 (chapter 32) as selenoxides eliminate at room temperature. The stereochemistry is developed directly from that in 177 as it transforms during the [3,3] shift. 

Allyl vinyl ethers have also been obtained by elimination reactions, e.g., intramolecular bromo-etherification/base-catalyzed hydrogen bromide elimination164 166( 0r the phenylseleno etherifi-cation/selenoxide elimination reaction158 167. Tertiary allylic alcohols have been vinylated by a Michael-type addition to a vinyl sulfoxide followed by elimination of benzenesulfenic acid168. 

Asymmetric methoxyselenenylation. A chirally constituted Ar SeBr reagent induces asymmetric addition to double bonds. Chiral allyl ethers are accessible after oxidation and selenoxide elimination. 

Sulfides and selenides both stabilize an a-carbanion (see Section 1.1.5.2) and alkylation followed by elimination provides a route to substituted alkenes. Some examples of selenoxide eliminations are given in Schemes 2.24—2.26. Like the other syn eliminations described in this section, the regioselectivity of selenoxide elimination can be poor. Elimination normally takes place preferentially towards a conjugating (3-substituent or away from an electronegative p-substituent. This latter facet allows a good method for converting epoxides into allylic alcohols. 

Selenoxides are even more reactive than amine oxides toward p elimination. In fact, many selenoxides react spontaneously when generated at room temperature. Synthetic procedures based on selenoxide eliminations usually involve synthesis of the corresponding selenide followed by oxidation and in situ elimination. We have already discussed examples of these procedures in Section 4.7, where the conversion of ketones and esters to their a,j5-unsaturated derivatives was considered. Selenides can also be prepared by electrophilic addition of selenenyl halides and related compounds to alkenes (see Section 4.5). Selenide anions are powerfiil nucleophiles that can displace halides or tosylates and open epoxides. Selenide substituents stabilize an adjacent carbanion so that a-selenenyl carbanions can be prepared. One versatile procedure involves conversion of a ketone to a bis-selenoketal which can then be cleaved by w-butyllithium. " The carbanions in turn add to ketones to give jS-hydroxyselenides. Elimination gives an allylic alcohol. 

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