Selenoxides synthesis

Selenoxides are even more reactive than sulfoxides toward (3-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 4.3.2, where the conversion of ketones and esters to their a, (3-unsaturated derivatives is considered. Selenides can... 

In another elegant approach (Scheme 18), a synthesis of 5-alkenyl-substituted 1,2,4-oxadiazoles relies upon a selenoxide. -elimination at the 5-a-carbon of the selenium resin-supported 1,2,4-oxadiazole 152. Access to compound 152 was achieved in two steps from the supported oxadiazole 150, which underwent deprotonation and alkylation at the 5-a-carbon to give the a-alkylated selenium resin 151. 1,3-Dipolar cycloaddition then gave the selenium resin-supported 1,2,4-oxadiazole 152 <2005JC0726>. 

The most versatile approach to disulfonium dications - reaction of triflic anhydride with monosulfoxides of bis-sulfides - has certain limitations in the case of selenium. Most importantly, selenoxides that contain (3-hydrogen atoms are labile.120 122 Trimethylsilyl triflate was used instead of triflic anhydride for synthesis of dication 112 from a selenoxide 111 (Scheme 43).123... 

In the case of the most reactive compounds, substitution at the carbon atom of diselenonium and ditelluronium dications is also a possible pathway. For example, formation of diselenide 117 from selenoxide 115 was explained by demethylation of intermediate dication 116 with trifluoroacetate anion.126 Dealkylation of salt 118, which is stable up to —20°C, leads to formation of nitrilium salt 119. The latter is transformed to amide 120 upon hydrolysis.64 Dealkylation of intermediate diselenonium dication 122 was suggested as the key step in the oxidative synthesis of 1,2,4-diselenazolidines 123 from eight-membered heterocycles 121 (Scheme 46).127... 

On the other hand, optically active telluroxides have not been isolated until recently, although it has been surmised that they are key intermediates in asymmetric synthesis.3,4 In 1997, optically active telluroxides 3, stabilized by bulky substituents toward racemization, were isolated for the first time by liquid chromatography on optically active columns.13,14 The stereochemistry was determined by comparing their chiroptical properties with those of chiral selenoxides with known absolute configurations. The stability of the chiral telluroxides toward racemization was found to be lower than that of the corresponding selenoxides, and the racemization mechanism that involved formation of the achiral hydrate by reaction of water was also clarified. Telluroxides 4 and 5, which were thermodynamically stabilized by nitrogen-tellurium interactions, were also optically resolved and their absolute configurations and stability were studied (Scheme 2).12,14... 

Furthermore, the first catalytic synthesis of allenes with high enantiomeric purity [15c, 25] was applied recently to the pheromone 12 by Ogasawara and Hayashi [26] (Scheme 18.7). Their palladium-catalyzed SN2 -substitution process of the bromo-diene 16 with dimethyl malonate in the presence of cesium tert-butanolate and catalytic amounts of the chiral ligand (R)-Segphos furnished allene 17 with 77% ee. Subsequent transformation into the desired target molecule 12 via decarboxylation and selenoxide elimination proceeded without appreciable loss of stereochemical purity and again (cf. Scheme 18.5) led to the formation of the allenic pheromone in practically the same enantiomeric ratio as in the natural sample. 

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). 

Selenoxide elimination.3 A short synthesis of royal jelly acid (2) from a commercially available starting material (1) involves phenylselenenylalion followed by concurrent ozonation of a double bond and selenoxide elimination (equation I). 

In a further development of this approach, the synthesis of cr,/J-acetylenic acyl silanes has been achieved as shown in Scheme 4514. Oxidation of the 3-selenenyl allenyl ethers (16) with m-chloroperbenzoic acid at —78 °C gave the corresponding unstable selenoxides, which underwent in situ [2,3] sigmatropic shift producing acetals (17). Loss of selenenyl ester on work-up gave the cr,/J-acetylenic acyl silanes in ca 50% yields. 

Further, medium-sized lactones have been prepared by a thermal elimination-Claisen rearrangement sequence, of unsaturated selenoxide cyclic acetals (equation 198)710. The reaction affords reasonable yields of these useful lactones upon treatment with DBU and a siloxy species at 185 °C. The reaction has been used as the key step in the synthesis of (-l-)-laurencin, which contains an 8-membered cyclic ether moiety711. 

The final step in a recent synthesis of cannabichromene (2) is the aromatization of the cyclohexenone ring of 1. Reagents used for this purpose also attack the double bond in the side chain, but the desired reaction was effected by treatment of the lithium enolate of 1 with benzeneselenenyl chloride followed by selenoxide elimination in the presence of 3,5-dimethoxyaniline.5... 

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 readily available reagent diphenyl selenoxide has been used as a mild and selective oxidant in the synthesis of aporphines (and homoaporphines). When the benzylisoquinoline (13) was treated with one equivalent of the reagent at room temperature in methanol, and the product was O- methylated with diazomethane, the aporphine (14) was obtained in 80% yield. The alternative use of chloranil, which is a commonly used oxidant for catechols, yielded less than 10% of (14).20... 

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],... 

Additions of selenium electrophiles to double bonds have most frequently been used as part of a synthetic sequence, because the addition products are very versatile building blocks in synthesis. They can undergo a variety of subsequent transformations and can, therefore, serve as precursors for the generation of radicals 27 in radical reactions. Using a selenoxide elimination, new double bonds as shown in 28 can be generated. After oxidation of the selenide to the seleneone the selenium moiety can be replaced by a second nucleophile to generate compounds of type 29 (Scheme 2). 

As shown in Scheme 42, selenoxides are crucial intermediates in the selenoxide elimination reactions. These are syn-eliminations which proceed via an intramolecular mechanism to yield alkenes as reaction products. The regioselectivities of these eliminations are dependent on the nature of the substituent Y in the / -position as shown in Scheme 44.286 The mild reaction conditions for these elimination reactions make them highly useful in organic synthesis and theoretical studies on this reaction have been carried out as well.286... 

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... 

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