Selenium electrophile

The corresponding reactions using selenium electrophiles are called Selenenylcyclization.94 95 Carboxylate (selenylactonization), hydroxy (selenyletherification), and nitrogen (selenylamidation) groups can all be captured in appropriate cases. 

Part B of Scheme 4.5 gives some examples of cyclizations induced by selenium electrophiles. Entries 9 to 13 are various selenyletherifications. All exhibit anti stereochemistry. Entries 14 and 15 are selenyllactonizations. Entries 17 and 18 involve amido groups as the internal nucleophile. Entry 17 is an 5-exo cyclization in which the amido oxygen is the more reactive nucleophilic site, leading to an iminolactone. Geometric factors favor N-cyclization in the latter case. 

The mechanism of the asymmetric methoxyselenenylation of alkenes has been investigated using competition experiments and computational methods (Scheme 8). The experiments have demonstrated that the formation of the intermediate seleniranium ion (48) is reversible. Ions of type (49), generated in the addition of chiral selenium electrophiles to alkenes, are the key intermediates in the asymmetric methoxyselenenylation their stability is strongly dependent on the strength of the selenium-heteroatom interaction. Calculations have been carried out to determine the relative stabilities of the diastereoisomeric seleniranium ions (49). The results obtained from the calculations support the experimental flndings. ... 

Scheme 4.4 gives some examples of cyclizations induced by selenium electrophiles. 

Chiral solvomercuration was accomplished by carrying out the reaction of alkenes with Hg(OAc)2 in the presence of chiral quaternary ammonium salts synthesized from natural ephedrine.642 Chiral secondary alcohols may be isolated with ee values up to 96%. Chiral nitrogen-containing diselenides are transformed by perox-odisulfate to selenium electrophiles, which may add to alkenes to form oxyseleny-lation products. These are, however, not isolated but oxidized to induce oxidative p-hydride elimination to afford chiral allyl methyl ethers with ee values up to 75%.643... 

Grignard additions, 9, 59, 9, 64 indium-mediated allylation, 9, 687 in nickel complexes, 8, 150 ruthenium carbonyl reactions, 7, 142 ruthenium half-sandwiches, 6, 478 and selenium electrophiles, 9, W11 4( > 2 in vanadocene reactions, 5, 39 Nitrites, with trinuclear Os clusters, 6, 733 Nitroalkenes, Grignard additions, 9, 59-60 Nitroarenes, and Grignard reactivity, 9, 70 Nitrobenzenes, reductive aminocarbonylation, 11, 543... 

Recently, Wirth and Uehlin further extended the selenium-based solid-phase assisted chemistry by introducing a new polymer-bound chiral selenium electrophile 29. Regio-and stereoselective 1,2-methoxyselenylation of propenylbenzene gave intermediate adduct 30 which was cleaved by oxidative elimination via the selenoxide to yield the corresponding allylmethyl ether (Scheme 12) [38]. 

Well before the wide use of organoselenium compounds in chemistry, it was discovered that electrophilic selenium compounds of the type RSeX add stereospecifically to alkenes.45 Since that time this reaction has been an important tool in the portfolio of organic chemists and has been used even for the construction of complex molecules. Comprehensive reviews on this chemistry have appeared46-49 and in recent times the synthesis of chiral selenium electrophiles and their application in asymmetric synthesis has emerged. As shown in Scheme 1, the addition reactions of selenium electrophiles to alkenes are stereospecific anti additions. They involve the initial formation of seleniranium ion intermediates 1 which are immediately opened in the presence of nucleophiles. External nucleophiles lead to the formation of addition products 2. The addition to unsymmetrically substituted alkenes follows the thermodynamically favored Markovnikov orientation. The seleniranium ion intermediates of alkenes with internal nucleophiles such as 3 will be attacked intramolecularly to yield cyclic products 4 and 5 via either an endo or an exo pathway. Depending on the reaction conditions, the formation of the seleniranium ions can be reversible. 

There are various ways to generate and synthesize selenium electrophiles and some of these compounds are commercially available. The addition reaction can also be dependent on the counterion X of these reagents and several protocols have been developed to exchange the counterions. The most commonly used electrophile is the phenylselenyl electrophile and compounds like phenylselenenyl chloride 6 and phenylselenenyl bromide 7 are commercially available. They can also be easily generated from diphenyl diselenide 8 by treatment with sulfuryl chloride or elementary chlorine or bromine, respectively. Diselenides in general are very versatile precursors for selenium electrophiles. For addition reactions using external nucleophiles the use of selenenyl halides can lead to complications, because chloride or bromide ions can also act as nucleophiles and lead to undesired side-products. An... 

Figure 3 Selected chiral diselenides as precursors for the corresponding selenium electrophiles.

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). 

But due to the importance of nitrogen functional groups, the addition reactions of selenium electrophiles to alkenes using nitrogen nucleophiles represent another synthetically relevant process. Nitriles have been used as versatile... 

The seleniranium ion intermediates in the cyclization reactions can be either generated from the corresponding /3-hydroxyselenides as shown in Scheme 6 or from suitably substituted alkenes. Depending on the alkene and on the selenium electrophile, cyclizations can be performed with high selectivities. The size of the electrophilic reagent has... 

Many of the chiral selenium electrophiles have also been employed in cyclization reactions. Various internal nucleophiles can be used and access to different heterocycles is possible. Not only oxygen nucleophiles can be used for the synthesis of heterocyclic compounds, but also nitrogen nucleophiles are widely employed and even carbon nucleophiles can be used for the synthesis of carbacycles with new stereogenic centers. Oxygen nucleophiles have been widely used and some selected examples of selenolactonizations of unsaturated acids 50 and 52 and seleno-etherifications of unsaturated alcohols 54 and 56 are shown in Scheme 10. 

These reactions have also been performed using enantiomerically pure selenium electrophiles to access heterocyclic compounds with stereogenic centers. The yields and selectivities obtained using some selected chiral electrophiles generated from the diselenides are given in Table 2. 

As already mentioned, the nature of the selenium electrophile, the counter ion, solvents, and external additives coordinating to the electrophilic species influence the course of such cyclizations. They can also be used to control such processes with high degrees of efficiency. This has recently been demonstrated by the selective cyclization of substrate 58, which contains an alcohol and a carboxylic acid functionality as internal nucleophiles. Depending on the cyclizing nucleophile, electrophilic 5-m -cyclizations of alkene 58 can lead to two different... 

It is possible to perform selenenylation-deselenenylation sequences with only catalytic amounts of selenium species. This reaction sequence provides double bond transpositioned allylic ethers, allylic esters, or allylic alcohols 240 from the corresponding alkenes (Scheme 71). This sequence can be performed electrochemically, and the selenium electrophile is generated from catalytic amounts of diphenyl diselenide.467,468 It has been shown that the electrophilic selenium species can also be generated using diselenides and peroxosulfates together with copper (ii)... 

An inorganic selenium electrophile, selenium oxychloride (SeOCl2), has been utilized to prepare fused selenophenes <2002JOC2453>. Deprotonation of bis(cyanide) 104 with LDA followed by treatment with selenium oxychloride gave the benzo[c]selenophene 105 (Equation 15). This sequence also allowed for the preparation of a thieno[3,4-f]selenophene. 

An approach amenable to the preparation of various fused selenophenes and benzo[3]selenophenes involves the treatment of 1,4-dilithiated intermediates with bis(phenylsulfonyl)selenide 112 <1994CPB1437>. The synthetic sequence to the selenolo[2,3-/ ]selenophene 113 from 3-ethynylselenophene 110 is shown in Scheme 11 <1997H(45)1891>. A stereoselective hydroalumination of 110 with diisobutylaluminium hydride (DIBAL-H) followed by bromination with NBS gave dibromo compound 111. Dilithiation of 111 followed by treatment with selenium electrophile 112 gave 113. 

Selenium electrophiles add to conjugated dienes, only forming 1,2-adducts. Although Maricovnikov addition is seen, only a few examples have been reported. With allenes the additions are re ospeciric, with the i enylseleno group usually adding to the rp-carbon. Unfortunately, all four stereoisomers of halide attadc are seen with unsymmetrically substituted allenes. ... 

The addition of selenium electrophiles to activated >iT-bonds (Le. enol ethers) occurs readily. Enol ethers react with benzeneselenenyl loride to produce cis- and tranr-a-chloro-P-phenylseleno adducts. These adducts can be transformed into a,P-dichlorides or allylic chlorides. If the reaction is carried out in the presence of alcohols, stereoisomers of p-seleno mixed ketals are isolated (equation 12). ... 

It has been found that selenium electrophiles add to electron-deficient alkenes to form mixtures of adducts. Benzeneselenenyl chloride adds to chlorocyclohexene (17), producing a mixture of adducts (equation 13). 1,1-Difluoroethylene furnishes only one regioisomer (equation 14). Benzeneselenenyl... 

Benzeneselenenyl chloride adds to alkynes to produce mixtures of trans-alkene adducts. For example, the addition of benzeneselenenyl chloride to the alkyne (18) produces the alkene (19), which can be transformed to yield the unusual diene (20 equation 16). Alkynic alcohols give anti-Miukovnikov addition products under kinetic control. The reaction is thought to proceed dirough the selenirenium ion (21 equation 17). Selenium electrophiles add to a, -alkynic caibonyl moieties to produce cis adducts in good yield (equation 18). ... 

Another method of hydroxyselenenation involves trapping the seleniranium ion by water. The use of N-phenyl eleno-succinimide (N-PSS) or -phthalimide (N-PSP) as the selenium electrophile facilitates the reaction, since the sucdnimide or phthalimide anion is not as nucleophilic as water. With dienes, trans-annular cyclizations can occur, forming bis(phenylseleno) ethers in good yields (equation 22). ... 

Selenium electrophiles add to a wide range of ir-bonds, usually with good regiochemical and stereochemical results, to form a variety of selenium-containing intermediates. These intermediates can be further elaborated to desired products. 

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