Phenylselenenyl chloride

Benzeneselenenyl chloride (benzeneselenyl chloride, phenylselenenyl chloride) [5707-04-0] M 191.5, m 59-60 , 64-65 , b 92 /5mm, 120 /20mm. Purified by distn in vac and recrystn (orange needles) from hexane [Foster J Am Chem Soc 55 822 1933, Foster et al. Reel Trav Chim, Pays-Bas 53 405, 408 1934-, Behaghel and Seibert Chem Ber661 4 1933.] HIGHLY TOXIC. 

Fluorinated tertiary selenoetheis are prepared by reaction of branched per-fluoroolefins with an alkali metal fluoride and phenylselenenyl chloride 1S2] (equation 31)... 

When reactions with phenylselenenyl chloride are carried out in aqueous acetonitrile solution, (3-hydroxyselenides are formed as the result of solvolysis of the chloride.59... 

Various electrophilic selenium reagents such as those described in Scheme 4.3 can be used. V-Phenylselenylphthalimide is an excellent reagent for this process and permits the formation of large ring lactones." The advantage of the reagent in this particular application is the low nucleophilicity of phthalimide, which does not compete with the remote internal nucleophile. The reaction of phenylselenenyl chloride or V-phenylselenenylphthalimide with unsaturated alcohols leads to formation of (3-phenylselenenyl ethers. 

Compounds 120 were used as the starting material for establishing the stereoselectivity of the reaction of allenephosphonates with phenylselenenyl chloride (Scheme 49) [114],... 

Thionucleosides are of considerable interest, and can be prepared stereoselectively by the electrophile-initiated addition of the base to a thiofuranoid glycal. For example, reaction of substrate 15 with the protected uracil 16 and phenylselenenyl chloride gave compound 17 as the sole detectable stereoisomer (Equation 3) <1998TL3713, 2002JOC5959, 2003NN763, 2004OL2645>. 

The regiochemistry of the addition of phenylselenenyl chloride to allylic alcohols and their esters [109] can simply be rationalized by using the polarity alternation rule except in those cases where steric factors become the controlling parameters. 

Most of the types of cyclofunctionalization reaction discussed in this chapter have been shown to result in stereospecific anti addition across the ir-bond. This result suggests that the important intermediates are ir-complexes (B) or onium ions (C) rather than carbocations (E). In the case of cyclofunctionalization with some electrophiles, such as phenylselenenyl chloride, it has been shown that the formation of addition products such as (D) occurs faster than the cyclization.4 Stereospecific trans addition in these reactions then requires conversion to intermediates (B) or (C) before nucleophilic attack, since nucleophilic attack on intermediate (D) and substitution of X with inversion would result in syn addition. Thus, in the discussions below, intermediates (B) and/or (C) are considered to be the key... 

Cyclization to yield fused ring y-lactones has also been effected using A V-dialkylamide derivatives as the nucleophile, as shown in equation (8).29 39-40 Isolation of the fused ring iminolactone from cyclization of an yV-monoalkylamide derivative with phenylselenenyl chloride has been repotted also.41... 

Examples of 5-exo cyclizations in which the hydroxy group is constrained by a five-membered ring are shown by equation (53). The stereoselectivity in these cyclizations ranges from quite high in iodocy-clization (9 1 in H2O and >20 1 in CH2CI2) to only moderate (2—3 1) with mercury and phenylselenenyl chloride. P This type of cyclization has been widely applied to synthesis of prostacyclins.146 Similar cyclizations with dimethyl(methylthio)sulfonium fluoroborate have been reported recently.35... 

Whereas chlorine or iodine as electrophiles do not provide clean addition products61 , phenylselenenyl chloride opens siloxycyclopropanes forming a-selenenylated Y-oxoesters 81). Usually, however, this process is better conducted in the presence of Lewis acids at low temperature (vide infra, section 4.5.1). 

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... 

The cyclization of 3-methyl-4-pentenamide (7) proceeds with 1,2-asymmetric induction when phenylselenenyl triflate22, easily prepared from phenylselenenyl chloride and silver trifluoro-methanesulfonate in dichloromethane or toluene, is employed as the electrophile. By in situ addition of the amide at 0 3C an 83 17 mixture of the trans- and cw-lactones 8 is obtained in 49% yield. 

The second example27 belongs to the category of addition via onium-type intermediates . It exemplifies how the choice of the electrophile may affect the stereochemical course of the cyclization. When the hydroxy cnones rac-4a, b were treated with mercury(II) trifluoroacetate, both (E)- and (Z)-enone afforded basically the same yield and distribution of the diastereomer-ic cyclization products rac-5a, b. However, when phenylselenenyl chloride was used as electrophile, the (Z/Zj-isomers rac-4a, b produced quite contrasting ratios of the products rac-5 a, b. This result was interpreted in terms of EjZ equilibration in a single-bonded cationic adduct of the mercuric ions vs. nucleophilic attack on a rigid epi-selenonium ion27. 

Treatment of the hydroxy enamide rat -1 with phenylselenenyl chloride gave the 2,5-disubstitut-ed tetrahydrofurans rac-254, with predominant cis orientation of the 2,5-substituents. 

Additional application of oxidants such as hydrogen peroxide to the selenoethers thus formed gives rise to the corresponding alkenes. Thus, the consecutive treatment of the ribose derivative 3 with phenylselenenyl chloride and hydrogen peroxide resulted in a mixture of the a- and /5-anomeric C-glycosides showdomycin (4) and epishowdomycin (epi-4)55. 

Selenolactonization of ( )-2,4-cyclohexadieny acetic acid with phenylselenenyl chloride occurred exclusively in a 1,4-(fl ri)-fashion with high stereoselectivity. The resulting selenide underwent rearrangement after oxidation to the stereochemically defined cts-lactone with a tram-hydroxy group25 27. 

Selenolactonization A solution of 138 mg (1 mmol) of 2,4-cyclohexadienylacctic acid in 20 mL of dry CH2C1j is stirred with 101 mg (1 mmol) of Et3N at 30 °C for 15 min, cooled to — 72 °C and treated slowly with 211 mg (1.1 mmol) of phenylselenenyl chloride. It is allowed to warm to r.t. and further stirred for 1 h. The solution is concentrated and chromatographed using 50% CH2C12 in hexane as eluant. The selenolac-tone so obtained (70%) is crystallized from Et2() as colorless needles mp 80 C. 

In the syntheses of fragments of the antiparasitic compounds avermectins or milbemycins selenocycloetherification was used for the construction of a highly substituted hexahydroben-zofuran derivative (Table 8, entry 8)29. The intramolecular cyclization of a cyclohexadienyl hydroxymethyl ketone with phenylselenenyl chloride proceeded stereoselectively in a 1,4-fash-ion resulting in an anti orientation of oxygen and selenium. This was followed by oxidation and rearrangement. 

Phenylselenenyl chloride remains the reagent of choice for direct selenenylation of ketones. The bromide is less suitable since a competing bromination of the substrate may occur diphenyl diselenide and areneselenenyl amides are not sufficiently reactive towards ketones. The selenenylation reaction of ketones often displays high chemo-, regio- and stereoselectivity. Thus, in the reaction of phenylselenenyl chloride with the trione 1 only one carbonyl group is selectively functionalized 2. 

The acid-catalyzed reaction of phenylselenenyl chloride with 3-deoxy-7V-ethoxycarbonyl-7,8-dihydromorphinone allows introduction of the phenylseleno substituent at C-7 in 5 with R configuration4. 

A solution of 7 g (21.4 mmol) of 3-deoxy-jV-ethoxycarbonyl-7,8-dihydromorphine. 4.93 g (25.7 mmol) of phenylselenenyl chloride and 4 mL of 37% HCI in 110 mL of EiOAc is stirred at 25 "C for 5 h. Then, the mixture is washed with H20, sat. NaHCO, and sat. NaCl, dried and evaporated. Recrystallization of the residue from EtOH/EtOAc yields virtually pure 5 yield 8.9 g (86%) as pale yellow crystals. An analytical sample is obtained by filtration of this material through silica gel and recrystallization from EtOH/EtOAc mp 151.5-154.5 CC. 

Selenenylation of the bicyclic epoxyketone dihydrostramonin B (6) in ethyl acetate with phenylselenenyl chloride in the presence of Dowex 50-X8(H4) affords the selenide 7 in 77% yield as a mixture of diastereomers5. 

The direct selenenylation technique is well suited to ketones that are not acid labile but cannot be applied to acid-sensitive derivatives however, in such cases an alternative procedure which employs basic conditions is commonly used. The ketone is first converted to the lithium enolate, usually with lithium diisopropylaniide, and then selenenylated with phenylselenenyl chloride or bromide or diphenyl diselenide8. 

The reaction is rapid even at low temperature and is generally carried out at — 78 °C. The kinetic enolates are produced from unsymmetrical ketones under these conditions and the phenylseleno group is introduced at the less substituted position usually with high regio- and diastereoselectivity. Thus, the reaction of tricyclic ketone 11 with lithium diisopropylamide followed by reaction with phenylselenenyl chloride gives a mixture of a-selenenylated enones 12 in 3 1 ratio9 . 

Kinetic dcprotonation of 3,4,4a,5,6,7-hexahydro-4a,8-dimethyl-l(2//)-naphthalenone and treatment of the resulting enolate with phenylselenenyl chloride affords the (2S )-2-phenylse-leno ketone (2S )-14 exclusively. When (2S )-14 is deprotonated and reprotonated with saturated ammonium chloride it is converted into the (2/ )-enantiomeru. 

The Michael addition of organometallic nucleophiles to enones in the presence of copper(I) salts produces enolates which on treatment with phenylselenenyl bromide give a-seleno ketones. For example, the reaction of the zirconium enolate of 15 with a mixture of phenylselenenyl bromide and diphenyl diselenide affords a mixture of diastereomeric (2R)- and (2V)-phenylse-leno)cyclopentanones 16 in 50% and 31 % isolated yield, respectively12. The analogous reaction with phenylselenenyl chloride gives only the tram-isomer in 27% yield formation of the cw-product is not observed12. 

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