Study of chemical compounds containing carbon-selenium bonds
Organoselenium chemistry is the science exploring the properties and reactivity of organoselenium compounds,
chemical compounds containing
carbon-to-
seleniumchemical bonds.[1][2][3] Selenium belongs with oxygen and sulfur to the
group 16 elements or chalcogens, and similarities in chemistry are to be expected. Organoselenium compounds are found at trace levels in ambient waters, soils and sediments.[4]
Selenium can exist with
oxidation state −2, +2, +4, +6. Se(II) is the dominant form in organoselenium chemistry. Down the group 16 column, the
bond strength becomes increasingly weaker (234
kJ/
mol for the C−Se bond and 272 kJ/mol for the C−S bond) and the
bond lengths longer (C−Se 198 pm, C−S 181 pm and C−O 141 pm). Selenium compounds are more
nucleophilic than the corresponding sulfur compounds and also more acidic. The
pKa values of XH2 are 16 for oxygen, 7 for sulfur and 3.8 for selenium. In contrast to
sulfoxides, the corresponding selenoxides are unstable in the presence of β-protons and this property is utilized in many
organic reactions of selenium, notably in selenoxide oxidations and in selenoxide eliminations.
Structural classification of organoselenium compounds
Selenols (R−SeH) are the selenium equivalents of
alcohols and
thiols. These compounds are relatively unstable and generally have an unpleasant smell.
Benzeneselenol (also called selenophenol or PhSeH) is more acidic (
pKa 5.9) than
thiophenol (pKa 6.5) and also oxidizes more readily to the
diselenide. Selenophenol is prepared by reduction of diphenyldiselenide.[7]
Diselenides (R−Se−Se−R) are the selenium equivalents of
peroxides and
disulfides. They are useful shelf-stable precursors to more reactive organoselenium reagents such as selenols and selanyl halides. Best known in organic chemistry is
diphenyldiselenide, prepared from
phenylmagnesium bromide and selenium followed by oxidation of the product PhSeMgBr.[8]
Selanyl halides (R−Se−Cl, R−Se−Br) are prepared by halogenation of diselenides. Bromination of diphenyldiselenide gives phenylselanyl bromide (PhSeBr). These compounds are sources of "PhSe+".
Selenides (R−Se−R), also called selenoethers, are the selenium equivalents of
ethers and
sulfides. One example is
dimethylselenide ((CH3)2Se). These are the most prevalent organoselenium compounds. Symmetrical selenides are usually prepared by alkylation of alkali metal selenide salts, e.g.
sodium selenide. Unsymmetrical selenides are prepared by alkylation of selenoates. These compounds typically react as
nucleophiles, e.g. with
alkyl halides (R'−X) to give selenonium salts[RR'R"Se]+X−. Divalent selenium can also interact with soft heteroatoms to form hypervalent selenium centers.[6] They also react in some circumstances as electrophiles, e.g. with
organolithium reagents (R'Li) to the
ate complexR'RRSe−Li+.
Selenoxides (R−Se(=O)−R) are the selenium equivalents of
sulfoxides. Most are unstable, undergoing the
selenoxide elimination, but can be notionally oxidized to selenonesR−Se(=O)2−R, the selenium analogues of
sulfones.
Selenuranes are
hypervalent organoselenium compounds, formally derived from the tetrahalides such as SeCl4. Examples are of the type Ar−SeCl3.[9] The chlorides are obtained by chlorination of the
selenenyl chloride.
Seleniranes are three-membered rings (the parent compound is selenirane or selenacyclobutane C2H4Se) related to
thiiranes but, unlike thiiranes, seleniranes are kinetically unstable, extruding selenium directly (without oxidation) to form
alkenes. This property has been utilized in synthetic organic chemistry.[10]
Selones (R2C=Se) are the selenium analogues of ketones. They are rare due to their tendency to
oligomerize.[11] Diselenobenzoquinone is stable as a metal complex.[12]Selenourea is an example of a stable compound containing a C=Se bond.
Thioselenides (R−Se−S−R), compounds with selenium(II)–sulfur(II) bonds, analogous to
disulfides.
Selenium, in the form of organoselenium compounds, is an essential micronutrient whose absence from the diet causes cardiac muscle and skeletal dysfunction. Organoselenium compounds are required for cellular defense against oxidative damage and for the correct functioning of the immune system. They may also play a role in prevention of premature aging and cancer. The source of Se used in biosynthesis is
selenophosphate.
Selenocysteine, called the twenty-first amino acid, is essential for ribosome-directed protein synthesis in some organisms.[14] More than 25 selenium-containing proteins (selenoproteins) are now known.[15] Most selenium-dependent enzymes contain
selenocysteine, which is related to
cysteine analog but with selenium replacing sulfur. This
amino acid is
encoded in a special manner by DNA.
Selenosulfides are also proposed as biochemical intermediates.
Selenomethionine is a selenide-containing amino acid that also occurs naturally, but is generated by post-transcriptional modification.
Organoselenium chemistry in organic synthesis
Organoselenium compounds are specialized but useful collection of reagents useful in organic synthesis, although they are generally excluded from processes useful to pharmaceuticals owing to regulatory issues. Their usefulness hinges on certain attributes, including
the weakness of the C−Se bond and
the easy oxidation of divalent selenium compounds.
Vinylic selenides
Vinylic selenides are organoselenium compounds that play a role in organic synthesis, especially in the development of convenient
stereoselective routes to functionalized
alkenes.[16] Although various methods are mentioned for the preparation of vinylic selenides, a more useful procedure has centered on the
nucleophilic or
electrophilic organoselenium addition to terminal or internal
alkynes.[17][18][19][20] For example, the
nucleophilic addition of selenophenol to alkynes affords, preferentially, the Z-vinylic selenides after longer reaction times at room temperature. The reaction is faster at a high temperature; however, the mixture of Z- and E-vinylic selenides was obtained in an almost 1:1 ratio.[21] On the other hand, the adducts depend on the nature of the
substituents at the
triple bond. Conversely, vinylic selenides can be prepared by
palladium-catalyzed hydroselenation of
alkynes to afford the Markovnikov adduct in good yields. There are some limitations associated with the methodologies to prepare vinylic selenides illustrated above; the procedures described employ diorganoyl diselenides or
selenophenol as starting materials, which are volatile and unstable and have an unpleasant odor. Also, the preparation of these compounds is complex.
In terms of
reaction mechanism, SeO2 and the allylic substrate react via
pericyclic process beginning with an
ene reaction that activates the C−H bond. The second step is a [2,3]
sigmatropic reaction. Oxidations involving selenium dioxide are often carried out with catalytic amounts of the selenium compound and in presence of a
sacrificial catalyst or co-oxidant such as
hydrogen peroxide.
SeO2-based oxidations sometimes afford carbonyl compounds such as
ketones,[22] β-
Pinene[23] and
cyclohexanone oxidation to 1,2-cyclohexanedione.[24] Oxidation of
ketones having α-methylene groups affords diketones. This type of oxidation with selenium oxide is called
Riley oxidation.[25]
In presence of a β-hydrogen, a selenide will give an
elimination reaction after oxidation, to leave behind an
alkene and a
SeO-selenoperoxol. The SeO-selenoperoxol is highly reactive and is not isolated as such. In the elimination reaction, all five participating reaction centers are
coplanar and, therefore, the reaction stereochemistry is
syn. Oxidizing agents used are
hydrogen peroxide,
ozone or
MCPBA. This reaction type is often used with
ketones leading to
enones. An example is acetylcyclohexanone elimination with
benzeneselenylchloride and
sodium hydride.[26]
The
Grieco elimination is a similar selenoxide elimination using o-nitrophenylselenocyanate and tributylphosphine to cause the elimination of the elements of H2O.
References
^A. Krief, L. Hevesi, Organoselenium Chemistry I. Functional Group Transformations., Springer, Berlin, 1988ISBN3-540-18629-8
^S. Patai, Z. Rappoport (Eds.), The Chemistry of Organic Selenium and Tellurium Compounds, John. Wiley and Sons, Chichester, Vol. 1, 1986ISBN0-471-90425-2
^Paulmier, C. Selenium Reagents and Intermediates in Organic Synthesis; Baldwin, J. E., Ed.; Pergamon Books Ltd.: New York, 1986ISBN0-08-032484-3
^Wallschläger, D.; Feldmann, F. (2010). Formation, Occurrence, Significance, and Analysis of Organoselenium and Organotellurium Compounds in the Environment. Metal Ions in Life Sciences. Vol. 7, Organometallics in Environment and Toxicology. RSC Publishing. pp. 319–364.
ISBN978-1-84755-177-1.
^Okazaki, R.; Tokitoh, N. (2000). "Heavy ketones, the heavier element congeners of a ketone". Accounts of Chemical Research. 33 (9): 625–630.
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^Amouri, H.; Moussa, J.; Renfrew, A. K.; Dyson, P. J.; Rager, M. N.; Chamoreau, L.-M. (2010). "Discovery, Structure, and Anticancer Activity of an Iridium Complex of Diselenobenzoquinone". Angewandte Chemie International Edition. 49 (41): 7530–7533.
doi:
10.1002/anie.201002532.
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^Zeni, Gilson; Stracke, Marcelo P.; Nogueira, Cristina W.;
Braga, Antonio L.; Menezes, Paulo H.; Stefani, Helio A. (2004). "Hydroselenation of Alkynes by Lithium Butylselenolate: an Approach in the Synthesis of Vinylic Selenides". Organic Letters. 6 (7): 1135–8.
doi:
10.1021/ol0498904.
PMID15040741.
^Dabdoub, M (2001). "Synthesis of (Z)-1-phenylseleno-1,4-diorganyl-1-buten-3-ynes: hydroselenation of symmetrical and unsymmetrical 1,4-diorganyl-1,3-butadiynes". Tetrahedron. 57 (20): 4271–4276.
doi:
10.1016/S0040-4020(01)00337-4.
^Doregobarros, O; Lang, E; Deoliveira, C; Peppe, C; Zeni, G (2002). "Indium(I) iodide-mediated chemio-, regio-, and stereoselective hydroselenation of 2-alkyn-1-ol derivatives". Tetrahedron Letters. 43 (44): 7921.
doi:
10.1016/S0040-4039(02)01904-4.
^Comasseto, J (1981). "Stereoselective synthesis of vinylic selenides". Journal of Organometallic Chemistry. 216 (3): 287–294.
doi:
10.1016/S0022-328X(00)85812-X.
^Riley, Harry Lister; Morley, John Frederick; Friend, Norman Alfred Child (1932). "255. Selenium dioxide, a new oxidising agent. Part I. Its reaction with aldehydes and ketones". Journal of the Chemical Society (Resumed): 1875.
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