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II. Selenides

  • Page ID
    24018
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    A. Reaction Mechanism

    The SH2 mechanism pictured in Scheme 1 and the stepwise process shown in Scheme 2 both are considered possibilities for explaining the reac­tion between a phenyl selenide and a tin- or silicon-centered radical.6 The tris(tri­methylsilyl)silyl radical (1) is used in illustrating these two mechan­isms because it plays a significant role in the choice between them.2 A way for making this choice begins with the observation that the absolute rate constant for reaction of 1 with cyclohexyl phenyl selenide to give cyclo­hexane (kSe) is 9.6 x 107 M-1s-1 and the rate constant for reaction of 1-bromo­octane to give octane (kBr) is 2.0 x 107 M-1s-1. If every cyclohexyl and 1-octyl radical is formed irreversibly and abstracts a hydrogen atom from (CH3Si)3SiH (Scheme 3), then the ratio kSe/kBr should be equal to the ratio of cyclo­hex­ane to octane formed when an equal-molar mixture of the selenide and bromide react with a limited amount of 1. When an experiment to test this possibility is conducted, the ratio of cyclohexane to octane in the product mixture is 0.08, a value far less than the 4.8 ratio predicted from the absolute rate constants (Scheme 3).2 This result is inconsistent with a process in which both the bromide and selenide react according to the SH2 mechanism shown in Scheme 3. The 0.08 ratio is consistent with the bromide reacting as pictured in Scheme 3 but the selenide producing an intermediate that can return to the starting materials (Scheme 4). A likely intermediate in such a reaction is one with a hypervalent selenium atom.2 The results from this comparative experiment, therefore, favor the stepwise mechanism for selenide reaction shown in Scheme 2 over the concerted process pictured in Scheme 1.

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    B. Reactions

    1. Reduction

    Carbohydrates that have a selenophenyl group attached to a pyranoid ring react with tri-n-but­yltin hydride, triphenyltin hydride, or tris(trimethyl­silyl)­silane to replace the selen­ium-con­taining group with a hydrogen atom.7–19 Such a reaction is the final step in the disac­cha­ride synthesis shown in Scheme 5.7 Although reduction involving seleno­phenyl group replacement is usually at C-2 in monosaccharides or at C-2' in disaccharides and nucleosides, reaction in monosaccharides also has been observed at C-117,18 and at C‑6.20

    II4s5.png

    The polymer 3,21,22 with selenium attached to the aromatic rings in polystyrene, reacts with the glycal 2 in the presence of the partially protected sugar 4 to produce the carbo­hy­drate-con­taining polymers 5 and 6 (Scheme 6).21 (The polymer-bound reagent 3 has the advantage that it is odorless, safer, and more convenient to handle than C6H5SeCl, which is toxic and foul smelling.21) Reaction of 5 and 6 with tri-n-butyltin hydride releases the carbo­hydrates from the polymers and, at the same time, completes the reduc­tion process.

    II4s6.png

    Replacing a selenophenyl group in a five-membered ring by a hydro­gen atom is a common reaction for nucleosides and nucleoside analogs.23–32 This replacement can be conducted either at 80-110 oC with AIBN initi­ation (eq 1),23 or at room temperature with Et3B–O2 as the initiator (eq 2).26 [Selenophenyl group replace­ment, when initiated by Et3B–O2, can occur at temperatures as low as ‑75 oC (eq 3).31] Tri-n-butyltin hydride is the normal hydrogen-atom transfer in such reactions, but tris(tri­methyl­silyl)silane (eq 4)28 and 1,4-cyclohexadiene (eq 5)30 also are effective in this role. Yields from reac­tion of Bu3SnH with carbohydrates containing selenophenyl groups remain high when the oxygen atom in a furanoid ring is replaced by a sulfur atom.33–35

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    2. Addition

    Carbohydrate radicals generated from phenyl selenides undergo char­acteristic addition re­ac­tions with com­pounds con­tain­ing multiple bonds.19,36–39 These radicals add not only to decidedly electron-deficient double bonds, such as that found in t-butyl acrylate, but also to less elec­tron-de­ficient double bonds, such as that present in sty­rene.19,37,38 Product yields from addi­tion to sty­rene are lower, however, because hydrogen-atom abstraction from tri-n-butyltin hydride to give the reduction product com­petes effectively with addition to a less electron-deficient multiple bond (eq 6). Conditions are critical to the success of these addition reactions because only hydrogen-atom ab­straction is observed unless Et3B–O2 is the initiator and the reaction is run at room temperature.38 As is typical for reactions of this type (i.e., ones that form intermediate pyranos-1-yl radicals), the stereo­selectivity of addition is controlled by the kinetic anomeric effect [Section III.B of Chapter 11 in Volume I].

    II4(6).png

    3. Cyclization

    The reaction shown in Scheme 740 illustrates the established prefer­ence of unsaturated ra­di­cals for forming five-membered rings even when six-membered ones are possible.40–43 This reac­tion (Scheme 7) also reveals a complication in radical cyclization caused by internal hydrogen-atom abstraction, a process that leads in this instance to epimerization at C-5. Only carbon-centered radicals that are very reactive, such as the primary radical 7, are able to abstract a hydrogen atom from a carbon–hydrogen bond fast enough to be of consequence. Epimerization at C-5 in this reac­tion can be reduced or even eliminated by increasing the tri-n-butyltin hydride concen­tration to the point that internal hydrogen-atom abstraction by 7 no longer competes successfully with abstraction from Bu3SnH (Scheme 7).40

    II3s7.png

    Cyclization of unsaturated carbohydrates in which a selenophenyl group is attached to a pyranoid ring is marked by a surprising variety of new ring systems that can be produced. In addition to the expected five-40–44 and six-membered45 rings, formation of seven-membered,46 eight-membered,47,48 and even nine-membered49–54 rings also takes place. Larger rings usually are generated when a radical center and a multiple bond are linked through a silicon–oxygen con­nec­tor.46–52 Reactions of this type often produce carbo­hy­drates in which two saccharide units are linked by a methylene bridge (Scheme 8.)48 Although bridges containing silicon and oxygen atoms are common, reactions also occur between monosaccharides connected by other combin­ations of atoms.53,54

    II3s8.png

    In cyclization reactions a selenophenyl group attached to a furanoid ring behaves in a man­ner similar to one attached to a pyranoid ring; that is, reaction pro­duces a radical that adds to a connected multiple bond. The connecting group some­times contains a nitrogen atom (eq 7)55 or an oxygen atom56–58 (eq 856) or the collection of atoms that make up an ester link­age,59,60 but as is the case for compounds with pyranoid rings, a radical centered in a furanoid ring frequently has the unsaturated group tethered to the five-membered ring through a silicon–oxygen bridge61–69 (eq 961). Reported radical cyclization of this type, such as that shown in eq 10,62 often involves reac­tion of a nucleoside.

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    Although in most carbohydrates a selenophenyl group undergoing reaction is bonded to a ring carbon atom, cyclization70,71 (and addition72) reac­tions also can start with a ring-open struc­ture. An example is given in eq 11.70 Cycli­zation of the ring-open selenide 8 begins with electron transfer from samarium(II) iodide. The intermediate samar­ium ketyl formed during this reaction dis­places a benzyl group from selenium to give a ring system that contains a selenium atom (Scheme 9).73 This is an unusual method for ring formation because it takes place by group dis­place­ment rather than addition to a multiple bond.

    II3(11).png

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    4. Group Migration

    Group migration is a characteristic reaction of a pyranos-1-yl radical that has an acyloxy group attached to C-2. Since phenyl selenides are one type of precursor for these radicals, it is reasonable to expect selenides to be substrates for such a migration.5,74,75 The reaction shown in eq 12 justifies this expectation.5 (Acyloxy-group-migration reactions are discussed in Sec­tion V. of Chapter 8.)

    II3(12).png

    5. Radical-Cation Formation

    In the reaction shown in Scheme 10 abstraction of the selenophenyl group from 9 by Bu3Sn· gives the pyranos-1‑yl radical 10, which then frag­ments to produce the radical cation 11.76 This radical cation then undergoes a combination of cyclization, proton loss, and hydrogen-atom abstraction to give the final product. Investigating radical-cation formation from nucleotides con­taining selenophenyl groups is used to study the mechanism of DNA strand scission.77,78

    II3s10.png

    6. Radical Combination

    Replacement of a selenophenyl group with a hydrogen atom typically depends on the ability of a reagent such as tri-n-butyltin hydride both to pro­vide a chain-carrying radical (Bu3Sn·) and to serve as a hydrogen-atom transfer. If this reagent is replaced by one that lacks hydrogen-donating ability but retains the capacity to generate a chain-carrying radical, selenophenyl group loss still will occur, but hydrogen-atom abstraction cannot be depended upon to complete the reaction. If unsaturated reactants are present, radical addition is pos­sible, but if such compounds are absent, radical combin­ation can take place (eq 13).4 {[Combination of the type shown in eq 13 also happens when pyranos-1-yl radicals are formed from glycosyl bromides [Chapter 2, Section III.G.1] and glycosyl phenyl sulfones [Chapter 3, Section VII.B.1.c.]}

    II3(13).png


    This page titled II. Selenides is shared under a All Rights Reserved (used with permission) license and was authored, remixed, and/or curated by Roger W. Binkley and Edith R. Binkley.

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