Radicals from selenides

Entry 5 is an example of the use of fra-(trimethylsilyl)silane as the chain carrier. Entries 6 to 11 show additions of radicals from organomercury reagents to substituted alkenes. In general, the stereochemistry of these reactions is determined by reactant conformation and steric approach control. In Entry 9, for example, addition is from the exo face of the norbornyl ring. Entry 12 is an example of addition of an acyl radical from a selenide. These reactions are subject to competition from decarbonylation, but the relatively slow decarbonylation of aroyl radicals (see Part A, Table 11.3) favors addition in this case. 

Entry 11 involves generation and cyclization of an alkoxymethyl radical from a selenide. The cyclization mode is the anticipated 5-exo with a cis ring juncture. This is a case in which the electronic characteristics of the radical are not particularly favorable (ERG oxygen in the radical), but cyclization nevertheless proceeds readily. The reaction in Entry 12 was used to prepare a precursor of epibatidine. Entry 13 shows a 6-endo cyclization that is favored by steric factors. The 6-endo cyclization is also favored with a tetrahydropyranyloxy substituent in place of the ester, indicating that the electronic effect is not important. Entries 14 to 16 involve acyl radicals generated from selenides. The preferred 6-endo cyclization in Entry 15 is thought to be due to the preference for the less-substituted end of the double bond. Entry 17 is an example of a 5-exo-dig cyclization. 

Scheme 3. Preparation of selenide radical precursors from lactones...

From this data, one can see why alkyl iodides are generally more reactive than bromides, which in turn are more reactive than chlorides in atom transfer reactions. Likewise, phenyl tellurides are more reactive than phenyl selenides. In general, the rates of atom transfer to alkyl radicals from organoiodides are comparable to those from organotellurides. Comparable rates of atom transfer are also observed for bromides and phenyl selenides. Chlorides are not as useful in atom transfer addition reactions because of their comparatively slow rates of atom transfer, and atom transfer reactions of phenyl sulfides are not commonly observed. 

Homolytic cleavage of the carbon-boron bond of a trialkylborane can be promoted by oxygen. The so-formed alkyl radical can be used in synthesis (for radical reactions, see Section 4.1). Indeed, triethylborane in air can be used to generate radicals from precursors such as alkyl iodides or selenides. Hydroboration followed by addition of an a,(3-unsaturated aldehyde or ketone leads to transfer of an alkyl group from the boron atom via an alkyl radical intermediate. The reaction takes place by addition of the alkyl radical to the conjugated system to form an enol borinate, hydrolysis of which gives the aldehyde or ketone product (5.37). 

As exemplified in the following cases, this addition reaction has often been used as the first step in the preparation of vinyl sulfones. The adduct must therefore undergo a subsequent elimination reaction. A base is needed to perform dehydrohalogenation. The selenides resulting from the addition of selenosul-fonates can be eliminated very smoothly through oxidation. Thus, Yus and co-workers [104] have based a very simple method for the preparation of j9-sulfonyl-a,j9-unsaturated compounds on the addition of tosyl iodide to Michael acceptors (equation (50)) whereas Barton et al. [105] have shown that the addition of phenylseienotosylate to electron-rich olefins, catalyzed by Ru(II) complexes, is efficient (equation (51)). An alternative approach is the Ce(IV)-mediated addition of arylsulfinates to electron-rich olefins which proceeded directly to the olefinic product resulting from oxidative elimination of the intermediate alkyl radical (equation (52)) [106]. 

M.-Llui sa Bennasar of the University of Barcelona prepared J. Org. Chem. 2008, 73, 9033) the acyl selenide 11 from the indole 10. While the radical derived from 11 might have been expected to undergo 5-exo cyclization, in the event the 6-endo mode dominated, to give Dasycarpidone 12 and its diastereomer. 

Mixed aryl selenides have also proven to be excellent ree ents for group transfer reactions.Photolysis of selenides in an inert solvent such as benzene can initiate chain reactions. Substituted radicals can be generated in this manner, from a-selenoe-... 

The acyl selenide 19 affords the decarbonylated )S-lactam in good yield. A N-hydroxypyridine-2-thione ester 20 is used in the key step to construct the chiral cis-cyclopropane structure in compounds designed as antidopaminergic agents. The observed high cis selectivity is due to the hydrogen abstraction from the sterically demanding (TMSlsSiH, which occurs from the less-hindered side of the intermediate cyclopropyl radical. 

The number of reported reactions in which the radical derived from the decomposition of AIBN plays a role in the termination process has increased considerably. Often these reactions are not radical chain reactions, since the initiator is used in stoichiometric amounts. A few examples of rearomatization of cyclohexadienyl radicals by disproportionation have been reported herein. Below are some other examples, where the phenyl selenide 61 reacts with (TMSfsSiH (3 equiv), AIBN (1.2 equiv) in refluxing benzene for 24 h to give the coupling product of radicals 63 and 64 in good yields (Scheme 9).i24,i25 these cases,... 

The synthesis of a-substituted phosphonates 89, via the electrophilic addition of phosphorylated C-radicals 88 (generated by reaction of BujSnH to the readily accessible a-phosphoryl sulfides (or selenides)) and electrophilic addition to electron rich alkenes, has been described [57] (Scheme 26). A large excess of alkene is necessary to minimize the competitive formation of the undesired compound 90 resulting from direct reduction of the initial radical 88. The ratio 89/90 has been measured for each example. The synthesis of the a-mono- or a,a-di-substituted (R or phosphonates 89 shows that the free radical approach... 

For the route A, acyl radicals donors like iS are readily generated from acyl selenides (ISa) or acyl cobalt derivatives (iSb) and radicals acceptors 2S are usually multiple bonds as in methyl vinyl ketone (2Sa) -although some homolytic substitutions are possible. On the other hand, nitriles GSal are useful acceptors (3S) in radical cyclisations and 4Sa is an obvious synthon equivalent of radical donor 4S (See Table 7.2). 

Secondary alkyl selenides are reduced by (TMS)3SiH, as expected in view of the affinity of silyl radicals for selenium-containing substrates (Table 4.3) [40]. Reaction (4.23) shows the phenylseleno group removal from the 2 position of nucleoside [50]. Similarly to 1,3-dithiolanes and 1,3-dithianes, five- and six-membered cyclic selenoacetals can be monoreduced to the corresponding selenides in the presence of (TMS)3SiH [51]. The silicon hydride preferentially approached from the less hindered equatorial position to give transicis ratios of 30/70 and 25/75 for the five-membered (Reaction 4.24) and six-membered cyclic selenoacetals, respectively. 

Selenenyl groups can be abstracted from acyl selenides to generate radicals on reaction with stannyl radicals.201 202 203 Normally, some type of stabilization of the potential reaction site is necessary. Among the types of selenides that are generated by selenenyl abstraction are x-sclcncnyl cyanides and a-selenenyl phosphates. 

Of all the radical reactions, the exo-l,5-cycIization of a hex-5-enyl radical to cyclopen-tylmethyl radical and its subsequent trapping by various reagents have attracted the most attention from synthetic chemists (Scheme 1) [4-7]. Starting materials that are most often used for the tin method (initiation of the chain by trialkyl tin radical) are halides, sulfides, selenides, or thionocarbonates. The generation and cyclization of the radical proceeds under exceptionally mild neutral conditions, and these conditions are compatible with a wide variety of common functional groups. A prototypical example of an application in carbohydrate chemistry is shown in Scheme 2 [8]. Readily available 2,3-di-O-isopropyl-ideneribonolactone 1 was converted into the bromoacrylate 2 in three steps. Radical... 

Three types of compounds may be considered to be derived from hydrogen selenide, H2Se, namely RSeH, R2Se and RSeR, where R and R are aliphatic radicals. 

Free-radical cyclization of phenyl selenide 15 to indolizidinone 16 represented a key step in the total synthesis of (—)-slaframine (equation 52). The two pairs of diastereomers were first separated and then hydrolyzed to the corresponding alcohols in 76% overall yield77. (TMS)3SiH-mediated acyl radical reactions from phenylseleno esters 17 have recently been utilized for the stereoselective synthesis of cyclic ethers78. In fact, the experimental conditions reported in equation 53 are particularly good for both improving cis diastereoselectivity and suppressing decarbonylation. 

Selenides are more readily cleaved by tin radicals than thioethers. Products bound to cross-linked polystyrene by a C-Se bond can be released from the support either by treatment with an oxidant to yield alkenes [1, 55-58], or by treatment with tin radicals to yield alkanes... 

Intramolecular addition of acyl radicals to enoates proceeds in high yields. The acyl radicals are generated conveniently from acyl selenides. The application of this methodology in the stereoselective synthesis of cis-2,5-disubstituted tetrahydrofuran-3-ones is illustrated [95TL31],... 

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