Xanthate radicals from

All reactions of benzotriazole derivatives of the type Bt-CR RbS discussed above are based on electrophilic or nucleophilic substitutions at the ot-carbon, but radical reactions are also possible. Thus, the first report on unsubstituted carbon-centered (benzotriazol-l-yl)methyl radical 841 involves derivatives of (benzotriazol-l-yl)methyl mercaptan. 3 -(Benzotriazol-l-yl)methyl-0-ethyl xanthate 840 is readily prepared in a reaction of l-(chloromethyl)-benzotriazole with commercially available potassium 0-ethyl xanthate. Upon treatment with radical initiators (lauroyl peroxide), the C-S bond is cleaved to generate radical 841 that can be trapped by alkenes to generate new radicals 842. By taking the xanthate moiety from the starting material, radicals 842 are converted to final products 843 with regeneration of radicals 841 allowing repetition of the process (Scheme 134). Maleinimides are also satisfactorily used as radical traps in these reactions <2001H(54)301>. 

Cyclic enol ethers such as 8 are also easily epoxidized. R. Daniel Little of the University of California, Santa Barbara has found (J. Org. Chem. 2005, 70, 5249) that such an epoxide is reduced with Tifffl) regioselectively to the radical, that adds with remarkable diastereocontrol to enones such as 7 to give the adduct 9. Reductive cyclization converted 9 to the tricyclic ether 10. The C-Br bond of 10 was stable both to the Et,SiH conditions, and to the free radical removal of the xanthate derived from the alcohol. 

Similar homolysis of xanthates derived from galacto compounds 33 by a tin radical can form deoxy sugars or, in the presence of acrylonitrile, C-branched sugars at C-3 such as 34 [37, 38] according to Scheme 17. 

Radical deoxygenation of alcohols is important, and the reduction of xanthates prepared from alcohols, with Bu3SnH in the presence of AIBN is called the Barton-McCombie reaction (eq. 2.13) [37-51]. The driving force for the reaction is the formation of a strong C=0 bond from the C=S bond, approximately 10 kcal/mol stronger. This reaction can be used for various types of substrates such as nucleosides and sugars. Though methyl xanthates, prepared from alcohols with carbon disulfide and methyl iodide under basic conditions are very frequently used, other thiocarbonates, as shown in eq. 2.14, can also be employed. 

The generation of amidyl radicals from N-allylsulfonamides and their subsequent cyclization was probed by Moutrille and Zard [130]. This strategy allowed the preparation of lactams such as 140 by treatment of acylsulfon-amide 138 with lauryl peroxide and a xanthate in DCE (Scheme 44). However, when the stability of the generated amidyl radical (as with 137) was not high enough, the extrusion of sulfur dioxide turned to be too slow, and premature cyclization of the N-amidosulfonyl radical intermediate took place, leading to 139. 

Not only acyl, but also alkoxycarbonyl radicals can be generated from the corresponding xanthates, and their capture by addition to olefins produces esters or lactones, depending on whether the addition reaction is inter-or intra-molecular [53]. Grainger and Innocenti found that xanthates derived from carbamoyl chlorides were difficult to make and handle but, by replacing the xanthate salt by a dithiocarbamate, better precursors for the desired aminocarbonyl radicals were obtained [54]. Irradiation with a tungsten lamp proved more efficient than chemical initiation with lauroyl peroxide and lactams of various sizes could be readily obtained, as illustrated by the... 

Addition of carbon radicals to carbon-carbon double bonds is an important reaction that can be carried out under hydrogen transfer conditions [27], Peroxides are usually used as radical precursors and an application of this chemistry is presented in Scheme 3 (Eq. 3.1). More recently, reduction of alkyl radical by C-H hydrogen donor has been examined in order to find an environmentally friendly alternative to tin hydride. Zard has reported a simple and cheap alternative to tin hydride for Barton-McCombie deoxygenation reactions [80]. Heating of xanthates derived from carbohydrates in 2-propanol in the presence of dilauroyl peroxide affords the de-oxygenated products in good yields (Scheme 17, Eq. 17.1). 2-Propanol functions as... 

A commercially available polystyryldiphenylphosphine has been used to convert 3 -azido-3 -deoxy-nucleosides into the corresponding 3 -amino-3 deoxy-nucleosides, by formation and hydrolysis of phosphine imine intermediates. The formation of heterocyclic compounds on photolysis of glycosyl azides is covered in Section 6, and the formation of unsaturated sugars by radical elimination of vicinal phenyl selenide and xanthate azides from i ropriate saturated compounds is covered in Chapter 13. 

Vicinal diols could also be deoxygenated via their xanthate derivates, however a sacrificial olefin, such as 1-dodecene, was a necessary additive to prevent the phosphorous-centered radical from adding to the desired product. 

The salts of alkyl xanthates, A/,A/ -di-substituted dithio-carbamates and dialkyidithiophosphates [26] are effective peroxide decomposers. Since no active hydrogen is present in these compounds, an electron-transfer mechanism was suggested. The peroxide radical is capable of abstracting an electron from the electron-rich sulfur atom and is converted into a peroxy anion as illustrated below for zinc dialkyl dithiocarbamate [27] ... 

Phenacyl radicals can be generated from the corresponding xanthates and add in good yield to various substituted propenes. The products of the reaction can then be cyclized to tetralones using an equivalent of a peroxide.313... 

Epoxides will also participate in radical reactions and this usually results in ring opening of the epoxide. The addition of a radical derived from xanthate 38 to butadiene monoepoxide provides the addition product 39 in good yields as an E/Z mixture of olefins <06AG(I)6520>. This reaction presumably proceeds through the addition of the xanthate-derived radical to the olefin, which then opens the epoxide. 

Spiro tricyclic pyrrolizinone 171 was obtained with 65% yield (and almost poor stereoselectivity) by intramolecular radical cyclization of the xanthate 170 upon exposure of the latter to 2equiv of lauroyl peroxide, in a refluxing 3 1 mixture of methanol and 1,2-dichloromethane. The radical generated from the xanthate moiety cyclizes with the... 

A relevant reductive process, which has found wide application in organic synthesis, is the deoxygenation of alcohols introduced in 1975 by Barton and McCombie [58]. Reaction (4.28) shows that the thiocarbonyl derivatives, easily obtained from the corresponding alcohol, can be reduced in the presence of BusSnH under free radical conditions. The reactivity of xanthates and thiocarbonyl imidazolides [58] was successfully extended to 0-arylthiocarbonates [59] and (9-thioxocarbamates [60]. Several reviews have appeared on this subject, thus providing an exhaustive view of this methodology and its application in natural product synthesis [61-64]. 

Cyclohexyl xanthate has been used as a model compound for mechanistic studies [43]. From laser flash photolysis experiments the absolute rate constant of the reaction with (TMS)3Si has been measured (see Table 4.3). From a competition experiment between cyclohexyl xanthate and -octyl bromide, xanthate was ca 2 times more reactive than the primary alkyl bromide instead of ca 50 as expected from the rate constants reported in Tables 4.1 and 4.3. This result suggests that the addition of silyl radical to thiocarbonyl moiety is reversible. The mechanism of xanthate reduction is depicted in Scheme 4.3 (TMS)3Si radicals, initially generated by small amounts of AIBN, attack the thiocarbonyl moiety to form in a reversible manner a radical intermediate that undergoes (3-scission to form alkyl radicals. Hydrogen abstraction from the silane gives the alkane and (TMS)3Si radical, thus completing the cycle of this chain reaction. 

Radicals formed by fragmentation of xanthate and related thiono esters can also be trapped by reactive alkenes.217 The mechanism of radical generation from thiono esters was discussed in connection with the Barton deoxygenation method in Section 5.4. 

Tris[(2-perfluorohexyl)ethyl]tin hydride has three perfluorinated segments with ethylene spacers and it partitions primarily (> 98%) into the fluorous phase in a liquid-liquid extraction. This feature not only facilitates the purification of the product from the tin residue but also recovers toxic tin residue for further reuse. Stoichiometric reductive radical reactions with the fluorous tin hydride 3 have been previously reported and a catalytic procedure is also well established. The reduction of adamantyl bromide in BTF (benzotrifluoride) " using 1.2 equiv of the fluorous tin hydride and a catalytic amount of azobisisobutyronitrile (AIBN) was complete in 3 hr (Scheme 1). After the simple liquid-liquid extraction, adamantane was obtained in 90% yield in the organic layer and the fluorous tin bromide was separated from the fluorous phase. The recovered fluorous tin bromide was reduced and reused to give the same results. Phenylselenides, tertiary nitro compounds, and xanthates were also successfully reduced by the fluorous fin hydride. Standard radical additions and cyclizations can also be conducted as shown by the examples in Scheme 1. Hydrostannation reactions are also possible, and these are useful in the techniques of fluorous phase switching. Carbonylations are also possible. Rate constants for the reaction of the fluorous tin hydride with primary radicals and acyl radicals have been measured it is marginally more reactive than tributlytin hydrides. ... 

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