Reactions of Radicals with Tin Hydrides

The kinetics of many the reactions of radicals with tin hydrides have been studied because of their importance in organic synthesis. Examples are given in Table 15-5, and a more extensive list is given in a recent review by Chatgilialoglu and Newcomb.111 The solvents are not quoted in the table, but in general they are non-polar (e.g. octane or benzene) and the rates are not sensitive to the nature of the solvent. 

It will be seen that the rates decrease in the sequence Ph R2C=CH Me3CO RCF2 3R2C=0 RCH2 RC(=0) R2N ROO.  

The hydrostannolysis of organic halides was discovered when an attempt at the hydro-stannation of allyl bromide resulted instead in hydrodebromination.37 

Because of the apparent importance of tin hydrides in synthetic sequences, reactions of R3SnH with alkyl radicals were among the first radical 

Rate Constants for Reactions of Carbon-Centered Radicals with Tin Hydrides 

Radical Solvent, method Rate expression (log k) (9 = 2.3RT kcal/mol) Rate constant, (Ms) 1 (at 20°C unless noted) Ref. 

Me3COOC(Me)2CH2- Benzene 5 X Bu3SnH rate constant 95 

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In recent years, these reactions have found an important place in organic synthesis. We will consider in this chapter only the reactions of radicals with tin hydrides, and the basic hydrostannolysis processes that depend on these reactions. Hydrostannation reactions are covered in Section 4.4, and the reactions of stannyl radicals with substrates R X in Section 20.1.3. The further use of organotin hydrides in organic synthesis, which depends largely on transformations of the radicals R " in hydrostannolysis reactions, or of the radicals R3SnXY" in hydrostannation reactions, are beyond the scope of this book, but have been extensively reviewed.2 64 66 104 107... 

Allyl radicals substituted at only one of the terminal carbon centers usually react predominantly at the unsubstituted terminus in reactions with nonradicals. This has been shown in reactions of simple dienes such as butadiene, which react with hydrogen bromide, tetrachloromethane or bromotrichloromethane to yield overall 1,4-addition products . The reaction of allyl radicals with hydrogen donors such as thiols or tin hydrides has been investigated and reviewed repeatedly. In most cases, the thermodynamically more favorable product is formed predominantly. This accords with formation of either the higher substituted alkene or the formation of conjugated tt-systems. Not in all cases, however, is the formation of the thermodynamically more favorable product identical to overall 1,4-addition to the diene. In those cases in which allyl radicals are formed through reaction of dienes with tin hydrides or thiols, the... 

Several reactions of halogen-substituted carbon-centered radicals with silanes have been studied, but limited kinetic information is available for reactions of halogen-substituted radicals with tin hydrides. A rate constant for reaction of the perfluorooctyl radical with Bu3SnH was determined by competition against addition of this radical to styrenes, reactions that were calibrated directly by LFP methods.93 At ambient temperature, the n-C8F17 radical reacts with tin hydride two orders of magnitude faster than does an alkyl radical, consistent with the electron-deficient nature of the perflu-oroalkyl radical and the electron-rich character of the tin hydride. Similar behavior was noted previously for reactions of silanes with perhaloalkyl radicals. 

Few kinetic studies of reactions of alkyl radicals with tin hydrides other than Bu3SnH have been reported. Studies of the reactions of the tert-butyl radical with Me3SnH and Ph3SnH were performed by the rotating sector method,80 but an error in absolute values exists in that method as judged by differences in rate constants for reactions of Bu3SnH with alkyl radicals... 

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. ... 

An enantioselective reduction of an a-iodolactone under radical conditions has been reported [95CC481]. Treatment of 207 with tin hydride, magnesium(II) iodide and in the presence of a chiral amine gave the 8-lactone 208 in good yield and moderate enantioselectivity. This is one of the first examples of chiral Lewis acid mediated enantioselective radical reactions. 

The nucleophilic displacement reactions with azide, primary amines, thiols and carboxylatc salts arc reported to be highly efficient giving high (>95%) yields of the displacement product (Table 9.25). The latter two reactions are carried out in the presence of a base (DBU, DABCO). Radical-induced reduction with tin hydrides is quantitative. The displacement reaction with phenolates,61j phosphines,6M and potassium phthalimide608 gives elimination of HBr as a side reaction. 

The versatility, predictability and functional-group tolerance of free radical methodology has led to the gradual emergence of homolytic reactions in the armory of synthetic chemistry. Tin hydrides have been successfully employed in radical chemistry for the last 40 years however, there are drawbacks associated with tin-based chemistry. Organotin residues are notoriously difficult to remove from desired end products, and this, coupled with the fact that many organotin compounds are neurotoxins, makes techniques using tin inappro-... 

Photoreduction of aromatic and aliphatic nitro compounds gives hydroxylamines or amines, which is well reviewed.125 The radical reaction of primary nitro compounds with tin hydride does not give the denitrated product (see Chapter 7), but give the corresponding oximes (Eq. 

The reactions of atoms or radicals with silicon hydrides, germanium hydrides, and tin hydrides are the key steps in formation of the metal-centered radicals [Eq. (1)]. Silyl radicals play a strategic role in diverse areas of science, from the production of silicon-containing ceramics to applications in polymers and organic synthesis.1 Tin hydrides have been widely applied in synthesis in radical chain reactions that were well established decades ago.2,3 Germanium hydrides have been less commonly employed but provide some attractive features for organic synthesis. 

It is noteworthy that the absolute rate constants for the reaction of the benzophenone triplet with Et3SiH, n-C5HnSiH3, PhSiH3, and Cl3SiH have been measured by LFP,56 and comparison of the kinetic data with corresponding data for reactions of /-BuO radicals shows that these two transient species have a rather similar reactivity toward silanes. Furthermore, the xanthate and the p-methoxyacetophenone triplets were found to be more and less reactive, respectively, than the benzophenone triplet with Et3SiH.56 Similar behavior of excited states in reactions with tin hydrides is discussed in Section V. 

The limited kinetic data for reactions of tin hydride with nitrogen-centered radicals apparently demonstrates the combined effects of the enthalpies of the reactions and polarization in the transition states for H-atom transfer. The aminyl and iminyl radicals are electron-rich, and the N-H bonds formed are relatively weak these radicals react relatively slowly with tin hydride. On the other hand, the electrophilic amidyl and aminium cation radicals form strong N-H bonds and react rapidly with the tin hydride reagents. 

The deuterium KIE values are generally in the range expected for linear three-center hydrogen transfer reactions,44107 and they track nicely with the rate constants for the reactions with the faster, more exothermic reactions displaying smaller KIEs. The large KIE value for reaction of the benzyl radical is noteworthy in that it exceeds the theoretical maximum for the classical model in a manner apparently similar to that seen with tin hydride (see below). 

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