Fluorous hydride

Figure 6. Radical reductions with fluorous tin hydrides...

Unfortunately, the appeal of solid phase extractions on small scale fades as the scale increases due to the cost and inconvenience of using large amounts of fluorous silica gel. Here, modified techniques to reduce the tedium of repeated extractions are attractive. For example, Crich has recently introduced the minimally fluorous selenide C6Fi3CH2CH2C6H4SeH[171. This selenol is added in catalytic quantities to tin hydride reductions of reactive aryl and vinyl radicals. The high reducing capacity of the aryl selenide suppresses undesired reactions of product radicals without suppressing the reactions of the aryl and vinyl radicals themselves. After the reaction is complete, the selenol can be recovered by a modified continuous extraction procedure. 

The fluorous tin hydrides show a reactivity similar to that of tributyltin hydride,405 406 and the residues can be extracted into a fluorinated solvent. 

Reactions on a smaller scale tended to give better yields for the reduction of the fluorous tin bromide to fluorous tin hydride. 

On the heels of work by Zhu and Horvath and Rabai, perfluorocarbon solvents and fluorous reagents have been used increasingly in organic syntheses. Ruorous compounds often partition preferentially into a fluorous phase in organic/fluorous liquid-liquid extraction, thus providing easy separation of the compounds. Tris[(2-perfluorohexyl)ethyl]tin hydride combines the favorable radical reaction chemistry of trialkyltin hydrides with the favorable separation features of fluorous compounds. 

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. ... 

D. Tris[(2-peiiluorohexyl)ethyl]tin hydride (Note 7). A 1-L, three-necked flask and a stirring bar are dried in an oven. The fluorous tin bromide (13.8 g, 11.1 mmol) is dissolved in dry ether (275 mL) and transferred to the dried three-necked flask equipped with a thermometer, stirring bar, and an outlet to argon. The solution is cooled to O C. AIM solution of iithium aluminum hydride (LAH) in ether (11.1 mL, 11.1 mmol) is added dropwise over 45 min to the solution. The addition rate is adjusted to maintain a temperature between 0° and 1°C. The reaction mixture is stirred for 6 hr at 0°C. Water (75 mL) is slowly added (initially dropwise) with stirring to the ice-cold mixture. Sodium potassium tartrate (20%) (250 mL) is added and the mixture is transferred to a 1-L separatory funnel. The ethereal layer is separated and the aqueous layer is extracted three times with ether (3 x 100 mL). The combined extracts are dried with magnesium sulfate and vacuum filtered into a 1-L, round-bottomed flask. The solvent is evaporated under reduced pressure. The cmde product is distilled under a reduced pressure of 0.02 mm at 133-140°C to provide 11.3 g (9.69 mmol, 87%) of the pure product as an oil (Notes 8 and 9). 

All NMR samples were dissolved in chloroform. The fluorous tin hydride is only slightly soluble in chloroform. Therefore it is necessary to saturate this NMR sample. The NMR spectrum must be recorded quickly since the tin hydride reduces chloroform on standing in the light. 

Curran, D. P Hadida, S. Tris(2-(perfluorohexyl)ethyl)tin Hydride A New Fluorous Reagent for Use in Traditional Organic Synthesis and Liquid Phase Combinatorial Synthesis, J. Am. Chem. Soc. 1996,118, 2531. 

Tin hydrides bearing highly fluorinated substituents (fluorous chemistry) were used in the radical-mediated reduction of 1-bromoadamantane. The reaction was complete within 3 min under 35 W microwave irradiation (Scheme 4.42)68. 

Fluorous organometallic chemistry, examples, 1, 842 Fluorous solubles, in organometallic synthesis, 1, 81 Fluorous solvents, for hydroformylations, 11, 450 Fluorous tin hydrides, preparation and applications, 9, 346 Fluorovinyl groups, vinylic C-F bond activation, 1, 753 Fluoro vinyltitanocenes, synthesis, 4, 546 g tfZ-Fluorovinyltributylstannane, in carbonylative cross-coupling, 11,413... 

Although tin hydride is widely used as a reagent in ionic and radical reactions, it is prone to problems regarding its complete removal and its toxicity. The fluorous reagent tris[2-(perfluorohexyl)ethyljtin hydride ((C6Fi3CH2CH2)3SnFI 21) has normal tin hydride reactivity and can be completely extracted with perfluoromethylcyclohexane [34]. It can be used... 

Hadida S, Super MS, Beckman EJ, Curran DP, Radical reactions with alkyl and fluoroalkyl (fluorous) tin hydride reagents in supercritical C02, J. Am. Chem. Soc., 119 7406-7407, 1997. 

Organofluorine compounds are well known to be highly soluble in supercritical C02, and so typical radical reactions can be conducted in this media with a fluorous tin hydride.68 By using a catalytic amount of fluorous tin... 

Other means for generation and annulation of aryl radicals involve treatment of A -(t>-bromophenyl)propylamides with BusSnH/AIBN, which gives 3-alkylideneoxindoles <2(X)0J(P1)763>, or exposure of A -allyl(t>-iodoanilines) to fluorous tin hydride reagents, affording indolines <1999JA6607>. A set of indolines, for instance 239, have been obtained by radical cyclization of precursors such as 240, which were derived from A -allylanilines (Equation 76) <1999TL2533>. 

Curran [81-83] first demonstrated the value of this approach by the successful reduction of 1-bromoadamantane using the fluorous-soluble tin hydride reagent, tris(2-(perfluorohexyl)ethyl)tin hydride 34, (Fi3C6CH2CH2)3SnH. The fluorous tin hydride reagent was synthesised in three steps from 2-perfluorohexyl-1 -iodoethane in an overall yield of 65% (Scheme 6). In an attempt to mimic the... 

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