Halides, alkyl, reaction with tributyltin hydride

Alkyl halides can be reduced to alkanes by a radical reaction with tributyltin hydride, (C4H9)3SnH, in the presence of light (hv). Propose a radical chain mechanism by which the reaction might occur. The initiation step is the light-induced homolytic cleavage of the Sn— H bond to yield a tributyltin radical. 

Alkyl halides can be reduced to alkanes by a radical reaction with tributyltin hydride, (C HalsSnH, in the presence of light (kif) ... 

Another interesting use of TEMPO has been in free-radical substitution of alkyl halides. In this reaction, halides react with tributyltin hydride and TEMPO to yield A-alkoxyamine substitution products [18. This reaction is especially attractive in cases where anionic nucleophiles are sterically prevented from carrying out substitution reactions. An example of this can be seen in Barrett s synthesis of sucrose [18b], in which a stereoselective iodoetherification reaction was used to produce neopentyl alkyl iodide 13 (Scheme 5). Free radical substitution mediated by tributyltin hydride and TEMPO yielded A-alkoxyamine 14. The mechanism [19] involves TEMPO abstraction of hydrogen from tributyltin hydride [20] the stannyl radical then abstracts iodide from the substrate, and a second equivalent of TEMPO traps the resulting carbon radical. 

In the presence of proton and/or Lewis acid and strong nucleophiles bicyclo[3.2.0]heptan-6-ones are converted to 3-substituted cycloheptanones (Table 15). Bicyclo[3.2.0]heptan-6-ones rearrange to give 3-iodocycloheptanones on treatment with iodotrimethylsilane. Zinc(II) iodide or mercury(II) halides as catalysts enhance the rate and the selectivity of the reaction.31 If a second, enolizable carbonyl group is present, an intramolecular alkylation may follow the ring enlargement under these reaction conditions.32 Consecutive treatment with tributyltin hydride/ 2,2 -azobisisobutyronitrile affords reduced, iodo-free cycloheptanones, whilst treatment with l,8-diazabicyclo[5.4.0]undecene yields cycloheptenones.33 Similarly, benzenethiol adds to the central bond of bicyclo[3.2.0]heptan-6-ones in the presence of zinc(II) chloride and hydrochloric acid under anhydrous conditions to form 3-(phenylsulfanyl)cycloheptanones.34... 

The reaction of an alkyl halide with tributyltin hydride, using a radical initiator, results in the replacement of the halogen by hydrogen. The reaction follows a radical chain mechanism as outlined in Figure 21.3. Examples are provided in the following equations ... 

The reactions are commonly initiated with AIBN at ca. 80 °C in a solvent such as benzene or toluene, but alkyl halides have also been reduced at -60 °C with tributyltin hydride under sonication conditions.133-134 Some reductions of halides have been carried out by generating the tin hydride in situ from a molar equivalent of the reducing agent [lithium aluminium hydride, sodium borohydride, or poly(methylhydrosiloxane)] and a catalytic amount of organotin hydride, halide, or oxide. Reduction of halides has also been carried out under aqueous conditions, using 4,4 -azobis(4-cyanovaleric acid) (ACVA) as a water-soluble radical initiator.60... 

Tributyltin hydride, reaction with alkyl halides. 358 Tricarboxylic acid cycle, see Citric acid cycle... 

Although the tin hydride reductions of alkyl halides seem simple, one must be careful because these reactions occur by a free radical mechanism. This is important, because the carbon radical produced in the reaction can isomerize68,78 and one often obtains two different stereoisomers from the synthesis. Another problem is that chiral centres can be lost in tin hydride reductions when an optically active halide is reduced. One example of this is the reduction of benzyl-6-isocyanopenicillanate with tributyltin deuteride78 (Scheme 14). The amount of isomerization depends on the temperature, the concentration of the tin hydride and the presence of and /-substituents78-82. However, some authors have reported tin hydride reductions where no racemization was observed78. 

The same research group has further performed radical carbonylation reactions on the same microreactor system [36]. First, alkyl halides were initiated and effectively reacted with pressurized carbon monoxide to form carbonyl compounds. The principle was subsequently successfully extrapolated to the multicomponent coupling reactions. 1-Iodooctane, carbon monoxide and methyl vinyl ketone were reacted in the presence of 2,2 -azobis(2,4-dimethylvaleronitrile) (V-65) as an initiator and tributyltin hydride or tris(trimethylsilyl)silane (TTMSS) as catalyst (Scheme 15). 

Radical carbonylation reaction serves as a powerful tool for the synthesis of a range of carbonyl compounds. Radical carbonylation has been successfully applied to the synthesis of functionalized ketones from alkyl, aryl, and alkenyl halides.The radical aminocarbonylation reaction of alkynes and azaenynes provided efficient routes to 2-substituted acrylamides, lactams, and pyrrolidinones. For example, the aminocarbonylation of 4-pentyn-l-yl acetate 318 initiated by tributyltin hydride (Bu"3SnH) (30mol%) with AIBN (20mol%) gave acrylamide 325 in 92% yield (Scheme 43).A proposed mechanism starts from the addition of tributyltin radical 319 to alkyne... 

Tributyltin hydride (Bu3SnH) is used synthetically to reduce alkyl halides, replacing a halogen atom with hydrogen. Free-radical initiators promote this reaction, and free-radical inhibitors are known to slow it or stop it. Your job is to develop a mechanism, using the following reaction as the example. 

Radical substitution reactions can also be used to remove functional groups from molecules. A useful reagent for this (and, as you will see, for other radical reactions too) is tributyltin hydride, Bu3SnH. The Sn-H bond is weak and B SnH will react with alkyl halides to replace the halogen atom with H, producing BL SnHal as a by-product. 

A complementary sequence uses an alkyl halide 7.46 with a Z-substituent to create an electrophilic radical 7.47 in the presence of a nucleophilic alkene 7.48. In this case, the radical 7.49 expels the low-energy tributyltin radical to regenerate the tin radical achieving overall the allylation of the ester, catalytic in both the AIBN and the tin hydride. The Z-substituent in the radical 7.47 is necessary for an efficient reaction—in its absence the allylstannane has to be used in large excess. 

The reduction of chlorodeoxy sugars has been achieved [31,32] in high yield by means of tributyltin hydride in the presence of 2,2 -azobis(2-methylpropionitrile). The reaction with methyl 2,3-di-0-acetyl-4,6-dichloro-4,6-dideoxy-a-D-galactopyranoside at 60°C gave [31] methyl 2,3-di-0-acetyl-6-chloro-4,6-dideoxy-ot-D-xylo-hexopyranoside as the main product. A free-radical mechanism has been proposed [33] for the reduction of alkyl halides by organotin hydrides. In accordance with this proposal, the presence of the radical initiator 2,2 -azobis(2-methylpropionitrile) was essential for the reduction of chlorodeoxy sugars moreover, the relative reactivities of the two chlorine atoms in methyl 2,3-di-0-acetyl-4,6-dichloro-4,6-dideoxy-a-D-galactopyranoside follow a free-radical order. 

The free radical chain reaction between PhCOCHjHgCl and 1-morpholinocyclohex-cne has been reported to involve addition of the acceptor radical PhCOCHj- to the jS-position of the enamine followed by electron transfer to regenerate the attacking radical (Scheme 19). Photostimulated reactions of simple alkylmercury halides failed since an electrophilic radical is required. Photolysis of p-nitrobenzyl chloride in the presence of enamines gave the -/>-nitrobenzyl ketone on hydrolysis . Radical mediated reductive alkylation of acyclic-enamines has also been reported with radical precursors such as PhSCH2CN, PhS02CH2Cl and Me3CS02CH2SePh . Reductive alkylation also occurred with chloromethyl p-tolyl sulphone in the presence of tributyltin hydride and azobis(isobutyronitrile) (AIBN) (Scheme 20). 

Routledge et al. [7] investigated the formation of dihydrobenzofuran 1 from an aryl halide precursor (Scheme 1). With polystyrene, more than 1 equivalent of AIBN was required, while the reaction was complete within 20 h using 6 mol% of AIBN on TentaGel resin (which has a polyethylene spacer between the polystyrene and the site of compound attachment). Addition of t-butanol helped prevent an alternative y -elimination pathway. An attempt to force the latter was made with thiyl linker 2, but only trace amounts of the )9-elimination product 3 were formed. Also investigated were the cyclizations of iodides 4, in which the cyclization of an alkyl radical to an acetylene is approximately 10 times slower than the aryl radical cyclization to a double bond. A direct comparison of the same reaction on solution phase was attempted, but yields could not be determined for the latter because of contamination by tin residues. This illustrates one advantage of solid-phase radical reactions mediated by tributyltin hydride, namely the ease of product purification. 

Radicals can be generated by homolysis of weak a-bonds. Homolysis is effected by photochemical, thermal or redox (electron transfer) methods. A common method to initiate a radical reaction is to warm a peroxide such as benzoyl peroxide or azobi-sisobutyronitrile (AIBN) 1 (4.2). The radical -C(CN)Me2 generated from AIBN is rather umeactive, but is capable of abstracting a hydrogen atom from weakly bonded molecules such as tributyltin hydride (4.3). The resulting tributyltin radical reacts readily with alkyl halides, selenides and other substrates to form a carbon-centred radical. 

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