Tributyltin hydride, radical reactions with

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. 

Other primary hydrogen-deuterium kinetic isotope effects have been measured for radical reactions with tributyltin hydride. For example, Carlsson and Ingold167 found primary hydrogen-deuterium kinetic isotope effects of 2.7 and 2.8, respectively, for the... 

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

Phenylmenthol is also used as a chiral auxiliary in the reduction of several xan-thatesR. Standard radical reactions with tributyltin hydride at different temperatures yield the (-)-8-phenylmenthyl esters in moderate to good diastereomeric ratios. The bulk of the a-alkyl substituent shows a small influence on the selectivity. The absolute configuration of the products are assigned only for the (—)-8-phcnylmcnthyl 2-phenylpropanoate by reduction to the corresponding alcohols. 

Finally, Franz and coworkers171 measured the rate constants and primary hydrogen-deuterium kinetic isotope effects for the radical reactions between tributyltin hydride and the neophyl and the 2-allylbenzyl radical in diphenyl ether. The isotope effect in the first reaction was 1.64 at 192.5 °C and that in the second reaction was 1.91 at 236 °C. These values compare well with those predicted from Kozuka and Lewis s primary... 

It was found that a variety of radical precursors could be added, and that the specific electronic and steric effects exerted on the resulting radical effected the diastereoselectivity of the hydrogen atom transfer. Increasing the size of R group appeared to increase the selectivity of the trap. For instance, reaction with t-butyl radical and tributyltin hydride gave the highest selectivity, >98 2 (70% yield), for the trans product (77). Reactions with electron-deficient radicals suffered from low yields and decreased selectivity. Results also indicate that reactions with tributyltin hydride produced higher selectivities but lower yields than those per-... 

Six-substituted pyrrolizidinones may also be stereoselectively constructed via the radical cyclization of iV-allyliodolactams75. In all cases the reaction with tributyltin hydride gives only the diastereomer with the ring junction fw/s-orientated with respect to the substituent in the newly formed five-membered ring. 

Alkenes from vic-diols.1 Bis(dithiocarbonates) can be converted into alkenes by reaction with tributyltin hydride/AIBN (8,499). Diphenylsilanc and an initiator are equally effective and avoid use of toxic tin compounds. This radical reaction gives particularly high yields in reactions of nucleoside derivatives. 

Standard conversion of the alcohol of 87 into a phenylthionocarbonate derivative, then reaction with tributyltin hydride-AIBN, produced a radical centred at C-5 which added to the oxime ether double bond to produce the corresponding cyclitol. Further standard conversions gave 88. ... 

It was shown that a variety of readily available (Z) and ( )-enol phosphates are good stereoselective synthons. Thus as5unmetric epoxidation of these phosphates using Jacobsen s (Salen)Mn(ii) complex afforded a-hydroxy ketones in enantio-selectivity up to 96%. The reaction of enantiomerically enriched 2-methyl-2-nitro-3-(diphenylphosphatoxy)alkyl radicals (80) with tributyltin hydride and AIBN in benzene results in the formation of alkene radical/anion pairs (81) which are trapped intramolecularly, leading to pyrolidine and piperidine systems (82) with memory of stereochemistry (Scheme 17). ... 

Another type of reactivity was disclosed for difluorochloro group in pyrimidine series. Recently Iaroshenko, Langer and co-workers shown that difluorochloro substituted pyrimidines 1227 can be converted into corresponding difluoromethyl pyrimidines 1228 by radical reduction with tributyltin hydride in the presence of AIBN in moderate yields. In addition, CFaCl-substituted pyrimidines 1227 were transformed to the corresponding l,l-difluorobut-3-enyl pyrimidines 1129 by reaction with aUyltributyltin and AIBN. In this case the yields of transformation are lower in comparison with tributyltin hydride reduction (Schane 269) [412]. 

The reaction of tributyltin hydride with ring-substituted benzyl chlorides gives a Hammett p-factor of -1-0.81, confirming the "nucleophilic character of the BusSn- radical (303). 

Zard and coworkers [32] reported a simple approach to create another group of natural products, namely the lycopodium alkaloids [15]. These authors first investigated the reaction of O-benzoyl-N-allylhydroxylamide 3-60 with tributyltin hydride and ACCN in refluxing toluene, which led (after formation of the N-radical 3-61 in a 5-exo-trig/5-exo-trig cyclization) to the undesired pyrrolidine 3-62 in 48% yield. Nevertheless, a small structural modification, namely the placement of a chlorine atom at the allyl moiety as in 3-63, induced a 5-exo-/G-endo- instead of the 5-exo-/5-... 

The connection of radical and pericyclic transformations in one and the same reaction sequence seems to be on the fringe within the field of domino processes. Here, we describe two examples, both of which are highly interesting from a mechanistic viewpoint. The first example addresses the synthesis of dihydroindene 3-326 by Parsons and coworkers, starting from the furan 3-321 (Scheme 3.79) [128]. Reaction of 3-321 with tributyltin hydride and AIBN in refluxing toluene led to the 1,3,5-hexatriene 3-324 via the radicals 3-322 and 3-323. 3-324 then underwent an elec-trocyclization to yield the hexadiene 3-325 which, under the reaction conditions, aromatized to afford 3-326 in 51 % yield. 

Another complication that can arise in these reactions is that a cycloaddition reaction of the radical intermediate formed in the tin hydride reduction, to an adjacent carbon-carbon double bond, can compete with the simple reduction reaction. This occurs when a five- or six-membered ring can be formed in an intramolecular cycloaddition reaction. For example, Beckwith and Lawrence96 found both five- and six-membered rings in the product when l-bromo-2,2,5-trimethylhex-l-ene was treated with tributyltin hydride (Scheme 15). 

In one study, Ingold and coworkers166 measured the rate constants for the reactions of several alkyl radicals with tributyltin hydride using a laser flash photolytic technique and direct observation of the tributyltin radical. They also used this technique with tributyltin deuteride to determine the primary hydrogen-deuterium kinetic isotope effects for three of these reactions. The isotope effects were 1.9 for reaction of the ethyl radical, and 2.3 for reaction of the methyl and n -butyl radicals with tributyltin hydride at 300 K. 

Table 8 Rates of reactions of radicals with tributyltin hydride... 

It should be noted that addition of the tributyltin radical to 1-fluoro-1-(phenylsulfonyl)ethene provides phenyl vinyl sulfone as the only isolated product. However, 2-trimethylsilyl-1-fluoro-1-(phenylsulfonyl)ethene reacts with tributyltin hydride in the presence of AIBN to provide (E)-2-trimethylsilyl-1-fluoro-1-tributylvinylstannane. The vinylstannane is an equivalent for the synthon "H2C=CF " providing a convenient route to 2-fluoro-1-alkenes.8 The trimethylsilyl group can be removed with potassium fluoride in dimethyl sulfoxide-water or oxalic acid-methanol at the end of the reaction sequence. 

In a radical reaction of 2-iodomethylpiperidine (112) with tributyltin hydride, 2-(3-phenyl-2-propenyl)piperidine (113) and a 1 1 mixture of epi-mers of perhydropyrido[l,2-6][l,2]thiazine-l,1-dioxide (114) were obtained in 18 and 47% yield, respectively (77TL635). An identical mixture of 113 and the two epimers of 114 was also obtained from a 7 4 mixture of the Z and E isomers of 112, indicating that the starting C=C geometry is not maintained in the product 114. 

Crich and Rumthao reported a new synthesis of carbazomycin B using a benzeneselenol-catalyzed, stannane-mediated addition of an aryl radical to the functionalized iodocarbamate 835, followed by cyclization and dehydrogenative aromatization (622). The iodocarbamate 835 required for the key radical reaction was obtained from the nitrophenol 784 (609) (see Scheme 5.85). lodination of 784, followed by acetylation, afforded 3,4-dimethyl-6-iodo-2-methoxy-5-nitrophenyl acetate 834. Reduction of 834 with iron and ferric chloride in acetic acid, followed by reaction with methyl chloroformate, led to the iodocarbamate 835. Reaction of 835 and diphenyl diselenide in refluxing benzene with tributyltin hydride and azobisisobutyronitrile (AIBN) gave the adduct 836 in 40% yield, along with 8% of the recovered substrate and 12% of the deiodinated carbamate 837. Treatment of 836 with phenylselenenyl bromide in dichloromethane afforded the phenylselenenyltetrahydrocarbazole 838. Oxidative... 

Previously, vinyl radicals for cyclization reactions were produced by the reduction of vinyl halides with tributyltin hydride. In the present... 

Our approach was to use the unsaturated bromodeoxylactones in an intramolecular radical reaction, since these compounds possess both the radical precursor and the radical trap within the same molecule. Thus, reacting the unsaturated bromodeoxyheptonolactone 20 (Scheme 14) with tributyltin hydride and a radical initiator, the bicyclic lactone 65 a was obtained in a quantitative yield within 1 h. The stereocontrol in the reaction was determined by the structure of the product, since the compound obtained has two fused cyclopentane rings which can only be cis anellated. The radical A, which is the intermediate, was trapped by the tin hydride. The stereochemistry of the newly formed chiral center is determined by the configuration at C-4 in the educt 20 [45]. 

Photolysis of 3-phenyl-5(4//)-isoxazolone 152 gives 2,5-diphenylpyrazine 154 in 67% yield (Scheme 41) <1997JIC648>, probably through diradical intermediate 153. Radical chain reactions of a-azido ketones 155 with tributyltin hydride lead to symmetrical alkylpyrazines 156, albeit in low to moderate yields (Scheme 42) <2002T3485>. 

The stereospecific preparation of E- and Z-a-fluorovinylstannanes via the radical reaction of the corresponding a-fluorovinylsulfones with tributyltin hydride has been reported by McCarthy et al. These reagents undergo a variety of destannylation reactions including protolysis, deuterolysis, acylation, iodina-tion, electrophilic fluorination and the Stille coupling reaction [186-189] (Scheme 66). The last reaction has been employed successfully in the synthesis of a fluorinated thymidylate synthetase inhibitor [189] (Scheme 67). 

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