Radicals, reduction with tributyltin hydride

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]. 

Radical chain chemistry is often employed for the transformation of an alcohol to the corresponding deoxy derivative. The secondary alcohol 1 is first converted into a suitable thiocarbonyl derivative. The first derivatives investigated were thioxobenzoates 2, xan-thates 3, and thiocarbonylimidazolides 4 (Scheme 2). On reduction with tributyltin hydride, these derivatives afforded a good yield of the appropriate deoxy compounds [8-10]. 

These polymers underwent radical allylation [13] using allyltributyltin to give adducts 94 and 95, and reduction with tributyltin hydride to give the products 96 and 97 (Scheme 20). All products were obtained in high yield as white crystalline materials which could be easily separated from tin byproducts. The products were released from the polymer support by hydrolysis with lithium hydroxide. 

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. 

The reaction of the iodoalkene (178) with Pd(dppe)2 in HMPA followed by reduction with tributyltin hydride gave a mixture of the 6-exo trans product (179), the 6-exo cis product (180), and the 1-endo product (181) in a ratio of 1 1 2 in combined yield of 76% (Equation (18)), identical to the result of using hexalkylditin in benzene <90TL933>. This has led Curran and Chang to propose that the low valent palladium ene-halogenocyclization should be classed as a radical chain reaction that proceeds by way of an atom transfer mechanism and that palladium(O) may be a useful substitute for ditin in other iodine atom transfer reactions. 

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). 

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... 

A Although it would be possible to convert 3-bromo-4-melhylani-line (7.2) into the corresponding hydrazine, by diazotization and reduction, react it with cyclohexanone, and then subject the product hydrazone to a Fischer indolization, the bromine substituent would still remain in the indole (note two isomers would form). Of course, this substituent could be displaced reductively using tributyltin hydride and a radical initiator [AIBN, azobis(isobuty-ronitrile)], but the overall synthesis is clumsy and non-selective and there should be a simpler route. 

A sequence of reactions that was recently reported by Hanessian and Alpegiani nicely illustrates how the allylstannane method is useful for functionalization of complex, sensitive substrates and, more generally, how stereochemistry can be controlled in radical addition reactions (Scheme 40).138 Dibromo- 3-lac-tam (25) can be monoallylated with a slight excess of allyltributylstannane and then reduced with tributyltin hydride to provide 3-allylated (3-lactam (26) (the acid salt of which shows some activity as a 3-lactamase inhibitor). Stereochemistry is fixed in the reduction step hydrogen is delivered to the less-hindered face of the radical. Alternatively, monodebromination, followed by allylation, now delivers the allyl group from the less-hindered face to provide stereoisomer (27). Finally, allylation of (25) with excess allylstannane produces the diallylated product (not shown). 

Deoxygenation of primary and secondary alcohols.1 This deoxygenation has been effected by reduction of the thiocarbonyl esters with tributyltin hydride and AIBN as the radial initiator (11, 550). A newer, milder method uses diphenylsilane in a radical chain reaction initiated by triethylborane and air. Even secondary thiono-carbonates, particularly those derived from 4-fluorophenol, are deoxygenated at 25°. 

Cyclic thiocarbonates offer another class of substrates for radical deoxygenation (Scheme 3.9b). In particular, thiocarbonates formed from a diol derived from a primary and secondary hydroxyl are of particular interest, since they can be deoxygenated regioselectively with tributyltin hydride and AIBN.53 In these cases, the secondary position is deoxygenated owing to the higher stability of secondary over primary radicals. As expected, radical reduction of thiocarbonates derived from two secondary hydroxyls leads to a mixture of deoxygenated isomers.52b 53... 

A number of cyclic and sugar-derived halo acetals 273 were subjected to radical 5-exo cyclizations catalyzed by a cobalt salen catalyst 274 with NaB H4 as the stoichiometric reductant but in the presence of air (entry 11) [321, 322]. Under these conditions, bicyclic oxygenated tetrahydrofurans 275a were obtained in 50-84% yield. Diastereomeric isomers 275b were isolated as the minor components. The yields were similar to those obtained with tributyltin hydride. The oxygen concentration proved to be important, since air gave better yields... 

Hoshino et al. [33] reported the first example of an enantioselective radical reaction employing a chiral Lewis add complex. The enantioselective reduction of a-methoxy-methyl-a-iodolactone 41 with tributyltin hydride (BusSnH) in the presence of stoichiometric amounts of the chiral complex of a chiral diamine 42 and Mgl2, gave the reduced product 43 in 88 % yield with 62 % ee (Sch. 17). Reaction using Mg(C104)2, TiCU, Znl2,... 

Hydrostannation of carbonyl compounds with tributyltin hydride is promoted by radical initiation and Lewis or protic acid catalysis.The activation of the carbonyl group by the acidic species allows the weakly nucleophilic tin hydride to react via a polar mechanism. Silica gel was a suitable catalyst allowing chemoselective reduction of carbonyl groups under conditions that left many functional groups unchanged. Tributyltin triflate generated in situ from the tin hydride and triflic acid was a particularly efficient catalyst for the reduction of aldehydes and ketones with tributyltin hydride in benzene or 1,2-di-chloromethane at room temperature. Esters and ketals were not affected under these conditions and certain aldehydes were reduced selectively in preference to ketones. 

Reduction of bromide 320 under phase-transfer catalysis (PTC) conditions provided the 5-methylisoxazolidines 321 and 322 in 86% overall yield. Under the same conditions, the diastereomer 323 remained unchanged. The 5-methyl derivative 324 was obtained along with a substantial amount of pyrrolidine 325 by treatment with sodium cyanoborohydride in boiling DMF (Equations 58 and 59) <1997T739>. Isoxazolidines 320 and 323 underwent a radical-induced rearrangement upon treatment with tributyltin hydride (see Section 4.03.10). 

Huang-Minlon reduction of a similar compound, the method was inapplicable. So, we adopted the method of radical reduction of xanthate (+)-65 instead.42 Ketone (+)-63 was stereoselectively reduced with lithium tri-sec-butylborohydride (L-Selectride), yielding axial alcohol (+)-64 in 92% yield, which was then con-verted to xanthate (+)-65 in quantitative yield by treatment of lithium alkoxide of the alcohol with carbon disulfide and then with iodomethane. Xanthate (+)-65 was next reduced with tributyltin hydride, giving the desired methylene compound (+)-66 in 92% yield. After deprotection of the acetal group of (+)-66 (98% yield), ketone (+)-67 was converted to olefin (-)-68 in 98% yield by formation of tosyl-... 

Reductive removal of the halogen atom with either Raney-Ni or with tributyltin hydride in the presence of AIBN (azobisisobutyronitrile) as a free-radical initiator furnishes the halide-free lactone. Halolactonization followed by base-induced anti- im-ination of H-I with DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) produces the unsaturated lactone. 

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... 

Reductive dehalogenation with tin hydrides can be carried out without interference of a number of functional groups. However, a C-C double bond in a 1,5 relationship to the intermediate cyelopropyl radical can function as a trap and result in formation of bicyclo[3.1.0]hexane derivatives. Thus, treatment of l,l-dibromo-2-(but-3-enyl)cyclopropane with tributyltin hydride afforded a 15 85 mixture of l-bromo-2-(but-3-enyl)cyclopropane (13) and 1-bromo-2-methyl-bicyclo[3.1.0]hexane (12). Under similar conditions l-bromo-2,8,8-trimethyltricyclo-[3.2.1.0 ]octan-3-one (15) was obtained in 6% yield from an isomeric mixture of 7,7-dibromo-4-isopropenyl-l-methylbicyclo[4.1.0]hept-2-one the main product, isolated in 86% yield, was an isomerie mixture of 7-bromo-4-isopropenyl-l-methylbicyclo[4.1.0]hept-2-one (14). ... 

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