Tributyltin hydride-2.2 -azobis

Reaction of an A-(o-halogcnobenzoyl)pyridoindole 360 with tributyltin hydride and azobis(cyclohexanecarbonitrile) gives the /vrr -fused pyrrolonaphthyridine 361 along with the (6 5 6) pyridoindolizine 362 (Equation 129). Compound 361 is obtained by the action of tributyltin hydride on the Ar-benzoyl-chloropyridoindolc 363 (Equation 130)... 

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). 

Propargyl bromide Propyne, 3-bromo- (8) 1-Propyne, 3-bromo- (9) (106-96-7) Tributyltin hydride Stannane, tributyl- (8,9) (688-73-3) Azobisisobutyronitrile Propionitrile, 2,2 -azobis[2-methyl- (8) Propanenitrile, 2,2 -azobis[2-methyl- (9) (78-67-1)... 

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. 

The exocyclic C(2)-S bond of a 2-thiopenem 50 can undergo radical reactions. As depicted in Scheme 28, its desulfurative stannylation reaction with azobis(isobutyronitrile) (AIBN) and tributyltin hydride leads to a penem stannane 51 <1995TL775>. The latter allows subsequent palladium(0)-mediated cross-coupling reactions with... 

Although radical chain processes occur spontaneously at moderate temperatures, it is usually desirable to faciliate the chain propagation by addition of an initiator. 2,2 - Azobi-sisobutyronitrile (AIBN = 2,2 -dimethyl-2,2 -azobis[propanenitrile]) is an ideal initiator, its decomposition rate is solvent independent. Such a reaction is described for a prototype 5-hexenylbromide with tributyltin hydride initiated by In [23] as an illustration in Scheme VII/10. 

The radical ring extension of a-alkyl-p-tin substituted cyclohexanones in the presence of azobis(isobutyronitril) (AIBN) and tributyltin hydride in diluted solution results in good to excellent yields of the ring-extended products [83] (Fig. 5). 

Radical denitration of nitro-substituted isoxazolidines was accomplished with tributyltin hydride and 2,2 -azobis-isobutyronitrile (AIBN) in refluxing benzene <2003S1419>. 

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 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... 

Another modification made off the C-2 position of 1 is the trichloroacetimidate derivate (104), which was prepared by treating 57 with trichloroacetonitrile and DBU in C1CH2CH2C1 at 0 °C to yield product 104 in a 37% yield (Scheme 16) [39], Efforts were also made to remove the C-2 hydroxyl of 57 entirely. Hydroxyl 57 was treated with 1,1-thiocarbonyldiimidazole and catalytic DMAP in CH2C12 to afford imidazole 105 in 64% yield [50], Imidazole 105 was then refluxed with 2,2 -azobis (2-methylpropionitriIe) (AIBN) and tributyltin hydride in toluene to bestow C-2 dehydroxylated 57 in a C-8 epimeric mixture of C-8 a-H and p-H in 13 and 27% yield (106 and 107), respectively [50], Additionally, dilactone 108 was obtained by treating 57 with a mixture of chromium trioxide and pyridine in CH2C12 in a 37% yield [50],... 

Radical cyclizations of nucleophilic N-alkyl radicals 96 onto the benzimidazole 2-position, mediated by tributyltin hydride and activated by quater-nizing the pyridine-like N-3 of imidazole with camphorsulfonic acid, have recently been reported (Scheme 20) [67]. These new five-, six- and seven-membered homolytic aromatic substitutions of nucleophilic N-alkyl radicals onto the benzimidazole-2-position occurred upon the use of large excesses of the azo-initiator, l,T-azobis(cyclohexanecarbonitrile), to supplement the non-chain reaction. The intermediate 97 aromatizes in high yields to the cy-clized benzimidazoles 98. 

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). 

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. 

Primary alkyl phenyl tellurides undergo elimination to form terminal olefins in high yields on treatment with an excess of iV-chloro-iV-sodio-4-methyl-benzenesulphonamide (chloramine-T) in refluxing THF/ ufc-Dinitro compounds and /3-nitrosulphones are converted into olefins via free-radical elimination processes on treatment with tributyltin hydride in the presence of catalytic quantities of azobis(isobutyronitrile) (AIBN). Elimination from the dinitro compounds shows no stereocontrol by contrast, elimination from /3-nitrosulphones is highly stereoselective, e.g. (26)- (27), presumably because elimination from the intermediate radical is faster than rotation about the central carbon-carbon bond. 

Radical debromination was then performed with tributyltin hydride and catalytic amounts of azobis(isobutyronitrile) (AIBN). 

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