Reductive cyclization Tributyltin hydride

The stereoselectivity observed in the cyclization of 4-unsaturated amides is dependent on the electrophilic halogen species. With /V-chlorosuccinimide the trans/cis ratio is reduced to 3 2, while with A -bromosuccinimide the fra .v-isomer is obtained in >98% purity. The structures of the iodolactones 4 were confirmed by reduction with tributyltin hydride to the trans- and rw-2.4-dimethy]-y-lactones. The high 1,3-trans selectivity strongly contrasts with the results obtained when 2-methyl-4-pentenoic acid is cyclized under thermodynamic conditions with iodine in acetonitrile. In this case a 92% yield and a 32 68 mixture of the f/ww/m-com pounds was obtained. 

This preparative method is one having the most general utility. It utilizes in situ reduction of suitable vicinal trans-nzido sulfonates to intermediary amino sulfonates, which undergo base-induced cyclization to epimines. Elevated temperatures are often required to complete the cyclization. The reduction by hydrazine with Raney nickel originally used was later largely replaced by lithium aluminum hydride reduction in tetrahydrofuran or diethyl ether. Re-duction by sodium borohydride, hydrogenation over Adams catalyst, and reduction by tributyltin hydride have also been reported on occasion. Reductive cyclization by LiAlH4, which is now the method of choice, proceeds... 

John and coworkers78 also observed cyclization to a five-membered ring heterocycle in their hydride reduction of methyl 6/i-isothiocyanatopenicillanate with both tributyltin hydride and triphenyltin hydride (Scheme 16). John and coworkers also found this type of ring closure when an isocyanide was reduced with tributyltin deuteride. The mechanism of this arrangement (Scheme 17) has been confirmed by deuterium labelling. 

Chloropyridinecobaloxime(III) 279 also serves as a convenient source of nucleophilic cobalt, and as a means of promoting radical cyclizations [77]. For example, its reduction in the presence of a bromoalkyne such as 280 leads to the formation of a radical 281 which closes onto the alkyne, leading eventually to the ,Z-alkenes 283 and 284 in an 81% yield. Cyclizations of this type are obviously complementary to those effected using tributyltin hydride. 

A high degree of stereoselectivity was achieved in reductive radical cyclizations with Coordination of the oxime function (e.g. 108) with samarium cation seems to play an important role, since the identical reaction with a tributyltin hydride/radical initiator system produces poor stereoselectivity (equation 79). ... 

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... 

Reductive coupling of carbonyls to alkenes Titanium(IV) chloride-Zinc, 310 of carbonyls to pinacols Titanium(III) chloride, 302 Titanium(IV) chloride-Zinc, 310 of other substrates Samarium(II) iodide, 270 Reductive cyclization 2-(Phenylseleno)acrylonitrile, 244 Tributylgermane, 313 Tributyltin hydride, 316 Triphenyltin hydride, 335 Trityl perchlorate, 339 Reductive hydrolysis (see Hydrolysis) Reductive silylation Chlorotrimethylsilane-Zinc, 82... 

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... 

A further example of the stereoselective synthesis of /ran.v-subsiituted tetrahydropyrans is the radical cyclization of ethyl (4R)-(Z)-4-(2-bromo-l-ethoxyethoxymethyl)-2-hexenoate3" The radical cyclization is performed by heating the bromoacetal in the presence of tributyltin hydride and AIBN in benzene. A mixture of two diastereomers is formed in 97% yield. Reduction, benzylation, hydrolysis and oxidation gives the /ran.v-substituted ( + )-(4S,57 )-4-(2-benzyloxyethyl)-5-ethyltetrahydro-2//-pyran-2-one (5), which is a potential synthetic intermediate for (—)-emetine35. The highly selective formation of the tram-substituted pyrans is rationalized by an allylic strain effect that destabilizes the transition state leading to the cis- isomers. 

The atom-transfer cyclizations of 2-iodo-6-heptyne amides substituted with a chiral sultam derivative yield E Z mixtures of vinyl iodides38. The reductive dehalogcnation with tributyltin hydride and subsequent desilylation gives two diastereomeric methylenecyclopentanes in a ratio of 90 10. 

Homoallylic alcohols are also suitable for controlling the introduction of an alkyl chain, as shown by the synthesis of the diterpenoid atractyligenin61, The starting tricyclic alcohol is converted to the selenocarbonate, a suitable radical precursor. Treatment with tributyltin hydride initiates the stereoselective cyclization which affords the bridged lactone system, an intermediate in the diterpenoid synthesis. Due to the low cyclization rate, tributyltin hydride is added slowly to suppress the formation of noncyclized reduction products. 

The reaction of the bromoacetal, derived from (hydroxymethyl)cyclopentene, with tributyltin hydride affords m-fused acetals as a mixture of diastcreomers2. In the case of the unsubstituted alkene, due to the low rates for the cyclization, noncyclized reduction products are observed. Incorporation of an ester substituent accelerates ring closure to make cyclization the exclusive pathway. 

Radical chemistry has found some application in the synthesis of piperidines. An enhanced diastereoselectivity in the reductive cyclization of bromide 183 to the /raws-disubstituted piperidine 184 was found with t/ w(triniethyl)silane in place of tributyltin hydride <040BC2270> (Scheme 68). 

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