Five-membered rings Tributyltin hydride

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. 

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. 

The diacetoxymonomethoxy vinyl ether derivative shown has been used in a radical cyclisation procedure with tributyltin hydride to furnish a mixture of cyclic ethers in 87% yield of which 70% comprises a five-membered ring compound. Hydrolysis and oxidation of this with dichlordicyanobenzoquinone resulted in... 

Radical Reactions. The a-p-tolylsulfonylmethyl radical, generated using either tributyltin hydride, azobisisobutyro-nitrile, or hexabutyldistannane with UV irradiation, adds to enol ethers, enatnines, and silyl enol ethers. The addition to enam-mes shows considerable syn diastereoselectivity which can be explained on the basis of an allylic 1,3-strain model (eq 11). When an alkenic or alkynic moiety is present in the a-substituent of the a-p-tolylsulfonylmethyl radical, cyclization can occur to give five-membered ring compounds (eqs 12 and IS). ... 

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). 

Intramolecular cyclization of N-alkenyl-2-bromoindoles has been described. The formation of five as well as six-membered ring in the radical cyclization proceeds in good yield [95TL4857]. A novel intramolecular free radical aromatic ipso substitution reaction has been reported [95CC1353]. Treatment of 138 with tributyltin hydride generates an alkyl radical which attacks the alkene at the carbon bearing the sulfur substituent. This is followed by elimination of the sulfur substituent to provide the cyclized products 139 in moderate yields. The efficiency of the reaction is dependent on the size of the ring formed and on the sulfur substituent. 

Silylmethyl radical cyclizations are a related class of reactions in which the heterocycle serves a temporary purpose to direct the introduction of a methyl or hydroxymethyl group adjacent to the hydroxy group. Starting from the optically active allylic decalin alcohol, reaction with bromomethyl(chloro)dimethylsilane gives the a-bromosilyl ether. Treatment with tributyltin hydride affords the stereoselective cyclization to a five-membered siloxane62. The siloxane ring is converted either to the a.r-dihydroxy compound, or to the ot-methylated derivative63. 

The formation of eight-membered rings by radical cyclization has been found to occur using a-acyl radical species. The reaction occurs at a rate that is faster remarkably even than 5-exo-trig cyclization. Hence, the eight-membered lactone 92 was formed, rather than a five-, six- or seven-membered lactone, on treatment of the bromide 91 with tributyltin hydride (4.72). 

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