Radical chain reaction tributyltin hydride

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

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 formation of the C-C bond occurs in a radical chain reaction (Scheme 1). Bromine abstraction from halide 1 by tin radicals 23 leads to carbon radicals 3 that react with alkenes 4 to give product radicals 5. Trapping of 5 by tributyltin hydride yields products 6 and the tin radical 2. 

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°. 

The synthetic application of free-radical reactions has increased dramatically over the past twenty years. Nowadays, radical reactions can often be found driving the key steps of multistep chemical syntheses oriented towards the construction of complex natural products or other synthetic targets. The majority of radical reactions of interest to synthetic chemists are chain processes. Tributyltin hydride is by far the most commonly used reagent for the rednction of fnnctional groups and formation of C—C bonds either inter- or intramolecnlarly (cyclization) " , although, as already alluded to, there are several problems associated with organotin compounds. The main drawback consists of the incomplete removal of allegedly toxic tin by-products from the final material ... 

More recently, a radical-mediated variation of this addition-fragmentation has been explored. The reaction, summarized in Scheme 77 for a one-carbon expansion, involves the generation of a radical at the terminus of a chain by homolytic cleavage of a carbon-heteroatom bond. Addition of the radical to the carbonyl produces a bicyclic intermediate, which on cleavage of the alternate bond regenerates the ketone carbonyl group with formation of a new radical. The sequence is terminated by the reduction of the radical with the tributyltin hydride reagent. The near neutral conditions of the reaction avoid the reclo-... 

In recent years, the organotin hydrides have found extensive applications in organic syntheses which involve radical chain reactions in which the stannyl radical R3Sn is a chain-carrying intermediate. Tributyltin hydride has been used most widely, and is commercially available. 

Intramolecular cyclization of unsaturated acyl chlorides. Tributyltin hydride reduces acyl chlorides to aldehydes by a free-radical chain reaction involving an acyl radical (I, 1193). Cekovic10 now finds that treatment of acyl chlorides with a double bond in the S- or 6-position with tributyltin hydride (azobisisobutyronitrile initiation) gives cyclohexanone derivatives. Thus 5-hexenoyl chloride (1) is converted into cyclohexanone (2), and citronelloyl chloride (3) is converted into menthone (4). 

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). 

Scheme 3. Radical chain reaction of isonitriles with tributyltin hydride...

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. 

Full details have appeared of the deoxygenation of alcohols to alkanes by tripropylsilane reduction of their chloroformate esters (2,122). In a related procedure, alcohol selenocarbonates (69), prepared from the chloroformate esters, have been reduced to alkanes by tributyltin hydride. Both are believed to be radical-chain reactions. Primary allylic alcohols have been deoxygenated to terminal alkenes by the new stannylation-protodestannylation sequence shown in Scheme 32 the S-Sn exchange is another radical process. The intermediate allylstannanes may alternatively undergo a new oxidative destanny-lation as shown to give overall [l,3]-transposition of the allylic alcohol. ... 

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. 

One of the very rare examples of a combination of a radical with a pericydic reaction - in this case a [4+2] Diels-Alder cycloaddition - is depicted in Scheme 3.83 [133]. The sequence, elaborated by Malacria and coworkers, is based on the premise that the vinyl radical 3-341 formed from the substrate 3-340 using tributyltin hydride exists mainly in the Z -form. This is reduced by a hydrogen atom to form a 1,3-diene, which can undergo an intramolecular Diels-Alder reaction via an exotransition state reaction (the chain lies away from diene). 

Termination steps can be caused by radical-radical combinations which remove radicals from the chain reaction. An example of a chain reaction using the commonly encountered tributyltin hydride (BusSnH) to carry out a radical cyclisation is shown in Scheme 10.3 to illustrate SH2 and addition reactions. The radicals act as the chain carriers, each reacting with a neutral molecule, and when a radical is removed from the chain by termination, the chain breaks down. 

A simple example involves the reaction of the silyl ether 213, made from the corresponding 4-hydroxy-alkene by treatment with (bromomethyl)chloro-dimethylsilane, with tributyltin hydride and a radical initiator. Bromine abstraction and intramolecular cyclization with the double bond leads to the bicyclic 214, which upon oxidation with hydrogen peroxide gives the branched-chain 215 in an overall yield of 73% from the alcohol precursor of 213 (Scheme 21). When the sequence is conducted with the C-4 epimeric starting alcohol, the final product again has the hydroxymethyl group cis-related to the hydroxy group.217... 

The reaction of an alkyl halide with tributyltin hydride, using a radical initiator, results in the replacement of the halogen by hydrogen. The reaction follows a radical chain mechanism as outlined in Figure 21.3. Examples are provided in the following equations ... 

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