Radical Reactions of Organotins

The radical chemistry of organotins is overwhelmed by the tin hydride chemistry. In the past decades, the knowledge of kinetic parameters authorized the expeditious construction of complex molecules by using cascade radical reaction based on BujSn methodology. Moreover, these strategies also offered an excellent dia-stereocontrol, especially for the construction of polycyclic skeletons. These synthetic applications of BujSnH, which will not be covered in this chapter, were reviewed in recent years [279]. In addition to the tin hydride chemistry, there are several applications of organotins in radical syntheses involving mainly allylstan- 

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Recent advances in radical reactions have greatly benefited from the efficiency of organotin reagents as mediators. Radical reaction of alkyl iodides with trifluoromethyl phenylsulfonyl oxime ether 69 and hexamethylditin at 300 nm in benzene afforded the corresponding trifluoromethyl oxime ethers 70 in high yields (Scheme 37) . 

Occasionally, it may be required to study the fundamental radical reactions with organotins in benzene. However, the use of radical reactions with such toxic reagents and solvents cannot be considered in the chemical and pharmaceutical industries, even if the results in terms of organic synthesis are excellent and effective. Even in a fundamental study, it might not be wise to use 1 g of Bu3SnH and 5 ml of benzene. Hence, radical chemists should develop new and less toxic radical reagents and reaction media in order to reduce the damage to nature. 

Tin enolates are one of the most versatile reagents for carbon-carbon bond formation. They are used either in ionic or radical reaction manner. Organotin enolates exist as equilibrium mixtures of keto and/or enol forms, and their ratio largely depends on their substituents and conditions (Equation (66)).220 In general, an enol form has high nucleo-philicity in ionic system and thus only the enol form is often shown in a reaction scheme. 

The palladium-catalyzed reaction of organotin compounds was first published by Eaborn s group in 1976 [1]. It was initially taken as a variation of the Kharasch type reaction, namely, a radical reaction (Scheme 2). 

The radical chemistry of organotins is undoubtedly dominated by tin hydride chemistry, which has been at the source of radical chain reactions of valuable interest for organic synthesis. However, the demonstration of the ability of allyltin reagents to undergo homolytic cleavage of the carbon-tin bond goes back to the early and only ten years... 

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 ... 

The preparation and reactions of organotin phosphines continue to attract interest, and have been reviewed. Cyclodehydrogenation of the secondary phosphine (40) with azobenzene in the presence of AIBN gives the 1,2-stannaphospholans (41). Radical-initiated addition of di-n-butylstannane to the dialkynylphosphines... 

Radical reactions with organotin hydrides have been valuable for dehalogenation of organic halides. Bu3SnH/AIBN dehalogenation of a bicyclic carbamate furnished the ring-contracted product by carbamate rearrangement (Scheme 12.126) [229]. 

Pyranold Compounds.- A review on the formation of C-C bonds by radical reactions Involving organotin or organomercury compounds includes instances of the synthesis of C-glycosides by this approach. 

Free-radical copolymerization of trimethyl- or tributylvinyltin with styrene or methyl methacrylate results in low ( 10%) yield of copolymer. Moreover, both the reaction rate and viscosity decrease considerably with higher vinyltin content in the starting mixture 49). These findings imply that organotin monomers tend to inhibit free-radical copolymerization. 

The propensity of organotin hydrides for SET reactions has been utilized to initiate radical chain reactions. Anodically promoted oxidation of Ph3SnH to [Ph3Sn] at 0.80 V (vs SCE) initiates the cyclization of several haloalkyne and haloalkene ethers as well as of some fi-lactam derivatives. The catalytic cycle shown in Scheme 1 is based on... 

Tin-based reagents are not always snitable owing to the toxicity of organotin derivatives and the difficulties often encountered in removing tin residues from the final product. Therefore, the same authors have carried out additional experiments with 17d and several different alkyl halides under tin-free conditions. The treatment of 16d with tert-butyldiphenylsilyl chloride (TBDPSCl) and triethylamine in the presence of silver triflate in CH2CI2 affords the bis(silyloxy)enamine 17d in 92% yield (Scheme 17). When the radical reaction was carried out with ethyl iodoacetate in the presence of 2,2 -azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70) as the initiator in CH2CI2, the oxime ether 19 was obtained in 83% yield (Scheme 17). 

As with the silanes, some of the most useful synthetic procedures involve electrophilic attack on alkenyl and allylic stannanes. The stannanes are considerably more reactive than the corresponding silanes because there is more anionic character on carbon in the C—Sn bond and it is a weaker bond.103 104 There are also useful synthetic procedures in which organotin compounds act as carbanion donors in palladium-catalyzed reactions, as discussed in Section 8.2.3 Organotin compounds are also very important in free-radical reactions, which will be discussed in Chapter 10. 

It is known that the geometries of the reactants play an important role in the regio-and stereochemical outcome of radical reactions since they are commonly involved in early transition states. Previous attempts to affect rotamer populations during the reaction included, among others, control of temperature and addition of a Lewis acid. It was recently reported75 that organotin halides, common byproducts of radical reactions, act... 

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