Tin Free Radical Addition

Triethylborane or diethylzinc has been proposed to have multiple roles in radical additions to C=N bonds, including both initiation and chain propagation, offering the potential for a radical chain process without tin hydride [6, 7]. Accordingly, we attempted triethylborane mediated tin free additions of various halides, simply deleting BujSnH from the conditions outlined in Table 2.3 and using InCb as the Lewis acid (Table 2.5). As in the case of tin mediated additions, the secondary iodides worked quite well in additions to the propionaldehyde hydrazone (entries 2 4). Although other primary radicals were ineffective, chloroiodomethane did lead to 

The synthetic potential of fhe intermolecular radical additions would be dramatically enhanced by developing conditions compatible wifh primary radicals. Less stable T radicals (versus 2° or 3°) often suffer premature reduction by hydrogen atom abstraction processes and are impractical under Ets B/O2 initiation conditions due to fhe competition with ethyl radicals. These considerations led us to seek alternatives to triethylborane. 

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Table 4 Tin-free radical additions to 3a in the presence of InCl3...

Table 2.5 Scope of halide in tin free radical addition to 8a in the presence of InCL. O, O.

Addition of organometallic compounds to unsaturated esters 5-20 Addition of tin and mercury hydrides to unsaturated ketones 5-22 Free-radical addition of carboxylic esters to olefins... 

A tin-free radical cyclization of the xanthate 272 using dilauroyl peroxide (DLP), as the radical initiator, in chlorobenzene was used to give the 5//-pyrido[2,3-A azepin-8-one 273 (Scheme 35) <20040L3671>. The xanthate 272 was also made by an intermolecular free radical addition to allyl acetate, using the xanthate 271, as the radical precursor. Somewhat surprisingly in this latter case, intramolecular free radical attack on the pyridine ring did not take place. 

Distannylethenes are traditionally prepared by the free-radical addition of a tin hydride to a vinyltin the bis(tributylstannyl) derivative has been used in either single or double coupling reactions, for example by Echavairen and co-workers [52,53], who reacted it with acid chlorides, and Barrett et al. [54], who coupled it sequentially with alkenyl iodides. 

Using supported ditin compounds, it is possible to promote free radical addition of organic iodides to ttiple bonds and atom transfer cyclization of e-unsaturated iodoacetates or iodoamides using UV irradiation. In this latter case, tin contamination was found to be 5-34 ppm using 0.1 eq. of ditin reagent, and recycling of the tin reagent was also possible. 

Hydrostannylations. Hydrostannanes add to alkynes in uncatalyzed reactions at 60 °C. Phenylacetylene, for instance gives a mixture of ( )- and (Z)-vinylstannanes, wherein the tin atom has added to the terminal carbons. In the presence of Wilkinson s catalyst, however, the hydrostannylation proceeds at 0 °C to give mostly the regioisomeric vinylstannanes (eq 23). Terminal stannanes in the latter process seem to result from competing free radical additions. This may not be a complication with some other catalysts the complexes PdCl2(PPh3)2 and Mo( j -allyl) (CO)2(NCMe)2 also mediate hydrostannylations of alkynes, and they are reported to be 100% cis selective. Hydrostannanes and thiols react in a similar way to silanes and alcohols (eq 24). ... 

The reactions are performed by slow addition (10-15 h) of benzene solution of tri-K-butyltin hydride (1.3 eq.) and AIBN (0.7 eq.) to the boiling benzene solution of the corresponding Motherwell s precursor. Tri- -butyltin hydride in the presence of radical initiator such as AIBN is well known reagent for the generation of aryl radicals from aryl iodides and bromides [5]. Side-reactions in this approach are the formation of direct free-radical addition and dehalogenation products. The formation of the latter side-product is minimized by slow addition of tin hydride. However, the formation of direct free-radical addition, the Pschorr-type product is a serious side-reaction. For example, compound 423 at 75% conversion gives 34% of biaryl 424 as zp o-product (Motherwell reaction pathway), and 39% of biaryl 425, as the product of direct free-radical arylation, analogously to the Pschorr reaction pathway [1], Scheme 2. 

Trimethyl- and dimethyl-tin hydrides react photochemically with penta-carbonyltrifluorovinylrhenium to give reduced vinyl complexes (88)— (90) the rrawj ifluorovinyl complex (90) is the major product, and a free-radical addition-elimination mechanism has been postulated. Hydrido-pentacarbonylmanganese reacts with bis(trifluoromethyl)diazomethane to form the complex (CF3)2CH Mn(CO)j. The reaction of HMnCCX)) with... 

Additionally, organotin mercaptides can act as antioxidants, as they can sequester free-radical degradation mechanisms (48). The one drawback of mercaptide-based tin stabilizers is the discoloration of the sulfur after exposure to uv-radiation. Special precautions or formulations need to be developed for outdoor apphcations. 

When studying the free-radical copolymerization of methacrylic and acrylic acids with vinyl monomers, it was established that the addition of catalytic amounts of SnCl and (C6Hs)3SnH has a marked effect on the copolymer composition. It was found that complexes are formed by charge transfer between unsaturated acids and the above tin compounds. It has been suggested that the change in polymer composition is caused by the interaction of the tin compounds with a transition complex resulting in a decrease of the resonance stabilization of the latter 94,). 

Keywords Atom transfer reactions Boron C C bond formation Conjugate addition Radical initiators Radical reaction Tin-free... 

Sect. 3.2). However, this approach is limited to the few trialkylboranes that are easily available and cheap since only one of the three alkyl group is transferred. By using a triethylborane as a chain transfer reagent, the reaction could be extended to alkyl iodides as radical precursors. Bertrand [94,114] and Naito [95,97] reported both the use of triethylborane for the tin-free addition of alkyl iodides to imines. A typical example for a tentative of asymmetric addition to a glyoxylate imine is depicted in Scheme 50 (Eq. 50a). More recently additions to isatin imines were reported (Eq. 50b) as well as addition to 2H-aziridine-3-carboxylates by Lemos [100] and Somfai [101] (Eq. 50c). 

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). 

Derivatives of trifluoroethanethiol have limited though interesting chemistry. Unfortunately, metallated difluorothioenol chemistry has not been reported, because rapid nucleophilic attack occurs even by hindered bases such as LDA. Nakai et al. exploited this high electrophilicity in a tandem addition/elimina-tion-rearrangement sequence [146], but more recent applications have concerned free radical chemistry (Eq. 46). Chlorination of trifluoroethyl phenyl sulfide followed by exposure to tin hydride in the presence of an allylstannane resulted in C-C bond formation with a reasonable level of stereocontrol [147]. 

The addition of thiols to C—C multiple bonds may proceed via an electrophilic pathway involving ionic processes or a free radical chain pathway. The main emphasis in the literature has been on the free radical pathway, and little work exists on electrophilic processes.534-537 The normal mode of addition of the relatively weakly acidic thiols is by the electrophilic pathway in accordance with Markovnikov s rule (equation 299). However, it is established that even the smallest traces of peroxide impurities, oxygen or the presence of light will initiate the free radical mode of addition leading to anti-Markovnikov products. Fortunately, the electrophilic addition of thiols is catalyzed by protic acids, such as sulfuric acid538 and p-toluenesulfonic acid,539 and Lewis acids, such as aluminum chloride,540 boron trifluoride,536 titanium tetrachloride,540 tin(IV) chloride,536 540 zinc chloride536 and sulfur dioxide.541... 

A detailed mechanistic analysis of the factors affecting the success of these tin hydride mediated addition reactions has been provided by Giese.3 This analysis, which is especially illustrative of how experimental conditions for free radical reactions are planned, is summarized in Scheme 27. Three intermediate radicals, (8), (9) and (10), are involved. As is characteristic of all radical reactions, these radicals are simultaneously exposed to the same reagent pool and each can potentially undergo an addition reaction or an atom transfer reaction. The required reaction of the tributyltin radical (8) is atom ab-... 

A third tin-based method of free-radical production also utilizes tin radical addition to a carbon-sulfur double bond as a key reaction. In this case a thio-noester (usually a thiono carbonate) is the reactant. As in the previous method, addition of tin to the sulfur atom is followed by fragmentation to a carbon-centered radical. 

Radical carbonylation can also be conducted in a zinc-induced reduction system. A similar three-component transformation reaction to that illustrated in the second equation of Scheme 6.14 can be attained using zinc and protic solvents (Scheme 6.38) [59]. The observed stereochemical outcome is identical to that for the tin hydride-mediated reaction, providing a additional evidence for free-radical generation, radical carbonylation, and acyl radical cyclization taking place simultaneously, even in the zinc-induced system. In this system, however, the final step is reduction to form a carbanion and protonation. 

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