Barton-McCombie radical deoxygenation

D. Crich, On the use of S-(4-alkenyI)-dithiocarbonates as mechanistic probes in the Barton-McCombie radical deoxygenation reaction, Tetrahedron Lett. 29 5805 (1988). 

The Barton-McCombie radical deoxygenation [221-223] (vide infra Section 3.2) has also been applied for transforming v/c-diols into olefins. Commercially available diphenylsilane and the easily formed dixanthates can be conveniently used for this purpose, as in the following example in the sugar series [224],... 

In the Barton-McCombie radical deoxygenation reaction the hydroxyl group of an alcohol is replaced with a hydrogen atom. Even hindered secondary and tertiary alcohols may be deoxygenated by this method. In a typical procedure the alcohol is first converted to a thioxoester derivative, which is then exposed to tri-n-butyltin hydride in refluxing toluene. 

S.J. Danishefsky and co-workers developed a synthetic route to the neurotrophic illicinones and a total synthesis of the natural product tricycloillicinone. Illicinones were found to enhance the action of choline acetyltransferase, which catalyzes the synthesis of acetylcholine from its precursors. The application of Corey-Snider oxidative cycHzation and the Barton-McCombie radical deoxygenation provided a direct route to tricycloillicinone. 

Shioiri s group also employed a 2-lithiooxazole to construct the bis-oxazolyl methanol core of 904. Here, lithiation of a silyl-protected 4-oxazolemethanol 905a/ b followed by condensation with 902 afforded a racemic bis-oxazolyl methanol 906a/b in modest yield (Scheme 1.242). Attempts to improve the yield of 906 using a Lewis acid to coordinate the oxazole nitrogen, alternate bases, or addition of cosolvents were not successful. Barton-McCombie radical deoxygenation was used... 

To the best of our knowledge, only a few groups have developed such methodologies. Lythgoe and Waterhouse, in 1977, were the first to use the Barton-McCombie radical deoxygenation approach to induce the elimination of the aryl... 

The toxicity of organotin derivatives and the difficulty in removing tin residues has spurred considerable eflforts to devise catalytic systems or, preferably, completely tin-free processes for conducting radical reactions. The use of poly(methylhydrosiloxane) in conjunction with a small amount of hexabutylditin oxide, a combination of reagents initially proposed by Grady and Kuivila [21a], has recently been applied to Barton-McCombie type deoxygenations [21b]. Several silanes have been examined... 

The reduction of thiocarbonyl derivatives by EtsSiH can be described as a chain process under forced conditions (Reaction 4.50) [89,90]. Indeed, in Reaction (4.51) for example, the reduction of phenyl thiocarbonate in EtsSiD as the solvent needed 1 equiv of dibenzoyl peroxide as initiator at 110 °C, and afforded the desired product in 91 % yield, where the deuterium incorporation was only 48% [90]. Nevertheless, there are some interesting applications for these less reactive silanes in radical chain reactions. For example, this method was used as an efficient deoxygenation step (Reaction 4.52) in the synthesis of 4,4-difluoroglutamine [91]. 1,2-Diols can also be transformed into olefins using the Barton-McCombie methodology. Reaction (4.53) shows the olefination procedure of a bis-xanthate using EtsSiH [89]. 

The addition of silyl radicals to thiocarbonyl derivatives is a facile process leading to a-silylthio adducts (Reaction 5.37). This elementary reaction is the initial step of the radical chain deoxygenation of alcohols or Barton McCombie reaction (see Section 4.3.3 for more details). However, rate constants for the formation of these adducts are limited to the value for the reaction of (TMS)3Si radical with the xanthate c-C6HuOC(S)SMe (Table 5.3), a reaction that is also found to be reversible [15]. Structural information on the a-silylthio adducts as well as some kinetic data for the decay reactions of these species have been obtained by EPR spectroscopy [9,72]. 

An interesting neophyl-type radical rearrangement process has been established for the synthesis of azabicycles, which are not readily accessible by other means. Barton McCombie deoxygenation of xanthate 70 under slow addition of (TMS)3SiH and AIBN in refluxing toluene furnished the 2-azabenzonorbor-nane derivative in good yield (Reaction 7.72) [82]. 

The keto group of the trisubstituted dioxanone 133 generated by ozonolysis was removed by radical deoxygenation according to the Barton-McCombie protocol [80] via the alcohols 134 and the corresponding xanthate, leading after deben-zylation to the dioxane 135 in excellent yield. After conversion to the tosylate, cleavage of the acetonide and protection of the secondary alcohol function as a TBS ether provided access to oxirane 128 by cyclization with NaH in 99% yield and in virtually diastereo- and enantiomerically pure form (de, ee > 96%). 

Since its introduction by Barton and McCombie, the deoxygenation of thionocarbonyl derivatives of alcohols has become an important synthetic reaction and a valuable method for the generation of carbon-centered radicals.3-4 Xanthates, thionobenzotes, thionocarbonyl imidazolides, aryloxy thionocarbonate, N-phenylthionocarbamates and oxalate esters are conveniently deoxygenated with tin or silicon hydrides in boiling benzene or toluene.4-5... 

The Barton-McCombie deoxygenation reaction was invented for use in the manipulation of aminoglycoside antibiotics. It has become a popular method because of the mild conditions employed. Radical reactions have advantages over ionic reactions for carbohydrate chemistry. In this context, there is little neighboring group interference in cationic reactions and little elimination compared with normal nucleophilic displacement reactions. 

The initiation of the Barton Decarboxylation ( Bu3Sn-H -> Bu3Sn-) is effected with a radical initiator, and as with the Barton-McCombie Deoxygenation, the driving force for the reaction itself is the formation of the stable S-Sn bond. 

Deoxygenation of RiCHOH1 (11, 550). Radical deoxygenation of secondary alcohols via thiocarbonyl esters was introduced by Barton and McCombie. More recently, phenoxythiocarbonyl esters have been recommended for the radical deoxygenation (10, 306-307). Particularly rapid and quantitative reduction can be obtained using 2,4,6-trichlorophenoxy- or pentafluorophenoxythiocarbonyl esters. 

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