Reduction of xanthates

Wood [127] reported an innovative development of the Barton-McCombie deoxygenation of alcohols allowed to work under tin-free conditions. A trimethylborane-water complex proves to be an efficient reagent for the reduction of xanthates. Complexation of water by trimethylborane induces a strong decrease of O - H bond dissociation energy from 116 kcal/mol (water) to 86 kcal/mol (Me3B-water complex). 

Kibayashi and coworkers described the stannane-mediated reduction of xanthate (70) in their work towards the preparation the marine alkaloid (—)-lepadin B (equation 42)272, while Danishefsky and his associates provide an elegant, fully synthetic route to the neurotrophic tricycloilliconone (71) involving the reduction of xanthate (72) (equation 43)277. 

Radical deoxygenation of alcohols is important, and the reduction of xanthates prepared from alcohols, with Bu3SnH in the presence of AIBN is called the Barton-McCombie reaction (eq. 2.13) [37-51]. The driving force for the reaction is the formation of a strong C=0 bond from the C=S bond, approximately 10 kcal/mol stronger. This reaction can be used for various types of substrates such as nucleosides and sugars. Though methyl xanthates, prepared from alcohols with carbon disulfide and methyl iodide under basic conditions are very frequently used, other thiocarbonates, as shown in eq. 2.14, can also be employed. 

Dihydro-5,10-disilanthracene and AIBN can reduce xanthates and thiocarbonates in refluxing cyclohexane solution. Reduction of xanthates with monosilanes such as PhSiH3 and Ph2SiH2 initiated by AIBN does not work effectively because of their strong Si-H bond dissociation energies. However, the same reactions using either dibenzoyl peroxide or triethylborane as an initiator do induce the effective reduction of xanthates. 

Hypophosphorus acid, H3P02 in the presence of AIBN and a base (amine or NaHC03) can reduce organic halides and xanthates in dioxane or aqueous alcohols. Eq. 12.6a to 12.6d shows the reduction of xanthate, thionocarbonate, and iodoarene, and 5-exo-trig cyclization respectively [35-43]. 

The reactions of NHC boranes have also been studied mechanistically in some detail [10]. It has been possible to isolate and characterize fully the (methylthio-carbonylthio)boranes arising from the reduction of xanthates. 

Briggs et al. proposed a new strategy for the synthesis of tricyclic structures using acyl xanthates as precursor for acyl radicals [121]. Irradiation with visible light of a solution of acyl xanthate in presence of 1,6-diene 126 afforded czs-fused bicyclic compound 127 in a good yield (Scheme 38). Radical reduction of xanthate and subsequent aldol condensation leads to the formation of [5.5.5]-fused ring systems similar to those of the triquinane terpene family. 

Huang-Minlon reduction of a similar compound, the method was inapplicable. So, we adopted the method of radical reduction of xanthate (+)-65 instead.42 Ketone (+)-63 was stereoselectively reduced with lithium tri-sec-butylborohydride (L-Selectride), yielding axial alcohol (+)-64 in 92% yield, which was then con-verted to xanthate (+)-65 in quantitative yield by treatment of lithium alkoxide of the alcohol with carbon disulfide and then with iodomethane. Xanthate (+)-65 was next reduced with tributyltin hydride, giving the desired methylene compound (+)-66 in 92% yield. After deprotection of the acetal group of (+)-66 (98% yield), ketone (+)-67 was converted to olefin (-)-68 in 98% yield by formation of tosyl-... 

Thermolysis ° and radical-induced reactions (such as reductionf or termination ) offer a solution and can provide complete desulfurization. Radical-induced reduction of low molecular weight thiocarbonylthio compounds is well known.P Radical-induced reduction of xanthates is the basis of the Barton- McCombie reaction for deoxygenation of secondary alco-hols. ° Stannanes are the most efficient reagents for use in this process but are toxic and residual reagent and the devived reaction bydroducts can be difficult to remove. Hypophosphite salts/ including N-ethylpiperidine hjrpophosphite (17)/ have been recommended as an alternative to stannanes in the radical induced reductions. 

AAHeterocyclic carbene-borane complexes have been shown to be useful as hydrogen sources through radical mechanisms, as Chu et al [85] determined after their initial work with the reduction of xanthates mentioned earlier. Also, substituted imidazol-2-ylidene and triazol-3-ylidenes have been employed in the reduction of dodecyl iodide to dodecane without the addition of any radical initiator. Furthermore, even in the presence of usually borane-reactive species, such as ketones or alkenes, the reduction of the alkyl halide is the only reaction observed. Later, however, Ueng et al foimd that alkyl halides with nearby... 

An alternative procedure for the reduction of xanthates, as proposed by Roberts and co-workers, was to employ a catalytic amount of a thiol, in combination with triethylsilane. Using 1,1-di-f-butyl peroxide (DTBP) as radical initiator, /-dodecanethiol as an acceptor polarity-reversal catalyst, followed by triethylsilane as stoichiometric reductant. The thiol serves to transfer H-atom from the silane reductant to the intermediate radical species (R-). "... 

Phosphorus-based hydrogen donors were investigated with the goals of having a low-cost, metal-free reagent amenable to large scale deoxygenations of xanthates and thionocarbonates Dimethyl and diethylphosphite were successfully used for the reduction of xanthate 38 to 39, however, AIBN could not be used as initiator and was replaced with benzoyl peroxide. 

It was also determined that these phosphine-borane reagents show specific reactivity towards reduction of xanthates over bromide and chloride groups in a substrate. Bis(xanthates) could also be reduced to olefins without the necessity of adding a sacrificial olefin acceptor to protect the deoxygenation product. 

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