Alcohols thiocarbonylation

The mercapto form is much more strongly favored than is the hydroxy form for the corresponding oxygen compounds. A pertinent comparison in this respect is the greatly reduced inclination of enethiols to tautomerize to the corresponding thiocarbonyl compounds, in contrast to the facile ketonization of vinyl alcohols. 

Table 4 The effects of a-carbonyl and a-thiocarbonyl substituents on the relative stabilities of a-methyl benzyl alcohols R-[16]-OH and the corresponding styrenes R-[17] (Scheme 13)"...

An unexpected C-arylation was observed by Sherburn et al. in an attempted radical deoxygenation of a homoallylic secondary alcohol 83 via its thiocarbonyl-derivative 84 (scheme 17).1511 Thus, reaction of 84, obtained from 83 with ArOC(=S)Cl, with nBu3SnH yielded the 10-aiyl compound 87 As inter-... 

Studies have also been conducted on compounds containing a thio-carbonyl group. Photolysis of dimethylthiocarbamates produces128,129 mixtures of deoxy sugars and alcohols (see Table XVI). As the alcohols can be reconverted into dimethylthiocarbamates, and these re-irradiated, the synthesis and irradiation of these compounds offers a useful pathway to deoxy sugars. A simple mechanism for this reaction, based on the two possible a-cleavages resulting from thiocarbonyl excitation, is shown in Scheme 23. In addition, the possibility has been... 

The procedure given here is essentially that described previously by the submitters. -Chlorophenyl isothiocyanate has been prepared from sym-di-p-chloiophenyl thiourea with iodine in alcoholic solution, from ammonium p-chlorophenyldithio-carbamate and lead nitrate [cf. also Org. Syntheses, Coll. Vol. 1 447 (1932)], by the action of thiophosgene on />-chloroaniline and from -chloroaniline with thiocarbonyl tetrachloride in the presence of stannous chloride. ... 

A relevant reductive process, which has found wide application in organic synthesis, is the deoxygenation of alcohols introduced in 1975 by Barton and McCombie [58]. Reaction (4.28) shows that the thiocarbonyl derivatives, easily obtained from the corresponding alcohol, can be reduced in the presence of BusSnH under free radical conditions. The reactivity of xanthates and thiocarbonyl imidazolides [58] was successfully extended to 0-arylthiocarbonates [59] and (9-thioxocarbamates [60]. Several reviews have appeared on this subject, thus providing an exhaustive view of this methodology and its application in natural product synthesis [61-64]. 

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]. 

Deoxygenation of alcohols by means of radical scission of their corresponding thiocarbonyl derivatives. 

Tri-/ -butyltin hydride also serves as a hydrogen-atom donor in radical-mediated methods for reductive deoxygenation of alcohols.131 The alcohol is converted to a thiocarbonyl derivative. These thioesters undergo a radical reaction with tri-w-butyltin... 

Reaction of the bicyclic 1,3,4-oxadithiolane (113) with triphenylphosphine in refluxing toluene led to an equilibrium mixture of the 1,3-oxathietane (114) and the thiocarbonyl derivative (115) (Scheme 29) <93BCJ1714>. Raney nickel can be used to desulfurize both 1,2,4-trithiolanes (to methylene compounds) and 5,5-disubstituted 1,2,4-oxadithiolane 2-oxides (116) which give rise to secondary alcohols (Equation (20)) <90BSB265>. 

Phenols and alcohols also react with substituted thiocarbonyl ylides, although for the reaction with alcohols, acid catalysis is usually recommended (36,38,41,99). Some NH-azoles are sufficiently acidic to give 1,3-adducts without the addition of a... 

Besides alkoxy-, amino-, and amidocarbonylation reactions, a carbonylation process using a thiol as nucleophile, that is, thiocarbonylation, has been extensively studied.It has been shown that the thiocarbonylation takes place with 1-alkynes, " " " propargyl alcohols,allenes, " 1,3-dienes, propargylic mesylates, " and bicyclopropylidene . 

The more favourable equilibrium constants for the addition of thiols to the carbonyl group of aldehydes and ketones compared to those for the addition of alcohols are well documented (Jencks, 1964 Lienhard and Jencks, 1966 Kanchuger and Byers, 1979), if not fully understood. There appears to be a similar tendency for thiols to add to the carbonyl (or thiocarbonyl) group of esters (or thioesters) and several tetrahedral intermediates with one or more... 

Free Radical Deoxygenation of Thiocarbonyl Derivatives of Alcohols... 

Radical chain chemistry is often employed for the transformation of an alcohol to the corresponding deoxy derivative. The secondary alcohol 1 is first converted into a suitable thiocarbonyl derivative. The first derivatives investigated were thioxobenzoates 2, xan-thates 3, and thiocarbonylimidazolides 4 (Scheme 2). On reduction with tributyltin hydride, these derivatives afforded a good yield of the appropriate deoxy compounds [8-10]. 

The relative rates of acylation and of deoxygenation have been determined with these various reagents [44]. As expected, the pentafluoro reagent reacts the fastest with an alcohol under standard conditions, followed by the 4-fluoro reagent, and the phenyl derivative is the slowest. However, for the deoxygenation reaction the fastest group is the methyl xanthate. The slowest is the pentafluorophenyl derivative. This is not important because all of the thiocarbonyl derivatives mentioned give very fast radical reactions 144],... 

A useful variation for the deoxygenation reaction is to react the alcohol with thiophos-gene and then to treat the resultant thiocarbonyl group with the appropriate phenol [43],... 

This chapter shows how radical chemistry based on thiocarbonyl derivatives of secondary alcohols can be useful in the manipulation of natural products and especially in the deoxygenation of carbohydrates. From the original conception in 1975, the variety of thiocarbonyl derivatives used has increased, but the methyl xanthate function still remains the simplest and cheapest, when other functionality in the molecule does not interfere. Otherwise, selective acylation with aryloxythiocarbonyl reagents is important. Many of the functional groups present in carbohydrates and other natural products do not interfere with radical reactions. 

D. H. R. Barton, D. O. Jang, and J. C. Jaszberenyi, On the mechanism of deoxygenation of secondary alcohols by tin hydride reduction of methyl xanthates and other thiocarbonyl deri-vates, Tetrahedron Lett. 37 3991 (1990). 

Thiocarbonyl compounds for which the C=S group is linked to two heteroatoms, as in thionocarbonates, thionocarbamates, thioureas and trithiocarbonates, have been in general less directly involved as intermediates in synthesis, and we have considered here only xanthates which intervene in the Chugaev reaction (see Section 3.1) and Barton radical reactions (see Section 3.2). They are traditionally prepared by reaction of an alkoxide anion, generated from the alcohol and a strong... 

The radical deoxygenation of secondary alcohols through tri-n-butyltin hydride reduction of their xanthate derivatives was introduced in 1975 [227]. The reaction proceeds by thiophilic radical addition to the thiocarbonyl group of a tin radical followed by collapse of the carbon intermediate, as shown in the accompanying scheme. Hydrogen transfer completes the process. 

Deoxygenation of sec-alcohols.1 2 -Deoxynucleosides (1) can be deoxygen-ated efficiently to 2 3 -dideoxynucleosides (3) by reaction with N,N -thiocarbonyl-diimidazole in DMF (80°) to form imidazolides, which on reaction with methanol are converted into methylthionocarbonates (2). These crystalline derivatives are reduced by Bu3SnH to 3. 

Bis(p-methoxyphenyl) telluroxide (118) and the corresponding tellurone (119) have recently been shown to exhibit mild oxidizing properties towards easily oxidizable substrates. Thus the telluroxide (118) oxidizes thiocarbonyl compounds RR C=S to the corresponding ketone RR C—O364,365 and 3,4-di-f-butylpyrocatechol to 3,4-di-f-butyl-o-quinone.364 The tellurone (119) oxidizes benzyl alcohols to the corresponding carbonyl compounds, a reaction. .which is not observed with (118).366... 

Evidence has been presented591 that favours the involvement of thiirane intermediates in the formation of ( , )-divinyl sulfides (455) from the reaction of thiocarbonyl ylides (454) with activated alkynes, while the reaction of l-alkynyl-2,3-epithio alcohols (456) with a catalytic amount of Hg(II) has been shown to afford592 substituted thiophenes (457) (see Scheme 117). 

Dioxoosmium(VI) porphyrins were used to prepare dinitrogenosmium(II) porphyrins (path 1, P = OEP, TTP) via reduction with hydrazine hydrate in THF. The latter were transformed into bisalkoxides (path m) by autoxidation in alcohols, in dibromides (path n), thiocarbonyls (path p), nitridoosmium(VI) alkoxides (path q), or osmochromes (path r), respectively. 

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