S-Methyl xanthates

FREUDENBERG - SCHdNBERG Xanthate Rearrangement Rearrangement of S-methyl xanthates to S-methyIdithiocarbonatas (conversion of alcohols lo thiols via xanthates, also phenols to thiophenols via thiocarbamates). 

These include thiobenzoates, thiocarbonylimidazolides, and phenyl thionocarbonate esters.6 The S-methyl xanthate ester is a particularly convenient intermediate to prepare because of its ease of formation and the low cost of the reagents. Its use is precluded, however, by the presence of base-labile protecting groups and, in such cases, the thiocarbonylimidazolide or phenyl thionocarbonate ester will generally prove satisfactory. Additional methods for the radical deoxygenation of alcohols are described in a review by Hartwig.7... 

In the Chugaev reaction (Figure 4.14), O-alkyl-S-methyl xanthates are pyrolyzed to an alkene, carbon oxysulfide, and methanethiol at 200 °C. 

CHOH >CHi. A variety of thiocarbonyl derivatives of secondary alcohols are reductively cleaved by Bu,SnH. The S-methyl xanthate is a convenient derivative for use in this reaction because of convenience and low cost. ... 

From the first-order rate constants obtained in different solvents (in sealed ampoules), it is apparent that this isomerization is not very sensitive to the polarity of the medium, in accordance with an isopolar, six-membered activated complex [156]. A similar small solvent effect has been observed for the [3,3]sigmatropic rearrangement of allyl S-methyl xanthate to allyl methyl dithiol carbonate [559]. 

Another example of this type of substrate-induced diastereoselectivity is represented by the rearrangement of the S -methyl xanthate of cis-3,5-dimethyl-2-cyclohexenol 5, which takes place on heating at 140 °C for a few hours, to give 644. 

The Chugaev reaction of S methyl xanthates is a synthetically useful p5u olysiss process. The corresponding electron impact induced elimination is a prominent feature of xanthate mass spectra, (45). > The electron impact induced cleavage is at least partially cfs-stereospecific as the thermal reaction is... 

More recently. Barton was able to convert cyclododecylxanthate 129 into the corresponding dithiocarbonate at room temperature using trimethyla-luminium as catalyst (Scheme 50) [125]. The reaction takes place only with secondary xanthates, the hnear hexadecyl S-methyl xanthate not furnishing... 

Cram demonstrated that the Chugaev reaction is a syn elimination by showing that the pyrolysis of the S-methyl xanthate of diastereomeric 3-phenyl-2-butanols is stereospecific, as shown in equations 10.72 and 10.73.As noted, the eliminations also produced 3-phenyl-l-butene (in 30-40% yield). 

DL-frans-2-Dimethylaminocyclohexyl S-methyl xanthate distilled at 136 /6 mm DL-frans-2-dimethylaminocyclohexyl methyl dithiolcarbonate. Y 84.1%.— The cis-isomer undergoes elimination. F. e. of both courses of the reaction s. T. Taguchi and M. Nakao, Tetrahedron 18, 245 (1962) carbohydrate derivatives s. M. Cerny, J. Pacak, and V. Jma, M. 94, 632 (1963). 

Modified Ghugaev reaction. The Li-salt of (l-phenylcyclohexyl)methoxymethyl-carbinol, prepared from the carbinol with phenyllithium in ether according to J. Weinstock and F. G. Bordwell, Am. Soc. 77, 6706 (1955), allowed to react with GS2 then with methyl iodide, and the resulting crude S-methyl xanthate heated 4.5 hrs. at 190-195°crude 1-phenylcyclohexylacetaldehyde enol methyl ether. Y 64%.—This is one step in a multistep conversion of acids with a-quaternary G-atoms into j -subst. acetaldehyde derivatives. F. e. s. J. W. Wilt and B.H. Philip, J. Org. Ghem. 24, 616 (1959). 

The same group of workers also accounted for the thermal rearrangement reaction of di(ethylthio)propyl S-methyl xanthates and the rearrangement of 0,S-dialkyl dithiocarbonates that occurs under Friedel-Crafts reaction conditions. A new, general synthesis of l,3-dithiol-2-ones (451) is based on the acid-catalysed ring-closure reaction of the dithiocarbonates (452). The rearrangements of 2-aminoethyl alkyl trithiocarbonates (453) and alkylthio-thiocarbonyl thiocyanates (433) into dithiocarbonates (454) and alkylthio-thiocarbonyl isothiocyanates (455), respectively, have been described recently. 

The rate constant of R with (Me3Si)3SiH is about 105 M-1 s-1. The rate constants of (Me3Si)3Sf with alkyl halides and selenides are as follows 109M-1 s-1 for alkyl iodides 108 107 M-1 s-1 for alkyl bromides and alkyl methyl xanthates 107 M 1 s 1 for alkyl selenides 106 M 1 s-1 for alkyl sulfides. 

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. 

In a similar way, the reaction of xanthates under radical conditions leads to products and selectivities that are totally different from those in thermal rearrangements. The radical transformation usually furnishes unsubstituted hydrocarbons as reaction products. The major accomplishment of the reaction is the deoxygenation of secondary alcohols to furnish the corresponding hydrocarbons when tributylstannane is used with 0-cycloalkyl thiobenzoates or S-methyl dithiocarbamates [13]. However, the rearranged product may be observed as a byproduct [14,15]. 

Thus secondary or tertiary alcohols ROH can be reduced to RH via their thiocarboxy-lates R C(S)OR, or dithiocarbonates [xanthates, R S(CS)OR the Barton McCombie reaction] 147-149 for example cholesteryl thiobenzoate or S-methyl dithiocarbonate gives cholest-5-ene in 90% and 78% yield respectively (equation 15-47, R = Ph or MeS). The reaction works best for secondary alcohols the 0-t-alkyl xanthates are often rather unstable at room temperature, though the reactions can be carried out at low temperature with initiation by Et3B/02. The primary alkyl xanthates undergo C-O fission only at higher temperatures, when other reactions may compete. The thiocarbonyl imidazolides provide a variant on this theme, and the cholesterol derivative (15-5, R = /V-imidazolc) reacts with tributyltin hydride to give an 18% yield of cholestene.147... 

The Barton deoxygenation (or Barton-McCombie deoxygenation) is a two-step reaction sequence for the reduction of an alcohol to an alkane. The alcohol is first converted to a methyl xanthate or thioimidazoyl carbamate. Then, the xanthate or ihioimidazoyl carbamate is reduced with a tin hydride reagent under radical conditions to afford the alkane. Trialkylsilanes have also been used as the hydride source. Reviews (a) McCombie, S. W. In Comprehensive Organic Synthesis Trost, B. M. Fleming, I., Eds. Pergamon Press Oxford, U. K., 1991 Vol. 8, Chapter 4.2 Reduction of Saturated Alcohols and Amines to Alkanes, pp. 818-824. (b) Crich, D. Quintero, L. Chem. Rev. 1989, 89, 1413-1432. 

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