Xanthates, methyl

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). 

R R2CHOH -> RlR2CHCl. This transformation can be effected with retention of configuration in two steps conversion to the methyl xanthate followed by reaction with sulfuryl chloride (equation I). 

Bornene has been prepared from the reaction of 2-bromo-bornane-3-carboxyIic acid with aqueous sodium bicarbonate,6 by pyrolysis of isoborneol methyl xanthate,7 and by the j8-elimination of hydrogen chloride from bornyl chloride with sodium alkoxides in various solvents.2... 

Alcohols such as PhjCHCHjOH rearrange on treatment with acid they can be dehydrated by heating their methyl xanthates (Tschugaev reaictkMi). The pyrolysis proceeds by a cyclic transition state. Outline the steps using PhjCHCHjOH. ... 

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... 

Bla methoxy(thiocaibonyl)] disulfide, (CH3OCS)2 (I). Mol. wt. 214.34, m.p. 23.5°. The disulfide is prepared by reaction of potassium methyl xanthate, CH3OCSS, with chloramine-T at 25°.1... 

ETHYL METHYL KETONE (see 2-BUTANONE, p.47) ETHYL METHYL XANTHATE ... 

The first sugar derivative to be examined [10] was l,2 4,6-di-0-isopropylidenegluco-furanose 14. This was converted, in excellent yield, to the corresponding methyl xanthate 15. Reduction with tributyltin hydride in toluene under reflux afforded the desired 3-deoxy-derivative 16 in 80-90% isolated yield (Scheme 3). Hitherto, this had been a difficult and... 

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],... 

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). 

A very elegant, simple, versatile and high yielding synthesis of fused l,3-dithiol-2-ones has been described recently. In a representative example, treatment of 4-benzoyloxy-l-bromo-2-butyne with potassium O-methyl xanthate in methanol gave the expected xanthate ester in excellent yield. Refluxing of this ester in chlorobenzene for one hour in the presence of dimethyl fumarate gave 1 in quantitative yield. 

The first structure to be described is of the potassium salt of the methyl-xanthate anion (11), isolated in anhydrous form and with three independent KS2COMe entities comprising the crystallographic asymmetric unit the presence of three independent anions was also observed in a subsequent solid-state 13C NMR study (12). The molecular structure of the S2COMe anion is... 

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. 

A mixture of Bu3SnH (200 mg, 0.69 mmol) in p-cymene (3 ml) was added dropwise to a solution of methyl xanthate of hederagenin (50 mg, 0.087 mmol) at 150 °C. After 10 h, CC14 was added to the mixture and the mixture was refluxed for 3 h. After the reaction, the solvent was removed. A solution of iodine in ether was added to the mixture. The organic layer was washed with 10% KF aq. solution (5 ml), dried over Na2S04, and filtered. After removal of the solvent, methyl oleanoate was obtained by recrystallization [38]. 

Eq. 7.2 shows a typical deoxygenative reaction of hederagenin (3) via methyl xanthate (4) with Bu3SnH in the presence of AIBN under benzene refluxing conditions. 

In detailed reaction mechanism, two pathways are proposed, as shown in eq. 7.3. Path a is the formation of an alkoxy thiocarbonyl radical [I], together with Bu3SnSCH3, while path b is the formation of an adduct radical [II] onto methyl xanthate (1) by Bu3Sn Based on the study with 119Sn-NMR, it was found that the deoxygenation reaction proceeds via path b [4, 5]. Other examples are shown in Tables 7.1 and 7.2. 

Phenyl thiocarbamate (16) is also reduced with the Bu3SnD/AIBN system to provide 2/-deoxy-2/-<7-3/,5/-0-TIPDS-uridine (17) with 100% of -content (eq. 7.8). The less toxic 1,1,2,2-tetraphenyldisilane (Ph4Si2H2)/AIBN or Et3B system also reduces methyl xanthate (18) in good yield (eq. 7.9). 

A mixture of methyl xanthate (0.2 mmol), Ph4Si2H2 (0.22 mmol), and AIBN (0.06 mmol) in ethyl acetate (1.5 ml) was refluxed for 16 h under an argon atmosphere. After the reaction, the solvent was removed and the residue was chromatographed on silica gel with column to obtain the reduction product [18]. 

As an oxidative condition, refluxing treatment of methyl xanthate (39) with [CH3(CH2)10CO2]2 (lauroyl peroxide) in isopropanol generates the corresponding reduction product (40). Here, the formed CH3(CH2) 10 plays the same role as Bu3Sn, and isopropanol donates an a-H hydrogen atom, as shown in eq. 7.18 [42, 43]. 

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

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