1.2- Dixanthates

Treatment of 1,2-dixanthates (32) derived from 1,2-diols, with Bu3SnH in the presence of AIBN under refluxing conditions generates the corresponding olefins (33) via radical... 

In general, thermodynamically stable trans olefins are formed, while cis olefins are obtained in the case of 1,2-dixanthates derived from cycloalkan-l,2-diols. Here, instead of the Bu3SnH/AIBN system, environmentally benign Ph4Si2H2/AIBN, Ph2SiH2/AIBN, and Af-ethylpiperidine hypophosphite/AIBN systems can also be used. As a typically useful method, preparation of D4T (2/,3/-didehydro-3/-deoxythymidine) analogue, which has the same potent anti-HIV activity as AZT, is shown in eq. 7.16. In practice, D2C (2/,3/-dideoxycytidine) and D4C (2/,3/-didehydro-2/,3/-dideoxycytidine) were also prepared by this method [39, 40]. 

Since it seemed likely that a xanthate function beta to a carbon radical would eliminate to furnish a double bond, we studied the tin hydride reduction of 1,2-dixanthates.1112 This provided an efficient new synthesis of olefins which was independent of the stereochemistry of the glycol. It was particularly suitable for the conversion of protected ribosides 23 via the dixanthates 24 into the corresponding olefins 25 from which biologically important dideoxynucleosides 26 were readily obtained by hydrogenation and deprotection.13... 

Deoxygenation of alcohols by the radical pathway requires prior conversion into derivatives such as thionocarbamates. The reduction is carried out in the presence of (r-BuO)2. Alkenes are obtained from 1,2-dixanthates under such conditions. 

Elimination. The formation of olefins from the vic-diols via 1,2-dixanthates is very important, especially after the discovery of anti-HIV nuclosides such as D4C (2, 3 -didehydro-2, 3 -dideoxycytidine) and D4T (2, 3 -didehydro-3 -deoxythymidine). Treatment of adenosine 1,2-dixanthates with the TPDS-AIBN method under refluxing conditions in ethyl acetate generates the corresponding 2, 3 -dideoxygenated adenosine nucleoside in quite good yield as shown in eq 7. ... 

Dideoxygenation via 1,2-dixanthate elimination is also possible and, in acyclic systems, will usually generate the more stable trans olefin. For example, treatment of the bis(xanthate) 22 with tin hydride in refluxing toluene gave selective formation of the -alkene 23. 

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],... 

To a solution of the dixanthate (0.185g, 0.4mmol) in dry toluene (3ml), diphenylsilane (147 ml, 0.8 mmol) was added under argon. Then the solution was brought to the boil and treated with portions (300 ml) of a solution of AIBN in toluene (262.4 mg AIBN dissolved in 6.0 ml of dry toluene) at 30 min intervals. The reaction was monitored by TLC. When the reaction was complete (5 h), the solvent was evaporated under vacuum and the olefin isolated by column chromatography on silica gel (eluent CH2C12), giving (1) (93.5 mg, 94%). 

Interestingly, when a fi-substituted alcohol is used in the Barton-McCombie reaction and if a [3-elimination process occurs faster than the hydrogen transfer step, then the formation of a double bond is observed. We have just seen such an example with a dixanthate (see Section 3.1.3). Many others are known as in [3-hydroxy sulfides [231] and [3-hydroxysulfones [232,233] in a modified Julia synthesis of olefins. 

MALDI-TOF mass spectrometry analysis of poly(methyl acrylate) prepared by the free-radical polymerization of methyl acrylate (MA) in the presence of a cyclic dixanthate under y-ray irradiation revealed that there are at least three distributions, i.e., molecular mass for [ 1-(MA) -H]+ of cyclic polymers, [1-(MA) -THF-H]+, and [1-(MA) -(THF)2-H]+ of linear polymers were observed. The relative content of the cyclic polymers markedly increases at a lower temperature, which may be related to the reduced diffusion rate and the suppressed chain-transfer reaction at the low reaction temperature [39]. 

A mixture of AIBN (262 mg) in toluene (6 ml) was added over 30 min intervals to a refluxing solution of 2/,3/-dixanthate of adenosine (0.4 mmol) and Ph2SiH2 (0.8 mmol) in toluene (3 ml) under an argon atmosphere. After 90 min, the solvent was removed and the residue was chromatographed on silica gel to give 2/,3/-dideoxy-2/,3/-didehydroadeno-sine in 95% yield [36]. 

Thus, were the xanthate ion itself to adsorb and retain its charge, lateral repulsion would make it impossible for the surface coverage on the mineral to be a high one, and the desired hydrophobicity of the surface would not be achieved. In the electrochemical mechanism described by Salami and Nixon, the adsorption can become a charge-transfer reaction, continuing by the participation of oxygen until the surface is fully covered with dixanthate (and hence wettable). The mechanism is thus an electrochemical oxidation. 

Fig. 12.90. The adsorption of the xanthate occurs as a charge-transfer reaction made possible by the reduction of oxygen and leading to the adsorption of dixanthate, which makes the surface hydrophoric and hence attractive to bubble adhesion.

The rest of the chapter has been devoted to special topics and in materials science there are many possibilities. Those selected include the mechanism of the flotation of minerals in which the addition of a certain organic to the solution causes a specific mineral to become hydrophobic so that it is exposed to air bubbles, the bubbles stick to it and buoy the mineral up to the surface, leaving unwanted minerals on the bottom of the tank. It turns out that the mechanism of this phenomenon involves a mixed-potential concept in which the anodic oxidation of the organic collector, often a xanthate, allows it to form a hydrophobic film upon a semiconducting sulfide or oxide, but only if there is a partner reaction of oxygen reduction. This continues until there is almost full coverage with the dixanthate, and the surface is thereby made water-repelling. 

Similarly the dixanthate olefin synthesis, which works well with tin hydride, can also be performed with Ph2SiH2.19 Reduction of dixanthate 24 (B = adenosine) in refluxing toluene afforded 25 (B = adenosine) in 95 % yield. Initiation was by AIBN or benzoyl peroxide. 

The use of a B-523 dextran dixanthate as a bonding agent for fibers of cellulose, glass, and synthetic materials was patented by Novak in 1956. 

The eliminative reduction of vicinal-glycols via a dixanthate to alkenes involves the radicals as illustrated in Scheme 2.42. 

Carbon disulfide inserted into the Te—O bonds of dimethyl tellurium dialkoxides with formation of dimethyl tellurium dixanthates . 

The diorgano tellurium dixanthates are rather unstable in solution, decomposing with a half-life of 79 h in benzene and 6 min in ethanoP. These compounds can be kept in air for several weeks however, on prolonged contact and at elevated temperature decomposi-... 

Dixanthates such as 167 also undergo rearrangement reactions under similar radical conditions to afford 3,5-cyclic dithioorthoformate 168 instead of the expected deoxygenation products (O Scheme 75) [119]. 

In the case of heating dixanthate 169 at 200 °C, orthotrithiocarbonates 170 and 171 are formed via a regioselective cyclization and with inversion of configuration. A similar procedure can also be applied to the 4,6-dixanthate 172 giving 173 and 174 (O Scheme 76) [120]. 

The most commonly encountered difficulty is the formation of the metal salt of the alcohol. Wynberg,2 using standard procedures, was able to obtain the dixanthate (1) in only 5-10% yield. He then found that use of dimsylsodium as the base and... 

I3MSO as the solvent (homogeneous reaction) gives the dixanthate in 50-60% yield. A footnote states that the xanthates of cholesterol and of n-octanol were obtained by this improved procedure in 90% yield. 

The chemistry of )9-(thiocarbonyloxy)alkyl radicals stands in complete contrast to that of the (acyloxy)alkyl radicals, with elimination, while not the rule, being the norm [I]. The difference between the acyloxy and thiocarbonyloxy series is likely a consequence of the much weaker thiocarbonyl bond and the related higher stability of sulfur-centered radicals. The method has been developed in combination with the Barton deoxygenation method (Volume 1, Chapter 1.6) as a means of converting a vicinal diol, via the dixanthate, into an alkene (Scheme 33) [60-62]. Tributyltin hydride has been the reagent of choice for this reaction but it may also be conducted with the triethylsilane/benzoyl peroxide couple [63] and, doubtless, tris(trimethylsilyl)silane. 

Scheme 33. Alkene formation from vicinal dixanthates...

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