Dithioketals desulfurization

Desulfuration.1 This complex as such or in combination with 2,2 -bipyridyl (bpy) or triphenylphosphine (a NiCRAL) can effect desulfuration of heteroarenes. aryl thioethers, dithioketals, sulfoxides, or sulfones in DME or THF at 63° in 1.5-30 hours. NiCRA is sufficient for aryl thioethers, dithioketals, but NiCRALs are more efficient for desulfuration of heteroarenes. Yields can be comparable with those obtained with Raney nickel. 

Desulfuration-dimerization of dithioketals.1 Dithioketals when refluxed with W(CO)6 in chlorobenzene are converted into the corresponding dimeric alkenes. 

For the reduction of aliphatic ketones to hydrocarbons several methods are available reduction with triethylsilane and boron trifluoride [772], Clemmensen reduction [160, 758] (p. 28), Wolff-Kizhner reduction [280, 281, 759] (p. 34), reduction of p-toluenesulfonylhydrazones with sodium borohydride [785], sodium cyanoborohydride [57i] or borane [786] (p. 134), desulfurization of dithioketals (jaeicaipioles) [799,823] (pp. 130,131) and electroreduction [824]. 

Most frequently mercaptoles (dithioketals) are desulfurized to hydrocarbons... 

Desulfurization of 1,3-dithiolanes.9 Selective hydrogcnolysis of dithioketals and dilhioacetals is possible with 4 equivalent of this hydride in the presence of A1BN. Yields are 75-95%. The other products are ethane and (Bu3Sn)2S. 

The lower reactivity of Raney Ni towards sulfones allows the chemoselective desulfurization of (4) with Raney W-2, but an appreciable amount of reduction of keto groups was observed. Raney Ni W-2 also tolerates sulfonamides in this work an ionic mechanism was suggested in order to explain the substitution reaction observed. Lactones,keto lactones," and unsaturated lactoneswere tolerated during the desulfurization of sulfide or dithioketal" groups, but deactivated (e.g. by acetone) Raney Ni was generally used. In contrast, carbon-halide bonds are cleaved where the desulfurization is stereoselective only because the product is the thermodynamically more stable d5-lactone (equation 2)." e-" f... 

LAH-CuCh used in moderate to large excess desulfurizes sulfides and dithioketals in good to very good yields (55-87%), but with allyl sulfides, migration of the double bond occurs. Finally vinyl phenyl sulfones are reductively cleaved in good yields (65%) without reduction of C=-C bonds even by an excess of reagent. ... 

Use of excess alkali metal in liquid ammonia or an amine (generally EtNH2 or ethylenediamine, EDA) is also a widespread procedure used to desulfurize sulEdes, dithioketals and sulfones. - - From the numerous works published, a number of interesting features emerge. Thus desulfurization of sulfides in liquid NH3-THF tolerates esters and ketones, while Li-EtNH2 cleaves the C—S bonds of unsaturated substrates without side reactions (Scheme 1). Sodium in liquid ammonia was found to be a better... 

Benzothiazolyl alkyl sulfides, prepared from the corresponding alcohols, are easily desulfurized (87-99%) by TBTH-AIBN. This reaction constitutes a good indirect deoxygenation of alcohols. Desulfurization of dithioketals may be controlled. Thus 1,3-dithiolanes with 1 mol equiv. of TBTH lead to 3-alkyl (or 3-aryl) thiols (64-82%), while 4 mol equiv. of TBTH leads to the completely desulfurized derivative. Desulfurization of heterocyclic thiones is also performed with this reagent. In passing, it should be noted that generation of radicals from C—S bonds and tin hydrides in the presence of radical initiators is of large synthetic interest. ... 

Although of little synthetic interest at the present time, mention must be made of desulfurizations by transition metal carbonyls. Thus thiols and/or sulfides are desulfurized by complexes such as [MofCOIe], [Fe3(CO)i2], [Co2(CO)s] and [Os3(CO)i2]. Coupling desulfurizations of dithioketals have been performed with [W(CO)6] or [Mo(CO)6], and a recent review gives further information about the hydrodesulfurization of thiophenes. 

In general, thiocarbonyl halides (59) function as thioacylation reagents with a variety of nucleophiles to yield the appropriate thio derivatives (60) (Scheme 31). For example, (59) on condensation with thiols, amines, potassium cyanide or potassium thiocyanide yields the corresponding thio compounds (60). Thiolocarboxylic acids (50) characteristically acylate alcohols and amines with desulfuration (Scheme 32). Dithiocarboxylic acid esters (54b) react with organolithium or Grignard reagents to give the dithioketals (61) after treatment with an alkyl halide (Scheme 33). 

Raney nickel desulfurization of the dithioketal 52 to 53 was accomplished in high yield (>80 ) on a 10-30 g scale however, the yields decreased substantially (24-29 ) when the reaction was done on a larger scale (>100 g). 

Reductive desulfurization of the dithioketals 5.14 and 5.15 is performed under the same conditions as for thioethers [G02] LAH in the presence of copper salts or borohydrides in the presence of nickel salts (Figure 5.8). The deoxygenation of tertiary amine-oxides such as 5.16 and 5.17 can be performed with borohydride exchange resin-copper sulfate in methanol at room temperature or under reflux. This reaction tolerates other functional groups such as carbon-carbon double bonds, chlorides, epoxides, esters, amides, nitriles, sulfoxides, and sulfones [SA4] (Figure 5.8). 

The studies of Ban and Wakamatsu culminated in the preparation of three natural compounds from a single synthetic route (Scheme 1.15). The enediol bis silyl ether 63 was converted to the dianion and immediately alkylated with l-iodo-3-butanol to give glycol 64 as a mixture of diastereomers in 87% yield. Diol fragmentation with lead tetraacetate afforded keto lactone 65 in quantitative yield. Formation of the dithioketal and subsequent Raney nickel desulfurization then gave 66 (81%). Macrocyclic lactone 66 is the simple natural product... 

Stereoselective hydrogen transfer reactions on oxacyclic radical intermediates are useful as shown in the synthesis of lauthisan (32) [126]. A key step in the total synthesis of brevetoxin B by Nicolaou [127] (Scheme 65) features conversion of the hydroxy dithioketal 189 into the oxoeene system 190 via cyclic hemithioketal formation and stereoselective radical-mediated desulfurization. More recently, Tachi-bana employed the same reaction sequence in the partial synthesis of ciguatoxin ]128]. 

The final steps then required desulfurization of the dithioketal and conversion of the /-ether group into the A -3)3-ol. Raney nickel did reduce the dithioacetal group, but also reduced the /-ether group. Titanium(IV) chloride in combination with LiAlHi led to the desired selective reduction to 4. The final step involved... 

Dithioketals and dithioacetals can be induced to undergo reductive desulfurization on heating alcoholic solutions of those dithio-derivatives in the presence of moist Raney nickel (see, e.g., page 746). These sulfur compounds are prepared by treating the aldehyde or ketone with 1,2-ethanedithiol (CAUTION STENCH) in the presence of an add catalyst (an addition to the carbon of the carbonyl with loss of water, a process that will be discussed at length, vide infra) (Scheme 9.13). 

Finally, in this vein, as pointed out earlier (Chapter 8), thiols behave much the same as alcohols and thus 1,2-ethanedithiol reacts with cyclohexanone to produce the corresponding dithioketal (via the corresponding thiohemiketal) as shown in Scheme 9.63. Reductive desulfurization of the dithioketal with, for example, Raney nickel, in the presence of hydrogen (Ft2), yields the alkane (Chapter 8, Scheme 8.106). 

The reaction of hydrazine with dithioketals (Georgian et al., 1959) has promise to be a good desulfurizing agent. The gaseous by-products can be collected over water and reduce permanganate. Most likely the products are nitrogen and ethylene. 

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