Dithioketals, alkylation

Cyclic dithioketals and acetals represent another important class of sulfur containing chiral auxiliaries, which are available in chiral form by biooxidation. Biotransformations were performed on a preparative scale using whole-cells (wild type and recombinant) and isolated enzyme. Again, enantiocomplementary oxidation of unsubstituted dithianes (linear and cyclic, R = H) was observed when using and CPMOcomo (Scheme 9.28) [211,212]. Oxygenation of functionalized substrates (R = substituted alkyl) with gave preferably trans... 

Reduction of cyclic five-membered ethylene monothioketals with calcium in liquid ammonia cleaves the bond- between carbon and sulfur and yields alkyl -mercaptoethyl ethers (7-88%) [795]. Cyclic five-membered ethylene dithioketals (ethylenemercaptoles) afford, analogously, alkyl -mercaptoethyl thioethers (yields 85%) [795]. 

Table 6. Cyclopropanone dithioketals from base catalyzed cyclization of 3-halo-alkyl dithioketals...

Carbonyl transposition.1 Tetrafluoroboric acid is the most effective acid for rearrangement of a-hydroxy ketene dithioketals to a,p-unsaturated thiol esters. This rearrangement is particularly useful for rearrangement of the tertiary allylic alcohols formed by addition of organometallic reagents to a-keto ketene dithioketals, which are readily available by reaction of ketone enolates with carbon disulfide followed by alkylation with methyl iodide. 

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. ... 

The presence of a sulfur atom on a carbon enhances the acidity of a proton on that carbon, and in dithioacetals and dithioketals that proton (RSCH2SR) is even more acidic. 1,3-Dithianes can be alkylated if a proton is first removed by... 

The reaction of aldehydes or ketones with thiols, usually with a Lewis acid catalyst, leads to dithioacetals or dithioketals. The most common catalyst used is probably boron trifluoride etherate (BF3 OEt2). Similarly reactions that use 1,2-ethanedithiol or 1,3-propanedithiolleadto 1,3-dithiolanes, such as 18 or l,3-dithianes. " Dithioa-cetals can also be prepared from aldehydes or ketones by treatment with thiols in the presence of TiCU, SiCU, LiBp4, AKOTfls, with a disulfide RSSR (R = alkyl or aryl), or with methylthiotrimethylsilane (MeSSiMe3). " ... 

As mentioned above, one major drawback of the Trost methodology is its restriction to the parent compound. It was the Cohen group who found an alternative approach to phenylthiocyclopropyl lithium chemistry by using a reductive lithiation of readily accessible cyclopropanone dithioketals which also works for alkyl-substituted cyclopropanes. The anions obtained by reduction with two equivalents of lithium naphthalene or preferably lithium l-(dimethylamino)naphthalene (LDMAN) can effectively be trapped by apt electrophiles (equation 112). 

The dithiane-derived anion can be generated by the action of Bu°U in THF at -78 C or with complex bases NaNH2-RONa at room temperature. Lithiated dithiane can also be prepared in situ by sonica-tion of n-butyl chloride with lithium in the presence of dithiane. Dithioacetals or ketals are resistant to acidic or basic hydrolysis. Regeneration of the carbonyl group from the dithioketal sometimes presents difficulties but can be carried out by hydrolysis in polar solvents (acetone, alcohols, acetonitrile) in the presence of metallic ions such as Hg , Cu, Ag, 71 177 qj j m ise Alternatively, alkylative hy lysis... 

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). 

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... 

Protonation of the potassium salt 357 in water gave the dithiacyclobutane 358. When 357 was treated with primary alkyl halogenides, the corresponding dialkyl compounds 359 were formed. With RS—COCl dithioketals 360 were obtained. ... 

Dithioketal, removal of 536 Dithiolanes, alkylation of 527 conversion to thiols 243 optical dissymmetry effects 366-368 oxidation, with 1-chlorobenzotriazole 525... 

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