1.3- Dithianes desulfurization

The phosphine-mediated desulfurization of substituted 1,2-dithianes to the corresponding tetrahydrothiophenes proceeds stereospecifically for the corresponding reactions of cis- and /ra r, 5-dihydroxy-l,2-dithianes 124 and 125/126, three different phosphines R3P (R=Et, Ph, (CH2)2COOH-HCl) were employed <2003H(60)47>. The reaction is pH-dependent under mildly acidic conditions, the thiols 127 and 128 were obtained under neutral or moderately basic conditions, however, the 4-hydroxy-3-mercaptotetrahydrothiophenes 129-131 were formed (Scheme 32). Erom 124 and 125 racemic 129 and 130 were obtained, while for 126 the stereospecific product 131 was isolated the identity of... 

In the desulfurization of 3,6-disubstituted-l,2-dithianes with chiral phosphines (Scheme 33) <2000J(P1)1595>, enantiomerically enriched tetrahydrothiophenes 134 with up to 36% ee were obtained. Both yield and ee proved to be dependent on solvent, temperature, and the phosphine employed. 

A one-pot procedure for the transformation of 6-thiopurine nucleosides to 6-aminopurines was developed using DMDO as the oxidant in the presence of a stoichiometric amount of various amines <1996T6759>. For example, 6-thio-9-(2, 3, 5 -tri-0-acetyl-/3-D-ribosyl)purine was readily converted to the 6-alkylamino derivatives (6-amino, 75% yield 6-methylamino, 55% yield). Similarly, A -6-acetyl-8-thio-9-(2, 3, 5 -tri-0-acetyl-/3-D-ribosyl)adenosine was converted to A -6-acetyl-8-methylamino-9-(2, 3, 5 -tri-0-acetyl-/3-D-ribosyl)adenosine (DMDO, methylamine, CH2CI2, 25 °C, 83% yield). Less nucleophilic 2-mercaptopurine derivatives did not undergo the displacement reaction, however, and only the products of dithiane formation and desulfurization were isolated. 

Another useful application of this reaction stems from the fact that dithianes can be desulfurated with Raney nickel (4-36). Aldehydes can therefore be converted to chain-extended hydrocarbons 1510... 

The conjugate addition of aryl dithiane anions to 2-butenolide has been examined as a route to ( )-podorhizol and ( )-isopodophyllotoxone (78JOC985). The dithiane of piperonal (802) was deprotonated and reacted with 2-butenolide to give the lactone anion which was trapped in turn with 3,4,5-trimethoxybenzaldehyde to afford a mixture of the threo and erythro aldol products (803). Desulfurization of the erythro dithiane with Raney nickel gave ( )-podorhizol (804 Scheme 188). 

The dithiane derivative 60 (Scheme 14) is such a compound, it being made from 2,3 5,6-di-0-isopropylidene-D-mannose by treatment with 2-lithio-l,3-dithiane to give a heptose dithioacetal that was refunctionalized at C-2-C-3 by way of the C-l anion and then converted to the 6,7-epoxide following selective acid-catalyzed cleavage of the 6,7-acetal ring. Treated with n-butyllithium it gives, in 70% yield, the cyclized 61, which is efficiently convertible into validatol 62, a component of validamycin A, by desulfurization with Raney nickel and de-O-protection by use of boron tribromide in dichloromethane [31]. 

Diethyl-3,5-octadiene 174 Dithiane oxides alkylation of 84 carbanions of 84 Dithianes alkylation of 76,79 as acyl anion equivalents 75 carbanions of 76,79 cleavage of 14-18.76,79 desulfurization of 78 oxidation of 23... 

Dithioacetals (see also dithianes and dithiolanes) alkylation of 98 as acyl anion equivalents 75 carbanions of 87,97-102 cleavage of 14-18,98,102 desulfurization of 78 metal-catalysed coupling 127 reaction with Grignard reagents 127 reductive lithiation of 89 synthesis of 12-19,97-102 Dithioacids synthesis of 40... 

As the product 39 still contains the xanthate group, alternative radical transformations can be performed, which also include its removal with tris(trimethylsilyl)silane. Further manipulations of the dithiane ring comprise desulfurization or hydrolysis, thus confirming the use of such xanthates as the synthetic equivalent of a methyl and formyl radical. Two examples of the use of this chemistry for the extension of alkene-containing sugars were successfully examined, as illustrated in Scheme 27. 

In contrast, the unexpected hydrogenolysis of a tertiary alcohol was observed during the desulfurization either of 1,3-dithiane derivatives or of their monosulfoxides, as exemplified in Scheme 3. It is intriguing that even deactivated W-2 Raney Ni did not improve the result, but a low temperature did allow convenient desulfurization with a minimum amount of side product. 

Thioacetals, prepared from the corresponding ketones, have also been reduced to alkenes using moderately active Raney nickel as the desulfurization agent (Scheme 37). This form of Raney nickel does not reduce the newly formed alkene or react with other isolated carbon-carbon double bonds. Note that under these conditions the saturated hydrocarbon often observed in Raney nickel desulfurizations is not formed. Similar conditions have been used for the conversion of cyclodecanone to cyclodecene. While thioacetals have also served as intermediates in the analogous conversion of enones into dienes, a mixture of diene products is obtained. For instance, dithiane generation from 17p-hydroxy-A -androsten-3-one, followed by desulfurization affords a 4 1 mixture of 17P-hydroxy-A -androstadiene and 17P-hy-droxy-A -androstadiene, respectively. ... 

Stereoselective addition of a dithiane anion to chiral 2-methyl-3-trimethylsilyl-3-buterud combined with the stereoselective addition of a Grignard reagent to the chi a-alkoxy ketone affords a practical method for the construction of a,y-dimethyl-a,3-dihydroxy compounds, useful intermediates for the synthesis of erythronolides (Scheme 33). -Hydroxy cartmxylic esters were synthesized by the addition of ethyl l,3-dithiolanyl-2-carboxylate enolate to a chiral aldehyde, followed by desulfurization. ... 

Acetolysis of 19-mesyloxy-4-androstene-3,17-dione-3-thioketal under buffered conditions yields the steroidal 3-eno[3,4-b]dithiane 18 in 73% yield. In the absence of buffer, acetolysis leads exclusively to 19-acetoxy-4-androstene-3,17-dione 3-dithioacetal in 65% yield. Subsequent desulfurization of 18 with Raney nickel affords 5f ,19-cycloandrost-3-en-17-one in 81 % yield.The rearrangement of 3-eno[3,4-6]dithiane constitutes a homoallylic cyclopropanation accompanied by sulfur migration. 

Carbenes undergo insertion reactions at the disulfide bond to form 1,3-dithianes or cause desulfurization (Scheme 11) <85TL5817, 87PAC983). 

The synthesis began with the treatment of 3,4-anhydro-l,2-0-isopropylidene-D-erythritol 90 with 2-alkyl-2-lithio-l,3-dithiane 92 to give 93 (Scheme 16). Reductive desulfurization of 93 and transacetalization of the resulting 94 by the following reaction sequence (1. acidic hydrolysis 2. protection of the primary hydroxyl group 3. ketalization and 4. basic hydrolysis) afforded the primary alcohol 95. The Swern oxidation of 95 yielded the aldehyde 96. 

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