1.3- Dithiane formation

The synthesis of 1,3-dioxanes and congeners by transformation of a ring of the same size is not highly developed. Only a few examples of such reactions, typically transacetalizations, have been reported. An important issue of 1,3-dithiane formation, namely the stench of the 1,3-propanedithiol, has been addressed by Liu and co-workers. They found that... 

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. 

Extension of the mechanism for acetal formation into dithioacetal (dithiane) formation. 

Dithiane formation was also observed. N-Methyl-thiophthalimide, N-methyldithiophthalimide and xanthene-9-thione similarly undergo photoaddition to diphenylketene to yield spiro-thietan-2-ones, and thioimides add to diphenyl-N-( -tolyl)keten-imine to give analogous 2-iminothietanes. A detailed examination of the photoaddition of dithioimides to alkenes has establish-... 

Rudrawar S, Besra RC, Chakraborti AK (2006) Perchloric acid adsorbed on silica gel (HC-lO -SiOj) as an extremely efficient and reusable catalyst for 1,3-dithiolane/dithiane formation. Synthesis 16 2767-2771... 

Aldehydes were converted into the corresponding esters by initial dithian formation, metallation, reaction with dimethyl disulphide, and finally hydrolysis of the 2-thiomethyl-l,3-dithians so obtained with HgClj-HgO in aqueous alcohols.The yields of methyl or ethyl esters were high but attempts to prepare t-butyl esters by this route failed and produced only acids in moderate yield. Thiomethylation or deuteriation of the allylic lithio-salt (113) occurred exclusively a to sulphur. Dithianyl carbanions... 

The possibility of activating the indole nucleus to nucleophilic substitution has been realized by formation of chromium tricarbonyl complexes. For example, the complex from TV-methylindole (215) undergoes nucleophilic substitution with 2-lithio-l,3-dithiane to give a product (216) which can be transformed into l-methylindole-7-carbaldehyde (217) (78CC1076). 

A carbonyl group can be protected as a sulfur derivative—for example, a dithio acetal or ketal, 1,3-dithiane, or 1,3-dithiolane—by reaction of the carbonyl compound in the presence of an acid catalyst with a thiol or dithiol. The derivatives are in general cleaved by reaction with Hg(II) salts or oxidation acidic hydrolysis is unsatisfactory. The acyclic derivatives are formed and hydrolyzed much more readily than their cyclic counterparts. Representative examples of formation and cleavage are shown below. 

Williams and McClymont have observed that acylation reactions of the dianion of 2-(5-oxazolyl)-l,3-dithiane (15) lead to formation of 4,5-disubstituted oxazole products through a Comforth rearrangement pathway under base-induced, low-temperature conditions. For example, deprotonation of 15 with LiHMDS (3.0 equivalents) at -78°C, followed by addition of benzoyl chloride or p-chlorobenzoyl chloride and warming to 0°C, provided 16 in 74% and 47% yield, respectively. 

Intermediate 10 must now be molded into a form suitable for coupling with the anion derived from dithiane 9. To this end, a che-moselective reduction of the benzyl ester grouping in 10 with excess sodium borohydride in methanol takes place smoothly and provides primary alcohol 14. Treatment of 14 with methanesulfonyl chloride and triethylamine affords a primary mesylate which is subsequently converted into iodide 15 with sodium iodide in acetone. Exposure of 15 to tert-butyldimethylsilyl chloride and triethylamine accomplishes protection of the /Mactam nitrogen and leads to the formation of 8. Starting from L-aspartic acid (12), the overall yield of 8 is approximately 50%, and it is noteworthy that this reaction sequence can be performed on a molar scale. 

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

To create a setting favorable for the formation of the E-ring of ginkgolide B, it is first necessary to modify the reactivity potential of ring F in 23. Exposure of a solution of 23 in methylene chloride to 1,3-propanedithiol and titanium(iv) chloride at 0°C results in the formation of dithiane 24 in quantitative yield. Oxidation of the primary alcohol with PDC in the presence of acetic acid gives aldehyde 25 in a yield of 75 %. 

Similarly, in another example, alkylation of 111 with diepoxide (—)-115 (1 equiv.) in the presence of HMPA (1.3 equiv.) furnished diol (+)-117. Protection of (+)-117 to form the acetonide, removal of the silyl protecting groups (TBAF), and hydrolysis of the dithiane with Hg(Cl04)2 provided the diketone (+)-118. Hydroxy-directed syn-reduction of both carbonyl groups with NaBI U in the presence of Et2BOMe, and triacetonide formation, followed by hydrogenolysis and monosilylation, afforded the desired Schreiber subtarget (+)-119, which was employed in the synthesis of (+)-mycoticins A and B (Scheme 8.31) [56b]. 

Considering the formation of saturated five-membered heterocycles with two heteroatoms, it is worth to note the possibility to prepare 1,3-dioxolanes, dithiane, oxathianes 148 [93] and dioxolanones 149 [94] by condensation of the corresponding carbonyl compounds under microwave irradiation in acid medium (Scheme 52). The reaction, which is very useful for the protection of carbonyl compounds or for the preparation of useful synthetic intermediates, has also been carried out under batch conditions over Montmorillonite KIO clay in more than 150 g scale, using a 1 L quartz reactor [95]. 

Bohman and Allenmark resolved a series of sulphoxide derivatives of unsaturated malonic acids of the general structure 228. The classical method of resolution via formation of diastereoisomeric salts with cinchonine and quinine has also been used by Kapovits and coworkers " to resolve sulphoxides 229, 230, 231 and 232 which are precursors of chiral sulphuranes. Miko/ajczyk and his coworkers achieved optical resolution of sulphoxide 233 by utilizing the phosphonic acid moiety for salt formation with quinine. The racemic sulphinylacetic acid 234, which has a second centre of chirality on the a-carbon atom, was resolved into pure diastereoisomers by Holmberg. Racemic 2-hydroxy- and 4-hydroxyphenyl alkyl sulphoxides were separated via the diastereoisomeric 2- or 4-(tetra-0-acetyl-D-glucopyranosyloxy)phenyl alkyl sulphoxides 235. The optically active sulphoxides were recovered from the isolated diastereoisomers 235 by deacetylation with base and cleavage of the acetal. Racemic 1,3-dithian-l-oxide 236... 

The following is an example for a sequential one-pot epoxide formation/nucleophilic opening process using (S)-4-(benzyloxy)-l,2-butanediol, iV-(p-tohienesulfonyl)-imida-zole, and 2-lithio-l,3-dithiane ... 

On the other hand, 1,4-dithiane monosulfoxide 48 reacts under the same conditions like a simple aliphatic sulfide. It is suggested that formation of the... 

The value of 2-acyl-1,3-dithiane 1-oxides in stereocontrolled syntheses has been extended to the enantioselective formation of (3-hydroxy-y-ketoesters through ester enolate aldol reactions <00JOC6027>. 

---