Dithiolane, fluorination

Cleavage of 2,2-dibutyl 1,3-dithiolane with fluorine in anhydrous hydrogen fluoride results in the formation of 5,5-difluorononane [7] (equation 3)... 

Fluorination of 1,3-dithiolanes in aqueous acetonitrile offers novel methodology for the deprotection of thiolanes to the parent ketones (Fig. 91) [162]. 

An amine with labile fluorine atoms, A -(l,l,2,3,3,3-hexafluoropropyl)diethylamine, generated in situ by the interaction of perfluoroprop-l-ene and diethylamine, was found to work well as a source of fluorine in the reactions of 1,3-dithiolanes with 1,3-dibromo-5,5-dimethylhydan-toin or A -iodosuccinimide. The reactions run in dichloromethane at — 78 to — 20 C give gem-difluorides in 50-70% yield.76... 

The fluorination of oxathiane is described in Section 25.1.1.3.84 1,4-Dithiane reacts quite differently107 from dioxane and oxathiane over potassium tetrafluorocobaltate(III). The major products (ca. 60 % of the product mixture, itself in ca. 50 % yield) are the result of rearrangement to the 2-methyl-l, 3-dithiolane skeleton, e.g. 1-3. Fluorinated 1,4-dithiancs comprised about 30% of the product the major product is 4. The extent of fluorination, that is the number of fluorine atoms introduced, is much greater than that of dioxane under comparable conditions (tetrahydrothiophene and tetrahydrofuran show a similar contrast). 

The same reagent combination—that is, NO+BF.4 (used in an excess of 1.2 equivalent) in conjunction with PPHF—also induces desulfurative fluorination of phenylsulfides521 (Scheme 5.51). A possible mechanism includes the intermediate cation 131, which undergoes fluorination via an SN2 or SN1 pathway. Dithiolanes,... 

Terminal perfluoroolefins have two fluorine atoms at the double bond. The carbon atoms of the latter bear a significant positive charge, and the nucleophilic agents easily replace the fluorine atoms at the multiple bond. The reactions of binucleophilic reagents with terminal perfluoroolefins form heterocyclic systems. The first step of the reaction involves a nucleophilic attack at the carbon atom of the double bond, generating a carbanion. The latter is stabilized by elimination of the fluoride ion and formation of a new double bond. Subsequent cyclization by the intramolecular attack of the nucleophilic center at the double bond leads to the formation of a heterocyclic system. For example, when a reaction mixture of hexafluoropropylene and sodium dialkylaminodithiocarbamate in dimethylacetamide is heated with aqueous sodium tetraphenylborate, one obtains the tetraphenylborate salt of 2-dialkylamino-4-trifluoromethyl-4,5-difluoro-l,3-dithiolan-2-yl (78JFC(12)193). This compound is formed by intramolecular cyclization of the S-nucleophilic center. 

The method is particularly well-suited to the fluorination of dithioketals of aromatic ketones (Table 12). To achieve reasonable yields with dithioketals of aliphatic or alicyclic ketones, the addition of trifluoromethanesulfonic acid or hydrogen fluoride/pyridine is required. In general, dithiane derivatives give better yields than dithiolane derivatives. 

The (difluoroiodo)arene reagents can be synthesized by anodic oxidation of4-substituted iodo-benzenes. l-(Difluoroiodo)-4-methoxyben/ene is used as a fluorinating agent for l.. -dithio-lanes without isolation and purification. The electrolytic solution is simply mixed with a solution of the dithiolane. The electrolytic cell is depicted in Figure 2. 

Examples of the reaction arc given in Table 12. Similar yields are obtained when l-(difluoro-iodo)-4-nitrobenzene is used as the fluorinating agent. Only catalytic amounts of the reagent are required if an electrochemical synthesis is used where the (difluoroiodo)arene serves as an in-cell mediator for the fluorination of the dithiolane. 

Dithiolanes are fluorinated in very low yields. Electron-accepting substituents in the para-position favor fluorination. whereas electron-donating groups lower the yields (Table 13). 

A very generally applicable method for converting a variety of different functional groups into their partially or fully fluorinated analogs is the oxidative fluorodesulfuration of thiocarbonyl compounds, dithiolanes, dithianes, and dithianylium salts. 

Oxathiolanes, 1,2-Dithiolanes, 1,3-Dithiolanes, and 1,2,3-Trithio-lanes Only three types of fluorinated 1,3-oxathiolanes derivatives are known ... 

Five-membered fluorine-containing heterocyclic compounds with two or three sulfur atoms are more extended. A ring expansion reaction of thietanes into 1,2-dithiolanes involving heating with sulfur was used. ... 

Fluorine-containing 1,3-dithiolanes can be prepared by the reaction of trifluor-omethylketones or trifluoroacetoaldehyde with ethanedithiole in the presence of boron trifluoride. ... 

Table 3. Fluorination of 2-substituted 1,3-dithiolan-4-ones (Pt anode, 0.1 mol/dm, NaC104/ MeCN, lOOmV/s) (02T9273)...

Anodic fluorination of 2-substituted l,3-dithiolan-4-ones (87M28) and 1,3-ox-athiolan-5-ones 9 give monofluoro derivatives 10 (Scheme 10, Table 5) (03JFC(121)93, 99JOC133) (Scheme 10). 

In Et4NF -4HF 2-substituted l,3-dithiolan-4-ones are converted into mono-fluoro derivatives (98EA(43)1985). Table 5 presents data on anodic fluorination of 2-sub-stituted l,3-oxathiolan-5-ones, forming monofluoro derivatives 10 (03JFC(121)93, 99JOC133). The fluoride ion plays a very important role in this process. As can be seen from Table 5, the Et3N 3HF system is unsuitable for anodic fluorination of the... 

Ring synthesis by radical-radical coupling, as well as intramolecular radical substitution, is an alternative method for producing rings, which does not rely on the addition of a radical to an unsaturated bond. Cyclopropanes have been prepared from diiodides by the reaction of a catalytic amount of a fluorinated tin hydride with NaCNBHs in a fluorinated-organie solvent mixture. The rate constant for the reaction was determined using PhsSiH as a chain carrier and found to be 5 x 10 at 80 °C (Scheme 18). The cyclization of 2,2-diethylpropane-1,3-thiol and 4,4-diethyl-1,2-dithiolane in the presence of 2,5-dimethylhexa-2,4-diene and AIBN has been shown to proceed via a radical-chain mechanism (Scheme 19). ... 

Dithioacetales 104 have been transformed into difluoromethyl derivatives 105 a one-pot desulfurative fluorination of dithiolane led to the synthesis of difluoroalkylthiophene. Treatment of the dithioacetales 104a, b with pyridinium polyhydrogen fluoride (PPHF) and nitrosyl tetrafluoroborate at 0 °C led to 3-(l,l-difluoroheptyl) thiophene 105a (40 %) or 3-(l,l-difluorononyl)thiophene 105b (30 %) [65]. 

The first is fluorination of cyclopenta[c]thiophene-4,6-dione 106 by treatment with A-fluoro-6-(trifluoromethyl)pyridinium-2-sulfonate (MEC-04B) in ethyl acetate to give l,3-dibromo-5,5-difluorocyclopenta[c]thiophene-4,6-dione 107 in 84 % yield. Then, conversion of the two carbonyl groups to difluoromethylene groups was accomplished via formation of the bis-l,3-dithiolane derivative 108 followed by desulfurative fluorination with hydrofluoric acid-pyridine complex and dibromatin (l,3-dibromo-5,5-dimethylhydantoin) in dichloromethane to afford 1,3-dibromohe xafluorocyclopenta[c]thiophene 109 in a two-step yield of 73 % [Id, 67]. 

---