1,2-Dithiolanes

An original method has recently been developed starting either from 1.3-dithiolane (10) or from 1.3.4-thiadiazole-2-thione derivatives (11) (Scheme 4) (3). This method does not work when Ri is an aryl group. 

For 1,3-dithiolanes the ring is flexible and only small energy differences are observed between the diastereoisomeric 2,4-dialkyl derivatives. The 1,3-oxathiolane ring is less mobile and pseudoaxial 2- or 5-alkyl groups possess conformational energy differences (cf. 113 114) see also the discussion of conformational behavior in Section 4.01.4.3. 

Dithiolane (132) derivatives also possess non-planar skeletons the most important conformation is probably of symmetry C2 (half-chair). The dithiolane ring may be quite flexible and a minimum energy. conformation is only well defined if there is a bulky substituent at the 2-position. 

Dithiolanes are not affected by these conditions, but a 1,3-oxathiolane is cleaved (100% yield). 

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. 

Dioxolanes and 1,3-dioxanes are readily converted to 1,3-dithi-anes and 1,3-dithiolanes in good to excellent yields. 

Attempted cleavage using Hg(II) salts gave material that could not be distilled. 1,3-Dithiolanes can also be cleaved with Ag20 (MeOH, H2O, reflux, 16 h-4 days, 75-85% yield). 

For (n = 2, 3) A chlorobenzotriazole, CH2CI2, —80° NaOH, 50% yield.1,3-Dithianes and 1,3-dithiolanes, used in this example to protect C3-keto steroids, were not cleaved by HgCl2-CdC03. 

Electrolysis 1.5 V, CH3CN, H2O, UCIO4 or Bu4N-"C104, 50-75% yield. " 1,3-Dithiolanes were not cleaved efficiently, by electrolytic oxidation. 

Acyclic monothio acetals and ketals can be prepared directly from a carbonyl compound or by transketalization, a reaction that does not involve a free carbonyl group, from a 1,3-dithiane or 1,3-dithiolane. They are cleaved by acidic hydrolysis or Hg(II) salts. 

HgCl2, CaC03, THF, H2O, 0°, rapid. These derivatives are less susceptible to oxidation and hydrogenolysis than are the 1,3-dithiane and 1,3-dithiolane precursors. 

The section on the cleavage of 1,3-dithianes and 1,3-dithiolanes (pp. 203-205), should be consulted since many of the methods described there are also applicable to the cleavage of oxathiolanes. 

Cyclohexane-1,2-dione reacts with ethylene glycol (TsOH, benzene, 6 h) to form the diprotected compound. Monoprotected 1,3-oxathiolanes and 1,3-dithiolanes are isolated on reaction under similar conditions with 2-mercaptoethanol and eth-anedithiol, respectively. ... 

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)... 

The preparation of e/n-difluoro compounds by the oxidative fluorodesul-furization ot 1,3-dithiolanes readily proceeds by treatment with a pyridinium polyhydrogen fluoride-Af-halo compound reagent the latter serves as a bromonium ion source [2], l,3-Dibromo-5,5-dimethylhydantoin is the most effective of several At-halo oxidants. It is believed that /V-halo compounds combine with hydrogen fluoride to generate in situ halogen fluorides, the oxidants. Formation of gem-difluorides from dithiolanes derived from ketones is efficient and rapid, even at -78 °C, whereas the reaction of dithiolanes derived from aldehydes requires higher temperature (0 °C) (equation 4). 

Me3SiI, CH2CI2, 25°, 15 min, 85-95% yield. Under these cleavage conditions, 1,3-dithiolanes, alkyl and trimethylsilyl enol ethers, and enol acetates are stable. 1,3-Dioxolanes give complex mixtures. Alcohols, epoxides, trityl, t-butyl, and benzyl ethers and esters are reactive. Most other ethers and esters, amines, amides, ketones, olefins, acetylenes, and halides are expected to be stable. 

---