Thietanes 1.2- dithiolanes

Animal Sources. The marine annelid worm Lumbrineris hetero-poda produces an insect toxin nereistoxin, 24, 4-N,N-dimethyl-amino-1,2-dithiolane (5 ). The mink MusteXa vison) affords 2,2-dimethylthietane, 14, and 3,3-dimethy1-1,2-dithiolane, 25 (28,63, 64), the ferret Musteta putoris) secretes 14, 25, cis- and trans-2,3-dimethylthietane, 2-propyl- and 2-pentyl-thietane, cis and trans-3,4-dimethyl-l,2-dithiolane, and 3-propyl-l,2-dithiolane (65), and the stoat (Mustela erminea) contains 2-ethyl-, 2-propyl-, and 2-pentyl-thietane, and 3-ethyl- and 3-propyl-l,2-dithiolane in its anal gland (5, ). These several thiaheterocycles from mustela species probably function as scent markers. 

Gotthard, however, showed that by lowering the thione concentration the thietane-dithiolane yield ratio could be systematically directed to favor the four-membered heterocycle. A low thione concentration inhibits addition of the intermediate diradical to another thiophenone molecule to produce the dithiane (Scheme 5). 

An interesting synthetic approach to thietanes is the selective desulfurization of cyclic disulfides.The treatment of dithiolanes with a diethyl-aminophosphine results in a ring contraction to thietanes, (Eq. 19). This has been demonstrated with a-lipoic acid, a coenzyme with a dithiolane structure involved in the biological oxidation of pyruvic acid. The reaction is proposed to be initiated by the electrophilic attack of the phosphorus on the ring sulfur atom, resulting in the formation of an acyclic internal phosphonium salt, which by subsequent elimination of a phosphine sulfide, closes to the four-membered ring. °... 

Thietanes can also be prepared by ring contraction of higher-membered heterocyclic rings. Thermolysis of the dithiolane dioxide 129 in benzene leads to trans-2-phenyl-3-benzoylthietane (130) and benzalacetophenone (Eq. 20). 

A limited number of examples have been published of the insertion of sulfur into thietane rings giving 1,2-dithiolanes such as (45) (76BCJ2491) and (46) (70TL441, 71CPB1022). 

Oxirane taxol derivatives have also been found to be convenient starting materials for the synthesis of taxols fused with a thietane ring. The oxirane-derived taxine B derivatives 118 and 119 have undergone reaction with potassium thioacetate in dimethylformamide (DMF) at 60°C <2000TL4891, 2001JOC5058>, leading to the formation of thietane-derived taxine B derivatives 57 and 121. In the case of the bromine derivative 118, the thietane-taxol 57 was not the exclusive product and the 1,2-dithiolane derivative 120 occurred as the major product (Equations 35 and 36). 

Gunatilaka et al. <1999JOC2694> reported the synthesis of the thietane-derived 5,20-thiapaclitaxel derivative 33 by the action of lithium sulfide on the oxirane-derived paclitaxel derivative 122. This reaction led to the thietane derivative 33 in 56% yield and to minor amounts (13%) of 1,2-dithiolane-derived taxol 123 (Scheme 18). 

The gradual addition of potaetium periodate to a dilute aolution of l,S-propaneditluol in aodium hydroxide yields thietane or ite poly-mota aulfur preoijutatee, In acid aolution, the produot ie usually 1,2-dithiolane.i Methyl 6,8-dithiolootanoate and potaeeium periodate yielde 2-thietanevaleric add. ... 

Data on the separation of thietane by gas chromatography have been reported along with data on other sulfur compounds. Thin-layer chromatographic separation of thietane from 1,2-dithiolane and 1,2.3-trithiane works well on silica gel. Thietane forms a hydrate (dec 11.7°) with water. Its clathrate structure was investigated by use of the nmr line shapes of the deuterium oxide hydrate. ... 

Thermolysis of 4-benzoyl-3-phenyl-l,2-dithiolane 2,2-dioxide at 230° in a sealed tube gives 3-benzoyl-2-phenylthietane in 55% yield. ° Photolysis of 1,2-dithiolanes gives low yields of thietanes. ... 

Heating several thietanes with sulfur or selenium yields 1,2-dithiolanes and a 2-selenathiolane, for example, 107 from 19, respectively. The reaction of 108 with sulfur provides a synthesis of thioctic acid. ° A somewhat similar reaction involves heating thietane with aluminum oxide whereby 1,2-dithiolane and hydrogen sulfide are produced, but the dithiolane yield is very low. A photochemical ring-expansion of 99 has been described in Section 11.5.1. ° Treatment of thietane with hexafluoroacetone gives a six-membered cyclic sulfenate. ... 

Kitazume, T Otaka, T. Takei, R. Ishikawa, N. Preparation and reactions of 4-alkoxy-2,2-bis(trifiuoromethyl)thietanes and 5-alkoxy-3,3-bis(trifluoromethyl)dithiolanes. Bull. Chem. Soc. Jpn. 1976, 49(9), 2491-2494. 

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. ... 

Crump, D. R. 1980. Thietanes and dithiolanes from the anal gland of the stoat (Mustela erminea). J. Chem. Ecol. 6, 341-347. 

There are cyclic thioethers, but they are not encountered very often in this book. The three-membered ring thioether (70) is called thiirane, the four-mem-bered ring thioether (71) is called thietane, and the five-membered ring thioether (72) is called thiolane (tetrahydrothiophene). Finally, the six-membered ring thioether (73) is named thiane (tetrahydrothiopyran). A five-membered ring with two sulfur atoms is called a dithiolane, and 74 is named 1,3-dithiolane. The six-membered ring compound with two sulfur atoms is a dithiane 75 is named 1,3-dithiane, whereas 76 is 1,4-dithiane. Both 74 and 76 were noted in Chapter 18 (Section 18.6.7) because they are the dithioacetal derivatives of formaldehyde formed when formaldehyde reacts with 1,2-ethanedithiol or 1,3-propanedithiol, respectively. 

Chloromethyl Oxirans react with barium hydroxide that is saturated with HjS to give 3-hydroxy-thietans. Aldehyde-dimedone adducts give thietans (80) when treated with SCl2. Ring-contraction of a dithiolan with tris(diethylamino)-phosphine gives a 2-propyl-thietan. Treatment of (81) with triphenylphosphine and diethyl azodicarboxylate gives (82). 

Chloropropyl thioesters are formed by the reaction of thietan with acid chlorides. Hydrogen chloride alone gave a small amount of 3-chloro-propanethiol at room temperature but polymeric material at 30—100 Charge-transfer complexes of thietan with electron-acceptors such as maleic anhydride, tetranitromethane, or tetracyanoethylene are believed to be intermediates in polymerization. The cationic polymerization of 3,3-dimethylthietan has been described. Treatment of 2-thietanones with MeCOSCl gave l,2-dithiolan-3-ones. ... 

---