Thiiranes synthesis

Few procedures are available for the synthesis of steroid thiiranes because the rigidity of the steroid nucleus prohibits the application of many methods of thiirane synthesis. The only general methods involve the con-... 

The use of thiocyanic acid for thiirane synthesis is usually compatible with many functional groups found in natural steroids. The method has found application in androstanes, pregnanes, cholestanes, cholanates and cardeno-lides. However, the presence of a,j5-unsaturated carbonyl groups may decrease the yield of the thiocyanatohydrin due to conjugate addition of thiocyanic acid. Indeed, the 1,4-addition of thiocyanic acid has been carried... 

The thiirane synthesis was also studied using optically active oxazoHne 175 in which the methoxy group oxygen atom provides additional complexation of Li. However, asymmetric induction was rather low. Enantiomeric excesses and configuration of the prevailing enantiomers are indicated in Scheme 55. 

Tominaga and coworkers [82,83] reported a thiirane synthesis starting from 2-mercapto-l,3-thiazole derivative 180 bearing a trimethylsilyl group (Scheme 56). Treatment of 180 with CsF in acetonitrile and then with an aldehyde provided adducts 182 that fragmented via the spiro-isomer 183. Interestingly, the use of TASF as the fluorine anion source provided alcohols 185. The latter products were slowly transformed into the respective thiiranes 184 and thiazolidinone on storage (Table 9). 

The same authors have shown that xanthates 206 (Scheme 61) may also be used for thiirane synthesis as in the case of the adduct 207 which fragmented under the reaction conditions to give 184. Attempted use [78] of a chiral auxiliary failed—reaction of 0-menthyl thiocarbonate 210 with various aldehydes and ketones provided the respective thiiranes in good yields but with a negligible enantiomeric excess. 

Thiiranes and Thiirenes Monocyclic Table 38 Thiirane synthesis without solvent (see Equation (37)). 

The problem of the synthesis of highly substituted olefins from ketones according to this principle was solved by D.H.R. Barton. The ketones are first connected to azines by hydrazine and secondly treated with hydrogen sulfide to yield 1,3,4-thiadiazolidines. In this heterocycle the substituents of the prospective olefin are too far from each other to produce problems. Mild oxidation of the hydrazine nitrogens produces d -l,3,4-thiadiazolines. The decisive step of carbon-carbon bond formation is achieved in a thermal reaction a nitrogen molecule is cleaved off and the biradical formed recombines immediately since its two reactive centers are hold together by the sulfur atom. The thiirane (episulfide) can be finally desulfurized by phosphines or phosphites, and the desired olefin is formed. With very large substituents the 1,3,4-thiadiazolidines do not form with hydrazine. In such cases, however, direct thiadiazoline formation from thiones and diazo compounds is often possible, or a thermal reaction between alkylideneazinophosphoranes and thiones may be successful (D.H.R. Barton, 1972, 1974, 1975). 

Schemes 110-113 outline the most common general methods for accomplishing the synthesis of thiiranes by formation of a C—S bond (75RCR138,66CRV297, 64HC(19-1)576). The methods in Schemes 111-113 are variations of Scheme 110 they differ in the details of the generation of the thiolate anion which effects the ring closure by a displacement reaction. The methods of converting oxiranes to thiiranes, to be discussed separately (Section 5.06.4.3), involve a displacement like thafof Scheme 110 as the final step.

Methylene thiirane is obtained by thermolysis of several spirothiirane derivatives which are formally Diels-Alder adducts of methylenethiirane and cyclopentadiene or anthracene <78JA7436). They were prepared via lithio-2-(methylthio)-l,3-oxazolines (c/. Scheme 121). A novel synthesis of the allene episulfide derivatives, 2-isopropylidene-3,3- dimethylthiirane (good yield) or its 5-oxide (poor yield), involves irradiation of 2,2,3,3-tetramethyl-cyclopropanethione or its 5-oxide (81AG293). Substituents on the thiirane ring may be modified to give new thiiranes (Section 5.06.3.9). The synthesis of thiirane 1-oxides and thiirane 1,1-dioxides by oxidation is discussed in Section 5.06.3.3.8 and the synthesis of 5-alkylthiiranium salts by alkylation of thiiranes is discussed in Section 5.06.3.3.4. Thiirene 1-oxides and 1,1-dioxides may be obtained by dehydrohalogenation of 2-halothiirane 1-oxides and 1,1-dioxides (Section 5.06.4.1.2). 

In general, the methods of synthesis and reactions of oxiranes and thiiranes fused to ordinary or large rings are not particularly affected by the ring fusion. The reader is referred to Chapters 5.05 and 5.06, and reviews cited there, many of which include fused-ring examples. 

Thiirane, 2-phenyl-conformation rotational barriers, 7, 138 polymerization, 7, 144 Thiirane, tetraaryl-synthesis, 7, 175 Thiirane, tetrafluoro-halogenation, 7, 148 polymerization, 7, 144 reactions... 

This chapter will deal exclusively with three-membered rings containing the hetero atoms O, S and N, and fused to the steroid skeleton. Because of the conformational requirements in steroids, not all of the usual methods of synthesis of three-membered rings are applicable to the fused ring system. For the synthesis of steroids to which an aziridine, oxirane or thiirane is attached either in the side chain or at a ring position but not directly fused to the nucleus, the methods discussed in this chapter, as well as others, are applicable. 

The chapter is divided into three sections, devoted to the discussion of the synthesis of (1) oxiranes (epoxides), (2) aziridines (ethylene imines) and (3) thiiranes (episulfides). 

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