Thionolactone

There are, however, two useful alkylating-redudng methods. One is the methylenation of the ester carbonyl group with Tebbe s reagent, the other is the conversion of thionolactones to cyclic thioketals and subsequent reduction. 

It has been shown that Lewis acid catalyzed isomerization of thionolactones provides access to thiolactones. For example, exposure of the substrate 22 to catalytic amounts of BF3 OEt2 led to efficient conversion to the thiolactone 23. Such transformations were also found to give minor amounts of lactone or dithiolactone side products <06TL6067>. Substituted tetrahydrothiophene derivatives have also been obtained from 1,4-dithiane-2,5-diol and 2-nitroethyl acetate derivatives by a base induced sequence featuring a Michael addition and a Henry reaction <06TL8087>. 

Addition to thionolactones cyclic ethers. A wide variety of alkyliithium reagents add to the C=S group of thionolactones. The adducts, after reaction with CH,I, can be isolated in high yield as mixed methyl thioketals. The methylthio group can be removed by reduction with triphenyltin hydride (AIBN) to give cyclic ethers. The reaction is not dependent on the ring size and can be stereoselective, as shown by the synthesis of the ether lauthisan (2) from a thionolactone (1). 

When a,/3-unsaturated esters are the target molecules, the use of a thioaldehyde or thioketone is advisable for the easy elimination of H2S from the intermediate thiol adduct. This strategy has been applied to thiolactams 94a and to thionolactones 94b, opening a route to vinylogous carbamates 95a143 and carbonates 95b144(equation 57). 

Thionolactones.1 Lactones can be converted into thionolactones by O-alkylation with Meerwein s salt followed by reaction with sodium hydrosulfide in acetonitrile. Hydroxy thionoesters are usually formed as by-products. 

Notes A combination of phosphorus pentasulfide and hexamethyldisiloxane can be used to prepare thionoesters and thionolactones in comparable yields and with a simplified workup.1 A solvent-free conversion of ketones, lactones, esters and amides, to the corresponding thio analogs with Lawesson s Reagent.2 See also Belleau s and Daw ,v Reagents. 

Nicolaou and his group [139, 354,355] used this nucleophilic addition to thionolactones as a route to cyclic ethers, via an efficient desulfurization step with tin hydrides (Ph3SnH or n-Bu3SnH). ( )-Lauthisan and a brevetoxin A fragment were prepared according to this scheme. 

Cyclization can also occur, as in the reported synthesis of thionolactones [234],... 

Cyclic stereocontrol using this transposition was investigated in the thionolactone series [499],... 

Analysis of the reaction mixture from equimolar amounts of anhydrous sodium hydrosulfide and N,N-dimethyliminobutyrolactoniurn fluoroborate (164) in acetone at room temperature revealed the thioamidoalcohol 165A only (32). However, when the reaction was run at -78°C, and the mixture acetylated (-78°C), the thionolactone 166 and N,N-dimethylacetamide (167) were the major detectable products. 

The oxygen atom in jl can be replaced by sulfur, and the same prediction is maintained. We have already seen that this is indeed the case for cyclic oxonium and sulfonium ions (Chapter 2). It is essentially for the same reason that lactones, thionolactones (Chapter 3) as well as lactams and their derivatives (Chapter 4) behave in exactly the same manner. Indeed, an axial attack on 12 (X=0, 5, or MR) leads to an intermediate having a chair conformation (12 13) while an equatorial attack necessarily leads to the less favorable boat conformation (12 14). 

Boron trifluoride and indium(III) triflate were found to catalyse efficiently the isomerization of thionolactones (26) to thiolactones (27) in good yields. When applied to an optically active y-thionolactone [(/ )-28], the isomerization reaction proceeded with complete inversion of configuration to [(S)-29] by using BF3,OEt2 (Scheme 9). The proposed mechanism (Scheme 10) implicates a double S -type process involving two molecules of thionolactone, each complexed with BF3, that progresses to the product via the dimer (30).49... 

Cyclic ethers from lactones. The ready addition of RLi to the C=S group of thionolactones (14, 9) has been used to prepare functionalized cyclic ethers from lactones of the same ring size. The first step involves Lawesson thionation of lactone... 

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