0-thiolactones

4 Modem Free Radical Methods for the Synthesis of Carbonyl Compounds 

---

Compounds of type (6), (7), (8) and (9), although not strictly derivatives of a saturated heterocyclic system, will be discussed in this chapter. Our discussion of (7) begins and ends here, since oxiranethiones or a-thiolactones are apparently unknown (80AG(E)276). Little is known of (8) and its derivatives, oxiranimines or a-iminolactams. They have been postulated as intermediates in the thermal decomposition of aziridinones (a-lactams) (Scheme 1) but there is no well-established case of the isolation of an oxiranimine (80AG(E)276). 

Thiirane 1,1-dioxides extrude sulfur dioxide readily (70S393) at temperatures usually in the range 50-100 °C, although some, such as c/s-2,3-diphenylthiirane 1,1-dioxide or 2-p-nitrophenylthiirane 1,1-dioxide, lose sulfur dioxide at room temperature. The extrusion is usually stereospeciflc (Scheme 10) and a concerted, non-linear chelotropic expulsion of sulfur dioxide or a singlet diradical mechanism in which loss of sulfur dioxide occurs faster than bond rotation may be involved. The latter mechanism is likely for episulfones with substituents which can stabilize the intermediate diradical. The Ramberg-Backlund reaction (B-77MI50600) in which a-halosulfones are converted to alkenes in the presence of base, involves formation of an episulfone from which sulfur dioxide is removed either thermally or by base (Scheme 11). A similar conversion of a,a -dihalosulfones to alkenes is effected by triphenylphosphine. Thermolysis of a-thiolactone (5) results in loss of carbon monoxide rather than sulfur (Scheme 12). 

Thiirane, 2-keto- — see a-Thiolactones Thiirane, 2-mercaptomethyl-thiophosphate insecticide, 7, 183 tuberculosis inhibition by, 7, 183 Thiirane, 2-methyl-adducts... 

A thiophene-annelated thiadiazole has been prepared from hydrazone 47, which was obtained from the thiolactone 46. Reaction of the hydrazone at room temperature with thionyl chloride resulted in an 8 1 mixture of 48 and 49. Heating the reaction to 80°C in dichloroethane provided 48 exclusively. ... 

Therapeutic Function Treatment of hepatic disorders Chemical Name 2-Acetamido-4-mercaptobutyric acid 7-lactone Common Name Acetylhomocystein thiolactone acetamido thiobutyrolactone Structural Formula o... 

In the event, macrocyclic bis(thiolactones) perform admirably in the macrocycle-to-bicycle bridging reaction (see Scheme 5).17 For example, the eis-fused tetracycle 25 can be produced, in 80%... 

Scheme 5. Bridging macrocycles to form bicycles the first successful experiments with bis(thiolactone) 24. The terms bis(thiolactone) and dithiolactone are used in this chapter to describe compounds of type 24 even though such systems are sometimes referred to as dithionolactones or dithioxolactones.

The productive transformation of a macrocycle to a bicycle can also be executed simply by irradiating a bis(thiolactone). For example, irradiation of a solution of bis(thiolactone) 24 in toluene for... 

Scheme 6. Photo-induced bridging of bis(thiolactones) synthesis of dithiatopazine (31), the first stable 1,2-dithietane.

As attractive as the transannular bridging of bis(thiolactones) to bicyclic bis(oxepane) frameworks is, our inability to convert the disulfide bridging product (see 25, Scheme 5) to a mmv-fused bre-vetoxin-type bis(oxepane) (see 28) necessitated the development of a modified, stepwise strategy. This new stepwise approach actually comprises two very effective methods for the construction of cyclic ethers the first of these is the intramolecular photo-induced coupling of dithioesters, and the second is the reductive cyclization of hydroxy ketones. We will first address the important features of both cyclization strategies, and then show how the combination of the two can provide an effective solution to the problem posed by trans-fused bis(oxepanes). 

Scheme 12. Construction of cyclic ethers from thiolactones.

The conversion of a thiolactone to a cyclic ether can also be used as a key step in the synthesis of functionalized, stereochemically complex oxacycles (see 64—>66, Scheme 13). Nucleophilic addition of the indicated higher order cuprate reagent to the C-S double bond in thiolactone 64 furnishes a tetrahedral thiolate ion which undergoes smooth conversion to didehydrooxepane 65 upon treatment with 1,4-diiodobutane and the non-nucleophilic base 1,2,2,6,6-pentamethylpiperidine (pempidine).27 Regio- and diastereoselective hydroboration of 65 then gives alcohol 66 in 89 % yield after oxidative workup. Versatile vinylstannanes can also be accessed from thiolactones.28 For example, treatment of bis(thiolactone) 67 with... 

Oxazolones (azlactones) are a form of activated lactones, so they are included in this section. CAL-B is an effective catalyst for the DKR of various racemic four-substituted-5 (4H)-oxazolones, in the presence of an alcohol, yielding optically active N-benzoyl amino acid esters as illustrated in Figure 6.24 [40]. Enantioselective biotransformations of lactides [72,73] and thiolactones ]74] have also been reported. 

In the preparation via diazotisation and bromination of homocysteine thiolactone, presence of unreacted diazo intermediate led to an explosion during distillation of the product. 

A range of thiolactones was obtained by virtual screening with the rationale to be covalently cleaved by FabDSer92. Among them, 4 was described as a potent E. coli FabD inhibitor with antibiotic properties although no further biological data was provided [12]. 

It is interesting to note that orthometallation occurs preferentially at the aryl ring in the thiolactone 69 despite the availability of oxygen as a potential donor ligand oxidation of the dinuclear complex 70 by ceric ion gives the condensed isobenzothiophene derivative 71 in unspecified yield152 (Scheme 85). 

---