Y-Thiolactone

Phenylthietane (321) was opened with lithium and a catalytic amount of DTBB (5%) in THF at —78°C to generate the most stable benzylic intermediate 322 which, by reacting with an electrophile at the same temperature followed by hydrolysis with water, gave functionalized thiols 323 (Scheme 94) . When carbon dioxide was used as electrophilic reagent, 2-phenyl y-thiolactone was directly obtained. 

Addition of Na2S to the methylidene complex 307 gives rise to a trinu-clear sulfonium salt (308) (108). The action of a protic nucleophile, like H2S, on the prochiral phosphinoketene ligand in 309 (R = Me, Ph) leads to five-membered chiral metallaheterocycles (310), which are organometallic derivates of y-thiolactones (197). 

Irradiation of crystalline 0-methyl A -(2,2-dimethylbut-3-enoyl)-A -phenyl-thiocarbamate (174 R R = -(CH2)4-) which exists in chiral space group P2 promotes intramolecular [2 + 2] thietane formation (175 same R R ) followed by rearrangement to give the optically active y-thiolactone (176 same... 

Thiolactones and substituted thiolactones with four to seven ring atoms have been prepared. Except for y-thiolactones, they have been polymerized. Other general procedures for making A-B type poly (thiol esters) are the internal addition reaction of w-unsaturated thio acids (VII),... 

Poly( y-mercapto acids). y-Thiobutyrolactone did not polymerize in bulk at 155°C with potassium ferf-butoxide as initiator (17). This is probably because of an unfavorable monomer-polymer equilibrium, resulting in a low ceiling temperature. It might be possible to overcome these difficulties by using lower polymerization temperatures or high pressure techniques, or both. A similar behavior has been reported for y-butyrolactone (18), which could be polymerized at elevated temperatures at 20,000 atm. It is likely that substituted y-thiolactones are even more difficult to polymerize. 

The next four examples shown in Table 3 demonstrate that tin hydride-mediated radical carbonylation can be efficiently combined with intramolecular Sh2 type reaction of acyl radicals at sulfur, providing good yields of y-thiolactones [37]. The ability of the ert-butyl radical as an Sh2 type leaving group is inferior to that of the benzyl radical [38]. Nevertheless, the fer/-butyl radical in this case has an advantage over the benzyl radical, since the starting benzylthiobutyl radical suffers an unde-... 

In ahnlicher Weise konnen y-Lactone in y-Thiolactone ubergefiihrt werden (10 56%)1 ls-... 

Without additional reagents y -Thiolactone ring opening C-Cleavage... 

Halogeno-y-thiolactones from y,6-ethylenecarboxylic acid thioamides O... 

Scheme 1 y-Thiolactone entity as a reactive thiol precursor the thiol is released by aminolysis and a subsequent thiol-click occurs, incorporating Ri and R2 residues... 

The most commonly used y-thiolactone derivative is homocysteine-y-thiolactone 1, a five-membered cyclic thioester of homocysteine (Scheme 2). Large-scale preparation of 1 requires an acid-catalyzed intramolecular condensation of methionine [77] or homocysteine [78], both bioresource compounds. The hydrochloric acid salt of the racemate 1 is a white solid that displays long-term stability at room temperature and is readily available as a bulk chemical at low cost. 

Homocysteine-y-thiolactOTie 1 is a valuable synthetic building block however, its implementation in polymer science as a versatile functional handle requires some special attention. In order to take part in a PPM, thiolactone 1 needs to be transformed into monomers and/or initiators and subsequently used in a (controlled) polymerization, while maintaining the integrity of the thioester ring. Because the intrinsic instability of the neutral homocysteine-y-thiolactone 1 leads to the formation of the corresponding diketopiperazine adduct [79], an efficient... 

Scheme 2 Chemical structure of homocysteine-y-thiolactone 1 and synthetically valuable derivatives...

An important homocysteme-y-thiolactone derivative is iV-acetyUiomocystei-nethiolactone or citiolone 2 (Scheme 2), a commercial compound that was introduced as a thiolating agent for proteins. This thiolation consists of aminolysis of the water-soluble A -acetyUiomocysteinethiolactone 2 by the e-NH2 groups of lysine residues [92-94]. Thiolation of a large variety of macromolecular biochemical systems has been reported [80, 94—106]. 

A first literature precedent describes the reaction of y-thiobutyrolactone with propiolic acid under basic hydrolysis conditions, generating the corresponding acrylic acid 4 (Scheme 3a) [113]. As an alternative to this sequential hydrolysis and conjugate addition (thio-Michael addition), the lysis of thiolactones under basic conditions is often carried out in the presence of an alkylating agent. Because of the high nucleophilic character of the liberated thiol, 5-alkylated compounds are the final products of these reactions [108]. Methanolysis of homocysteine-y-thiolactone hydrochloride l.HCI and subsequent alkylation by treatment with an alkyl halide in a one-pot fashion has been reported as a simple method for the synthesis of S-alkylhomocysteines 5 (Scheme 3b) [114, 115]. 

Scheme 10 Synthesis of two different types of vinylic thiolactone-containing monomers N-(4-vinylbenzenesulfonyl) homocysteine-y-thiolactone 6 and iV-(acryloyl) homocystei-ne-y-thiolactone 7...

Another possibility for the introduction of thiols at the polymer side chains, as well as their further modification, is described in the chapter on thiolcatones by Espeel and Du Prez in this book [5]. In their approach, polymers with y-thiolactone side groups were used as starting materials. The thiolactones were ring-opened by aminolysis in a first step, yielding thiol moieties (Scheme 2). The introduction of another residue can be enabled by a subsequent thiol-X reaction, for example the... 

Scheme 2 Formation of thiol moieties at polymer side chains by aminolysis of y-thiolactones and subsequent thiol-X reaction, enabling the introduction of two new residues...

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