Thiol esters synthesis from thiols

Related to the original Suzuki coupling is the ketone synthesis from acid chloride and trialkyl boranes and thiol esters with arylboronic acids. - The latter procedure is Pd-catalyzed and Cu-mediated. 

Monothioacetals 1,3-Oxathiolanes Thiolactams S extrusion, 59-60, 261 Thiols synthesis from haloalkanes, 169, 269 Thionation of lactones, 110-111 Thiones olefination of, 35 Thionocarbonates. See Carbonothioates Thionolactones, 110-111 Thionyl chloride prepn. of acyl halides, 143 prepn. of carboxylic esters, 347 prepn. of haloalkanes from alcohols, 32 Thiophenoi. See Benzenethiol Thiotosylatc. See Benzenesulfonothioic add... 

Masamune S, Kamata S, Schilling W (1975) Syntheses of Macrolide Antibiotics. III. Direct Ester and Lactone Synthesis from 5-/ert-Butyl Thioate (Thiol Ester) J Am Chem Soc 97 3515... 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Amines, thiols, eOH (p. 226), etc., will also add to the 0-carbon atom of 0-unsaturated carbonyl compounds and esters, but the most important reactions of C=C—C=0 systems are in Michael reactions with carbanions reactions in which carbon-carbon bonds are formed. A good example is the synthesis of l,l-dimethylcyclohexan-3,5-dione (dimedone, 100) starting from 2-methylpent-2-ene-4-one (mesityl oxide, 101) and the carbanion 0CH(CO2Et)2 ... 

Symmetrical 5,5-dialkyl dithiocarbonates have been obtained by thermal rearrangement of the corresponding (9,5-dialkyl esters in the presence of Aliquat [43]. This procedure is not suitable for the preparation of unsymmetrical 5,5-dialkyl dithiocarbonates, as it has been reported that disproportionation of the products can lead to a mixture of the symmetrical and unsymmetrical esters. Alternatively, they can be prepared by a base-catalysed disproportionation of 5-alkyl-O-methyl dithiocarbonates [44] (Table 4.9). These methods for the synthesis of the 5,5-dialkyl esters are more convenient than the traditional procedures from the thiol and phosgene. 

As indicated above, the traditional base-catalysed hydrolysis of 0,5-dialkyl thio-carbonates for the synthesis of thiols is generally unsatisfactory, as oxidation leads to the formation of disulphides. Under phase-transfer conditions, the procedure produces thioethers to the virtual exclusion of the thiols, as a result of the slow release of the thiolate anions in the presence of the electrophilic ester. However, a simple modification of the reaction conditions provides an efficient one-pot reaction [50] from haloalkanes (Table 4.15) via the intermediate formation of the thermally labile (9-/ert-butyl-5-alkyl dithiocarbonates (Scheme 4.8). 

From a chemical point of view, the El/ubiquitin thiol ester should be competent to donate ubiquitin to a substrate amino group. In fact, aminoacyl-errzyme thiol esters are used in exactly this way in non-ribosomal polypeptide synthesis, a process that was discovered around the same time as ubiquitin-protein conjugation [5]. In spite of the attractive simplicity of this model, however, biochemical reconstitution studies showed that besides El two additional fractions were required to conjugate ubiquitin to a model substrate. They were called ubiquitin carrier protein (E2) and ubiquitin-protein ligase (E3), respectively, since the respective factors seemed to act sequentially [6]. Interestingly, the E2 factor apparently formed a thiol ester with ubiquitin. Based on these results, Hershko and co-workers proposed the ubiquitin conjugation cascade (Figure 5.1). 

The Pd-catalyzed allylic alkylation of sulfinate ions, thiols, and thiocarboxylate ions with racemic cyclic and acyclic allylic esters in the presence of bisphosphane BPA generally provides for an efficient asymmetric synthesis of allylic sulfones, sulfides, and thioesters. The Pd-catalyzed rearrangements of allylic sulfinates and allylic O-thiocarbamates, both of which proceed very efficiently in the presence of BPA, are attractive alternative ways to the asymmetric synthesis of allylic sulfones and allyUc thioesters also starting from the corresponding racemic alcohols. 

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