Thiolacetic addition reaction

The much simpler steroid, 253, was fortuitously found to fulfill this role when injected into animals. Its lack of oral activity was overcome by incorporation of the 7a-thioacetate group. Reaction of the ethisterone intermediate, 77b, with a large excess of an organomagnesium halide leads to the corresponding acetylide salt carbonation with CO2 affords the carboxyllic acid, 251. This is then hydrogenated and the hydroxy acid cy-clized to the spirolactone. Oppenauer oxidation followed by treatment with chloranil affords the 4,6-dehydro-3-ketone (254). Conjugate addition of thiolacetic acid completes the synthesis of spironolactone (255), an orally active aldosterone antagonist. ... 

Although thiolacetic acid additions are free-radical reactions (60), it was found recently that the addition to electron-poor olefins can be base catalyzed (61) (eqs. [14], [15]). Thus the (S)-(-) adduct is obtained with an e.e. of 54% when cyclohexenone is treated with thiolacetic acid in benzene in the presence of catalytic amounts of cinchonine. The reaction appears to be quite general, although very high e.e. s (>80%) have not yet been achieved. 

The yields of thietanone depend on the number of methyl groups attached to the 1,3-dihaloketones, a relationship attributed to the gem effect. Thus the unsubstituted thietane failed to form. Thietanes have been synthesized by a series of reactions involving addition of thiolacetic acid to a vinyl ketone, reduction with LiAlH4, substitution of the acyl group by the nitrile function, and subsequent ring closure to a cis-trans mixture of 119 (Eq. 11). 

Sulfanylalkanoyl amino acids and peptides are prepared by reaction of the (acetyl-sulfanyl)- or (benzoylsulfanyl)alkanoic acids or acid chlorides with a-amino esters or peptide esters, followed by deprotection of the sulfanyl and carboxy groups. 8 101114 16 27 29 For example, the 3-(acetylsulfanyl)alkanoic acids 7 are prepared from the condensation of ethyl (diethoxyphosphoryl) acetate 5 with various aldehydes according to the Horner-Emmons reaction, providing the a, 3-unsaturated ethyl esters 6 (a mixture of Z- and E-isomers, 50 50), followed by saponification of the ethyl esters and Michael addition of thiolacetic acid. The 3-(acetylsulfanyl)alkanoic acids 7 can be coupled with a-amino esters or peptide esters and subsequent hydrolysis of the 3-(acetylsulfanyl) derivatives provides the desired products 8 (Scheme 2). 14 ... 

Addition to a,p-unsaturated carbonyl compounds. This reaction was an important step in syntheses of thioctic acid developed in two laboratories. A Lederle group" heated the ketone (2) with thiolacetic acid on the steam bath for 20 min. and obtained... 

Radical addition to alkynes. Thiolacetic acid reacts vigorously with alkynes to give mono and di adducts. In some cases the yield is improved by irradiation or addition of a peroxide, but the main value of initiation hes in improved reproducibility of the experiments. The reaction provides a means of converting a terminal acetylene into an aldehyde. ... 

Chiral boranes have been recommended as Lewis acids catalysts by Reetz [689], Yamamoto [787, 788], Kiyooka [795, 1302], Masamune and their coworicers [796, 797], These groups used, respectively, boranes 2.61, 3.9 (R = H, R = /-Pr), 3.10 (R = i-Pr or tert-Bu, R = H) and derivatives of 3.12 and 3.13. These boranes are very efficient catalysts in asymmetric additions of symmetrically substituted ketene silylacetals 6.113 to aldehydes (Figure 6.94). Similar reactions can also be conducted with enoxysilanes derived from methylketones or from tert-Bu thiolacetate [787, 794, 796], Oxazaborolidine 3.10 derived from tryptophan 3.11 is also a very potent catalyst [794],... 

Take, for example, the reaction of methanol or methane thiol with proto-nated thiolacetic acid (Scheme II). The observed product of acyl transfer is II corresponding to loss of H2S. If II is formed by way of an addition intermediate, then formation of the intermediate by an independent route should give the same product II. However, reaction of the thionic ester III with water failed to give II or any product that could be ascribed to the intervention of a tetrahedral addition intermediate I (15). 

Thiol Substitution Reactions. Vital to the usefulness of 2-(trimethylsilyl)ethanethiol is that it behaves as a typical thiol. Base mediated reactions that proceed as expected include alkylation and nucleophilic ring openings. Moreover, addition-eliminations on unsaturated systems, Michael additions, and c -additions to triple bonds (eq 2) are all routine. To access 2-(trimethylsilyl)ethyl thioethers, a useful procedure is hydrolysis of 2-(trimethylsilyl)ethyl thiolacetate and alkylation of the thiolate in a single pot. ... 

It may be further added that Brown " employed peroxide as an initiator in the reaction of MA with thiolacetic acid as mentioned earlier. Its necessity was not explored and may be unnecessary in that particular case. Dmuchovsky and coworkers have also shown that added radical inhibitor has no effect on the rate of thiol disappearance.Since the peroxide-catalyzed addition of thiol to olefin is known, only its contribution in relatively facile nucleophilic addition processes is questioned. 

Dufiach et a. successfully added thiolacetic acid to alkenes using either InCls or In(OTf)3 as catalysts [105]. The same system, but with ln(OTf)3, was used for both inter- and intramolecular addition of thiols to alkenes. These reactions proceed with high Markovnikov regioselectivities, with most reactions producing only one regioisomer. Non-Markovnikov additions were observed for vinyl cyclohexane, owing to isomerization of the double bond. (Figure 8.52)... 

The double bond in unsaturated dioxopiperazines is more inert than that of acylenamino acids towards addends. The acid catalysed addition of mercaptans and thiolacetic acid to various dehydrodioxopiperazines has been described by Machin and Sammes 242). The kinetically controlled reaction leads to the formation of the a-product, admittedly in very moderate yield in the case of addition of thiolacetic acid. 

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