Addition Reaction of Thiols

Radical-addition processes have been studied using vinylphosphines (radical addition at either C or P), allylhydrazine, a-methylstyrenes, and methyl oleate (C-9 and C-10 adducts are formed in nearly equal amounts).  

Harada, and K. Kitahara, Chem. and Pharm. Bull, (Japan), 1975, 23, 2415. 

The other studies of thiol addition to alkynes in the recent literature involve the ionic mechanism, the major interest being the stereoisomer ratios of the resulting vinyl sulphides. -An interesting study of the addition of 2 equivalents of PhCHaSH to acetylenedicarboxylic acid in alkaline solution includes an assessment of factors allowing control of the proportions of the resulting racemic and me.ro-l,2-bis(benzylthio)succinic acids. 

Addition of CbFsSH to various unsaturated systems and the kinetics of addition of propanethiol to benzylideneanilines in non-aqueous solvents provide examples of related reactions. 

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S-Nucleophiles are very reactive in 1,3-addition reactions with nitrile oxides. A series of a-glucosinolates 27 (R = CR1=NOH R1 =Ph, CH2PI1, CH2CH2PI1, ( )-CH=CHPh, 3-indolylmethyl) was prepared by addition reactions of thiol 27 (R = H) with nitrile oxides (123). The indolyl-substituted glucosinolate was then converted to a-glucobrassicin 28. 

Cyclization of either of the thiols (24) with acid provided the saturated thia-PGIi analogs (26) as a 2.7 1 mixture of the exo and endo isomers.271 Although many addition reactions of thiols to alkenes are radical reactions catalyzed by light, oxygen, or other radical initiators, conversion to (26) was not effected under photolytic conditions or with AIBN. A radical chain mechanism for selenothiolactonization has also been reported recently.275... 

In addition, reactions of thiols with sulphoxides (see below) can influence the course of reaction. 

Kanemasa et al. reported an asymmetric conjugate addition reaction of thiol to A-crotonyl oxazolidinone in the presence of Ni(II)-DBFOX/Ph catalyst [20] (Table 8.2). In this reaction. Proton Sponge (1) is indispensable for high enantioselectivity, and thioether was obtained in 84-99% yield with 91-94% ee. 

Table 8.2 Asymmetric conjugate addition reaction of thiol...

In this section we describe the available literature on the addition reaction of thiols and selenols RZH (Z = S, Se). We do not discuss non-catalytic addition reactions carried out without transition metal catalysts as this topic has already been addressed in several publications (see [100-103,139-142] and references therein). It was shown that the non-catalytic reactions led to a different outcome the anti-Markovnikov products are formed in the addition of RZ H to alkynes. Our goal is to concentrate on the selective formation of the scarcely available Markovnikov isomer by RZH addition to the triple bond of alkynes. 

We also reported a clean and efficient Michael addition reaction of thiols on chalcones using PhosILCl [144], The method provides several advantages such as simple workup, enviromnental friendliness, mild conditions, and excellent yields. In addition, the IL was chosen as a green solvent, recovered, and reused several times in subsequent reactions. 

Scheme 10.26 Enantioselective conjugate addition reactions of thiols catalyzed by 22.

Our laboratory has developed analogous domino thio-click Michael-aldol approach to heterocyclic thio-chromene systems [8], using 2-thio salicylic aldehyde. The base-catalyzed thio-click reaction proceeds via a conventional stereoselective Michael addition reaction of thiol to C-4 position of levoglucosenone and a concomitant domino cyclization of intermediate thio adduct to form C—C bond at C-3 of functionalized levoglucosenone as illustrated in Scheme 6.3. 

Mukaiyama T, Azawa T, Saigo K, Takei H. Addition reaction of thiol to olefin by the use of TiCL. Chem. Lett. 1973 355-356. 

Addition Reactions of Thiols.—Ethylthiopicrate adds EtS to give the first gem-di(alkylthio) analogue (9) of a Meisenheimer adduct. Thiophenoxide-1,3,5-trinitrobenzene adducts (heats of formation have been measured )... 

In the transition-metal-catalyzed addition reactions of thiols to terminal alkynes, several addition products, i.e., Markovnikov-type adduct 1, Markovnikov addition and then double-bond-isomerization product 2, a n -Markovnikov adduct 3, double hydrothiolation product 4, and bisthiolation product 5, may be formed (Scheme 2). Controlling the product selectivity can be attained by the selection of transition metal complexes as catalysts, the use of additives, and/or the optimization of the reaction conditions (solvent, temperature, molar ratios of the starting materials, and so on). 

The Michael addition reaction of amines and thiols with bismaleimides or functionalized monomaleimides is a versatile tool ia the synthesis of chain-extended maleimide-terroinated prepolymers. These prepolymers generally are soluble ia organic solvents from which they can be processed to prepreg and molded to high quaUty, void-free laminates. 

With the success in Lewis acid-catalyzed thiol conjugate addition reactions mentioned above, we further tried to apply the J ,J -DBFOX/Ph-nickel(II) aqua complex catalyst to the catalyzed asymmetric conjugate addition reactions of hydroxyl-amines [88, 89]. However, after some preliminary examinations, we found that... 

The chemical reactivity of crown-ether complexes with neutral molecules has received little attention. Nakabayashi et al. (1976) have reported crown-ether catalysis in the reaction of thiols with l-chloro-2,4-dinitrobenzene. The catalytic activity was attributed to deprotonation of thiols by dicyclohexyl-18-crown-6 in acetonitrile solution. Blackmer et al. (1978) found that the rate of aquation of the cobalt(III) complex [333] increases on addition of... 

By far most of the reports on addition reactions of hetero-nucleophiles to activated dienes deal with sulfur-nucleophiles17,48,80,120-137, in particular in the synthesis of 7/3-sulfur-substituted steroids which, like their carbon-substituted counterparts (Section n.A), are of interest because of their ability to inhibit the biosynthesis of estrogens80,129-137. Early investigations17,120-122 concentrated on simple acyclic Michael acceptors like methyl sorbate and 2,4-pentadienenitrile. Bravo and coworkers120 observed the formation of a 3 1 mixture of the 1,6- and 1,4-adduct in the reaction of methyl sorbate with methanethiol in basic medium (equation 39). In contrast to this, 2,4-pentadienenitrile adds various thiols regioselectively at C-5, i.e. in a 1,6-fashion (equation 40)17,121,122, and the same is true for reactions of this substrate with hydrogen sulfide (equation 41), sodium bisulfite and ethyl thioglycolate17. 

The first 1,6-addition reactions of thiolates to steroid dienones were examined well before the discovery of the antiestrogenic properties of 7o -substituted steroids. Ralls and coworkers129 and Djerassi and coworkers130 studied thiol additions to A3,5-steroids for example, the reaction of 3,5-cholestadien-7-one with ethanethiol was reported to proceed with high 1,6-regioselectivity and -stereoselectivity (equation 47)129. In a series of papers, Brueggemeier and coworkers131-137 described the synthesis and biochemical evaluation of numerous 7at-sul fur-substituted steroids which were prepared by Michael addition to steroid dienones. Thus, 4,6-androsta-3,17-dienone was treated with various... 

Chalcogenolato complexes of mercury can be prepared by a variety of methods. Early preparations involve the reactions of thiols with mercury cyanide,1 the reaction of mercury salts with alkali chalcogenolates, electrochemical methods,2 and the oxidative addition of dichalcogenides to metallic mercury.3 The last method is very convenient for the preparation of complexes with sterically undemanding ligands, but becomes less facile as the... 

The thiylation of conjugated dienes and allenes proceeds as expected. Thus, the acid-catalyzed reaction of thiols with 1,3-dienes affords the 1,4-addition product,552 whereas the nucleophilic addition to allene provides the product arising from sulfur attack at the central carbon (equations 303 and 304).553... 

Consequently, the Michael addition reaction of sugar thiol proceeds smoothly with the formation of P- (l-2)-2,3-dideoxy-2-C-nitromethyl-thio-disacharides in 63-70 % yield (scheme 6). 

Scheme 2 Michael addition reaction of acrylates, vinylsulfones, and maleimides with thiol...

In addition to the simple and reagent-induced diastereoselectivity observed in the reaction of thiols with unsaturated compounds, an interesting kinetic resolution takes place when racemic 5-trimethylsilyl-2-cyclohexenone is treated with 0.55 equivalents of 4-methylbenzenethiol in the presence of cinchonidine12. The reaction results in the formation of the tram-adduct tram-14 as the major product together with small amounts of the m-addition product cis-14 and unreacted starting cyclohexenone that is partially resolved. 

Chiral Ligand for other Stereoselective Reactions. The effect of the addition of dihydroquinidine-derived alkaloids on the product enantioselectivity has also been investigated in the addition reaction of Diethylzinc to aldehydes, in the addition of aromatic thiols to conjugated cycloalkenones, and in the heterogeneous hydrohalogenation of a,a-dichlorobenzazepinone-2. In these cases, the dihydroquinidine derivatives were not the optimal ligands. 

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