Additions of thiols

Addition proceeds readily at 70 C-80°C and is complete in 18-25 h. When AIBN is used, N-(p-alkylthioethyl)pyrroles are obtained in 70%-94% preparative yields (Table 2.19). Under comparable conditions without an initiator, the yields of adducts drop to 20%-30%. 

SCHEME 2.198 Synthesis of N-(P-alkylthioethyl)pyrroles by free-radical addition of thiols to N-vinylpyrroles. 

SCHEME 2.199 Free-radical N-vinylpyrroles. addition of mercaptoacetic acid O-methyl ester ( 

The system AIBN/CClj promotes the radical addition of thiols to N-vinylpyrroles giving rise to p-adducts. For example, from 2-phenyl-N-vinylpyrrole and ethane- and butanethiols, the corresponding N-(p-alkoxyethyl)-2-phenylpyrroles are synthesized in 54% and 50% yields, respectively [660], 

diverse N-a- and N-(P-alkyl(aryl)thioethyl)pyrroles can be readily synthesized by the reaction of N-vinylpyrroles with thiols. In most cases, the reactions proceed almost quantitatively, and their orientation can be controlled by the initiation conditions. This opens up interesting prospects of N-vinylpyrroles application for grafting the pyrrole rings to enzymes and biologically important amino acids containing SH groups with the purpose of their property modification. 

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General acid catalysis is a catalysis by a Br(4nsted acid (other than the lyonium ion) acting by donating a proton. The addition of thiols to the carbonyl group is general acid catalyzed. ... 

Konig et al. have achieved thioether functionalization of T8[CH = CH2]8 via the radical addition of thiols such as thiophenol, cyclohexylthiol, and 2-mercaptopyridine in the presence of azobisisobutyronitrile (AIBN) as a radical initiator (Table 13), while Gao et al. have also used this method to prepare very highly functionalized POSS by reacting T8[CH = CH2]8 with thiol-terminated glycosides giving glycoclusters in 70% yield (Figure 22). 

Addition of thiol acids to alkenes addition of thiols to ketenes... 

PSL, AMANO) has been found to catalyze the Markovnikov-type addition of thiols to vinyl esters (Scheme 5.23) [114] and acylases aminoacylase [115], penicillin G acylase [116], and acylase from AspergiUus oryzae [117], the same kind of addition of various nitrogen nucleophiles. Unfortunately, most additions described above are nonstereoselective. 

Scheme 5.23 Lipase-catalyzed Markovnikov addition of thiols to vinyl esters.

By using LaNa3-tris(binaphthoxide) (LSB) 55, catalytic asymmetric Michael addition of thiols to cycloalkenones took place to provide the adduct 56 with high ees in good yields (Eq. 7.41) [48]. 

Thiolates, generated in situ by the action of ammonium tetra-thiomolybdate on alkyl halides, thiocyanates, and disulfides, undergo conjugate addition to a, (1-unsaturatcd esters, nitriles, and ketones in water under neutral conditions (Eq. 10. II).29 Conjugate addition of thiols was also carried out in a hydrophobic ionic liquid [bmim]PF6/water-solvent system (2 1) in the absence of any acid catalyst to afford the corresponding Michael adducts in high to quantitative yields with excellent 1,4-selectivity under mild and neutral conditions (Eq. 10.12). The use of ionic liquids helps to avoid the use of either acid or base catalysts... 

Szeimies recently published an impressive example of a steric effect on a Sr2 reaction at carbon for the addition of thiols to the central bond of bicyclo[ 1.1.0]-systems87. From the radical chain addition of thiophenol to 32 the stereoisomeric cyclobutanes 33a and 33b are obtained exclusively in 56% yield. The thiylradical... 

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at -78 °C gives anti-(J-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of a/jti-(3-nitro selenides (Eq. 4.9)12 and a/jti-(3-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into P-amino alcohols with the retention of the configuration, which is a useful method for anri-P-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the P-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14... 

Furthermore, a neighboring group participation of a phenylthio function is observed in the Lewis acid-catalyzed nucleophilic substitution reaction of various P-nitrosulfides. Because the P-nitrosulfides are readily available, by the Michael addition of thiols to nitroalkenes (see Michael addition Chapter 4), this reaction is very useful. The P-nitrosulfides are prepared stereoselectively, and the reaction proceeds in a stereo-specific way (retention of configuration) as shown in Eqs. 31-34.35... 

Ono and coworkers have extended the radical elimination of v/c-dinitro compounds to P-nitro sulfones151 and P-nitro sulfides.138,152 As P-nitro sulfides are readily prepared by the Michael addition of thiols to nitroalkenes, radical elimination of P-nitrosulfides provides a useful method for olefin synthesis. For example, cyclohexanone is converted into allyl alcohol by the reaction shown in Eq. 7.110. Treatment of cyclohexanone with a mixture of nitromethane, PhSH, 35%-HCHO, TMG (0.1 equiv) in acetonitrile gives ahydroxymethylated-P-nitro sulfide in 68% yield, which is converted into the corresponding allyl alcohol in 86% yield by the reaction with Bu3SnH.138 Nitro-aldol and the Michael addition reactions take place sequentially to give the required P-nitro sulfides in one pot. 

A diverse group of organic reactions catalyzed by montmorillonite has been described and some reviews on this subject have been published.19 Examples of those transformations include addition reactions, such as Michael addition of thiols to y./bunsatu rated carbonyl compounds 20 electrophilic aromatic substitutions,19c nucleophilic substitution of alcohols,21 acetal synthesis196 22 and deprotection,23 cyclizations,19b c isomerizations, and rearrangements.196 24... 

The 1,3-dipolar addition to terminal alkenes of nitrile oxides, generated from nitromethylene derivatives of bicycloheptane, provides 9,ll-ethano-13,15-isoxazolinoprostanoids, PGH analogs, with alkyl, phenyl, or additional heterocyclic fragment in the oo-chain (461). Chemical transformations of 9,11-ethano-13,15-isoxazolinoprostanoids furnish prostanoids with bifunctional fragments of P-hydroxyketone and a-aminoalcohol in the oo-chain. The reaction of P-hydroxy ketones with methanesulfonyl chloride gives rise to prostanoids with an enone component in the oo-chain. 9,ll-Ethano-16-thiaprostanoids have been prepared, for the first time, by nucleophilic addition of thiols to the polarized double bond in the oo-chain. The 1,3-dipolar addition to terminal alkenes of nitrile oxides, generated from nitromethylene derivatives of bicycloheptane provides 9,ll-ethano-13,15-isoxazolinoprostanoids with an alkyl, phenyl, or additional heterocyclic fragment in the oo-chain (462). 

Shibasaki s lanthanide-alkaline metal-BINOL system, discussed in Chapters 2 and 3, can also effect the asymmetric conjugate addition reaction. As shown in Scheme 8-35, enantioselective conjugate addition of thiols to a,/ -unsaturated carbonyl compounds proceeds smoothly, leading to the corresponding products with high yield and high ee.76... 

Scheme 8-35. LSB-promoted catalytic asymmetric conjugate addition of thiols to enones. Reprinted with permission by Am. Chem. Soc., Ref. 76.

E Emori, T. Arai, H. Sasai, M Shibasaki, A Catalytic Michael Addition of Thiols to a, -Unsaturated Carbonyl Compounds Asymmetric Protonations, J. Am Chem Soc 1998,120, 4043-4044. 

Conjugate additions of thiols to a 2,3-allenoate proceed easily [236b, 249, 250],... 

Single phase reduction Here, Au3+ ions are reduced to Au(I) by the addition of thiols followed by the complete reduction to Au(0) by adding reducing agents such as sodium borohydride (NaBH4) [2].The reaction can be represented as,... 

Recently, some doubts have appeared on this widely accepted mechanism, because sulfenamides, but not TV-hydroxyarylamines, were found upon addition of thiols to isolated semimercaptals (from nitrosobenzene and 4-chloronitrosobenzene reacted with... 

Japanese workers (50,51) were the first to observe optical activity in the addition of thiols to electron-poor olefins (eq. [9]) The e.e. was not determined, but these observations led us to attempt using a cinchona alkaloid as the catalyst in the addition of thiophenol to cyclohexenone. The reaction lends itself admirably to a scope, limitations, and mechanism study, and the results have been published in detail (19). An important mechanistic difference between the addition of the dodecanethiol to isopropenyl methyl ketone and the addition of thiophenol to a cyclohexenone (eq. [1]) lies in the sequence of chirality-producing steps. In the former case, chirality is produced when the proton adds to the a-caibon atom of the ketone—after thiol addition has taken place. In the latter... 

The base-catalysed addition of thiols to Jt-electron-deficient alkenes is an important aspect of synthetic organic chemistry. Particular use of Triton-B, in place of inorganic bases, has been made in the reaction of both aryl and alkyl thiols with 1-acyloxy-l-cyanoethene, which behaves as a formyl anion equivalent in the reaction [1], Tetra-n-butylammonium and benzyltriethylammonium fluoride also catalyse the Michael-type addition of thiols to a,P-unsaturated carbonyl compounds [2], The reaction is usually conducted under homogeneous conditions in telrahydrofuran, 1,2-dimethoxyethane, acetone, or acetonitrile, to produce the thioethers in almost quantitative yields (Table 4.22). Use has also been made of polymer-supported qua-... 

Conjugate addition of thiols to a,p-unsaturated carbonyl compounds... 

Asymmetric induction of the Michael addition of thiols to electron-deficient alkenes (4.6.1) has been achieved in high overall conversion using both free [e.g. 12-20] and polymer-supported [e.g. 21, 22] cinchona alkaloids and their salts [23-25], but with varying degrees of optical purity. The corresponding asymmetric Michael addition of selenophenols to cyclohex-2-enones is promoted by cinchoni-dine to give a chiral product (43% ee) [26],... 

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