Sulfides Michael addition

Michael-Type Additions. Michael additions are generally used to prepare methyl 3-mercaptopropionate (eq. 10) and mercaptopropionitrile (eq. 11) by the reaction of methyl acrylate or acrylonitrile and hydrogen sulfide using a basic catalyst. This reaction proceeds as shown ... 

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... 

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

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. 

Sodium sulfide or hydrosulfide can be used in double Michael additions thus the bridged thiopyran (11) is formed from 2,7-cyclooctadienone (12),12 and dihydrodithiin oxides (13) and related compounds are similarly produced from unsaturated sulfoxides (14).13... 

In the asymmetric synthesis of the optically active a-acylaziridines 260 described recently by Furukawa et al. (293), the optically active o-methoxyphenylphenylsulfimide 157, which plays the role of the optical activity inducing agent, is converted to the corresponding sulfide. In this reaction, which involves a typical Michael addition of 157 to the carbon-carbon double bond followed by elimination of sulfide, the optical purities of the chromatographically purified... 

Much milder conditions are used in the double Michael addition approach, in which a divinyl ketone is condensed with hydrogen sulfide in mildly basic medium (equation 77) (77JOC2777). Enol acetates (R1 = MeCC>2) may be used, and the product obtained then contains a 2-mercapto function (R1 = SH see also equation 82) (59% yield). Although this is a very versatile synthesis, its biggest drawback is the lability of simple divinyl ketones, and phenyl substitution at position 2 is frequently used to overcome this. 

Carbocyclization of m-alkcnyl-z-methoxybcnzy I lithiums to form five- or six-membered rings has been studied 101 the five-membered ring is formed with a cis-stereochemical relationship between the methoxy substituent and the adjacent methyl group. Intramolecular carbolithiation of vinyl sulfides at — 105°C in THF has been found to occur non-stereospecifically with regard to the newly formed C—Li centre.102. The stereochemistry of selective tandem Michael addition alkylation reactions of vinylphosphonates has been explored.103... 

The Michael addition mechanism, whereby sulfur nucleophiles react with organic molecules containing activated unsaturated bonds, is probably a major pathway for organosulfur formation in marine sediments. In reducing sediments, where environmental factors can result in incomplete oxidation of sulfide (e.g. intertidal sediments), bisulfide (HS ) as well as polysulfide ions (S 2 ) are probably the major sulnir nucleophiles. Kinetic studies of reactions of these nucleophiles with simple molecules containing activated unsaturated bonds (acrylic acid, acrylonitrile) indicate that polysulfide ions are more reactive than bisulfide. These results are in agreement with some previous studies (30) as well as frontier molecular orbital considerations. Studies on pH variation indicate that the speciation of reactants influences reaction rates. In seawater medium, which resembles pore water constitution, acrylic acid reacts with HS at a lower rate relative to acrylonitrile because of the reduced electrophilicity of the acrylate ion at seawater pH. 

The use of heteroaryl vinyl sulfides and vinyl dithiocarbamates (166) as hetero-Michael addition acceptors has been described. Combined chelating and electron-withdrawing effects were postulated to stabilize the transient anionic species and allow smooth Michael-induced ring closure to produce C-glycosides (167).191... 

Molecular orbital theory also predicts that a nucleophile of the sulfide type will bond at the carbon terminus of a conjugated ene carbonyl system that is, the nucleophile will bond with the electrophile in the Michael addition mode of reaction (20). Thus, the reaction of polysulfide dianion with an enone represented by a chalcone may proceed initially in such a manner as shown in Scheme 2, which reproduces one of the several pathways... 

The synthesis of pent-4-en-l-yn-3-ones from alkynes involves their deprotonation and condensation with ot,(3-unsaturated aldehydes and subsequent oxidation of the allylic alcohol. A double thia-Michael addition occurs when the enynone is treated with sulfide which leads to 2,3-dihydrothiopyran-4-ones bearing different substituents at the 2- and 6-positions (Scheme 217) <2006TL5095>. 

A series of tetrasubstituted thiazole derivatives 28 has been prepared via a multi-component tandem protocol <07T10054>. Reaction of bis(aroylmethyl)sulfides 23 with aryl aldehydes and ammonium acetate in 1 2 1 ratio under solvent-free microwave irradiation affords 28 in good yields. This reaction presumably starts with Knoevenagel condensation of sulfide with 2 equiv. of aryl aldehydes to give 24. Michael addition with ammonia and concomitant cyclocondensation lead to 26. Base-catalyzed ring opening of 26 to 27 and ring... 

Copper compounds are catalysts for the Michael addition reaction (249), olefin dimerizations (245, 248), the polymerization of propylene sulfide (142), and the preparation of straight-chain poly phenol ethers by oxidation of 2,6-dimethylphenol in the presence of ethyl- or phenyl-copper (209a). Pentafluorophenylcopper tetramer is an intriguing catalyst for the rearrangement of highly strained polycyclic molecules (116). The copper compound promotes the cleavage of different bonds in 1,2,2-tri-methylbicyclo[1.1.0]butane compared to ruthenium or rhodium complexes. Methylcopper also catalyzes the decomposition of tetramethyllead in alcohol solution (78, 81). 

Instead of preparing the sulfoxide chirophore via a separation of diastereoisomers, the dia-stereoselective oxidation of a sulfide offers an interesting alternative. Thus Michael addition of 10-mer-captoisobomeol (414) to methyl propiolate furnished (Z)-vinyl sulfide (415) which underwent a hydroxy-directed oxidation (MCPBA) to give the (sulfur-R)-vinyl sulfoxide (416) in a highly selective manner (Scheme 100). ... 

Sulfides were also involved in a unique three-component, stereospecific Michael addition. The reaction described in Scheme 29 can be explained as follows regiospecific addition of the nucleophile to the exocyclic double bond of the a-methylenecyclopentenone, followed by trapping of the resulting enolate by methyl acrylate, and attack of the anion thus formed on the endocyclic double bond of the cy-clopentenone moiety to result, after protonation, in the bicyclo[2.2.1]heptan-6-one as a single stereoisomer (68% overall yield Scheme 29). 

Acylation of a simple thiol with an alkyl carboxylate is not a very suitable method for preparation of S-alkyl thiocarboxylates. Transesterification is, however, possible if either the thiol or the carboxylic ester is activated. The enhanced reactivity of boron, aluminum and silicon thiolates has been utilized for the synthesis of a large variety of thiocarboxylic S-esters, including hydroxy derivatives (from lactones). a,P-Unsaturated thiol esters, e.g. cinnamoyl or 2-butenoyl derivatives, are also accessible. Michael addition, an undesirable side reaction of thiols, is completely avoided if alkyl trimethylsilyl sulfides ortris(arylthio)boranes are applied. ... 

Michael additions. Chiral sulfides are obtained on reaction of thiols with conjugated carbonyl compounds. 

Nucleophilic addition to the C-C double bond (Michael addition) is followed by ring closure with elimination of the sulfide (R2S). This reaction mode requires an electron-deficient alkene (typically a, 6-unsaturated carbonyl compounds and acrylonitriles) and represents an important synthetic method, see Section 1.1.1.1.2., and Houben-Weyl Vol. Ell, pl44ff. 

Possibly more popular are the protected sulfones25,26 such as 94, again easily made by Michael addition at either the sulfide or sulfone27 oxidation state as sulfur nucleophiles are excellent Michael donors. 

---