Sulfur nucleophiles, addition with

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 action of sulfur nucleophiles like sodium bisulfite and thiophenols causes even pteridines that are unreactive towards water or alcohols to undergo covalent addition reactions. Thus, pteridin-7-one smoothly adds the named S-nucleophiles in a 1 1 ratio to C-6 (65JCS6930). Similarly, pteridin-4-one (73) yields adducts (74) in a 2 1 ratio at C-6 and C-7 exclusively (equation 14), as do 4-aminopteridine and lumazine with sodium bisulfite. Xanthopterin forms a 7,8-adduct and 7,8-dihydropterin can easily be converted to sodium 5,6,7,8-tetrahydropterin-6-sulfonate (66JCS(C)285), which leads to pterin-6-sulfonic acid on oxidation (59HCA1854). 

The tetraimidosulfate anion [S(NtBu)4] , isoelectronic with 804 , is prepared by a methodology similar to that employed for the synthesis of triimidosulfites. The reaction of the sulfur triimide S(N Bu)3 with two equivalents of LiNH Bu produces the solvated monomeric complex [(thf)4Li2S(N Bu)4] (10.21) (Eq. 10.8). The nucleophilic addition of... 

Stereoselective epoxidation can be realized through either substrate-controlled (e.g. 35 —> 36) or reagent-controlled approaches. A classic example is the epoxidation of 4-t-butylcyclohexanone. When sulfonium ylide 2 was utilized, the more reactive ylide irreversibly attacked the carbonyl from the axial direction to offer predominantly epoxide 37. When the less reactive sulfoxonium ylide 1 was used, the nucleophilic addition to the carbonyl was reversible, giving rise to the thermodynamically more stable, equatorially coupled betaine, which subsequently eliminated to deliver epoxide 38. Thus, stereoselective epoxidation was achieved from different mechanistic pathways taken by different sulfur ylides. In another case, reaction of aldehyde 38 with sulfonium ylide 2 only gave moderate stereoselectivity (41 40 = 1.5/1), whereas employment of sulfoxonium ylide 1 led to a ratio of 41 40 = 13/1. The best stereoselectivity was accomplished using aminosulfoxonium ylide 25, leading to a ratio of 41 40 = 30/1. For ketone 42, a complete reversal of stereochemistry was observed when it was treated with sulfoxonium ylide 1 and sulfonium ylide 2, respectively. ... 

Complexes 79 show several types of chemical reactions (87CCR229). Nucleophilic addition may proceed at the C2 and S atoms. In excess potassium cyanide, 79 (R = R = R" = R = H) forms mainly the allyl sulfide complex 82 (R = H, Nu = CN) (84JA2901). The reaction of sodium methylate, phenyl-, and 2-thienyllithium with 79 (R = R = r" = R = H) follows the same route. The fragment consisting of three coplanar carbon atoms is described as the allyl system over which the Tr-electron density is delocalized. The sulfur atom may participate in delocalization to some extent. Complex 82 (R = H, Nu = CN) may be proto-nated by hydrochloric acid to yield the product where the 2-cyanothiophene has been converted into 2,3-dihydro-2-cyanothiophene. The initial thiophene complex 79 (R = R = r" = R = H) reacts reversibly with tri-n-butylphosphine followed by the formation of 82 [R = H, Nu = P(n-Bu)3]. Less basic phosphines, such as methyldiphenylphosphine, add with much greater difficulty. The reaction of 79 (r2 = r3 = r4 = r5 = h) with the hydride anion [BH4, HFe(CO)4, HW(CO)J] followed by the formation of 82 (R = Nu, H) has also been studied in detail. When the hydride anion originates from HFe(CO)4, the process is complicated by the formation of side products 83 and 84. The 2-methylthiophene complex 79... 

In addition there are certain other methods for the preparation such compounds. Upon heating of the thionocarbonate 2 with a trivalent phosphorus compound e.g. trimethyl phosphite, a -elimination reaction takes place to yield the olefin 3. A nucleophilic addition of the phosphorus to sulfur leads to the zwitterionic species 6, which is likely to react to the phosphorus ylide 7 via cyclization and subsequent desulfurization. An alternative pathway for the formation of 7 via a 2-carbena-l,3-dioxolane 8 has been formulated. From the ylide 7 the olefin 3 is formed stereospecifically by a concerted 1,3-dipolar cycloreversion (see 1,3-dipolar cycloaddition), together with the unstable phosphorus compound 9, which decomposes into carbon dioxide and R3P. The latter is finally obtained as R3PS ... 

The hydration reaction just described is typical of what happens when an aldehyde ot ketone is treated with a nucleophile of the type H-Y, where the Y atom is electronegative and can stabilize a negative charge (oxygen, halogen, or sulfur, for instance). In such reactions, the nucleophilic addition is reversible, with the equilibrium generally favoring the carbonyl reactant rather than the tetrahedral addition product. In other words, treatment of an aldehyde or... 

An illustrative example of the Michael reaction is that of the thiirene dioxide 19b with either hydroxylamine or hydrazine to give desoxybenzoin oxime (87) and desoxybenzoin azine (88), respectively, in good yields6 (see equation 29). The results were interpreted in terms of an initial nucleophilic addition to the a, j8-unsaturated sulfone system, followed by loss of sulfur dioxide and tautomerization. Interestingly, the treatment of the corresponding thiirene oxide (18a) with hydroxylamine also afforded 86 (as well as the dioxime of benzoin), albeit in a lower yield, but apparently via the same mechanistic pathway6. 

Sulfoxides (R1—SO—R2), which are tricoordinate sulfur compounds, are chiral when R1 and R2 are different, and a-sulfmyl carbanions derived from optically active sulfoxides are known to retain the chirality. Therefore, these chiral carbanions usually give products which are rich in one diastereomer upon treatment with some prochiral reagents. Thus, optically active sulfoxides have been used as versatile reagents for asymmetric syntheses of many naturally occurring products116, since optically active a-sulfinyl carbanions can cause asymmetric induction in the C—C bond formation due to their close vicinity. In the following four subsections various reactions of a-sulfinyl carbanions are described (A) alkylation and acylation, (B) addition to unsaturated bonds such as C=0, C=N or C= N, (C) nucleophilic addition to a, /5-unsaturated sulfoxides, and (D) reactions of allylic sulfoxides. 

The results of studies of the acid-catalyzed hydration of oxygen-, sulfur-, seleno-and nitrogen-substituted alkenes and the relevance of this work to partitioning of the corresponding carbocation intermediates (Chart 1) between deprotonation and nucleophile addition was reviewed in 1986.70. We present here a brief summary of this earlier review, along with additional discussion of recent literature. 

Compound 874, as a representative of derivatives with an electron-withdrawing substituent at C-[1 of the vinyl group, is easily prepared by elimination of one benzotriazole from 2,2-/fo(benzotriazol-l-yl)ethyl methyl ketone 873. The stereoselective elimination catalyzed by NaOH gives exclusively the (E) isomer of derivative 874. Addition of nucleophiles to the double bond of vinyl ketone 874 followed by elimination of benzotriazole leads to a,P unsaturated ketones 875. Amines used as nucleophiles do not need any catalysis, but reactions with carbon and sulfur nucleophiles require addition of a base. The total effect is nucleophilic substitution of the benzotriazolyl group at the i-carbon of orji-iinsaturatcd ketone (Scheme 142) <1996SC3773>. 

The complexes of sulfur trioxide with various nucleophiles (dioxane, pyridine etc.) are mild sulfonating reagents. Unlike other complexes of sulfur trioxide, dimethyl sulfide-sulfur trioxide readily adds to conjugated multiple bonds. Consequently, not only the sulfo group but also the dimethyl sulfide group add at the multiple bond. The reactions of dimethyl sulfide-sulfur trioxide complex with butadiene, isoprene and 2,3-dimethylbutadiene take place as conjugated l,4- -additions of dimethyl sulfide and sulfonate groups at the double bonds of the diene (equation 103).124... 

The addition-elimination mechanism also provides a reasonable explanation for nucleophilic substitution reactions at sulfur that occur with retention of configuration. It is assumed that nucleophilic attack occurs at sulfur in an apical position opposite a substituent... 

The first reaction is p-elimination in cysteine, serine, phosphoserine, and threonine residues due to attack by hydroxide ion, leading to the formation of very reactive dehydroalanine (DHA). In a cystine residue, this results in rupturing of the disulfide bond and liberation of a sulfide ion and free sulfur (Figure 13.4). Nucleophilic additions of the s-amino group of the protein-bound lysine to the double bond of DHA residue causes crosslinking of the polypeptide chain. After hydrolysis, a mixture of L-lysino-L-alanine and L-lysino-D-alanine, with probably a small proportion of dl and dd isomers,... 

An unexpected endo selectivity in addition of certain carbon and sulfur nucleophiles to the O, / -unsaturated (arene)ruthenium(II)cyclopentadienyl compound (154) has been reported. This stereochemistry has been compared with that of the 5 n2 reactions but a detailed theoretical approach is yet to be undertaken. ... 

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