Thiol adduct

Trimethylsilyl sulphides R SSiMes give y-alkoxy-allyl sulphides R SCHR -CH=CHOMe with propenyl acetals in the presence of AICI3, and sulphides R SCHaR by their reaction with aldehydes R CHO followed by reduction with LiAlH4-AlCl3 of the resulting adduct. Thiols can be converted into unsym-... 

Glycosidic thiol groups can be introduced into glycosyl bromides by successive reactions with thiourea and aqueous sodium disulfite (D. Horton, 1963 M. Cemy, 1961, 1963). Such thiols are excellent nucleophiles in weakly basic media and add to electrophilic double bonds, e.g., of maleic esters, to give Michael adducts in high yields. Several chiral amphiphiles have thus been prepared without any need for chromatography (J.-H. Fuhrhop, 1986 A). 

The thioboration of terminal alkynes with 9-(alkylthio)-9-borabicyclo[3.3.1]-nonanes (9-RS-9-BBN) proceeds regio- and stereoselectively by catalysis of Pd(Ph,P)4 to produce the 9-[(Z)-2-(alkylthio)-l-alkeny)]-9-BBN derivative 667 in high yields. The protonation of the product 667 with MeOH affords the Markownikov adduct 668 of thiol to 1-alkyne. One-pot synthesis of alkenyl sulfide derivatives 669 via the Pd-catalyzed thioboration-cross-coupling sequence is also possible. Another preparative method for alkenyl sulfides is the Pd-catalyzed cross-coupling of 9-alkyl-9-BBN with l-bromo-l-phe-nylthioethene or 2-bromo-l-phenylthio-l-alkene[534]. 

The addition of aromatic and aUphatic thiols, RSH and ArSH, and a thioacetic acid to isoprene yields mainly the trans-l,4-adduct (56). The aromatic thiyl radicals, ArS , add almost entirely to the first carbon atom however, aUphatic thiyl radicals, RS, also add to the fourth C atom in significant amounts. 

Thiols and phosphines add to maleic anhydride to give a-thiosuccinic anhydrides (82) and phosphoranylidene—maleic anhydride adducts (83). Triethyl phosphite [122-52-1] reacts with maleic anhydride to give the yhde stmcture (23) (84). Hydrolysis of this adduct (23) leads to succinic acid... 

These effects can be attributed mainly to the inductive nature of the chlorine atoms, which reduces the electron density at position 4 and increases polarization of the 3,4-double bond. The dual reactivity of the chloropteridines has been further confirmed by the preparation of new adducts and substitution products. The addition reaction competes successfully, in a preparative sense, with the substitution reaction, if the latter is slowed down by a low temperature and a non-polar solvent. Compounds (12) and (13) react with dry ammonia in benzene at 5 °C to yield the 3,4-adducts (IS), which were shown by IR spectroscopy to contain little or none of the corresponding substitution product. The adducts decompose slowly in air and almost instantaneously in water or ethanol to give the original chloropteridine and ammonia. Certain other amines behave similarly, forming adducts which can be stored for a few days at -20 °C. Treatment of (12) and (13) in acetone with hydrogen sulfide or toluene-a-thiol gives adducts of the same type. 

Most azolium ions are sufficiently reactive to be attacked by amines. Sometimes the initial adducts are stable ammonia and primary and secondary amines add to 1,3-dithiolylium salts at the 2-position to give compounds of the types NT3, RNT2 and R2NT, respectively, where T = the l,3-thiol-2-yl group (80AHC(27)l5l). 

Nucleophiles like alcohols [2, S], hydrogen sulfide [2], thiols [2,10], ammonia, amines, hydrazines, hydroxylamines [2 11, 12, 13, 14, 75], azides [2], other pseudohalides [2], phosphonates [2,16,17,18,19, 20], and phosphanes [2,19] add rapidly across the CO or CN double bond to yield stable adducts The phosphonate adduets undergo a subsequent aleohol—lester rearrangement [19, 20] (equation 2)... 

Enantioselectivities were found to change sharply depending upon the reaction conditions including catalyst structure, reaction temperature, solvent, and additives. Some representative examples of such selectivity dependence are listed in Scheme 7.42. The thiol adduct was formed with 79% ee (81% yield) when the reaction was catalyzed by the J ,J -DBFOX/Ph aqua nickel(II) complex at room temperature in dichloromethane. Reactions using either the anhydrous complex or the aqua complex with MS 4 A gave a racemic adduct, however, indicating that the aqua complex should be more favored than the anhydrous complex in thiol conjugate additions. Slow addition of thiophenol to the dichloromethane solution of 3-crotonoyl-2-oxazolidinone was ineffective for enantioselectivity. Enantioselectivity was dramatically lowered and reversed to -17% ee in the reaction at -78 °C. A similar tendency was observed in the reactions in diethyl ether and THF. For example, a satisfactory enantioselectivity (80% ee) was observed in the reaction in THF at room temperature, while the selectivity almost disappeared (7% ee) at 0°C. 

The time-dependence of enantioselectivity in the reaction thiophenol with 3-cro-tonoyl-2-oxazolidinone catalyzed by l ,J -DBFOX/Ph-Ni(C104)2-3H2O at room temperature in THF is shown in Scheme 7.44. After 3 h, the yield of the thiol adduct is 70% with the enantioselectivity of 91% ee, but the enantioselectivity was 80% ee at the completion of reaction after 24 h (yield 100%). Although the catalyst maintains a high catalytic activity, and hence a satisfactory enantioselectivity, at the early stage of reaction, the deterioration of catalyst cannot be neglected thereafter even under neutral conditions. 

The strained bicyclic carbapenem framework of thienamycin is the host of three contiguous stereocenters and several heteroatoms (Scheme 1). Removal of the cysteamine side chain affixed to C-2 furnishes /J-keto ester 2 as a possible precursor. The intermolecular attack upon the keto function in 2 by a suitable thiol nucleophile could result in the formation of the natural product after dehydration of the initial tetrahedral adduct. In a most interesting and productive retrosynthetic maneuver, intermediate 2 could be traced in one step to a-diazo keto ester 4. It is important to recognize that diazo compounds, such as 4, are viable precursors to electron-deficient carbenes. In the synthetic direction, transition metal catalyzed decomposition of diazo keto ester 4 could conceivably furnish electron-deficient carbene 3 the intermediacy of 3 is expected to be brief, for it should readily insert into the proximal N-H bond to... 

Dehydrocoelenterazine (D) forms an addition product (E) when treated with acetone in the presence of benzylamine (Takahashi and Isobe, 1993). Thiol compounds, such as DTT (dithiothreitol) and glutathione, also add to D, forming an equilibrium mixture containing F (Takahashi and Isobe, 1994). These adducts are chemiluminescent. 

Unsymmetrical disulfides can be prepared by treatment of a thiol RSH with diethyl azodicarboxylate (EtOOCN=NCOOEt) to give an adduct, to which another thiol R SH is then added, producing the disulfide RSSR. ... 

The cycloaddition of alkynes with the tributylphosphine-carbondisulfide adduct 131 results in the in situ formation of the ylides 132 which react with aldehydes to give the novel 2-arylidene or 2-alkylidene-l,3-dithioles 133 (Scheme 36) [132]. Concerning ylides C-substituted by sulfur we can also mention a publication on the behavior of various keto-stabilized ylides towards acyclic and cyclic a s-disulfides allowing the synthesis of substituted thiazoles, thiols, and dithiols [133]. 

In the case of 271a and 271b, covalently bound adducts of 271a, b and CO2 (e. g., carbamic acid derivatives) were detected. This was absent in the case of thiol derivative 271c. The concentration of this material could be reduced by heating (a solution to 90 °C for 1 h) and increased by exposing to a CO2 atmosphere. 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

The degradation of carbon tetrachloride to COj by a Pseudomonas sp. (Criddle et al. 1990), although a substantial part of the label was retained in nonvolatile water-soluble residues (Lewis and Crawford 1995). The nature of this was revealed by isolation of adducts with cysteine and N,N -dimethylethylenediamine in which intermediates formally equivalent to COCI2 and CSCI2 were trapped, presumably formed by reaction of the substrate with water and a thiol, respectively. Further consideration of these reactions is given in Chapter 7, Part 3. 

The authors proposed the complex [PdCl(SPh)(PhSH)]n 15 as an active catalyst, with thiol acting as a ligand of Pd(II) (Eq. 7.11). On the other hand, the reaction using RhCl(PPh3)3 as a catalyst precursor furnished the anti-Markovnikov ds-adducts 16 when a terminal acetylene was employed as a substrate (Eq. 7.12). 

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]. 

A thio-substituted, quaternary ammonium salt can be synthesized by the Michael addition of an alkyl thiol to acrylamide in the presence of benzyl trimethyl ammonium hydroxide as a catalyst [793-795]. The reaction leads to the crystallization of the adducts in essentially quantitative yield. Reduction of the amides by lithium aluminum hydride in tetrahydrofuran solution produces the desired amines, which are converted to desired halide by reaction of the methyl iodide with the amines. The inhibitor is useful in controlling corrosion such as that caused by CO2 and H2S. 

If cellular redox state, determined by the glutathione status of the heart, plays a role in the modulation of ion transporter activity in cardiac tissue, it is important to identify possible mechanisms by which these effects are mediated. Protein S-,thiolation is a process that was originally used to describe the formation of adducts of proteins with low molecular thiols such as glutathione (Miller etal., 1990). In view of the significant alterations of cardiac glutathione status (GSH and GSSG) and ion-transporter activity during oxidant stress, the process of S-thiolation may be responsible for modifications of protein structure and function. 

Phenols are important antioxidants, with vitamin E being the most important endogenous phenolic membrane-bound antioxidant. Membrane levels of vitamin E are maintained through recycling of the vitamin E radical with ascorbate and thiol reductants. Vitamin E is a mixture of four lipid-soluble tocopherols, a-tocopherol being the most efiective radical quencher. The reaction of a-tocopherol with alkyl and alkylperoxyl radicals of methyl linoleate was recently reported. These are facile reactions that result in mixed dimer adducts (Yamauchi etal., 1993). 

Radical attack yields nucleobase radical adducts that must undergo either oxidation or rednction to yield a stable final prodnct. The cellular oxidant in these reactions may be molecnlar oxygen or high-valent transition metal ions (e.g., Fe ), while the reduc-tant may be either thiols, snperoxide radical, or low-valent transition metal ions (e.g., Fe ). In many cases, the base remains largely intact and the seqnence of chemical events can be readily inferred. In some other cases, more extensive base decomposition occurs. Here, we will consider a set of representative examples that provide a framework for understanding virtnally all radical-mediated base damage reactions. 

Silyl acetals of thiol esters have also been studied. With TiCl4 as the Lewis acid, there is correspondence between the configuration of the silyl thioketene acetal and the adduct stereochemistry.314 L-Isomers show high anti selectivity, whereas Z-isomers are less selective. 

Further investigation of the original QM1 also demonstrated that simple thiols could react reversibly although regeneration of QM1 was very slow.25 In contrast, a later model of anthracycline was shown to form stable adducts with a thiol despite the lability of corresponding adducts formed by oxygen and nitrogen nucleophiles.26... 

In contrast to the lability of certain dN adducts formed by the BHT metabolite above, amino acid and protein adducts formed by this metabolite were relatively stable.28,29 The thiol of cysteine reacted most rapidly in accord with its nucleophilic strength and was followed in reactivity by the a-amine common to all amino acids. This type of amine even reacted preferentially over the e-amine of lysine.28 In proteins, however, the e-amine of lysine and thiol of cysteine dominate reaction since the vast majority of a-amino groups are involved in peptide bonds. Other nucleophilic side chains such as the carboxylate of aspartate and glutamate and the imidazole of histidine may react as well, but their adducts are likely to be too labile to detect as suggested by the relative stability of QMs and the leaving group ability of the carboxylate and imidazole groups (see Section 9.2.3). 

The above section already introduced the influence of leaving groups at the benzylic position that eliminate to form and regenerate QM3, and the trend extends beyond adducts formed by the deoxynucleosides as expected. The standard benzylic acetate of QMP4 eliminates completely from the deprotected phenol under neutral aqueous conditions and ambient temperature within approximately 20 h, while an equivalent benzyl bromide eliminates completely within 5 min.48 Benzylic phosphates are also extremely labile, and, if the phosphate backbone of DNA is able to trap QM, the resulting products are likely to be too labile for standard detection.53,54 In contrast, amines and thiols are much less susceptible to elimination from the benzylic position and require forcing conditions to regenerate the parent QM.26,30 The benzylic alcohol derivative also appears stable under almost all thermal conditions and only eliminates routinely to form a QM after photochemical excitation.55... 

Angle, S. R. Yang, W. pH-Dependent stability and reactivity of a thiol-quinone methide adduct. Tetrahedron Lett. 1992, 33, 6089-6092. 

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