Aldehydes with thiols

Literature reveals that in the oxidative cyclization of aldeltyde and o-phenylene-diamine, the formation of the required 2-aiyl-l/f-benzimidazole is accompanied by the occurrence of 1-benzylated 2-aryl-1/f-benzimidazoles as side products [46], and sometimes these disubstituted derivatives have been isolated as the main product [47, 48]. The present protocol gives 2-aryl-1/7-benzimidazole selectively. Further, we extended our studies on oxidative reactions of aldehydes with o-aminothiophe-nol. Although thiols are good nucleophiles and SET agents [49], in present studies, no substitution of the halogen atom or the nitro group, dealkylation/debenzoy lation, took place as reported earlier [50-52]. Fmiher, the dithioacetal formation is a common reaction of aldehydes with thiols [53] no competitive dithioacetal formation was observed imder the present conditions. Doping of Mn promotes the activity and... 

The synthesis of thioesters through the coupling aldehydes with thiols has been achieved using common iron salts as catalysts (Scheme 5.33) [54], The reactions required an oxidant, and tert-butyl hydroperoxide was found to be effective tmder the reaction conditions. The reactions were carried out in pure water and afforded moderate to excellent yields of the thioesters. The scope of the chemistry was quite broad as both alkyl and aryl aldehydes as well as alkyl- and arylthiols were successfully coupled as well as several heteroaromatic aldehydes. Overall, this is a practical approach to the preparation of thioesters. 

A wide variety of products can be obtained by thioalkylation (42). The reactants ate usually an aldehyde, a thiol, and either a phenol, a sulfone, an amine, or a heterocychc compound. Phenols primarily react with formaldehyde in a process known as thiomethylation (eq. 26). Other types of reactions are depicted in equations 27 and 28. 

Aldehydes and ketones react with thiols to yield thioacetals just as they react with alcohols to yield acetals. Predict the product of the following reaction, and propose a mechanism ... 

Aldehydes and ketones have been converted to sulfides by treatment with thiols and pyridine-borane, RCOR -I- R"SH —+ RR CHSR", in a reductive alkylation reaction, analogous to 16-6. 

When a reverse procedure was applied, i.e. enzymatic acetylation of racemic 3, formed in situ from the appropriate aldehydes and thiols, the reaction proceeded under the conditions of dynamic kinetic resolution and gave enantiomerically enriched acetates 2 with 65-90% yields and with ees up to 95% (Equation 2). It must be mentioned that the addition of silica proved crucial, as in its absence no racemization of the initially formed substrates 3 occurred and the reaction stopped at the 50% conversion. 

Carbonyl compounds react with thiols, RSH, to form hemi-thioacetals and thioacetals, rather more readily than with ROH this reflects the greater nucleophilicity of sulphur compared with similarly situated oxygen. Thioacetals offer, with acetals, differential protection for the C=0 group as they are relatively stable to dilute acid they may, however, be decomposed readily by H20/HgCl2/CdC03. It is possible, using a thioacetal, to reverse the polarity of the carbonyl carbon atom in an aldehyde thereby converting this initially electrophilic centre into a nucleophilic one in the anion (31) ... 

The base-catalyzed joint reaction of nitroalkenes with thiophenol in the presence of aldehydes gives y-phenylthio-P-nitro alcohols in one pot (Eq. 4.5).8 The joint reaction of nitroalkenes with thiols and a,p-unsaturated nitriles (or esters) has also been achieved. (Eq. 4.6).9 P-Nitro sulfides thus prepared show unique reactivity toward nucleophiles or tin radicals. The nitro... 

Barrett and coworkers have explored hetero-substituted nitroalkenes in organic synthesis. The Michael addition of nucleophiles to 1-alkoxynitroalkenes or 1-phenylthionitroalkenes followed by oxidative Nef reaction (Section 6.1) using ozone gives a-substituted esters or thiol esters, respectively.41 As an alternative to nucleophilic addition to l-(phenylthio)-nitroalkenes, Jackson and coworkers have used the reaction of nucleophiles with the corresponding epoxides (Scheme 4.4).42 Because the requisite nitroalkenes are readily prepared by the Henry reaction (Chapter 3) of aldehydes with phenylthionitromethane, this process provides a convenient tool for the conversion of aldehydes into ot-substituted esters or thiol esters. 

Figure 5.14 PDPH reacts with thiol-containing compounds through its pyridyl disulfide end to form reversible disulfide linkages. Its hydrazide end then may be subsequently conjugated with an aldehyde-containing molecule to form hydrazone bonds. Glycoproteins may be crosslinked using this approach after periodate activation to...

Reductive Thiolation. Treatment of aldehydes with triethylsilane, thiols, and boron trifluoride monohydrate 217 yields sulfides in a one-flask process. For example, this method gives a 97% yield of benzyl isopropyl sulfide from benzaldehyde and 2-propanethiol (Eq. 204).365... 

Tetramethylthiuram disulphide (TMTD) has proved to be a useful reagent for the thiocarbamoylation of amine containing compounds. Thus, reaction of a series of hydrazones of aromatic aldehydes with TMTD in a 1 1 ratio gave amongst other products, 4,4-dimethylthiosemicarbazide 86 and 5-dimethylamino-l,3,4-thiadiazole-2-thiol 85. It was confirmed that 86 was an intermediate in the synthesis of 85 as treatment of 86 with TMTD gave 85 in 85% yield <00RCB344>. 

In an extension of the procedure, thiols react with gem-dihaloalkanes (Table 4.4) to produce thioacetals [ 10,20-23] and the reaction can be employed in the Corey-Seebach synthesis of aldehydes and ketones (see ref. 24 and references cited therein), gem-Dichlorocyclopiopanes having an electron-withdrawing group at the 2-position react with thiols to produce the thioacetals [25]. In the corresponding reaction of the thiols with biomochloromethane exclusive nucleophilic substitution of the bromo group by the thiolate anion occurs to yield the chloromethyl thioethers [13, 14] (Table 4.5). 

The iodoetherification strategy was applied to the synthesis of the smaller fragment coupling component 109 as well (Scheme 16). Silylation of alcohol 104 [30] (76% de) allowed the separation of the pure desired diastereomer, which in turn was subjected to hydroboration/oxidation, sulfide formation with thiol 105, and oxidation to give sulfone 106. The requisite y-triethylsilyloxy alkene functionality in 107 was constructed as a diastereomeric E) Z)=l.2 l mixture by another sulfone-based olefination of aldehyde 90 with 106. Treatment of 106 with... 

DESULFURIZATION WITH RANEY NICKEL Preparation of Aldehydes from Thiol Esters [1101]... 

Several procedures are known, including Rh catalysis, for the exo cyclization of alkenyl aldehydes such as 1 to ketones such as 2. Kiyoshi Tomioka of Kyoto University recently reported (J. Org. Chem. 2005, 70,681) that efficient cyclization can be achieved by merely heating the aldehyde with a catalytic amount of a tertiary thiol, with A1BN as the initiator. Addition takes place even to unactivated aikcnes, and both five- and six-membered ring ketones can be formed. It is a measure of the mildness of the method that cyclization of 1 gives 2 as a 1 1 mixture, even though trans is much the more stable diasteromer. 

Carboxylic esters have been reduced to aldehydes with DIBALH at -70°C, with di-aminoaluminum hydrides,1224 with LiAlH E NH,1226 and with NaAlH4 at -65 to -45°C, and (for phenolic esters) with LiAlH(0-/-Bu)3 at (fC.1227 Aldehydes have also been prepared by reducing ethyl thiol esters RCOSEt with Et3SiH and a Pd-C catalyst.1228... 

The three-component method is applicable to the synthesis of various C(6)- or C(7)-functionalized PGs. Scheme 11 illustrates the tandem conjugate addition-aldol reaction that affords 7-hydroxy-PGE derivatives (18). Both saturated and unsaturated C7 aldehydes can be used as a side-chain units. The aldol adducts can be transformed to naturally occurring PGs (5a, 19) and, more importantly, to a variety of analogues such as tumor-suppressing A7-PGA, (20) or 7-fluoro-PGI2, a stabilized prostacyclin (21). The unique cellular behavior displayed by A7-PGA methyl ester is well correlated to its chemical reaction with thiols (20). 

Peptide thioesters (Section 15.1.10) are generally prepared by coupling protected amino acids or peptides with thiols and are used for enzymatic hydrolysis. Peptide dithioesters, used to study the structures of endothiopeptides (Section 15.1.11), may be prepared by the reaction of peptide nitriles with thiols followed by thiolysis (Pinner reaction). Peptide vinyl sulfones (Section 15.1.12), inhibitors of various cysteine proteases, are prepared from N-protected C-terminal aldehydes with sulfonylphosphonates. Peptide nitriles (Section 15.1.13) prepared by dehydration of peptide amides, acylation of a-amino nitriles, or the reaction of Mannich adducts with alkali cyanides, are relatively weak inhibitors of serine proteases. 

Thioacetals and -ketals. A1C13 is an effective catalyst for the condensation of aldehydes and ketones with thiols or dithiols. The reaction of thiols with carbonyl groups with an a-proton results in low yields but the reaction with dithiols proceeds in high yield.8... 

Sulfides. Aldehydes and ketones react with thiols in TFA in the presence of HI I, /pyridine to form sulfides (equation I).1... 

A new thiol auxiliary (45, R = COEt) participates in boron-mediated anti-aldol reactions with aldehydes with high yield and de.124 Reaction of the product with (g> nucleophiles displaces it (in the form of the thiol, 45 R = H), converting the aldol product under mild conditions into esters, thiolates, phosphonates, alcohols, or acids. 

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