Sulfur-based nucleophiles

When benzylbromide is allowed to react with 4-(3-mercapto-5-phenyl-[l,2,4]triazol-4-ylmethyl)-benzamide (32) in order to synthesize the corresponding thiobenzyl adduct 4-(3-benzylsulfanyl-5-phenyl-[l,2,4]tria-zol-4-ylmethyl)-benzamide (33), a nucleophilic sulfur-based resin (34) is employed to trap excess benzylbromide from the reaction mixture affording a final clean product (33).28 In addition, a basic Amberlite (OH-) is added to assist in the efficient deprotonation of the mercapto functionality in (34) as depicted in Fig. 13. 

The C-3 and C-5 position of BODIPY core skeleton is one of the most important points for the substitution to tune photophysical properties, including absorption and/or emission maxima as well as fluorescence quantum yields. First of all, the introduction of amine-based (15d-15g) or sulfur-based (15b-15c) nucleophiles can... 

However, formation of this bond through the conjugate addition of a soft sulfur nucleophile to a,P-unsaturated aldehydes is efficiently catalysed using iminium ion catalysis [116], Using diarylprolinol silyl ether 55 the addition of a series of sulfur based nucleophiles to a variety of a,P-unsaturated aldehydes was shown to be effective (73-87% yield 89-97% ee). The products were isolated as their p-hydroxy sulfide derivatives 73 after in situ reduction of the products (Scheme 33). 

Scheme 33 Conjugate addition of sulfur based nucleophiles...

Pyrazines undergo nearly all of the same reactions as pyrimidines, from nucleophilic substitution (SnAt) to palladium-catalyzed cross coupling reactions. Displacement of the chlorides via SnAt reactions with nitrogen (157 158) and sulfur-based nucleophiles (158... 

The voltammetric reduction of a series of dialkyl and arylalkyl disulfides has recently been studied in detail, in DMF/0.1 M TBAP at the glassy carbon electrode The ET kinetics was analyzed after addition of 1 equivalent of acetic acid to avoid father-son reactions, such as self-protonation or nucleophilic attack on the starting disulfide by the most reactive RS anion. Father-son reactions have the consequence of lowering the electron consumption from the expected two-electron stoichiometry. Addition of a suitable acid results in the protonation of active nucleophiles or bases. The peak potentials for the irreversible voltammetric reduction of disulfides are strongly dependent on the nature of the groups bonded to the sulfur atoms. Table 11 summarizes some relevant electrochemical data. These results indicate that the initial ET controls the electrode kinetics. In addition, the decrease of the normalized peak current and the corresponding increase of the peak width when v increases, point to a potential dependence of a, as discussed thoroughly in Section 2. 

The preparation and properties of the dithiocarboxylic acids and their metal complexes have been reviewed several times.38"11 The formation of C—C bonds in the direct reaction of CS2 requires sufficiently nucleophilic carbon bases, directly or potentially accessible in the form of ambifunction-al phenoxides, organometalfic compounds, CH acidic compounds, enamines or ketimines. Carba-nions react with CS2 to give dithiocarboxylates. The preparation and purification of the adds is performed via their salts. Metal complexes are in general readily available. The bonding in these complexes is mostly of the type (27) but a bonding mode (28) is also found. Action of elemental sulfur upon heavy metal complexes of (29) aromatic dithiocarboxylic acids yields the perthio complexes (29) of these compounds. 

It is appropriate at this point to summarize the tendency of various nucleophiles to add to the carbonyl group. In general, the strong bases (organometallics, hydrides, negative ions) are most effective among the neutral nucleophiles, the soft ones, for example the sulfur bases, tend to be more effective in addition than the hard ones, for example the oxygen bases. 

Nitrogen nucleophiles, in a similar manner to oxygen- and sulfur-based functionality, undergo transition metal-catalyzed cross-coupling with halopyridines. The use of palladium(O) catalysts is most effective in combination with chelating bis-(phosphine) ligands such as BINAP that prevent the formation of pyridine-palladium complexes that... 

The reaction of C 4-acetoxylated catechin 517 and epicatechin with nucleophiles under Lewis acid conditions to yield C-4-elaborated flavan-3-ols 518 has been described. The C 4 acetoxy group is activated by a Lewis acid, such as BFj-OEo or TMSOTf, allowing delivery of a variety of carbon-, nitrogen-, and sulfur-based nucleophiles in stereoselective fashion to this position (Scheme 94) <2002TL7753>. An SnI mechanism was invoked for the process. Table 4 displays the results for catechins. 

The solution is to use the anion of thiolacetic acid, usually the potassium salt. This reacts cleanly through the more nucleophilic sulfur atom and the resulting ester can be hydrolysed in base to liberate the thiol. 

In this chtq)ter oxidation of an activated C—bond adjacent to a sulfur atom refers to any process whereby a C—bond at the a-position of an alkyl sulfide is replaced by a C—bond, where X is a halogen atom or an oxygen-, nitrogen-, carbon-, or sulfur-based substituent (equation 1). Processes in which a stabilized anion is generated adjacent to the sulfur atom of a sulfide, foxide or sulfone and subsequently used as a nucleophile in addition or substitution reactions are excluded ftom this section. The use of such anions in organic synthesis is dealt with in Volume 1, ClhtqMer 23. 

Sulfur reacts with many organic molecules, and in such sulfur-sulfur bond-breaking reactions free radicals may be involved the reactions are often catalysed by amines and Lewis acids. Amines and other bases activate sulfur by formation of nucleophilic sulfur species, while Lewis acids cleave the sulfur-sulfur bond to give electrophilic sulfur moieties. 

The overall process of peptide bond scission is identical in all classes of peptidases and differences between the catalytic mechanisms are rather subtle. The attack on the carbonyl group of the peptide bond requires a nucleophilic agent, either oxygen or sulfur, in order to approach the slightly electrophilic carbonyl carbon atom. To remove a proton from the attacking nucleophile, general base catalysis will assist this process. Furthermore, some type of electrophilic action on the carbonyl oxygen increases the polarization of the C - O-bond. 

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