Thiolate nucleophiles

Scheme 6. Payne rearrangement/epoxide opening reaction thiolate nucleophile.

It was known from solution-based studies that an iodonium electrophile adds to the glycal linkage, in the presence of a sulfonamide, in a transdiaxial fashion.24 This results in formation of a 1 -a-sulfonamido-2-p-iodo product. Furthermore, displacement of iodine can be induced by nucleophilic attack of a thiolate nucleophile... 

Second-order rate constants for the reaction of thiolate nucleophiles with p-nitrophenyl acetate... 

The activation of a thiolate nucleophile by an ammonium membrane was reported by Cuccovia et al. (1979). 

Thiodisaccharides in the GlcNAc series were recently synthesized. The substitution reaction of the triflate at C-4 of 2-acetamido- and 2-azido-o- galacto-sides (34 d) and (34 e) in DMF with thiolate nucleophiles (8i) or (8j) and (30b) afforded the expected disaccharides (aroimd 50 and 68%), from which the deprotected (41) and (42) were obtained [39a, 32] (Scheme 13). The coupling of the triflate (34 f) with the thiol (8j) in DMF in the presence of cysteamine gave a 63% yield of the expected thiocfrsaccharide which was converted into (41) in high yield [39b],... 

We saw in Section 12.3.1 the use of the cyclodextrins as mimics for transacylases, a well-understood class of enzymes that perform the task of transferring an acyl group from one substrate to another (e.g. from an ester to water). Transacylase chemistry has also been addressed by Cram,5 who used chiral corands, such as 12.11, related to 3.106 bearing thiolate nucleophiles situated above and below the plane of the macrocycle. An acyclic analogue 12.12 was also prepared for comparison. The salient features of 12.11 are shown diagrammatically in Figure 12.4. 

The effect of different heteroatoms on the ring opening of substituted three-membered rings was investigated at the B3LYP/TZV+P level of theory.115 Two specific water molecules were included in the calculations and the COSMO method was used to include the bulk solvent. With the methyl thiolate nucleophile, thiirane was... 

Ring closure of Af-(]-cyanoalkyl)alkylidene Af-oxides (these compounds are nitrones, cf. Section 4.2) is induced by nucleophilic attack by the thiophenate ion (Scheme 2.1.10). The reactions are accelerated by the addition of small amounts of piperidine, but inhibited by temperatures above the melting points of the nitrones. In these reactions, 4-phenylthioimidazoles (23) are formed usually in 80-90% yields. Deficiencies in the general process include the problems of first making the nitrones, and the fact that other thiolate nucleophiles (methyl, ethyl, benzyl) are much less successful, giving only low yields of 4-alkyIthioimidazoles [63]. 

Fig. 26 In the first step of the reaction catalyzed by PTPases, the thiolate nucleophile of a conserved cysteine attacks the dianionic form of the substrate. The transition state is loose, and the leaving group is neutralized by proton transfer from the conserved Asp residue. In the second step the carboxylate of this residue deprotonates a nucleophilic water molecule. The transition state of the second step (not shown) is also loose, with a small degree of bond formation to the nucleophile.

To install the appropriate functionality at C2, solution phase chemistry has relied on a trans-diaxial addition of an iodonium electrophile in the presence of an amine to form an iodosulfonamide. Displacement of iodine proceeds presumably through an aziridine intermediate and may be induced by a thiolate nucleophile to fashion thioethyl 2-amidoglycosyl donors [38]. Successful transfer of this method to the solid support allowed polymer-bound glycals to be converted into thioethyl gly-cosyl donors. These donors were in turn coupled with a variety of glycosyl acceptors, including glycals [39]. 

The general reaction mechanism has been shown to involve typical steps for cross-coupling [98, 113]. Oxidative addition of an aryl halide generates a Pd(II) species that undergoes transmetalation to form a Pd(II)-thiolate. C-S reductive elimination provides the aryl sulfide and regenerates the Pd(0) catalyst. More recently, Hartwig reported a detailed mechanistic analysis of the Pd/Josiphos system derived from different Pd precursors. The dominant Pd species were found to be off the catalytic cycle, which accounted for differences in rates between stoichiometric and catalytic reactions [114]. Thioketones are also effective thiolate nucleophiles for C-S bond formation. The reaction involves tandem Pd-catalyzed thioenolate alkylation, followed by 5-arylation (8) [102]. Presumably, the arylation process proceeds by a similar mechanism to related Pd-catalyzed transformations. 

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