1.2- Aminothiol

The successful application of sulfanyl amines in the diastereoselective and enantioselective synthesis of as-3,4-disubstituted /3-sultams has been reported (Scheme 56). The protocol is based on the oxidation of the 1,2-aminothiols 178 with hydrogen peroxide and ammonium heptamolybdate. Chlorination of the resulting /3-aminosulfonic acids was achieved using phosgene. The /3-aminosulfonyl chlorides 179 obtained were cyclized under basic conditions and without epimerization to yield the t -3,4-disubstituted /3-sultams 180 (>96% de, ee) (Table 13) <2005S1807>. 

Rao and Tam[19 reported the connection of a 24-residue peptide to a small, lysine-based dendrimer (Scheme 7.3). The peptide connection was effected via treatment of the octameric, glyoxylyl-terminated dendrimer 15 with the 1,2-aminothiol polypeptide 16 to afford the thiazolidinyl peptide dendrimer 17. The thiazolidine linkage also introduces a new asymmetric center. 

A great variety of 1,4-dinucleophiles have also been employed in cyclizations with azines (85KGS1011). Among them are 1,2-diamines, 1,2-aminothiols, 1,2-amino alcohols, and their structural analogues, such as thiosemicarbazides, amidoximes, dithiocarbazates, etc. (Scheme 8). 

The asymmetric synthesis of c -3,4-disubstituted P-sultams 65, based on the oxidation of 1,2-aminothiols with H2O2 and ammonium heptamolybdate has been achieved <05S1807>. Different transition-state structures for the reactions of P-lactams and their sulfonyl analogues P-sultams with serine P-lactamases have been reported <05JA17556>. It has been discovered that the 3-oxo-P-sultam 66 is unusual in that it inhibits elastase by acylation resulting from substitution at the carbonyl center, C-N fission, and expulsion of the sulfonamide <05JA8946>. 

Further examples are epoxides, from which oxazolidinones [40] and y- and 8-lactones [41] have been synthesized, 1,3-diketones which were used in the syntheses of pyrazoles and isoxazoles [42], 1,2-aminothiols from which thiazolidines [43] were formed. 

Hgure4. Pseudoproline formation at the ligation side by a C-terminal aldehyde peptide reacting with a 1,2-aminothiol peptide at acidic pH. The reactive carboxyl and amino termini are positioned in close proximity for spontaneous peptide bond formation through an entropy-driven intramolecular 0- Alacyl transfer. 

Aminothiolate. The treatment of 1,2-aminothiol salt (19) with CS2 in the presence of Et3N leads to thiazoline (20) (eq 15). ... 

The initial study was performed using various thiols (R SH) as nucleophiles, which afforded 1,2-aminothiol derivatives 98 bearing two adjacent stereogenic centers in one-pot good yield process (up to 72%) with marvelous stereoselectivity (dr up to 96 4, >99% ee) [58a]. Likewise, the subsequent employment of an aza-nucleophile gave access to iyn-diaminated aldehydes 99 and 100, easily converted in 1,2,3-triaminated products or 1,3-diamino alcohols [58b]. In both cases, the mechanistic pathway involves the first soft nucleophile attack to the iminium intermediate A, followed by the addition of a suitable electrophile 96 to the enamine intermediate B, giving the nearly enantiopure products 98-100 (Scheme 2.28). 

Marigo et al. developed a multicomponent domino-conjugated nucleophilic thiol addition-electrophilic amination reaction that gave access to 1,2-aminothiol derivatives with >99% ee in a one-pot process using 128 as a catalyst (Scheme 1.72) [ 114]. The soft sulfur nucleophile 168 first reacted with the iminium ion intermediate, followed by addition of the enamine intermediate to the azodicarboxylates 169. In situ reduction and cyclization resulted in the formation of highly functionalized oxazolid-inones 170 in nearly enantiopure form. 

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