Aryl thioester

In a synthesis of 2,3-di(hetero)arylpyrido[3,2 [l,4]thiazepines developed by Couture, 2-chloro-3-formylpyridine is reacted with arylmethylamines to form the imines. Deprotonation with LDA at -78 °C followed by treatment with non enolisable aryl thioesters gives the title compounds which may be further annulated by irradiation in benzene in the presence of iodine and propylene oxide <96S986> (Scheme 14). 

Peptides typically are prepared for this ligation process using a-alkyl thioesters, because they are simple to make at the time of peptide synthesis. However, due to the relatively slow reaction kinetics of alkyl thioesters, most native chemical ligation processes have been catalyzed through the use of thiol compound additives, such as benzyl mercaptan or thiophenol (Dawson et al., 1997). These compounds react with the initial a-alkyl thioester to form another intermediate, an aryl thioester, which is more reactive toward the N-terminal cysteine on the other peptide to be coupled. A study... 

Simple alkyl or aryl thioesters are commonly assayed as substrates of hydrolases, witness the hydrolysis of phenyl thioesters by horse serum carbox-ylesterase [150], For most substrates investigated, e.g., phenyl thioacetate, phenyl thiopropionate, and phenyl thiobutyrate (7.66, R = Me, Et, and Bu, respectively), kcat values were found, which were a few times larger than those of corresponding nitrophenyl esters, whereas the affinities were lower by approximately one order of magnitude. Methyl and phenyl esters of various linear thioacids were also found to be good substrates of mammalian liver carboxylesterases and serum cholinesterases [151]. 

Thiol esters R1-C-SR2 II 0 >C=0 (1690) (s) (S-alkyl thioester) (1710) (s) (S-aryl thioester) The (+) mesomeric effect of sulfur is larger than its (-) inductive effect... 

The organolithium derived from 2-methylbenzamide reacts with alkyl and aryl thioesters to give 3-substituted isothiocoumarins 513 (Scheme 197) <1990S1133>. 

Poly(d -aryl thioesters) 394, treated with thiiranes in the presence of tetrabutylammonium chloride in DMA at 70 °C for 6 h, gave a new modified polymer 395 (Scheme 113) <1996MM6676>. Other examples of polymerization of thiiranes with poly(3 -aryl thioesters) were reported <1996MI68, 1997MI550, 1999MM1407>. 

Thiol esters of aromatic acids, ArC(0)SR, are cathodically reduced, with fission of the S-CO bond generating the arylcarbonyl radical and thiolate as in Eq. (25) [101]. The thiol may be obtained in good yield [102]—for example, L-cysteine in 83% yield from S-benzoyl-L-cysteine at a mercury cathode in DMF-water-tetramethylammonium chloride. The electroreduction of aryl thioesters [containing -C(0)SR, -C(S)OR, and -C(S)SR functions] has been studied, and some interesting products have been formed [103-105], as in Eqs. (26) through (29). Trithiocarbonates are reduced to the tetraalkyltetrathioethylenes [106]. 

In analogy to the active esters, thioesters are prepared by condensation of thiols with carboxylic acids/DC(3 or carboxylic acid chlorides. " Aryl thioesters react readily with nucleophiles like amines to give amides. Peptides are prepared without racemization. In the case of r-butyl thioesters activation is accomplished by treatment with Ag02CCp3. 

A new alternative has also been described. The furan is oxidatively meth-oxylated, and the product condensed with an alkyl or arylthiol by means of an acid catalyst in acetonitrile at ordinary temperatures it is presumed that a carbocation is intermediate. Although the method makes available aryl thioesters as well as alkyl thioethers, heterocyclic thiols and thiourea fail. The furylthioethers are not very stable and decompose if the reaction is prolonged.202... 

Trifluoromethyl-4-isopropyl-3-oxazolin-5-one (45) reacts with aryl-thioesters of arylsulfonic acids to yield derivatives which, on heating, give benzothiazines116 [Eq. (22). With arylsulfenyl chlorides, 2-... 

Pummerer rearrangement (5,3-4). The Pummerer rearrangement of P-hydroxy sulfoxides to derivatives of a-hydroxy aldehydes has been extended to the rearrangement of 3-keto sulfoxides. Thus rearrangement of (1) with acetic anhydride-sodium acetate in toluene under reflux gives the S-aryl thioester (2) in 74% yield. The ester is hydrolyzed by base to mandelic acid (3). In the absence of sodium acetate the normal product of the Pummerer rearrangement... 

KCL is made possible by the dramatic difference in reactivity between an aryl thioester and alkyl thioester. The significantly faster reaction kinetics of aryl thioesters enable selective hgation in the presence of an alkyl thioester, whose subsequent hgation is initiated by the addition of a catalyst such as MPAA. This approach provides the flexibihty of conducting a hgation from the N-terminal to the C-terminal direction (Scheme 16) [158-160]. 

The reaction with S-alkyl and S-aryl thioesters gives ketones in high yield with efficient utilization of the organocopper reagents (approximately stoichiometric amount required). The selectivity of this ketone synthesis is demonstrated by the conversion (LXXXII)-> (LXXXIII) (Anderson et al., 1974). 

In addition to the alkyl and aryl thioester derivatives of thiols this section will consider the S-alkyloxycarbonyl (ROCOSR ) derivatives as well as the iV-alkylthiocarbamates (RNHCOSR ) and dithiocarbonates (RSCOSR ). 

Phenylsulfonyl ketones rearrange in the presence of acetic anhydride-sodium acetate in toluene at reflux to give 5-aryl thioesters (eq 23). Upon hydrolysis, an a-hydroxy acid is obtained. 

Unsaturated thio- and seleno-esters of type (163) are available from allyl alkyl sulphides or selenides by reaction with dichloroketen and rearrangement as described earlier. Homologues (165) of aryl thioesters are available via the dipole-stabilized intermediate (164) so far the reaction has only been reported for 2,4,6-triethylphenyl thioesters. ... 

Sodium mercaptides are prepared from the mercaptans and aqueous or alcoholic solutions of sodium hydroxide or alcoholic sodium eth-oxide. The sodium mercaptide reacts with halides, chlorohydrins, esters of sulfonic acid, or alkyl sulfonates [6] to give sulfides in yields of 70% or more. A recent report describes a general procedure for synthesizing aryl thioesters by a nucleophilic displacement of aryl halide with thiolate ion in amide solvents. No copper catalysis is necessary as in an Ullmann-type reaction. 

The reaction of diethyl-arylketophosphine sulfide A with adamantyl-thioester E afforded the products F and G formed by change in the functionality in a somewhat better conversion, ca. 34%), than the reaction of A and B to give C and D (Scheme 4-1). At the same time, the reaction of an aryl thioester with TEDPDS also provided a much better conversion to furnish diethyl-aroylphosphine sulfide D (Scheme 4-2). ... 

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