Pyridine dithioesters

Benzotriazole methodology was also used to achieve the synthesis of cy-chc peptidominetics (146) via intramolecular acyl migration of the pyridine dithioesters (143) to form the diamides (144) followed by reaction with diamides (145) (Scheme 37) (2015OBC9492). 

In 2004, ruthenium-catalysed asymmetric cyclopropanations of styrene derivatives with diazoesters were also performed by Masson et al., using chiral 2,6-bis(thiazolines)pyridines. These ligands were prepared from dithioesters and commercially available enantiopure 2-aminoalcohols. When the cyclopropanation of styrene with diazoethylacetate was performed with these ligands in the presence of ruthenium, enantioselectivities of up to 85% ee were obtained (Scheme 6.6). The scope of this methodology was extended to various styrene derivatives and to isopropyl diazomethylphosphonate with good yields and enantioselectivities. The comparative evaluation of enantiocontrol for cyclopropanation of styrene with chiral ruthenium-bis(oxazolines), Ru-Pybox, and chiral ruthenium-bis(thiazolines), Ru-thia-Pybox, have shown many similarities with, in some cases, good enantiomeric excesses. The modification... 

The first synthesis of acylglycine dithioester derivatives was described by Storer et al.[86l Their synthesis begins with the Pinner reaction 86 88 89 of the corresponding aminoacyl nitrile 39 in the presence of ethanethiol and HC1 gas to produce a thioimidoester hydrochloride 40. Use of an alcohol instead of a thiol gives the thionoesterJ90 The thioimidoester 40 was then treated with H2S gas in the presence of pyridine to yield the dithioester 41 (Scheme 18).[861... 

A further modification of this method 86 was described by Neugebauer et alJ93 In this version, the nitrile was dissolved in dry liquid HF at a temperature below 0°C, instead of HC1 saturated CH2C12, to give the adduct [R1CNH]+HF2 44 (Scheme 20). This compound was reacted with a thiol to form a thioimidate hydrofluoride 45, which upon treatment with H2S/ pyridine solution provided the dithioester derivative 46. 

A modification of the Pinner reaction using liquid HF has been used to improve the yields of the dithioester products. The N-protected amino acid and peptide nitriles 6 dissolve in liquid HF at temperatures below 0°C and react with thiols to form the imidothioic acid ester hydrofluorides 7 that further react with H2S in pyridine at 0°C to form the dithioesters 8 (Scheme 2)J71 Several isotopic dithioesters have been synthesized by this method with improved yield (Table 2). The use of liquid HF at low temperature helps to dissolve the amino acid nitriles that are not very soluble under Pinner conditions (HCl-saturated CH2C12). 

Financial support was provided by the National Science Foundation (Grant CHE-94-13128). Prof. Alan Bond and Mr. Richard Webster provided advance information concerning their studies on the electrochemistry of pyridine 2,6-dithioesters and related substances84. 

In a modified Pinner reaction, the cyano group of the AT-acyl amino nitrile 41 was converted to the ethylthio iminium salt 42 on treatment with ethan-ethiol in liquid HF at 77 K. The iminium salt 42 was treated with H2S gas in pyridine at 0 °C to give a dithioester derivative of the iV-acyl amino acid 43 (Scheme 10) [42]. This method has also been used to synthesize dithioesters of dipeptides. 

Aryl methyl ketones can be converted to a-keto dithioates, as shown in Scheme 11 [43]. Therefore, on treatment with iodine and pyridine, the ketone 44 yields pyridinium salt 45, and 45 can then be treated first with elemental sulfur in the presence of triethylamine in DMSO and DMF and then with methyl iodide to give S-methyl a-keto dithioate 46. The reaction of l-(diethylamino)-2-(phenylthio)acetylene (47) with elemental sulfur in refluxing chlorobenzene gives compound 48 in which the dithioester and thioamide groups directly connected to each other (Eq. 17) [44]. 

The unambiguous synthesis of TO was accomplished starting from T. Treatment with iodomethane and then with hydrogen sulfide in pyridine, afforded the dithioester. This compound was oxidized with m-chloroperbenzoic acid in chloroform at 0 C, to give the thionoxide. This was reacted with morpholine in methanol and from the reaction... 

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