Thiopyridone synthesis

D-glucosamine, Tetrahedron Asymm., 5, 2137, 1994 (s) Barton, D. H. R., Chern, C.-Y., and Jas-zberenyi, J. Cs., Homologation of carboxylic acids by improved methods based on radical chain chemistry of acyl derivatives of N-hydroxy-2-thiopyridone, Tetrahedron Lett., 33, 5013, 1992 (t) Barton, D. H. R., Chem, C.-Y., and Jaszberenyi, J. Cs., Two carbon homologation of carboxylic acids via carbon radicals generated from the acyl derivatives of N-hydroxy-2-thiopyridone synthesis of n-l-2 a-keto-acids from Q, acids. (The three carbon problem). Tetrahedron Lett., 33, 5017, 1992. 

The photolysis of Barton esters (N-hydroxy-2-thiopyridone esters, 43) proved to be an efficient method for generating carbon-centered radicals that are exploited for the regioselective alkylation of electron-deficient olefins a thiopyridyl unit is likewise incorporated into the end products. In a recent application, Barton esters were found useful in the synthesis of natural and unnatural disubstituted maleimides or maleic anhydrides by way of two consecutive radical addition steps, as described in Scheme 3.27 [72]. 

The reactions based on A-hydroxy-2-thiopyridone derivatives are clearly radical chain reactions. In a recent paper,91 we have reported quantum yield measurements for a number of reactions based on iV-hydroxy-2-thiopyridone. Most of the reactions had quantum yields of 10-30. Synthesis of the N-hydroxyquinazolin-4-thione 139 (Ar = Ph, An, 1-Naph) by an improved route gave thiohydroxamic acids which were more sensitive to light than iV-hydroxy-2-thiopyridone. The quantum yield for bromination was in the range 30-60. More important, while the JV-hydroxy-2-thiopyridone system at — 30 °C, makes21 radicals only in a non-chain fashion, the derivatives of 139 continue radical chain reactions even at — 60 °C. 

Alkylation of thioamides with Meerwein s reagent (trialkoxonium fluoroborate) proceeds via a thioiminoester and subsequent base hydrolysis with sodium carbonate (equation 32). For the synthesis of 2-pyridones from 2-thiopyridones, chloroacetic acid has been used. ° Mild reaction conditions are provided by nitrosyl species which are derived from a variety of reagents excess NaNOa/HCP in aqueous medium, nitrosonium tetrafluoroborate in dichloromethane, dinitrogen tetroxide in acetonitrile at low temperature and f-butyl thionitrate. ... 

Benzothiazol-2-yl C-nucleosides were also obtained by a different mode of synthesis that involved the free radical coupling of the sugar subunit with the heterocycle residue. The 2-deoxy-D-ribofuranosyl free radical 170, formed by photolysis of the 2-thiopyridone-iV-(2,5-anhydro-3-deoxy)-D-allonoate 169, reacted with benzothiazolium camphorsulfonate to form a mixture of 2-(a and 3-2-deoxy-D-ribofuranosyl) benzothiazoles 171 (92CL1673) (Scheme 50). 

C-Glycopyranosides may be obtained from glycopyranosyl halides via intermolecular addition of glycopyranosyl radicals [129]. In a more useful example, the a-aminoacrylate 192 was used as the radical acceptor for preparation of C-glycosyl amino acids 193 and 194 [130] (Scheme 66). In a concise synthesis of showdomycin (197), Barton utilized the trigger reaction of the 7V-hydroxy-2-thiopyridone derivative and the exceptional radicophilicity of tellurides in concocting the conditions for the conversion from the anisyl telluride 195 to the intermediate 196 after oxidative elimination [131] (Scheme 67). In Keck s synthesis of (-t-)-pseudomonic acid C (201), the intermediate 200 was prepared via stereocontrolled intermolecular addition of the radical generated from the iodide 198 to the allylic sulfone 199 [132] (Scheme 68). 

Protection of amino group. The o-nitrophenylsulfenyl group has been used for protection of side-chain amino groups in peptide synthesis. The classical method for removal is treatment with acid, even acetic acid, but this method is not selective. The selective removal is now possible by cleavage with 2-mercapto-pyridine (2-thiopyridone) and 1 equiv. of HOAc in CH3OH, DMF, or CH2Cl2. ... 

In 1999, Katritzky reported a novel [3+2+1] synthesis of 2,4,6-trisubstituted pyridine derivatives that used the Michael addition of a-benzotriazolyl ketones to a,P-unsaturated carbonyl compounds. This reaction resembles the Krohnke pyridine synthesis and is an extension of Katritzky s earlier studies with benzotriazolyl derivatives that provided access to pyridones, 2-thiopyridones, 5-alkyl-2,4-diphenylpyridines and 2-aminopyridines. This approach is attractive as both components are readily synthesized or commercially available. The availability of these starting materials allows for an efficient access to structurally diverse 2,4,6-triaryl pyridines when combined with ammonium acetate in acetic acid at reflux. In addition, it is possible to access fused 2,3,4,6-tetrasubstituted pyridines from the requisite fused bicyclic ketone starting material. The preparation of the pyridine ring via benzotriazole methodology has resulted in improved yields for many compounds and the opportunity to synthesize molecules with a substitution pattern that would be difficult to prepare by other methods. 

Togo, Y Nakamura, N. Iwamura, H. Synthesis and photolysis of Al-(phenoxycarbonyloxy)-2-thiopyridone derivatives. A new unimolecular route to quantitative generation of phenoxyl radicals. Chem. Lett. 1991, 7, 1201-1204. 

The 2-thiopyridone (78) is reportedly a superior reagent for the activated ester approach to macrolides, requiring no further activation s (e.g. with Ag ions). The selenolactonization procedure has been used for a reasonably efficient synthesis (ca. 50% yield) of the macrolide derivatives (80 n = 11 or 13) from the unsaturated acids (79) using the iV-phenylseleno-derivatives of suc-cinimide or phthalimide as carriers of the PhSe function. Trost and Verhoeven have reported more examples of the efficient preparation of medium-sized macrolides via Pd° 7r-complexes of allyl acetates (2,152). Further reports have appeared on the preparation of ten-membered keto-macrolides by oxidative ring cleavage of suitable cyclic ethers (c/. 3, 142, 143). 

The Gif group have used methyl radicals formed by photolysis of N-acetoxy-2-thiopyridone to generate 5 -radicals in nucleoside systems. The formation of the 5, 8-cyclopurine nucleoside (26) by this method is shown in Scheme 4, as is a similar reaction in the pyrimidine series. In this case (27) could be reductively desulfurized with Raney nickel. The tellurides used as radical precursors were formed by displacement of 5 -0-mesylates.27 Free-radical cyclization was also employed in a synthesis of 6,l -propanouridine (29) from the known anhydronucleoside (28) as indicated in outline in Scheme 5.28... 

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