Synthesis of thiazoles and fused derivatives

The Hantzsoh reaction discovered in 1889 remains one of the most reliable routes to thiazoles and several applications of this reaction appeared during the past year 05JOC8991 05JA15644 05T1257 . This approach has been used twice to form both thiazole rings of the cyolopeptide dendroamide A 05H(65)95 . The first thiazolation of a-bromomethyl ketone 2 with thioamide 1 results in the formation of thiazole 3, which is converted into thioamide 4. This compound undergoes the second thiazolation with 5 to furnish oxazolyl bis-thiazole 6, a precursor to dendroamide A. 

Thiazoles can also be derived from 1,4-dicarbonyl compounds, which are available through the N-H insertion reaction of rhodium carbenoids 05JA15644 . For example, the dirhodium(II) carboxylate-catalyzed reaction of diazocarbonyl compound 8 in the presence of primary amide 7 leads to the formation of a-acylaminoketone 9, which is converted into thiazole 10 by treatment with Lawessons reagent. Thiazole 10 serves as one of the six thiazole building blocks in the total synthesis of thiopeptide antibiotic amythiamicin D. 

Thiazoles can be prepared from thiazolines by oxidation with activated manganese dioxide. This approach has been applied to the synthesis of dimethyl sulfomycinnamate (11 to 12) 05JOC1389 , the polyoxazole-thiazole based cyclopeptide YM-216391 (13 to YM-216391) 05CC797 , and didmolamides A and B (14 to 15) 05TL2567 . A facile preparation of thiazole 17 from thiazolidine 16 involves a brornmation-elirnination protocol 05JMC2584 . 

A one-pot four-component solution phase procedure has been developed for the synthesis of 2,4,5-trisubstituted thiazoles 25 05SL79 . The four components, the 3-substituted 3-bromo-2-isocyanoacrylate 18, the ketone or aldehyde 19, the primary amine 20, and the thiocarboxylic acid 21, can vary broadly, thus producing thiazoles with five potential diversity points. Presumably, condensation of 19 with 20 generates imine 22, which reacts regioselectively with 18 and 21 via the Ugi pathway. The intermediate Ugi product 23 is in 

2-Cyanothiazoles 33 are prepared from A -vinyl-l,2,3-dithiazolimines 31, obtained from the reaction of 4,5-dichloro-l,2,3-dithiazolium chloride 29 with aziridines 28 05H(65)1601 . Thermolysis of imines 31 brings about cyclization to give sulfur, hydrogen chloride and 2-cyanothiazoles 33, possibly by an electrocyclization and fragmentation process. Reaction of allenyl isothiocyanate 34 with a variety of nucleophiles (NuH) leads to 

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