Mori synthesis

The Hurd-Mori synthesis of 1,2,3-thiadiazoles from a-methylene ketones developed in 1955 is, even today, the method of choice for a number of 1,2,3-thia-diazole derivatives. Both the mechanism and the regiochemistry have been extensively studied, but since the isolation of the intermediate by Hurd and Mori (84CHEC-I(6)460), there has been no further work supporting the formation of this intermediate or its conversion into the aromatization product. In 1995 Kobori and coworkers published the isolation of several 1,2,3-thiadiazolin-1-oxides 186, finally demonstrating their participation in the formation of 1,2,3-thiadiazoles. Substituents R and R play an important role in the isolation of 1,2,3-thiadiazolin-1-oxide (95H(41)2413). 

The Hurd-Mori synthesis of 1,2,3-thiadiazoles s the most widely used method. The availability of aldehydes and ketones which can then be converted into their corresponding hydrazones and the high yields obtained on treatment of these hydrazones with thionyl chloride mean that this method should always be considered as the first choice. 

Thiadiazoles are prepared by cyclocondensation of tosylhydrazones derived from a-methylene ketones with thionyl chloride or sulfur dichloride Hurd-Mori synthesis) [148] ... 

Takanashi, S.I., and K. Mori, Synthesis of Lurlenic Acid and Lurlenol, the Sex Pheromones of the Green Flagellate Chlamydomonas, Liebigs Ann./Recueil, 825-838 (1997). 

Y. Oishi, A. Konno, J. Oravec, K. Mori, Synthesis and properties of fiuorine containing polybenzoxazole by in-situ silylation method, Photopolym. Sci. Technol. 19 (5) (2(X)6) 669-672. 

Two additional syntheses that did not address the vicinal stereochemistry problem are outlined here. They differ from the Mori synthesis in regard to the chemistry used to introduce the sidechain, but are similar in that they rely on reactions of a 4-substituted cyclohexanone to introduce the vicinal stereochemical relationship. 

Another enantioselective route to 116, that features catalytic asymmetric induction, is shown here (see Prostaglandins-12 for another example). This synthesis begins with racemic allylic acetate 123. A palladium-mediated ally-lation of dimethyl malonate in the presence of chiral ligands (for the Pd) provided 124 with excellent enantioselectivity. This material was converted to 116. Alkylation as per the Mori synthesis (Juvabione-16) gave 117, which was converted to 125 using another Pd-mediated malonate allylation. Malonate 125 was converted to 126 via an intermediate tetraol. The synthesis of juvabione (15) was then completed using a short reaction sequence. 

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