Synthesis of heterocycles via isocyanide-based multi-component reactions

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2011
Thesis identifier
  • T13389
Qualification Level
Qualification Name
Department, School or Faculty
  • This thesis deals with the development of a new multi-component reaction for the synthesis of heterocycles involving the process of insertion of isocyanides into a carbon-palladium bond. The application to the synthesis of oxazolines was explored and was shown to give good yields of 2-aryloxazolines. The reaction conditions developed use a PdCl₂/dppf catalytic system which enables the formation of an amidine intermediate. This intermediate then cyclises into the oxazoline. This reaction was performed on several aromatic systems, electron-rich or electron-poor, and appeared to be very tolerant of substitution pattern. The extension of these conditions to the synthesis of 2-arylbenzoxazoles has been studied. Excellent yields have been obtained for this transformation which suggests that these conditions could be applied to the synthesis of different types of heterocycles. The application to the synthesis of 2-arylbenzothiazoles appeared to be more challenging as a different reactivity was observed. Indeed, the same reaction conditions afforded the unsubstituted benzothiazole. However, a slight modification of the reaction conditions and the use of a copper species as co-catalyst enabled the 2-phenylbenzothiazole to be obtained. This required optimization in order to obtain a good yield for this transformation, and especially to prevent the Ullmann-coupling side-reaction from occuring. A yield of 59% which is noteworthy for a multi-component reaction, was finally obtained for the formation of 2-phenylbenzothiazole.
Resource Type
Date Created
  • 2011
Former identifier
  • 989246