Palladium catalysed carbonylation of terminal alkenes to alpha,beta-unsaturated esters & Allylic C-H functionalisation of unsaturated hydrazine carboxylates to vinyl isoxasolidines

2014-05-22T13:01:25Z (GMT) by Nolwenn Derrien
In the first part of the thesis, the aim was to devise a new simple catalytic system based on palladium to allow insertion of carbon monoxide in the presence of an alcohol into unsaturated systems with retention of the double bond to give an unsaturated ester. The process is known as oxidative carbonylation. To allow the process to become catalytic, the palladium needs to be reoxidised in situ. Optimal conditions for the catalytic system were developed and a wide range of substrates have been examined. Simple terminal alkenes and alkenes bearing functional group have been successfully carbonylated (yield 16%-87%). The method was applied to the synthesis of a known pharmaceutical intermediate. The aim of the second part was to develop an efficient system for the intramolecular oxidative amination of unsaturated hydrazine carboxylates to form novel vinyl oxazolidines. After optimisation of the reaction conditions, the scope and limitations of the reaction were established. Attempts were also carried out to develop an enantioselective version of the cyclisation. The method was applied to the synthesis of a known intermediate in a sequence towards (-)-kainic acid thus accomplishing a formal total synthesis of this compound.