An investigation into organocatalytic Michael additions

Dale, Peter (2015). An investigation into organocatalytic Michael additions. University of Birmingham. M.Sc.

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Abstract

Previous work in the Simpkins group includes the Michael addition reactions of triketopiperazines (TKPs). These were performed asymmetrically using modified cinchona alkaloid catalysts. The aim of this project was to expand the range of substrates that could be used in similar organocatalytic reactions.

Cyclic substrates such as hydantoins and the drug thalidomide did not show any reactivity under the Michael addition conditions. Acyclic substrates were also tested and some limited success was achieved with an α-phenyl amide substrate. However, a strongly basic guanidine catalyst was required, so investigations were therefore carried out into developing chiral guanidine catalysts.

In the course of the project a new method for the arylation of a TKP was developed which used diphenyliodonium triflate (DPIT) as the electrophile. The Phenyl-TKP was subsequently used in asymmetric Michael additions. A range of catalysts were screened, with a modified-quinine catalyst performing the best.

The PMB-protected TKP was also synthesised and this gave even better yields and selectivities when a range of unsaturated ketones were used.

In summary, a large number of substrates have been tested and a method for arylating TKPs has been developed. Furthermore, some excellent yields and selectivities have been achieved for organocatalytic Michael additions.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):