Towards the catalytic asymmetric bromination of alkenes

• Main Author: Cailleau, Thaïs
• Other Authors: Braddock, Chris
• Published: Imperial College London 2011
• Subjects: 547.4
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543368

This thesis relates our efforts towards the development of a general method for the catalytic asymmetric bromination of alkenes. Previous work within the group had reported the synthesis and the use of 2,6-di-[(4R,5R)-4,5-diphenyl-4,5-dihydro-1H-imidazol-2yl]-iodobenzene to catalyse the bromolactonisation of (±)-2-cyclopentene-1-acetic acid with some asymmetric induction observed. The reaction was initially postulated to proceed via formation of a hypervalent N-I(III)-Br bond in the catalyst, which by placing the electrophilic bromine in a chiral environment would allow for its selective delivery to the alkene substrate. Initial work aimed to acquire a better understanding of that reaction system and some mechanistic studies were undertaken. A different outcome to the one expected is reported and it was concluded that during the bromolactonisation reaction, no hypervalent iodine species was forming in situ and that instead a potential kinetic resolution via α-salt formation and diastereoselective halolactonisation mechanism was operating. These findings necessitated a redesign of the catalyst and the synthesis of various bis-amidine analogues is described. An unexpected rearrangement is also unveiled and its mechanism discussed. The new catalysts were screened in our asymmetric brominating system, using different alkene substrates, and the results are reported and discussed. Subsequent studies focused on elaborating a general method for the asymmetric dibromination of alkenes, where Br+ would be delivered by a stoichiometric chiral promoter. Screening of various alkene substrates to identify a suitable candidate is reported and discussed. The asymmetric dibromination of the chosen alkene is described and further investigations in order to elucidate the reasons for the lack of enantioselectivity observed are reported. Finally, attempts to synthesise Ts-DPEN following a similar route as previously developed within the group for the synthesis of DPEN is reported as a side chapter. Various attempts at the final benzoyl cleavage are described and discussed.