Transition-Metal-Catalysed Cycloadditions and Cross-Coupling Reactions

  • Andrew G Dalling

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

In Chapter 2, an atom economical Rh(I)-catalysed (3+1+2) cycloaddition protocol involving cyclopropylamides, carbon monoxide and tethered alkenes is described. The methodology enables the synthesis of stereochemically complex, sp3 rich N-heterocycles. Extensive optimisation upon substrates bearing substituted cyclopropanes revealed the requirement for an ortho-methoxy substituted triarylarsine ligand in order to promote efficient cyclisation. Subsequently, the cycloaddition of a broad range of substrates was possible to deliver the target N-heterocycles with high stereoselectivity. These studies provide the first examples of multicomponent cycloadditions that proceed through C-C bond activation of “simple” electron-poor cyclopropanes.
In Chapter 4, studies towards the Ir(I)-catalysed asymmetric hydroarylation of terminal alkenes to construct tertiary benzylic stereocentres is described. The synthesis of a broad range of SPINOL based chiral ligands was conducted in order to promote high enantioselectivity for the hydroheteroarylation of alkenes with furan and pyrrole-based heteroaromatics. Excellent yields and promising levels of enantioselectivity were obtained.
In Chapter 5, a collaborative effort to expand the scope of the Ir(I)-catalysed hydroarylation methodology is discussed. Construction of challenging all-carbon quaternary stereocentres was achieved through the hydroarylation of 1,1-disubstituted alkenes. An insight into the mechanism of the catalytic cycle was gained through mechanistic and computational studies. These studies suggest that the hydroarylation of 1,1-disubtituted alkenes proceeds through a different pathway to previous Ir(I) catalysed hydroarylation methodologies developed at Bristol. Investigations into the development of an asymmetric protocol to construct all-carbon stereocentres are also described.
Finally, in Chapter 6, the construction of challenging contiguous stereocentres is achieved through the hydroarylation of enantioenriched alkenes. The chemistry relies upon the use of an Ir(I) catalyst, modified with a chiral bisphosphite ligand. The stereochemistry of the ligand enables access to either the syn- or anti¬-diastereomers of the product in good yield and with high diastereoselectivity. The methodology provides an alternative to the prior art without need for prefunctionalised coupling partners.
Date of Award29 Sep 2020
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorJohn Bower (Supervisor)

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