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Thesis

Rh(III)-Catalyzed C-H Functionalizations as Strategies for Versatile Organic Building Blocks

Transition-metal catalyzed C-H functionalizations have impacted and changed synthetic approaches towards the construction of relevant complex molecules, comprising natural products, active pharmaceutical ingredients, and organic materials. This thesis describes the development of Rh(III)-catalyzed reactions via directed C-H functionalization and non-directed C-H functionalization. In this respect, acylated sulfonamides and N-sulfonyl ketimines were successfully employed as suitable directing groups, enabling directed C-H bond activation in the presence of a rhodium(III) catalyst. Subsequent migratory insertion of internal alkynes delivered a rich array of versatile benzosultams and chiral spirocyclic sultams, both of which are relevant structures in medicinal chemistry. Notably, the use of rhodium(III) complexes equipped with a suitable atropchiral cyclopentadienyl ligand enables enantioselective and high yielding access to the challenging spirocyclic sultam scaffolds. Complementary to the directed C-H bond functionalizations, application of Cp*Rh(III) complexes in non-directed C-H functionalization reactions have been disclosed. Specific applications of this challenging strategy include the synthesis of highly valuable polyarenes from completely unbiased arenes via double C-H activation, and subsequent addition of internal alkynes. This method provides a convenient handle to access highly substituted and highly soluble acenes, possessing valuable electronic and photo physical properties. Furthermore, non-directed C-H functionalization of electron-rich heterocycles was also developed. In this context, a Cp*Rh(III) catalyst enables a C2-selective activation of heteroarenes. Upon addition across an alkyne, a transmetalation to Cu(II) allows reductive C-O bond formation to deliver tetrasubstituted enol esters in a trans-selective fashion. A three-component coupling of heteroarenes, alkynes, and carboxylic acids was successfully demonstrated.

    Keywords: C-H Activation ; Asymmetric Catalysis ; Rhodium ; Alkyne ; Sultam ; Acene ; Enol Esters

    Thèse École polytechnique fédérale de Lausanne EPFL, n° 6929 (2016)
    Programme doctoral Chimie et Génie chimique
    Faculté des sciences de base
    Institut des sciences et ingénierie chimiques
    Laboratoire de catalyse et synthèse asymétriques
    Jury: Prof. Jérôme Waser (président) ; Prof. Nicolai Cramer (directeur de thèse) ; Prof. Jieping Zhu, Prof. Carsten Bolm, Dr Christof Sparr (rapporteurs)

    Public defense: 2016-2-26

    Reference

    Record created on 2016-02-23, modified on 2016-08-09

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