Dissertation: “New Strategies for Transition Metal-mediated (Hetero)arene Functionalization”

Fredric Ingner defends his doctoral thesis entitled: “New Strategies for Transition Metal-mediated (Hetero)arene Functionalization” within the subject of Chemistry with a specialization in Organic Chemistry.

Opponent: Dr. Joanna Wencel-Delord, University of Strasbourg, France

Supervisor: Associate professor Lukasz Pilarski, Department of Chemistry - BMC, Organic chemistry

Abstract

This thesis describes new approaches to achieve efficient and selective (hetero)arene derivatization using transition metals. The main focus falls on the use of strategies based on C–H activation and organo-main group reactivity to render the synthesis of various (hetero)arene derivatives more direct, efficient, regioselective and sustainable. In the first two papers, transition metals are used to expedite the synthesis of aryne precursors and aryne capture products, as well as to influence the regioselectivity with which arynes may be made to react (Papers I and II). Paper I describes a new approach to the synthesis of aryne precursors from readily available arylboronic acids via a Ru-catalyzed C–H silylation protocol. The method tolerates a wide range of functional groups, affords access to new aryne motifs and only requires a single purification over multiple synthetic steps. Paper II explores how regioselectivity of aryne capture reactions can be enhanced significantly by remote cyclometallation using Ru, Rh and Ir. This work marks the first demonstration of exclusive regioselectivity in aryne capture reactions using only inductive electronic effects of a remotely substituted electropositive group.Papers III and IV concerns the synthesis of diverse aryl-AuI complexes under sustainable conditions. Paper III describes the use of a class of nucleophilic arylboronates, Ar-B(triol)K, to prepare aryl-AuI complexes in green solvents under ambient conditions without the requirement of exogenous additives or complex, expensive or time-consuming purification steps. This work is built upon in Paper IV where reaction solvents could be avoided altogether by employing a mechanochemical protocol and automated milling. The conditions developed allowed for C–H auration of various previously inaccessible (hetero)arenes and even the late-stage C–H auration of biologically active molecules. Both papers describe experiments performed to elucidate the intermediates and mechanism of C–H auration.

Link to the thesis in DiVA