Catalytic Redox Neutral Cascade Alkylations with Alcohols

• Main Author: Lofberg, Christian
• Published: University of Leeds 2007
• Subjects: 541.39
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.486335

This thesis is divided into three main parts: Introduction, Results and Discussion and Experimental. The introduction (Chapter 1) reviews transition metal catalysed 'Redox Neutral' Hydrogen Autotransfer Processes where both the hydrogen donor and the hydrogen acceptor are incorporated into the final or target molecule, e.g. utilisation of alcohols as e1ectrophiles III C-N and C-C bond form~tions. The review also gives a brief introduction to the Meerwin-Ponndorf-Verley (MPV)-reduction and the reverse Oppenauer oxidation together with their modern transition metal catalysed versions and their mechanisms. The Results and Discussion section details the author's own work -and is divided into four Chapters: Chapter 2 describes the development of a highly efficient iridium catalysed selective monoalkylation cascade of arylacetonitriles with primary alcohols to afford a-alkylated nitriles in 67-93% yield. It was further demonstrated that such processes can'be achieved by conventional or microwave heating and that bis- and trisprimary alcohols are also processed efficiently. The mechanism was studied using deuterium labelled substrates and mechanism proposed. Chapter 3 describes the investigation of other activated methylene pronucleophiles such as 1.3-dimethylbarbituric acid which successfully undergoes selective mono C5alkylation with a variety ofalcohols under both conventional and microwave heating. Chapter 4 describes investigations into an uimsual C5-autoxidation process of the C5- , , monoalkylated barbiturates and its development into a novel iridium catalysed sequential one-pot C5-alkylation f.hydroxylation cascade of 1,3-dimethylbarbituric acid and alcohols giving the corresponding tertiary alcohols in 49-83% yield. The oxidation process is believed to involve singlet oxygen and shows interesting additive effects. Chapter 5. describes the successful extension 'of the iridium catalysed alkylation cascade into a novel bimetallic sequential one-pot Ir(III) / Pd(O) catalysed process which gives easy access to compounds of high molecular complexity from simple starting materials. This highly atom economic cascade involves the formation of three new C-C bonds, one tetrasubstituted carbon centre, one spirocyclic ring and one di- or trisubstituted exocyclic alkene regio- and stereoselectively. Chapter 6 (Experimental) contains full experimental details of the author's own work, together with appropriate physical, spectroscopic and analytical data for all new, compounds.