α functionalization of carbonyl compounds via Brønsted and Lewis base organocatalysis

Abstract

This thesis describes the development of new methodologies promoted by bifunctional Brønsted basic H-bonding catalysis and Lewis basic organocatalysts. Chapter 2 describes the synthesis of novel chiral guanidines and their application as Brønsted and Lewis base catalysts in a variety of processes. Chapter 3 screens an array of Brønsted basic organocatalysts for the synthesis of trans-dihydrobenzofurans. A tertiary amine-thiourea bifunctional catalyst is used for an intramolecular Michael addition using keto-enones. The desired dihydrozofurans were obtained in excellent yield and with excellent diastereo- and good enantiocontrol. Chapter 4 describes the use of an isothiourea catalyst, HyperBTM, for the formal [2+2] cycloaddition between homohydrides and perfluorinated ketones to furnish β-lactones. The products were obtained in excellent yield and with excellent diastereo- and enantioselectivity. A large scope of 36 examples is reported. The derivatizion of the obtained β-lactones via ring-opening with a range of nucleophiles gave access to an array of β-hydroxycarbonyl compounds. Oxetanes could be accessed by a two step protocol, consisting of β-lactone reduction to give a diol, followed by cyclization. Chapter 5 describes a mechanic investigation on the isothiourea-catalysed formal [2+2] cycloaddition. A variable time normalisation graphical analysis method was used to determine the partial orders for anhydride, ketone and catalyst. The catalyst resting state was determined to be free catalysts by use of a fluorine-labelled catalysts.