title: Hydrogenation and dehydrogenation with cyclometalated iridium (III) complexes
Creators: name: Talwar, Dinesh
Publisher: name: University of Liverpool Repository
Year: 2015

description: The selective hydrogenation and dehydrogenation of organic molecules is a fundamentally challenging and an attractive transformation for both, industry and academia. However, catalysts capable of undergoing both transformations under environmentally benign conditions are rare. In this thesis, our contribution to the development of a “universal” catalyst capable of achieving both hydrogenation and dehydrogenation of a wide range of organic compounds under mild conditions is presented. A general introduction covering the recent developments in the area of transfer hydrogenation of C=X (X = O, N) bonds, relevant applications of cyclometalated half-sandwich complexes and previous work in the area developed within our group is described in Chapter 1. In Chapter 2, Cyclometalated iridium complexes are shown to be highly efficient and chemoselective catalysts for the transfer hydrogenation of a wide range of carbonyl groups with formic acid in water. Examples include α-substituted ketones (α-ether, α-halo, α-hydroxy, α-amino, α-nitrile, α-ester), α-keto esters, β-keto esters, and α,β-unsaturated aldehydes. The reduction was carried out at substrate/catalyst ratios of up to 50000 at pH 4.5, requiring no organic solvent. The protocol provides a practical, easy and efficient way for the synthesis of β-functionalised secondary alcohols, such as β-hydroxyethers, β-hydroxyamines and β-hydroxyhalo compounds, which are valuable intermediates in pharmaceutical, fine chemical, perfume and agrochemical synthesis. In Chapter 3, the cyclometalated iridium complexes are shown to catalyse the transfer hydrogenation of various nitrogen heterocycles, including but not limited to quinolines, isoquinolines, indoles and pyridiniums, in aqueous solution under mild conditions. The catalyst shows excellent functional group compatibility and high turnover number (up to 7500), with loading as low as 0.01% being feasible. In Chapter 4, cyclometalated iridium complexes are found to be versatile catalysts for the direct reductive amination of carbonyls to give primary amines under transfer hydrogenation conditions with ammonium formate as both the nitrogen and hydrogen source. The activity and chemoselectivity of the catalyst towards primary amines is excellent, with a substrate to catalyst ratio of 1000 being feasible. Both aromatic and aliphatic primary amines were obtained in high yields. Moreover, a first example of a homogeneously catalysed transfer hydrogenative direct reductive amination (DRA) has been achieved for -keto ethers, leading to the corresponding -amino ethers. In addition, non-natural -amino acids could also be obtained in excellent yields with this method. Following the success of hydrogenation, cyclometalated iridium complexes were also found to be versatile catalysts for the oxidant-free, acceptorless dehydrogenation of various N-heterocycles, including tetrahydroquinolines, tetrahydroisoquinolines, tetrahydroquinoxalines and indolines. This protocol was also successfully applied to the total synthesis of alkaloids as presented in Chapter 5. Chapter 6 describes the development of a new strategy for the oxidant- and base-free dehydrogenative coupling of N-heterocycles at mild conditions. Under the action of an iridium cyclometalated catalyst, N-heterocycles undergo multiple sp3 C-H activation, generating a nucleophilic enamine that reacts in situ with various electrophiles to give highly functionalised products. The dehydrogenative coupling can be cascaded with Friedel-Crafts addition, resulting in double functionalisation of the N-heterocycles. The dehydrogenation products could also be saturated under either hydrogenation or transfer hydrogenation conditions, giving rise to structurally diverse products. Final conclusion and perspectives of the research covered in this PhD thesis are presented in Chapter 7.