SYNTHESIS AND APPLICATION OF ORGANOBORON COMPOUNDS FOR CATALYTIC AMIDE FORMATION AND BIFUNCTIONAL CATALYSIS

Abstract

This thesis introduces the synthesis and application of alkyl- and aryl- boronic acids as catalysts for efficient bond formation. Specifically, this thesis mainly focuses on
heterogeneous direct amide formation catalysed by solid-phase arylboronic acid, kinetic resolution of asymmetric N-acylation by a novel binaphthalene boronic ester species, and pyrrolidine boronic acid-catalysed enantioselective nitro-Michael addition.
The review on reported catalytic direct amide formation, especially organoboron catalysed amidation, gave a general idea of current development on the accessible toolbox
towards amide bond construction. Investigation confirmed the existence of a reactive B-XB bridged species, playing an important role in catalysis. Meanwhile, with increasing
interest in solid-phase heterogeneous catalysis, a series of polymer-based catalysts have been prepared neat for amide formation. Some of them possess visible advantages in
reactivity, reusability and recyclability over the reported homogeneous catalysts, which raised attention to enhance the overall efficiency of amidation by solid-based arylboronic
acid. Careful synthesis gave polymerised catalyst in high conversion (showed in red in the figure above), which was crushed into fine powder for batches. Catalytic performance and recovery of catalyst were tested in batch. Further employment in flow revealed the potential of the designed polymer catalyst towards an improved performance by optimised reaction conditions. Apart from the polymer basis, research discovered the likelihood of biaryl scaffold in various types of catalysis. A brief review was given on the kinetic resolution, with focus on kinetic resolution of asymmetric N-acylation. As shown in blue in the figure, this thesis suggests an optimised strategy to the kinetic resolution of asymmetric amide formation by a novel system of axially chiral binaphthalene diboronate. It was based on our reported naphthyl diboronate system, including biphenyl-diboronate yet to publish. Under optimised methodology, initial attempt exhibited considerable enantioselectivity in high conversion.
Finally, we continued to look into other asymmetric catalysis. A review on current progress in bifunctional asymmetric was given, including a homoboroproline catalyst reported for catalytic aldol reaction via an enamine intermediate. It was believed that boronic acid coordinated the reaction with either its strong Lewis-acidic boron centre or its Brønsted acid site as H-bond donor. Further investigation on the proposed homoboroproline suggested reactivity in catalytic nitro-Michael addition (showed in black in the figure above). The optimised reaction condition enhanced the performance of such catalytic system, with up to 64% e.e. obtained in 99% conversion.