Methods for C-C and C-N bond formation using earth-abundant metals

Abstract

The formation of C–C and C–N bonds via transition metal catalysis is important in both academia and industry. Traditionally, both these fields have been dominated by the use of precious metal catalysts, with two of the most prominent reactions being the Suzuki– Miyaura cross-coupling (C–C) and the Buchwald–Hartwig amination (C–N), both palladium-catalysed processes. The use of earth-abundant metals in C–C and C–N formation could increase the economy and sustainability of such processes, whilst also introducing potential alternative reactivity.

The Suzuki–Miyaura cross-coupling is an extremely popular method of C–C bond formation in industry.¹ The vast majority of investigation into this reaction concerns solely the palladium-catalysed process, however, the more abundant group 10 metal Ni has been shown to be proficient in this process, while also displaying access to an increased scope of electrophiles. Enclosed is a comparison of a nickel and palladium Suzuki–Miyaura cross-coupling using a comparable ligand system. The practicalities of changing to a nickel-catalysed system are discussed, as well as insights into mechanistic variances between the two systems.

The Chan-Lam amination is a copper promoted cross-coupling of amines and organoborons. Recently, there has been important disocoveries into the mechanism of the amination.² The following study discusses the serendipitous discovery of a debenzylative Chan–Lam amination. This novel transformation was investigated, examining the scope of reactivity, whilst also considering the mechanistic pathway via which the reaction proceeds.

The use of boron protecting groups is well known in the Suzuki–Miyaura cross-coupling,³ but not as well explored in the Chan-Lam amination. The following study demonstrates the use of MIDA boronates in the Chan-Lam amination. The methodology attempts to access products not currently available using Chan-Lam aminations and also explores the difficulties of using the MIDA boronates in these systems.

Date of Award	29 Jul 2020
Original language	English
Awarding Institution	University of St Andrews
Supervisor	Allan John Bell Watson (Supervisor)