N-heterocyclic carbenes in palladium-catalysed cross-coupling reactions

Abstract

PART I, CHAPTER II: APPLICATION OF [Pd(IPr*)(cin)Cl] IN CATALYSIS.
The direct S-arylation of unactivated aryl sulfoxides catalysed by [Pd(IPr*)(cin)Cl] (Scheme 1, 14) is described. Several arylmethyl sulfoxides were coupled to various halides in moderate to good yields (17 examples, 35 to 85%). The scope, the limitations of this methodology as well as the reaction mechanism are discussed.

PART I, CHAPTER III: [Pd(IPr)(cin)Cl] IN THE SUZUKI-MIYAURA REACTION USING A WEAK INORGANIC BASE and INSIGHT INTO THE REACTIVITY OF [Pd(NHC)(cin)Cl] (NHC = IPr, IPrꟲˡ and IPrᴮʳ) IN THE SUZUKI-MIYAURA REACTION.
N-Heterocyclic carbenes (NHCs) have been shown to be useful ligands for the Suzuki- Miyaura cross-coupling at low catalyst loadings. In the first section of this chapter, was investigated the development of a new methodology based on a commercially available and air-stable pre-catalyst [Pd(IPr)(cin)Cl] (Scheme 2, 41) under very mild conditions using a mixture of ethanol/water as solvent. This simple protocol allows the formation of various functionalised biaryls from aryl chlorides and boronic acids (37 examples, 49 to 99%) under air at low catalyst loadings. The method was also successfully scaled up to 10 grams.

In the second section of this chapter, three different pre-catalysts [Pd(NHC)(cin)Cl] with NHC = IPr, IPrꟲˡ and IPrᴮʳ (Scheme 3, 41, 100 and 101) were studied in the Suzuki-Miyaura reaction aiming to understand and improve the existing catalytic activity of [Pd(IPr)(cin)Cl] (41). In the course of this work, [Pd(IPrꟲˡ)(cin)Cl] (100) and [Pd(IPrᴮʳ)(cin)Cl] (101) were prepared using the acetone/potassium carbonate route and were fully characterised. The computational study of the activation pathway of the pre-catalysts was described. The catalytic activity was also assessed in an extensive scope with over 80 entries (33 examples, 0 to 99%).

PART II: PALLADIUM CROSS-COUPLING REACTION TOWARDS THE COMPLETION OF LEIODOLIDE A.
In 2006, Leiodolide A (Figure 1, 7) was isolated from the newly discovered Leiodermatium sp. In regard to its cytotoxicity and its structure with undefined stereocentres, the total synthesis of this molecule was found to be of interest. Herein is reported different methodologies assessed to perform a C(sp²)-C(sp³) cross-coupling reaction with a model system consisting of an alkyl chain and an oxazole moiety. Simultaneously, the synthesis of the northern fragment was carried out to support the results obtained from the preliminary study and on-going synthetic efforts.

Date of Award	7 Dec 2017
Original language	English
Awarding Institution	University of St Andrews
Supervisor	Gordon John Florence (Supervisor) & Steven Patrick Nolan (Supervisor)