A Study of the Asymmetric Synthesis and Transformations of Chiral Ferrocene-containing Compounds

Ferrocene is an organometallic compound that serves as a versatile scaffold in transition metal catalysis, medicinal chemistry, and organocatalysis. The synthesis of novel enantiopure ferrocene-containing compounds has become a prominent area of research. This PhD thesis explores the role of ferrocene in organic chemistry, highlighting its remarkable properties and applications. Additionally, this thesis examines the concept of chirality and the importance of asymmetric synthesis, with a particular focus on the development of novel ferrocene containing compounds. Following on from this, the asymmetric synthesis of an enantiopure planar chiral ferrocenyl monoketone is described. The planar chirality of the ferrocenyl monoketone was utilised to synthesise a diverse array of planar and centrally chiral tertiary α-ferrocenyl alcohols. The dehydroxylation of the tertiary α-ferrocenyl alcohol afforded an α-ferrocenyl tertiary carbocation, which appears as a common intermediate across three subsequent projects presented in this thesis. The unique reactivity and conditional stability of the α-ferrocenyl tertiary carbocation was exploited for the diastereoselective syntheses of three distinct classes of products. Firstly, the synthesis of a range of β-ferrocenyl alcohols via an acid/HFIP-mediated stereoinversion of the α-ferrocenyl chiral centre is described, underscoring the stability of the ferrocenyl carbocation in the appropriate reaction conditions. Conversely, the instability of the same α-ferrocenyl carbocation was revealed in the unexpected diastereoselective synthesis of novel tricyclic indenes. The di-C-H functionalisation of a charged ferrocenyl intermediate resulted in the deprotection of the organic fulvene ligand and a loss of iron. Further investigation of this unprecedented reaction resulted in the preparation of a variety of tricyclic indenes in moderate yields and enantioselectivities. Finally, the extraordinary reactivity of the α-ferrocenyl carbocation was showcased in the first reported diastereoselective synthesis of chiral α-ferrocenyl tetraarylmethanes. The Lewis acid-catalysed arylation of the ferrocenyl alcohols with suitable heteroaromatic nucleophiles afforded novel, enantiopure, spherical ferrocene-containing tetraarylmethanes in excellent yields. Mechanistic rationale is provided for the formation of each diverse product. The stereochemistry of the novel compounds described in each project was confirmed using X-ray crystallographic analysis.