Metallocenes in Regio- and Stereoselective Synthesis

Densely substituted cyclopentadienes and pentafulvenes are important compounds because these compounds serve as versatile precursors of metallocenes that show high activity in valuable catalytic transformations. For example, half-sandwich metallocenes of late transition metals, such as rhodium, iridium, and cobalt, are highly active catalysts for the C–H bond functionalization. As the structural modification of cyclopentadienyl ligands on the metallocenes improves catalytic efficiency and selectivity, the development of new methods for the synthesis of substituted cyclopentadienes and pentafulvenes is highly important. In this chapter, the synthesis of highly substituted cyclopentadienes and pentafulvenes and their application to the synthesis of half-sandwich metallocenes of late transition metals are described.

Cyclopentadiene and its substituted congeners have played an important role in organic chemistry since their discovery. Cyclopentadienyl and substituted cyclopentadienyl anions constitute currently a very important class of ligands for transition metal compounds. Cyclopentadienyl ligands in the respective metallocene complexes show usually high chemical inertness and stability. This property makes the metallocenes popular and indispensable catalysts in a plethora of organic transformations. This review focuses on development of synthetic pathways for preparation of selectively 1,2-disubstituted cyclopentadienes and their conversion to a wide variety of metallocenes. Application of 1,2-disubstituted metallocenes in catalytic processes is mentioned as well.

Chiral cyclopentadienyl groups and their respective metal complexes have been studied for several decades. However, it is only in the last decade that this field has gained significant momentum, primarily through the introduction of chiral C2-symmetrical 1,2-cyclopentadienes and unsymmetrically substituted chiral 1,2-cyclopentadienes and indenes as precursors for chiral complexes, especially those involving late transition metals. The utilization of chiral C2-symmetrical cyclopentadienyl (Cp) ligands allows for the circumvention of diastereomer formation upon complexation with the desired transition metal center. This is particularly advantageous for unsymmetrically substituted ligands, which often necessitate tedious racemate separation. In all cases, a multi-step synthesis is required, depending on the nature of the chiral backbone. Unsymmetrically substituted Cp rings can bypass the need for a multi-step synthetic approach but generally require the separation of racemates to obtain enantiomerically pure metal complexes. An alternative method involves conjugating achiral Cp-metal complexes to a carrier molecule, which enables the insertion of the conjugate into the active center of an enzyme protein hull. This approach establishes a chiral environment for asymmetric transformations. The resulting metal complexes find extensive applications in C-H functionalization reactions, as well as various cycloaddition reactions.

Due to its intrinsic beauty and unique properties, bis(η⁵-cyclopentadienyl)iron or ferrocene continues to attract the attention of chemists even after seven decades from its discovery. One of the particularly attractive and active fields is the preparation of planar-chiral ferrocene derivatives, which found manifold use as auxiliary ligands in enantioselective transition metal catalysis and organocatalysis. This chapter briefly illustrates the historical context and recent trends in this area, paying particular attention to the development of synthetic routes leading to planar-chiral ferrocenes.

The catalytic capabilities of Knölker-type complexes, mostly in the context of (transfer) hydrogenation chemistry, have been intensively studied during the past two decades. This happened mainly in response to the popular request for superseding catalysts that rely on scarce and expensive platinum group metals (PGMs). Indeed, the excellent abundance, very low price, and non-toxicity of Fe render these peculiar organoiron compounds ideal candidates for that purpose. The great structural malleability owing to their modular architecture further adds to the benefits of Knölker-complex-derived catalysts. Moreover, owing to their beneficial redox properties, these cyclopentadienone-tagged Fe complexes are also apt for usage in hydrogen autotransfer (hydrogen-borrowing) reactions. This fact opens up new vistas for atom-efficient and low-waste syntheses of a broad array of amines and more elaborated, pharmaceutically relevant heterocycles. However, the most important trait of Knölker-type complexes is their accessibility to chiral modification upon adjustment of the ligand framework which often encompasses the introduction of planar chirality or C2 symmetrical motifs. Furthermore, the pertinent Fe catalysts are amenable to pairing with enantiopure Brønsted acids such that dual catalysis becomes possible. Hence, promising approaches exist which might enable challenging and highly rewarding asymmetric (transfer) hydrogenation reactions that are effected by Fe complexes.

This chapter provides a brief overview of chemical transformations or syntheses mediated or catalysed by complexes of group 4 elements containing cyclopentadienyl and related ligands. Particular attention has been devoted to selectivity in a broad sense. While the text attempts to take a wider perspective, it focuses on selected recent trends and developments that fall approximately within the last decade (2013–2023). Covered topics comprise new approaches to the synthesis of chiral group 4 metallocenes, radical catalysis with Ti(III) species, photoredox catalysis with group 4 complexes, C–C bond formation and cleavage utilising low valent metallocenes, reactions involving hydro- and carbometallation steps, recent trends in polymerisation catalysis, and several other examples demonstrating the utility of early transition metals in organic synthesis.

The history of cyclopentdienyl complexes (or cyclopentadienyl salts) has been spanning already for more then 70 years and they have been always considered as typical representatives of truly manmade molecules. Although compounds possessing the cyclopentadiene scaffold have been isolated and characterized, those possessing the cyclopentadienyl anion have been avoiding discovery for a long period of time. Nonetheless, since the isolation of juglorubin in 1993, the family of naturally occurring compounds possessing the cyclopentadienyl anion is steadily growing. This review aims to give an overview of the current state of the art in this area.

The chapter deals with yet another type of natural compounds incorporating diazo cyclopentadienyl moiety. Natural diazofluorenes involving monomeric kinamycins as well as dimeric lomaiviticins count a few dozen members only, yet their stucture elucidation and synthesis reads like a thriller. Significant structure corrections that were enforced by discrepancies in properties of the natural and synthesized compounds have had a great impact on their total synthesis. This review covers the synthesis of the compounds in the period 2011–2021.