Abstract
The field of dearomatization has seen steady development due to the ability of dearomatization methods to rapidly transform cheap and abundant aromatic feedstock molecules from topologically simple (i.e., flat) structures into architecturally complex scaffolds. A commonly used method for effecting dearomatization is the binding of an aromatic compound to a transition metal. The most common way “transition metal-mediated dearomatization” is achieved is with the use of electron-deficient transition metal fragments to coordinate aromatic substrates in a hexahapto- (η6) fashion. Upon η6-coordination of an aromatic to an electron-deficient transition metal fragment, electron density is polarized from the aromatic to the metal, activating the bound aromatic to nucleophilic attack.
The main goal of the Harman Laboratory has been the development of a complementary method in which aromatic molecules are dearomatized by their dihapto- (η2) coordination to an electron-rich transition metal fragment. The key bonding interaction in the η2-case is a filled metal t2g (dπ) → aromatic π* interaction (i.e., π-backbonding). This interaction disrupts aromaticity, leaving the uncoordinated π-bonds with character significantly resembling a free conjugated diene. Furthermore, the exceptional π-basicity of these electron-rich transition metal fragments increases the electron density of the uncoordinated π-bonds, thereby activating them towards electrophilic addition.
Of the η2-dearomatization agents developed by the Harman Laboratory, the tungsten fragment {WTp(NO)(PMe3)} ([W]; Tp = hydridotris(pyrazolyl)borate) can be generated on the largest scale, is the most economical in terms of starting material cost, has a commercially available precursor, and is the strongest π-base, making it the most activating. As a result, the Harman Laboratory has solely focused on developing the chemistry of the [W] system over the past five years.
An in-depth understanding of the reactivity patterns enabled by the η2-coordination of an aromatic to [W] is crucial if the full potential of this methodology in organic synthesis is to be realized. While the reactivity of [W]–(η2-benzene) toward tandem electrophilic/nucleophilic additions has been well-explored, the reactivity patterns of electron-rich aromatics (e.g., anisole) and certain N-heterocycles coordinated to [W] in an η2-fashion have been less well-developed. The purpose of this thesis therefore is to explore the reactivity of these systems with the goal of developing novel applications of η2-dearomatization in synthetic chemistry.
This dissertation focuses on three main projects. The first project details the synthesis of 3,6-disubstituted cyclohexenes from [W]–(η2-anisole) via a double protonation/triple nucleophilic addition strategy. The second project explores the formation of η2-bicyclo[2.2.2]octa-2,5,7-trienes (η2-barrelenes) via [W]-promoted Diels–Alder (DA) reactions of η2-coordinated anisoles with alkyne dienophiles, the isolation of the free barrelene ligands via their decomplexation, and the ability of [W] to facilitate retro-Diels–Alder (rDA) reactions of η2-barrelene ligands to provide skeletally modified anisoles and [W]–(η2-acetylene). Lastly, the third project highlights the structure and reactivity of [W]–(η2-acetylene), with a particular emphasis on a DA/rDA reaction sequence between [W]–(η2-acetylene) and 1,2,4,5-tetrazines. The structure and reactivity of the resulting η2-pyridazine complexes are likewise discussed.
