Development of Crown Ether Nucleophilic Catalysts (CENCs) and their Application in Rapid Fluorination of Silicon for PET Imaging & Diversification Reactions of γ-Silyl Allenyl Esters to All-carbon Quaternary Stereogenic Centers

In this dissertation, we discuss the development of new phase transfer agents, which are
capable of rapid fluorination of silicon. These are 18-C-6 derivatives containing a
hydroxyl group in the side arm (podand), also known as C-pivot lariats. The syntheses of
these lariats including several that have not been previously reported and their efficient
purification are described. The synthesis route leads to a robust and generalized approach
to obtain these lariats on the gram scale. These agents were initially designed for
applications in positron emission tomography (PET). In this medical imaging modality,
tracer agents containing silicon have found promising utility as fluoride receptors for
more rapid radiolabeling. Phase transfer agents are generally required for 18F-labeling due
to the low solubility in organic reaction media and reactivity of cyclotron-generated
[18F]potassium fluoride. We envisioned that 18-C-6 derivatives may serve as both phase transfer agents as well as
nucleophilic catalysts (CENCs). In this conception, CENCs were rapidly pre-complexed
with KF followed by silicon fluorination, which takes advantage of a previously
established silicon dianion mechanism. In collaboration with researchers at the NIH, we
studied the effect of various linkers connecting the metal chelating unit to the
nucleophilic hydroxyl group on the radiofluorination of silicon under mild condition. A
hydrolysis resistant aryl silicon fragment has also been developed that contains various
functional groups for convenient attachment to the potential PET radiotracer agents.
In a second project, we demonstrate the unique reactivity of γ-silyl allenyl esters. Taking
advantage of the silyl group as a fluoride acceptor, these allenoates readily underwent
addition to a variety of carbon electrophiles, including aryl fluorides, to afford all-carbon
quaternary centers bearing an ethynyl group. Surprisingly, in the presence of aldehydes,
exclusive bis-substitution occurs at the γ-position to afford the dicarbinol. Details relating
to reaction optimization and substrate scope for both the reactions are presented.
Dicarbinol allenes were subsequently converted to highly substituted δ-lactones, a novel
6-hydro-2-pyrone as single diastereomers.