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The Tungsten-Promoted Dearomatization and Ring-Opening of Pyridine9 views
Author
Taylor, Caleb, Chemistry - Graduate School of Arts and Sciences, University of Virginia0009-0009-7237-227X
Advisors
Harman, Walter, AS-Chemistry (CHEM), University of Virginia
Abstract
In the development of pharmaceuticals, one of the most common cores is the 6-membered nitrogen-containing heterocycle, piperidine. Due to the ubiquity of piperidine in alkaloids, methods of dearomatization and functionalization of the nitrogen-containing 6-membered aromatic ring, pyridine, are highly sought after. These dearomatization techniques often progress through the partially saturated intermediates of dihydropyridine and tetrahydropyridine. The Harman laboratory has explored the dearomatization and functionalization of pyridine through dihapto-coordination (η2) to an electron-rich tungsten fragments, [W(Tp)(NO)PMe3)] (Tp = trispyrazolylborate, NO = nitrosyl, PMe3 = trimethylphosphine, W(Tp)(NO)PMe3) = [W]) . The π-backbonding of the [W] complex donates electron density into the pyridine ligand, stabilizing positive charges and allowing for the addition of nucleophiles and electrophiles. The dearomatization and functionalization of pyridine via coordination to the [W] complex has previously been demonstrated to allow for Diels Alder reactions and the addition of nucleophiles and electrophiles to the carbon atoms of the pyridine ring, producing substituted dihydropyridines and tetrahydropyridines. Additionally, η2-coordination to the [W] complex has previously been shown to promote ring-opening of pyridine to form azatrienes. Herein, η2-dearomatization via the [W] complex is demonstrated to guide the selective protonation and deuteration of tetrahydropyridine, promote the ring-opening of tetrahydropyridines, halt an alternative Zincke-reaction, and direct the formation of substituted multicyclic systems from pyridine.
Taylor, Caleb. The Tungsten-Promoted Dearomatization and Ring-Opening of Pyridine. University of Virginia, Chemistry - Graduate School of Arts and Sciences, PHD (Doctor of Philosophy), 2025-11-20, https://doi.org/10.18130/4zn5-e484.
