Azaphosphinines

Partner site with Johnson lab

In summer 2014 graduate student Chris Vonnegut accidentally discovered that treatment of an ortho-(arylethynyl)aniline with triphenylphosphite gave a class of heterocycles with contiguous nitrogen and phosphorus atoms. As shown in the figure below, the initial product of the cyclization reaction is the phosphaquinoline form (imidate, I). Subsequent hydrolysis affords the phosphaquinolinone form (amidate, A).

Since Chris’ discovery, we have been studying the structural and optical properties of these rarely-accessed scaffolds. The heterocyclic amidate core is structurally similar to coumarin and carbostyril, two well-studied fluorophores, with the difference being that the carbonyl in carbostyril has been replaced with an isolobal phosphonyl group. The structural similarities of the phosphaquinolinone scaffold to coumarin and carbostyril also extend to other features, including the highly tunable and substitution-dependent photophysical properties as well as the homodimerization seen in lactams.

These phosphorous-nitrogen heterocycles, which are properly named as azaphosphinines,  boast the benefit of containing a chiral center on the phosphorus atom (each dimer contains one R- and one S-enantiomer) and enhanced  homodimerization due to the highly polarized P=O bond. In addition, the tetrahedral center facilitates the selective binding of hydrogen sulfate, a typically difficult anion to host due to its geometry and combination of both hydrogen-bond donor and acceptors

Recent and ongoing work has focused on larger acene-expanded aniline derivatives as well as the inclusion of additional heteroatoms within the backbone to further modulate the photophysical and supramolecular capabilities of these fascinating heterocycles.

Relevant Publications

Azaphosphinines and Their Derivatives

J. N. McNeill, J. P. Bard, D. W. Johnson and M. M. Haley, Chem. Soc. Rev. 2023, 52, 8599-8634.
DOI: 10.1039/D3CS00737E

2‐λ⁵‐Phosphaquinolin‐2‐ones as Non-Cytotoxic, Targetable, and pH-Stable Fluorophores

J. P. Bard, S. G. Bolton, H. J. Howard, J. N. McNeill, L. N. Zakharov, D. W. Johnson, M. D. Pluth and M. M. Haley, J. Org. Chem. 2023, 88, 15516-15522.
DOI: 10.1021/acs.joc.3c01927

Impact of Internal Charge Transfer on the Photophysical Properties of Pyridine-Fused Phosphorus-Nitrogen Heterocycles

J. N. McNeill, M. A. Kascoutas, L. J. Karas, L. N. Zakharov, J. I.-C. Wu, D. W. Johnson and M. M. Haley, Chem. Eur. J. 2023, 29, e202203918.
DOI:10.1002/chem.202203918

Controlling Tautomerization in Pyridine-Fused Phosphorus-Nitrogen Heterocycles

Thionation of the 2‐λ⁵‐Phosphaquinolin‐2‐one Scaffold with Lawesson’s Reagent

Bard, J. P.; McNeill, J. N.; Warren, G. I.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Isr. J. Chem. 2021, 61, 217-221.
DOI: 10.1002/ijch.202000085

Bumpy Roads Lead to Beautiful Places: The Twists and Turns in Developing a New Class of PN-Heterocycles

Bard, J. P.; Johnson, D. W.; Haley, M. M. Synlett 2020, 31, 1862-1867.
DOI: 10.1055/s-0040-1707168

A highly fluorescent PN-heterocycle-fused pyrene derivative with strong self-dimerisation through hydrogen bonding

Bard, J. P.; Mancuso, J. L.; Deng, C.-L.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Supramol. Chem. 2020, 32, 49-55.
DOI: 10.1080/10610278.2019.1687896

Amplification of the Quantum Yields of 2-λ5-Phosphaquinolin-2-ones through Phosphorus Center Modification

Bard, J. P.; Bates, H. J.; Deng, C.-L.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. J. Org. Chem. 2019, 85, 85-91.
DOI: 10.1021/acs.joc.9b02132

PN-Containing Pyrene Derivatives: Synthesis, Structure, and Photophysical Properties

Deng, C.-L.; Bard, J. P.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Org. Lett. 2019, 21, 6427-6431.
DOI: 10.1021/acs.orglett.9b02332

Naphtho[2,1-e]-1,2-azaphosphorine-2-oxide Derivatives: Synthesis, Optoelectronic Properties, and Self-Dimerization Phenomena

Deng, C.-L.; Bard, J. P.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. J. Org. Chem. 2019, 84, 8131-8139.
DOI: 10.1021/acs.joc.9b00994

Exploiting the Hydrogen Bond Donor/Acceptor Properties of PN-Heterocycles: Selective Anion Receptors for Hydrogen Sulfate

C.-L. Deng, J. P. Bard, J. A. Lohrman, J. E. Barker, L. N. Zakharov, D. W. Johnson and M. M. Haley, Angew. Chem. Int. Ed. 2019, 58, 3934-3938.
DOI: 10.1002/anie.201814431

Synthesis, photophysical properties, and self-dimerization studies of 2-λ5-phosphaquinolin-2-ones

Bard, J. P.; Deng, C. L.; Richardson, H. C.; Odulio, J. M.; Barker, J. E.; Zakharov, L. N.; Cheong, P. H.-Y.; Johnson, D. W.; Haley, M. M. Org. Chem. Front. 2019, 6, 1257-1265.
DOI: 10.1039/C9QO00199A

Synthesis and Properties of Naphtho[2,3-e]-1,2-azaphosphorine 2-Oxides: PN-Anthracene Analogues

Takaesu, N. A.; Ohta, E.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Organometallics 2017, 36, 2491-2493.
DOI: 10.1021/acs.organomet.7b00281

Facile Synthesis and Properties of 2-λ⁵-Phosphaquinolines and 2-λ⁵-Phosphaquinolinones

Vonnegut, C. L.; Shonkwiler, A. M.; Khalifa, M. K.; Zakharov, L. N.; Johnson, D. W.; Haley, M. M. Angew. Chem. Int. Ed. 2015, 54, 13318-13322.
DOI: 10.1002/anie.201507696