Reports: UNI453797-UNI4: Investigating the Mechanism of Aryl-Alkyne Cyclization of Azaborine Containing Aromatics

Eric H. Fort, PhD, University of St. Thomas

Our grant aimed to understand the mechanisms of aryl-alkyne ring-closure for molecules containing boron-nitrogen (azaborine) bonds. In previous work, attempting to improve the synthesis of BN-pyrene, we found that we could induce an alkyne cyclization at relatively low temperatures without the presence of a catalyst. 1 This type of transformation is highly endothermic in the parent hydrocarbons. It was proposed that either low temperature carbene formation or electrocyclic closure could lead to improved routes to a number of azaborine bond containing polycyclic aromatic molecules. The mechanism had not been studied with azaborine molecules, and the low-temperature effect appears to be unique these systems. Through isotopic labeling and computational studies, we have been able to gain new insight into this unique closure.

During the first year of our funding we were able to develop an efficient method for isotopic labelling, synthesize isotopically labeled BN-pyrene, and begin computations to confirm our mechanistic hypothesis.2 We discovered that not only did the mechanism differ from the process found in the hydrocarbon, but it also was drastically lower in energy.3 We then spent the second year finishing that work and designing new molecules capable of harnessing this mechanism. The pursuit of new molecules lead us to the discovery of a novel ring closing pathway to aromatic azines. This past year with the extension of our funds, we have shown the new pathway to be very versatile in making molecules, and we hope to investigate the mechanism further.

With subtle changes to reaction conditions, we divert a double cross coupling to produce fused aromatic molecule acridine. There is no precedent for this mechanism, so we were able to demonstrate that it works with a wide variety of terminal alkynes. We hope to use this pathway to apply for future funding as it holds the unique opportunity to build molecules larger than acridine. We also plan on probing the mechanism further to try to make it more efficient.

As this was our extension year, the grant supported one student working on this project. The student presented her work at the National Meeting of the American Chemical Society in San Francisco last spring. She is currently applying to graduate programs and will be graduating in the spring of 2018.

We continue to pursue results related to the new molecules and mechanisms with support from my department. I plan on submitting a grant application related to this work this fall. The support of the Petroleum Research Fund has been vital to setting the foundational work in my laboratory and I will continue to build on that foundation for years to come.


Underline indicates undergraduate author:

1. Wadle, J. J.; McDermott, L. B.; Fort, E. H. Microwave assisted synthesis of 10b-aza-10c-borapyrene. Tetrahedron Lett. 2014, 55, 445-447.

2. Gelinas, B. S.; Jaye, J. A.; Mattos, G. R.; Fort, E. H. Rapid and efficient desilylation and deuteration of alkynylpyridines. Tetrahedron Lett. 2015, 56, 4232-4233.

3. Jaye, J. A.; Gelinas, B. S.; McCormick, G. M.; Fort, E. H.” Implications of the final ring closure to 10b-aza-10c-borapyrene for aryl–alkyne ring-closing mechanisms” Canadian Journal of Chemistry, 2017, 95, 357-362.