61st Annual Report on Research 2016

A. Specific Aims

The aims in the original application remain the same and have not been modified. Our goal is to determine the role of thermally-activated heavy-atom tunneling (TAHAT) in the cycloaromatization reactions of hydrocarbons yielding diradicals, namely (1) α,3-didehydrotoluene, (2) fulvenyl diradical, and (3) 1,5-didehydroindene. Thus far, we have successfully obtained quantitatively and qualitatively accurate descriptions of the cycloaromatization of (1) and (2). We have developed theoretical methodology including computer code to provide accurate vibrationally adiabatic ground-state curves for the formation of α,3-didehydrotoluene and fulvenyl diradical to determine the magnitude of thermally activated heavy-atom tunneling. Progress has been been made toward determining of the contribution of tunneling in cycloaromatizations leading to (3) 1,5-didehydroindene.

B. Studies and Results

A considerable fraction of the objectives in Aims #1, #2 and #3 were met in the first 2 years of the grant. The innovative potential of the project remains the same as was stated in the original application. We have computed and can accurately reproduce experimentally-derived thermochemical data for the cycloaromatization yielding α,3-didehydrotoluene and fulvenyl diradical. Our methodology has enabled the determination of thermally activated heavy-atom tunneling in reactions leading to α,3-didehydrotoluene and fulvenyl diradical. In collaboration with Dr. Charles Doubleday (Columbia University) a manuscript is in preparation on contribution of carbon atom tunneling on cycloaromatization leading to α,3-didehydrotoluene and contrasting it against fulvenyl diradical to be submitted for publication by the and of 2016.

Recently, we published a review article, in which quantum tunneling was discussed in the temperature range normally used to carry out C-C, C-N bond forming reactions, and hydrogen-atom transfer reactions, ca. -78 °C and higher. This work is based on recent studies and suggests that tunneling is widespread at typical reaction temperatures. This work has appeared in Tetrahedron.

Schematic illustration of tunneling in carbon-carbon and carbon-nitrogen bond formations, and hydrogen-atom transfer.

Since the beginning of the ACS PRF UR4 grant, 5 papers have been published. A book chapter "Overview of Computational Methods for Organic Chemists " in the book "Applied Theoretical Organic Chemistry" (D. Tantillo, ed.) has been submitted for publication as well. One of the papers has appeared in the Journal of Organic Chemistry in 2016 and described nitrogen-atom inversion and conformational inversion in enantiomerization of 1H-1-benzazepines. In 2015, a manuscript that described the detection of an oxygen-atom photoexchange process of N-nitrosamines, which may provide a clue to new factors significant in nitrosamine phototoxicity, was published also the Journal of Organic Chemistry. A paper was published Tetrahedron Letters in 2015 and described a unique oxidative ring-contraction of 3H-1-benzazepines to quinoline derivatives. Another manuscript has appeared in in the Journal of Physical Organic Chemistry that described the Bergman cyclization of an enediyne fused to a butylated hydroxytoluene (di)radical scavenger. This computed reaction was unique in not only reaching diradial intermediate but also a quinone methide intermediate.

In summary, the above papers published and in preparation describe tunneling, study planar chirality, and chemistry of reactive intermediates including diradicals and peroxy nitrosamines.

C. Significance

Years 1 and 2 has resulted in proof-of-concept data for our project on thermally activated tunneling in reactions. In addition to the impact on fundamental understanding of chemical reactivity and C-C bond formation, this research grant has had a significant effect on my career. Importantly, the PRF grant support has allowed my research group to collect critical data used in the presentations of an invited talk entitled Mechanistic Studies of Diradicals and Oxygen Exchange Processes at the Gordon Research Conference (GRC) on Physical Organic Chemistry in Holderness, New Hampshire on June 24, 2015. In addition, I was delighted to give an invited talk entitled The Discovery of the Bergman Cyclization Reaction and How It Impacted My Research Direction and Career and to chair a session honoring Professor Robert Bergman at the 35th Reaction Mechanisms Conference (RMC) at the University of California at Davis on June 23, 2014.

Furthermore, this research grant has had a significant impact on students in my group at Baruch College. It has provided my students with the opportunity to carry out computational research and collect results that earned them the first and the second prize at the 17th and the 18th Annual Undergraduate Research Symposium in the Chemical and Biological Sciences, University of Maryland, Baltimore County (UMBC) in 2014 and 2015. Two students had delivered oral presentations at the 250th American Chemical Society National Meeting & Exposition, Boston, August 16-20, 2015. Additionally, two students had given oral presentations at the 63rd Annual Undergraduate Research Symposium of the American Chemical Society at Queensborough Community College, on May 9, 2015. In summary, seven students have participated in the research project outlined in the grant thus far. One of the students, Anastasiya Badziai, was recently accepted to dental school at the University of Connecticut. Student, Kitae Kwon and Jade Marino Creto (currently in Brazil), have been in process of preparing to apply to Ph.D. programs in chemistry.

D. Plans

We will continue to address the Specific Aims in the next year of support, and will utilize our developed methodology to address contributions of tunneling in cycloaromatization reactions leading to 1,5-didehydroindene.