61st Annual Report on Research 2016

INTRODUCTION

This report documents progress in proposed research activity made by the PI during the first year of the award duration. The aim of the originally proposed work was to devise means for affecting photo-heterodimerization reactions between alkenes. As alkenes are prevalent in petroleum crude and in byproducts resulting from the refining process, it was rationalized in the proposal that understanding their photochemical reactivity would be of value in the refining process as well as discovering new uses for the byproducts. Alkene photo-heterodimerization – dimerization between two different alkenes – is especially more important in this context as there are very few examples in literature. It is known that alkenes predominantly yield photo-isomerization product(s) upon irradiation (scheme 1 in original proposal). Photodimerization is efficient when the reacting alkenes are (one excited and other in ground state) in close proximity.

RESEARCH FINDINGS

We proposed to use cavitand-mediation approach, a photodimerization strategy originally developed and currently explored in our group, to direct heterodimerization between two different alkenes. Cavitand-mediation approach involves encapsulating reacting alkenes within a macrocycle (in this case, cyclodextrin) and subjecting them to photoexcitation; the strategy proposed for heterodimerization involved taking advantage of the attractive/repulsive non-bonding interactions between alkenes, wherein size and/electronic complementarity between two reacting alkenes could used to form the hetero complex ( hetero complex = 1:1:1 arrangement = γ-cyclodextrin:alkene A:alkene B). Photoexcitation of the alkenes thus formed will result in photo-heterodimerization.

In the course of the last one year we had explored the proposed hetero-photodimerization reactions, as well as well as several additional homodimerization to understand the outcomes of the hetero-dimerization reactions better. We explored four of the alkene pairs originally proposed in the grant application, which are based on size and/or electronic complementarity. The experiments were performed as outlined in the proposal. The NMR spectra of the reaction mixtures showed that the photodimers were the major product in all the reactions, as predicted originally. The product distributions, however differed significantly. Alkene pairs A and B yielded heterodimer(s) as the major products, while pairs C, and D yielded homo dimers as the major products. The heterodimers from alkene pairs A and B were isolated and characterized. The NMR spectra of these reaction mixtures indicate syn H-H stereochemistry. Alkene pairs C and D yielded homodimers exclusively despite the steric and electronic complementarity respectively. We were intrigued by these results and delved further to understand origins of these selectivity.

For alkene pair C three products were observed: syn H-H dimer of the carboxylic acid, and equal amounts of syn H-H and anti H-T dimers of the ester. Cinnamic acid (CA) derivatives have yielded only the syn H-H dimer thus far; the formation of anti H-T dimer from the ester suggested that steric interaction between the methyl groups favored the corresponding precursor (head to tail) arrangement, leading us to realize that selectivity in CA homodimerization could be directed through steric interaction. We explored this understanding further by increasing the steric bulk of the alkyl group from methyl, to ethyl and isopropyl.

As expected the increased steric interaction favored the anti H-T arrangement exclusively leading to selectivity completely in favor of the corresponding photodimer. Encouraged by this finding, that the cavitand-mediation approach could now be useful in used to reliably and selectively produce the anti H-T and syn H-H dimer on demand, we explored more CA derivatives with diverse set of ester functionalities. In addition to studying these reactions in γ-CD, we also explored the reactions in 2-hydroxy propyl-γ-CD as well. The findings were published in the New Journal of Chemistry earlier this year (Nga, Clements, Pattabiraman, 2016). Furthermore, the characteristics of the complexes and structural features were explored computationally and through time-dependent studies.

In addition to already encountering a new aspect to the controlled photodimerization of CA it was interesting for us to note that all the reactions performed in this work proceeded to near-complete conversions. Our computational chemistry investigation suggest that a small fraction of the alkenes should be complexed such that the alkene bonds remain in a criss-crossed fashion, which is thought to be either a non-reacting conformation, or should result in additional set of dimeric products through a hula-twist mechanism. We believe that our published work has opened up the doors for studying photodimerization reactions in a new light, potentially, as the cavitand mediation methodology offers the means to study alkene chemistry in a more controlled fashion. Finally, the selectivity in hydroxy-CA-trifluoromethyl-CA pair is now understood to be due to the halogen-halogen interaction (between TFM groups), which is more attractive than the charge-transfer interaction.

SCHOLARLY PRODUCTIVITY AND DISSEMINATION

Findings from the work funded through the PRF grant resulted in one publication in a Royal Chemical Society journal (New Journal of Chemistry, 2016) earlier this year with undergraduate students; PRF support was acknowledged. The results were presented as research talks on three occasions in research conferences (2015 ACS MWRM, 2 talks at 2016 Nebraska Academy of Sciences); two of the talks were presented by the lead undergraduate student working (Nga Nguyen) in this project. In addition, I have been invited to present these findings in the 2017 Inter-American Photochemical Society meeting to be held in Sarasota, FL.

The photodimers synthesized in this project are structurally analogous to incarvillateine – active ingredient in Chinese pain relief herb. The PRF support has offered opportunity to collaborate with a pharmacologist to test the antinociceptive properties of the synthetic analogs we produce in our group. We are currently preparing an NIH-RO3 grant to seek funding for this project.

CLOSING STATEMENT

We have explored alkene pairs for heterodimerization reaction; two pairs yielded heterodimers and the other two yielded homodimers. These reactions provided insight into the structural and electronic factors that influence bimolecular excited-state reactivity of alkenes. Our research productivity was translated into one publication and four talks.