New Chemical Reaction for Generating Benzynes


Description of figure: An example of a hexadehydro-Diels-Alder cascade (1 to 3). Simple triyne substrates like 1 cycloisomerize to reactive benzyne intermediates like 2, which are then captured by various trapping agents (in this example, an internal silylether) to produce structurally complex benzenoid products like 3.

The research group of Professor Thomas Hoye (Chemistry) uses MSI for their investigations of the thermodynamics of reactions involving the highly reactive organic species benzyne. Benzynes (cf. 2 in graphic above) are widely studied because their reactions with other chemical substances are very useful. The resulting compounds (cf. 3, “benzenoid products”) are useful in the development and synthesis of pharmaceutical drugs, agrochemicals, dyes, and polymers.

Related to this work, the Hoye group recently published some interesting and unexpected results in the prestigious journal Nature. This paper describes the generality of a fundamentally new reaction: the hexadehydro-Diels-Alder reaction (“The Hexadehydro-Diels-Alder Reaction,” Nature, DOI: 10.1038/nature11518, 2012). This chemistry generates ortho-benzyne by a simple metal- and reagent-free thermal cycloisomerization of a triyne precursor (cf 1). This is important because metals and other reagents can affect the subsequent chemical trapping reactions of the benzyne (e.g. 2 to 3). Many new types of reactions have been discovered with this new strategy for benzyne synthesis. These are both synthetically useful and mechanistically interesting.

The group is now using MSI to understand these new reactivities from the computational perspective. They are using density functional theory (DFT) calculations to study both the thermodynamics and the transition structures of various stages of the overall process. They don’t yet completely understand the mechanism of the hexadehydro-Diels-Alder reaction itself, and the DFT calculations are being used to complement the group’s experiments. One main goal is to determine whether the reaction is stepwise (cf. 4b), proceeding through diradical intermediates (as has been suggested in other systems) or concerted (cf. 4a, which is suggested by experiments). If the reaction is, in fact, concerted, it will be compatible with radical-sensitive substrates, which increases the overall synthetic utility. Similar questions about the concerted (cf. 5a) vs. stepwise (cf. 5b) nature of the benzyne trapping steps (cf. 2 to 3) are also being explored through computation.

Other articles about this research have appeared in Chemical and Engineering News and the Department of Chemistry’s website.

See all Research Spotlights