The Anhydride-HDDA Reaction and Further Expansion of Hexadehydro-Diels–Alder-based Reaction Methodologies

Abstract

Since its serendipitous rediscovery in 2012, the hexadehydro-Diels–Alder (HDDA) reaction has served as a means of generating benzyne in situ via cycloisomerization of poly-yne precursors under thermal or photochemical conditions. This allows for the formation of complex benzenoid products in a single reaction step upon trapping of the insipient aryne. Aside from more fundamental mechanistic studies, my contributions to this science have fallen into three broad areas: i) formation of N-heterocycles, ii) single-step synthesis of functional materials, and iii) generation of HDDA benzynes at ambient conditions. The first area has seen extensive exploration by our lab and others; however, the latter two categories, especially the third, are still revealing interesting contemporary novelties. In my initial work, I found that trapping of HDDA benzynes with C,N-diarylimines led to a reversal in reactivity with respect to the case of classical benzynes, furnishing acridine, as opposed to phenanthridine, products (Chapter 2). Next, I trapped HDDA benzynes with arylhydrazines to form azoarenes. I then recognized that simple azobenzenes could also trap HDDA benzynes in a binary fashion that could be toggled photochemically (Chapters 3 and 4). A fundamental investigation into trapping of HDDA benzynes with electron-deficient alkenes then led to the discovery of a novel mode of strain release of ortho-annulated benzene rings (Chapter 5). Reaction of HDDA benzynes with phosphine chalcogenides revealed a new mode of aryne-aryne ligand coupling from a P(V) center (Chapter 6). Finally, diynoic acid condensation was leveraged to form anhydrides that uniquely undergo HDDA cycloisomerization below room temperature (Chapter 7).