A Metal-Free Cyclobutadiene Reagent for Intermolecular [4 + 2] Cycloadditions.

Cyclobutadiene is a highly reactive antiaromatic hydrocarbon that has fascinated chemists for over 60 years. However, its preparation and uses in chemical synthesis are sparing, in part due to its lengthy synthesis that generates hazardous byproducts including excess heavy metals. Herein, we report a scalable, metal-free cyclobutadiene reagent, diethyldiazabicyclohexene dicarboxylate, and explore its intermolecular [4 + 2] cycloaddition with various electron-deficient alkenes. We also demonstrate its utility in a three-step synthesis of dipiperamide G and a diverse array of product derivatizations including bromocyclobutadiene.

Aqueous Amine-Tolerant [2+2] Photocycloadditions of Unactivated Olefins.

The Kochi-Salomon reaction is the only photochemical [2+2] cycloaddition capable of combining two electronically unactivated olefins into a cyclobutane. Yet, the reaction has remained largely unexplored and suffers many drawbacks, most notably an intolerance to Lewis/Brønsted basic amines and amides. Since these groups are ubiquitous in biologically active pharmaceuticals, an amine-tolerant Kochi-Salomon reaction would greatly facilitate rapid exploration of novel drug scaffolds. Herein, we disclose a transformation that is run in water with the most widely available Cu(II) salts and mineral acids. Furthermore, we apply this methodology to synthesize a variety of amine-containing cyclobutanes, including known and novel pharmacological analogues.

Mechanochemical synthesis of an elusive fluorinated polyacetylene.

Polymer mechanochemistry has traditionally been employed to study the effects of mechanical force on chemical bonds within a polymer backbone or to generate force-responsive materials. It is under-exploited for the scalable synthesis of wholly new materials by chemically transforming the polymers, especially products inaccessible by other means. Here we utilize polymer mechanochemistry to synthesize a fluorinated polyacetylene, a long-sought-after air-stable polyacetylene that has eluded synthesis by conventional means. We construct the monomer in four chemical steps on gram scale, which involves a rapid incorporation of fluorine atoms in an exotic photochemical cascade whose mechanism and exquisite stereoselectivity were informed by computation. After polymerization, force activation by ultrasonication produces a gold-coloured, semiconducting fluoropolymer. This work demonstrates that polymer mechanochemistry is a valuable synthetic tool for accessing materials on a preparative scale.