No abstract

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.

<p>Polymer mechanochemistry has traditionally been employed to study the effects of mechanical force on one or two chemical bonds within a polymer. It is underexploited for the scalable synthesis of wholly new materials by activating bonds along the entire polymer, especially products inaccessible by other means. Herein we utilize polymer mechanochemistry to synthesize fluorinated polyacetylene, a long-sought-after air-stable polyacetylene that has eluded synthesis by conventional means. Our synthetic approach proceeds via ultrasonication of a force-responsive precursor polymer that was synthesized in five steps on gram scale. The synthesis is highlighted by rapid incorporation of fluorine in an exotic photochemical cascade whose mechanism and exquisite diastereoselectivity were elucidated by computation. </p>

Cyclobutadiene is a highly reactive antiaromatic hydrocarbon that has fascinated chemists for over sixty 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] cycloadditions with various electron-deficient alkenes. We also demonstrate its utility in a three-step total synthesis of dipiperamide G, and a diverse array of derivatizations including bromocyclobutadiene.

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.