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Abstract Herein, the synthesis of 1,2,3,4‐tetrasubstituted benzenoid rings, motifs found in pharmaceutical, agrochemical, and natural products, is described.[1]In the past, the regioselective syntheses of such compounds have been a significant challenge. This work reports a method using substituted arynes derived from aryl(Mes)iodonium salts to access a range of densely functionalized 1,2,3,4‐tetrasubstituted benzenoid rings. Significantly, it was found that halide substituents are compatible under these conditions, enabling post‐synthetic elaboration via palladium‐catalyzed coupling. This concise strategy is predicated on two regioselective events: 1) ortho‐ deprotonation of aryl(Mes)iodonium salts to generate a substituted aryne intermediate, and 2) regioselective trapping of said arynes, thereby improving previously reported reaction conditions to generate arynes at room temperature and in shorter reaction times. Density functional theory (DFT) computations and linear free energy relationship (LFER) analysis suggest the regioselectivity of deprotonation is influenced by both proximal and distal ring substituents on the aryne precursor. A competition experiment further reveals the role of arene substituents on relative reactivity of aryl(Mes)iodoniums as aryne precursors.
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Supramolecular construction of a cyclobutane ring system with four different substituents in the solid state
Abstract Methods to form cyclobutane rings by an intermolecular [2 + 2] cross-photoreaction (CPR) with four different substituents are rare. These reactions are typically performed in the liquid phase, involve multiple steps, and generate product mixtures. Here, we report a CPR that generates a cyclobutane ring with four different aryl substituents. The CPR occurs quantitatively, without side products, and without a need for product purification. Generally, we demonstrate how face-to-face stacking interactions of aromatic rings can be exploited in the process of cocrystallization and the field of crystal engineering to stack and align unsymmetrical alkenes in CPRs to afford chiral cyclobutanes with up to four different aryl groups via binary cocrystals. Overall, we expect the process herein to be useful to generate chiral carbon scaffolds, which is important given the presence of four-membered carbocyclic rings as structural units in biological compounds and materials science.
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- Award ID(s):
- 1708673
- PAR ID:
- 10227130
- Publisher / Repository:
- Nature Publishing Group
- Date Published:
- Journal Name:
- Communications Chemistry
- Volume:
- 4
- Issue:
- 1
- ISSN:
- 2399-3669
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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