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1. Diels−Alder Reactions of 1‐Alkoxy-1-amino-1,3-butadienes: Direct Synthesis of 6‐Substituted and 6,6-Disubstituted 2‐Cyclohexenones and 6‐Substituted 5,6-Dihydropyran-2-ones

   https://doi.org/10.1021/acs.orglett.1c01031  

   Elkin, P. K.; Durfee, N. D. (June 2021, Organic letters)

   Gaich, T. (Ed.)

   We report the cycloaddition reactions of 1-alkoxy-1- amino-1,3-butadienes. These doubly activated dienes are prepared on a multigram scale from crotonic acid chloride and its derivatives. The dienes undergo Diels−Alder (DA) and hetero-Diels−Alder (HDA) reactions under mild reaction conditions with a variety of electron- deficient dienophiles to afford cycloadducts in good yields with excellent regioselectivities. The hydrolysis of the DA cycloadducts provides 6-substituted and 6,6-disubstituted 2-cylohexenones, which are versatile building blocks for complex molecule synthesis. The corresponding HDA cycloadducts afford 6-substituted 5,6-dihydropyr- an-2-ones. 

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2. Controlling polymer architecture to design dynamic network materials with multiple dynamic linkers

   https://doi.org/10.1039/D0ME00015A  

   Vakil, Jafer R.; De Alwis Watuthanthrige, Nethmi; Digby, Zachary A.; Zhang, Borui; Lacy, Hannah A.; Sparks, Jessica L.; Konkolewicz, Dominik (August 2020, Molecular Systems Design & Engineering)

   null (Ed.)

   A one pot synthesis is applied to control the chain structure and architecture of multiply dynamic polymers, enabling fine tuning of materials properties by choice of polymer chain length or crosslink density. Macromolecules containing both non-covalent linkers based on quadruple hydrogen-bonded 2-(((6-(3-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl)ureido)hexyl)carbamoyl)oxy)ethyl methacrylate (UPyMA), and thermoresponsive dynamic covalent furan–maleimide based Diels–Alder linkers are explored. The primary polymer's architecture was controlled by reversible addition-fragmentation chain transfer (RAFT) polymerization, with the dynamic non-covalent (UPyMA) and dynamic covalent furfuryl methacrylate (FMA) units incorporated into the same backbone. The materials are crosslinked, taking advantage of the “click” chemistry properties of the furan–maleimide reaction. The polymer materials showed stimulus-responsive thermomechanical properties with a decrosslinking temperature increasing with the polymer's primary chain length and crosslink density. The polymers had good thermally promoted self-healing properties due to the dynamic covalent Diels–Alder bonds. Besides, the materials had excellent stress relaxation characteristics induced by the exchange of the hydrogen bonds in UPyMA units. 

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3. Vinylazaarenes as dienophiles in Lewis acid-promoted Diels–Alder reactions

   https://doi.org/10.1039/D1SC05095H  

   Davis, Anna E.; Lowe, Jared M.; Hilinski, Michael K. (December 2021, Chemical Science)

   Described are the first examples of Lewis acid-promoted Diels–Alder reactions of vinylpyridines and other vinylazaarenes with unactivated dienes. Cyclohexyl-appended azaarenes constitute a class of substructures of rising prominence in drug discovery. Despite this, thermal variants of the vinylazaarene Diels–Alder reaction are rare and have not been adopted for synthesis, and Lewis acid-promoted variants are virtually unexplored. The presented work addresses this gap and in the process furnishes increased scope, dramatically higher yields, improved regioselectivity, and high levels of diastereoselectivity compared to prior thermal examples. These reactions provide scalable access to druglike scaffolds not readily available through other methods. More broadly, these studies establish a useful new class of dienophiles that, based on preliminary mechanistic studies, should be amenable to conventional strategies for enantioselective catalysis. 

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4. A sequential cyclization/π-extension strategy for modular construction of nanographenes enabled by stannole cycloadditions

   https://doi.org/10.1039/d2sc00397j  

   Bergman, Harrison M.; Beattie, D. Dawson; Kiel, Gavin R.; Handford, Rex C.; Liu, Yi; Tilley, T. Don (May 2022, Chemical Science)

   The synthesis of polycyclic aromatic hydrocarbons (PAHs) and related nanographenes requires the selective and efficient fusion of multiple aromatic rings. For this purpose, the Diels–Alder cycloaddition has proven especially useful; however, this approach currently faces significant limitations, including the lack of versatile strategies to access annulated dienes, the instability of the most commonly used dienes, and difficulties with aromatization of the [4 + 2] adduct. In this report we address these limitations via the marriage of two powerful cycloaddition strategies. First, a formal Cp 2 Zr-mediated [2 + 2 + 1] cycloaddition is used to generate a stannole-annulated PAH. Secondly, the stannoles are employed as diene components in a [4 + 2] cycloaddition/aromatization cascade with an aryne, enabling π-extension to afford a larger PAH. This discovery of stannoles as highly reactive – yet stable for handling – diene equivalents, and the development of a modular strategy for their synthesis, should significantly extend the structural scope of PAHs accessible by a [4 + 2] cycloaddition approach. 

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5. Bifunctional Phosphine Ligand Enabled Gold‐Catalyzed Alkynamide Cycloisomerization: Access to Electron‐Rich 2‐Aminofurans and Their Diels–Alder Adducts

   https://doi.org/10.1002/ange.201908598  

   Li, Xingguang; Ma, Xu; Wang, Zhixun; Liu, Pei‐Nian; Zhang, Liming (October 2019, Angewandte Chemie)

   Abstract By using biphenyl‐2‐ylphosphines functionalized with a remote tertiary amino group as a ligand, readily available acetylenic amides are directly converted into 2‐aminofurans devoid of any electron‐withdrawing and hence deactivating/stabilizing substituents. These highly electron‐rich furans have rarely been prepared, let alone applied in synthesis, because of their high reactivities and low stabilities associated with the electron‐rich nature of the furan ring. In this work, these reactive furans smoothly undergo either in situ intermolecular Diels–Alder reactions to deliver highly functionalized/substituted aniline products or intramolecular ones to furnish carbazole‐4‐carboxylates in mostly good to excellent yields. This work offers general and expedient access to this class of little studies electron‐rich furans and should lead to exciting opportunities for their applications. 

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