Thiophenes and their Benzo Derivatives: Synthesis

Modular approaches, which allow a systematic variation of heteroaromatic cores and substituents, are crucial for the development of heteroaromatic drug candidates and organic functional materials. A new strategy involving the cyclization of heteroarenes tethered with alkynes through a norbornene bridge was developed. The precursors were readily prepared by a three‐component coupling process of heteroaryl halides, norbornadiene, and terminal alkynes. The Pd catalytic system derived from Pd(OAc)2 and 2‐(pyrazol‐1‐yl)pyridine transformed a variety of five‐membered heteroarenes to the corresponding benzofused products, including (di)benzothiophene, indazole, carbazole, indole, and benzofuran, with aryl and alkyl substituents at the C4(C7) position. During the cyclization process, the norbornene ring underwent a retro‐Diels‐Alder reaction, serving as an acetylene synthon. This approach was used to synthesize naphthalene derivatives from electron‐rich arenes, demonstrating its versatility in the annulation of (hetero)aromatic rings.

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Heteroaromatic Aldehydes with Unprecedented Catalytic Performance in Selective Radical Reactions: Synthesis of α‐Aminophosphonate Scaffolds

Aghahosseini

Ramazani

Taran

et al. 2019

Asian J Org Chem

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Heterocyclic compounds have gained immense importance because of their low resonance energy and strong hydrogen-bonding abilities, which provide good catalytic potential in a variety of organic transformations. Herein an unexpected metal-free catalytic performance of heteroaromatic aldehydes has been reported. Accordingly, a unique method for the synthesis of new scaffolds of peptidomimetic compounds, α-aminophosphonates has been developed, which was difficult using previous methods. The aerobic auto-oxidation of heteroaromatic aldehydes acts as a driving force for the coupling of aromatic N-benzylamines and hydrophosphoryl compounds according to a one-pot, metal-and solvent-free procedure. Heteroaromatic aldehydes, in addition to their individual ability to promote selective radical reactions through the auto-oxidation process, can provide hydrogen bonding frameworks at different stages of the reaction and thereby change the reaction pathways and induce new activities and selectivities, which unveiled their other important catalytic features. We believe that this highlights the catalytic potential of heteroaromatic aldehydes, which may offer an opportunity to change the traditional harsh conditions necessary to generate alkyl radicals.[a] Dr. reaction, as monitored by TLC, the reaction mixture was allowed to cool at room temperature. The mixture was then extracted with ethyl acetate three times and dried over MgSO 4 , filtered, and concentrated under reduced pressure. 4 5 6 7 8

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Thiophenes and their Benzo Derivatives: Synthesis

Cited by 8 publications

References 412 publications

Transition Metal‐Catalyzed Synthesis of Fused Five‐Membered Aromatic Heterocycles

Transition Metal‐Catalyzed Synthesis of Fused Five‐Membered Aromatic Heterocycles

Pd‐Catalyzed Cyclization of Alkynyl Norbornene Derivatives for the Synthesis of Benzofused Heteroarenes

Heteroaromatic Aldehydes with Unprecedented Catalytic Performance in Selective Radical Reactions: Synthesis of α‐Aminophosphonate Scaffolds

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