2025-06-03 早稲田大学
図 多環式構造構築のイメージ
＜関連情報＞
- https://www.waseda.jp/inst/research/news/80961
- https://www.cell.com/chem/fulltext/S2451-9294(25)00205-0
多環式化合物に対するオルトキノジメタンの簡便な生成 Facile generation of ortho-quinodimethanes toward polycyclic compounds
Kazuya Inagaki ∙ Yuna Onozawa ∙ Yuki Fukuhara ∙ Daisuke Yokogawa ∙ Kei Muto ∙ Junichiro Yamaguchi
Chem Published:June 2, 2025
DOI:https://doi.org/10.1016/j.chempr.2025.102615
The bigger picture
Ortho-quinodimethane (oQDM) has been regarded as an attractive diene in Diels-Alder reaction to synthesize biologically important benzo-fused cyclic compounds. However, the requirement of harsh conditions to generate oQDM from its precursor and laborious preparation of the precursor have limited efficiency in synthesis and product diversity, posing long-unsolved challenges in organic chemistry.
To address this, we developed a Pd-catalyzed multi-component reaction of 2-vinylbromoarenes, diazo species, and carbon nucleophiles to generate oQDM. Moreover, by attaching a dienophile moiety on a nucleophile, the generated oQDM undergoes Diels-Alder reaction, leading to the rapid construction of benzo-fused polycyclic skeletons. The high scalability and ability to synthesize a diverse range of complex skeletons, including a natural product, demonstrate significant potential for future applications in synthetic chemistry.
Highlights
- Generation of ortho-quinodimethanes (oQDMs) under mild conditions
- Multi-component reaction enables rapid access to diverse polycyclic skeletons
- In situ Diels-Alder reaction builds complex benzo-fused frameworks efficiently
Summary
The Diels-Alder reaction is a cornerstone of organic synthesis, enabling construction of complex molecular architectures through the cycloaddition of dienes and dienophiles. Among dienes, ortho-quinodimethane is an exceptionally powerful intermediate for building benzo-fused polycyclic skeletons found in biologically important molecules. However, the requirement for laborious precursor preparation remains a significant challenge. This study presents a palladium-catalyzed generation of ortho-quinodimethane via a multi-component reaction of readily available chemicals, specifically 2-vinylbromoarenes, diazo species, and carbon nucleophiles bearing a dienophile moiety, yielding polycyclic compounds. A key advance is the unprecedented reactivity of a benzyl-palladium intermediate, enabling C–C bond formation on the vinyl group. The convergent and diversity-generating nature of this reaction is demonstrated by the synthesis of a range of polycyclic compounds, including a natural product.
