Preparation of Highly Functionalized ortho-Naphthoquinone Methides and Their Subsequent Intermolecular [4 + 2]-Cycloadditions with Olefins
Abstract
Many natural products isolated from Rubiaceae plants, such as mollugin and rubioncolin B, contain 1-hydroxy-2-methoxycarbonylnaphthohydropyran skeletons. To access this framework, we developed a novel method for the preparation of highly functionalized ortho-naphthoquinone methides (o-NQMs) and subsequent intermolecular [4 + 2]-cycloaddition reactions with olefins. o-NQM precursors were prepared via Hauser-Kraus annulation of cyanophthalides with an α,β-unsaturated ester. Treatment of these precursors with a Lewis acid generated the corresponding o-NQMs, which underwent intermolecular [4 + 2]-cycloaddition with olefins to afford polycyclic compounds bearing the 1-hydroxy-2-methoxycarbonylnaphthohydropyran skeleton. This approach provides efficient access to the frameworks found in natural products and facilitates structural derivatization. The present methodology was further applied to synthetic studies toward rubioncolin B.
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BibTeX
@article{aijima2026preparation,
title = {{Preparation of Highly Functionalized ortho-Naphthoquinone Methides and Their Subsequent Intermolecular [4 + 2]-Cycloadditions with Olefins}},
author = {Takaaki Aijima and Jin Tokunaga and Haru Igusa and Yoshinari Sawama},
journal = {Chemical and Pharmaceutical Bulletin},
year = {2026},
month = sep,
doi = {10.1248/cpb.c26-00375},
url = {https://www.jstage.jst.go.jp/article/cpb/74/9/74_c26-00375/_article},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Preparation of Highly Functionalized ortho-Naphthoquinone Methides and Their Subsequent Intermolecular [4 + 2]-Cycloadditions with Olefins
AU - Takaaki Aijima
AU - Jin Tokunaga
AU - Haru Igusa
AU - Yoshinari Sawama
PY - 2026
DA - 2026/09/12
JO - Chemical and Pharmaceutical Bulletin
DO - 10.1248/cpb.c26-00375
UR - https://www.jstage.jst.go.jp/article/cpb/74/9/74_c26-00375/_article
AB - Many natural products isolated from Rubiaceae plants, such as mollugin and rubioncolin B, contain 1-hydroxy-2-methoxycarbonylnaphthohydropyran skeletons. To access this framework, we developed a novel method for the preparation of highly functionalized ortho-naphthoquinone methides (o-NQMs) and subsequent intermolecular [4 + 2]-cycloaddition reactions with olefins. o-NQM precursors were prepared via Hauser-Kraus annulation of cyanophthalides with an α,β-unsaturated ester. Treatment of these precursors with a Lewis acid generated the corresponding o-NQMs, which underwent intermolecular [4 + 2]-cycloaddition with olefins to afford polycyclic compounds bearing the 1-hydroxy-2-methoxycarbonylnaphthohydropyran skeleton. This approach provides efficient access to the frameworks found in natural products and facilitates structural derivatization. The present methodology was further applied to synthetic studies toward rubioncolin B.
SN - 1347-5223
SN - 0009-2363
ER -