Skeletal Transformation of Unactivated Arenes Enabled by a Low-Temperature Dearomative (3 + 2) Cycloaddition

Sajan Pradhan, Fahimeh Mohammadi, Jean Bouffard

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Simple aromatic compounds like benzene are abundant feedstocks, for which the preparation of derivatives chiefly begins with electrophilic substitution reactions or, less frequently, reductions. Their high stability makes them particularly reluctant to participate in cycloadditions under ordinary reaction conditions. Here, we demonstrate the exceptional ability of 1,3-diaza-2-azoniaallene cations to undergo formal (3 + 2) cycloadditions with unactivated benzene derivatives below room temperature, providing thermally stable dearomatized adducts on a multi-gram scale. The cycloaddition, which tolerates polar functional groups, activates the ring toward further elaboration. On treatment with dienophiles, the cycloadducts undergo a (4 + 2) cycloaddition-cycloreversion cascade to yield substituted or fused arenes, including naphthalene derivatives. The overall sequence results in the transmutation of arenes through an exchange of the ring carbons: a two-carbon fragment from the original aromatic ring is replaced with another from the incoming dienophile, introducing an unconventional disconnection for the synthesis of ubiquitous aromatic building blocks. Applications of this two-step sequence to the preparation of substituted acenes, isotopically labeled molecules, and medicinally relevant compounds are demonstrated.

Original languageEnglish
Pages (from-to)12214-12223
Number of pages10
JournalJournal of the American Chemical Society
Volume145
Issue number22
DOIs
StatePublished - 7 Jun 2023

Bibliographical note

Funding Information:
Acknowledgment is made to the Donors of the American Chemical Society Petroleum Research Fund for the support of this research (no. 61381-ND1). This work was also supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT, no. 2022R1A2C2004901) and by the Samsung Science and Technology Foundation under project number SSTF-BA2001-07. We thank Dr. Parantap Sarkar, Ms. Hee Young Byun, Ms. Mibin Cho, and Ms. Shinwon Kim for preliminary results, Dr. Hea Kyoung Lee of the Organic Chemistry Research Center at Sogang University for ESI-MS analyses, Dr. Sung Hong Kim of the Daegu branch of the Korean Basic Science Institute for EI-MS analyses, and finally, Dr. Youngmee Kim of Ewha Womans University for X-ray crystallography.

Publisher Copyright:
© 2023 American Chemical Society. All rights reserved.

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