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

03 March 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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, to provide 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's 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.


dipolar cycloaddition

Supplementary materials

Supporting Information
Experimental procedures and characterization data for novel compounds, computational details including coordinates (PDF).


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