TY - JOUR
T1 - Skeletal Transformation of Unactivated Arenes Enabled by a Low-Temperature Dearomative (3 + 2) Cycloaddition
AU - Pradhan, Sajan
AU - Mohammadi, Fahimeh
AU - Bouffard, Jean
N1 - Publisher Copyright:
© 2023 American Chemical Society. All rights reserved.
PY - 2023/6/7
Y1 - 2023/6/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85162045995&partnerID=8YFLogxK
U2 - 10.1021/jacs.3c02314
DO - 10.1021/jacs.3c02314
M3 - Article
C2 - 37222745
AN - SCOPUS:85162045995
SN - 0002-7863
VL - 145
SP - 12214
EP - 12223
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 22
ER -