Organic Letters
Letter
4). Upon treatment in the identical acid catalysis conditions,
the adduct gave only 7% desired anthracenyl aryl ether
product, along with 23% recovered 9-methylanthracene
(Scheme 3e). These results suggest that the ether product
likely emerges from the reaction between anthracene and Q
resulting from the retro-Diels−Alder reaction following the
above-mentioned mechanisms, rather than from the D−A
adduct following acid-catalyzed fragmentation mechanism.
Kinetic studies were also performed. The Hammett
relationship (ρ = −6.61 when varying the anthracene 9-
substituents; see Figure S3 of the Supporting Information)
indicated that a full carbocation is likely generated during the
rate-determining step. The kinetic isotope effect (KIE) result
(kH/kD = 2.03; see Figure S4 of the Supporting Information)
indicated that the reaction does not involve direct C−H bond
cleavage. The kinetic order of the catalyst (1.3 order for
HNTf2; see Figure S6 of the Supporting Information) suggests
that the Brønsted acid might be involved in the rate-
determining step in different forms, likely contributing to
both pathways A and B that consume PA−H+ in different rate
laws. In summary of the mechanism, although the real
mechanism is still perplexing, the ionic mechanisms initiated
by protonation of PA are consistent with current evidence in
hand.
Summarized in Scheme 4 are the substrate scopes of this
reaction with respect to aryl anthracene derivatives/analogues
and benzoquinones. Many functional groups on the anthracene
were tolerated, including halogens, nitrile, aldehyde, ketone,
ester, borate, and heterocycles (Scheme 4, 3ba−3ta). Cyclo-
addition products were negligible in most cases, except for 9-
methylanthracene which gave 10% of the cycloaddition
byproduct along with 40% aryl ether (Scheme 4, 3va).
Electron-withdrawing 9-substituents gave lower yield even at
higher temperatures. 9-Cyclohexylanthracene gave a C−C
bond formation product (4ua) instead of the C−O bond
formation product. The benzoquinones capable of this
transformation include substituted ones: methyl substituted
quinones (3ad−3fe), chloranil, and 2,6-dichloroquinone (3ab,
3ac), but naphthoquinones and anthraquinones did not give
any conversion. Moreover, N-protected p-benzoquinonimine
also participated in this reaction, giving exclusively the C−O
bond formation products (3af, 3wf, 3kg).
Scheme 5. Scope of Nucleophiles in Reactions of PA with
Separated Oxidants and Nucleophiles
a
a
Conditions: 1 (0.2 mmol), nucleophile 5 (0.2 mmol), chloranil (0.2
mmol), HNTf2 (5 mol %), DCM (1 mL), 40 °C, 24 h. All yields are
isolated yields after column chromatography.
chloranil (3ab, 3aab) were not observed, likely due to the
lower nucleophilicity of tetrachlorohydroquinone/chloranil
than that of electron-rich phenols.
Diversified PA-type substrates can be conveniently synthe-
sized from easily accessible diarylmethyl carbinols or their
acetates 7 under similar acid-catalyzed conditions.18 Thus, a
cascade reaction was developed, by simply adding Q and acid
catalyst to the acetates, to achieve various PAOP-type aryl
ethers that contain tunable polyaromatic motifs, aryl
substituents, and phenolic motifs (Scheme 6, 3aa−8da).
a
Scheme 6. Sequential Syntheses of Polycyclic Aryl Ethers
In the reaction between PA and chloranil, a considerable
yield of the 2:1 coupling byproduct was obtained (Scheme 4,
3aab). In addition, formation of PAOP-OMe shown in Scheme
3c demonstrated that a phenolic nucleophile can be
incorporated in the aryl ether at the presence of an oxidant.
Therefore, additional examples following this strategy are
summarized in Scheme 5. Structures derived from 1,4- and 1,2-
hydroquinone achieved good yields (6aa−6ad). While using
resorcinol, phloroglucinol, and trimethoxybenzene as nucleo-
philes, C−C bond formation products prevailed instead of C−
O bond formation, resulting in biaryl compounds (6ae−6aag).
Electron-donating substituents with a 1,3-substitution pattern
on a benzene ring may synergistically enhance the nucleophil-
icity of the 2-, 4- and 6-positions, overriding the nucleophilicity
of phenol hydroxyls. 2,3-Dihydroxynaphthalene also gave
biaryl coupling product 6af. Even unsubstituted anthracene
can be functionalized by trimethoxybenzene, giving 6xh as the
product. N-Tosyl-protected p-aminophenol gave excellent yield
of ether 6ai. Formation of all these products can be explained
by mechanism pathway A. Note that when phenolic
nucleophiles were used, coupling products between PA and
a
Conditions: 7 (0.2 mmol), 2a (0.2 mmol), HNTf2 (5 mol %), DCM
(1 mL), 40 °C, 24 h. All yields are isolated yields after column
chromatography. 1.5 equiv of 2a, 30 °C, 12 h.
b
All the anthracenyl-containing products synthesized in this
study exhibit excellent fluorescence properties. Their utility in
fluorescent labeling and detection can be preliminarily
demonstrated by the convenient synthesis of an artificial
fluorescent amino acid and its dopamine conjugate. A
fluorescent dopamine analogue 11 exhibiting ex/em = 397/
432 nm and fluorescent quantum yield (Φf) = 21.50% (Figure
D
Org. Lett. XXXX, XXX, XXX−XXX