Carbocation Lewis Acid Catalyzed Diels-Alder Reactions of Anthracene Derivatives

Article abstract of DOI:10.1021/acs.orglett.8b00619

The carbocation salt [Ph₃C][BArF] has been identified as a viable Lewis acid catalyst for the Diels-Alder reactions between anthracene derivatives and unsaturated carbonyl compounds with good selectivity and high efficiency.

Full text of DOI:10.1021/acs.orglett.8b00619

Letter
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Carbocation Lewis Acid Catalyzed Diels−Alder Reactions of
Anthracene Derivatives
Qichao Zhang, Jian Lv,* Sujia Li, and Sanzhong Luo*,†,‡
†
,‡
,†,‡
†,‡
†Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190,
China
‡
University of Chinese Academy of Sciences, Beijing 100049, China
*
S Supporting Information
ABSTRACT: The carbocation salt [Ph C][BArF] has been
3
identified as a viable Lewis acid catalyst for the Diels−Alder
reactions between anthracene derivatives and unsaturated
carbonyl compounds with good selectivity and high efficiency.
ue to the high energy barrier on dearomatization,
Scheme 1. Diels−Alder Reaction of Anthracenes
D
intermolecular Diels−Alder reactions of the arene ring
are generally difficult to achieve and require harsh conditions
1
with prolonged heating or UV irradiation. Anthracene is an
2
3
exception and is amenable to both thermal and photochemical
cycloadditions, since the initial disclosure by Diels and Alder in
2
a
1
931. The resulted anthracene Diels−Alder adducts are of
4,5
significant interest as organic functional materials. To address
the synthetic need, catalytic strategies have been actively pursued
6
−9
for an anthracene Diels−Alder reaction.
In Lewis base
catalysis based on HOMO activation, specific anthracene
derivatives such as anthracen-9-ones and 2-anthracen-9-yl
acetaldehydes are activated to react with electro-deficient
9
dienophiles in a highly stereocontrolled manner. Lewis acid
catalysis has also been widely reported to promote the Diels−
Alder reaction of 9-substituted anthracenes via LUMO activation
7
of the dienophiles (Scheme 1A). However, stoichiometric or
(
Table 1, entry 1). A survey of different carbocation Lewis acid
excess Lewis acid catalysts were normally required, and the
reactions were limited in the scopes of both anthracenes and
dienophiles.
was then followed, and the best results were obtained with
tritylium salt [Ph C][BArF] in situ generated by Ph CBr (1
equiv) and NaBArF (1 equiv) in 67% yield (Table 1, entry 6 vs
3
3
10
Since the discovery of the first trityl cation in 1901, stable
entries 2−5). We found that Ph CBr or NaBArF itself has no or
carbocations have been explored as organic Lewis acid catalysts
3
11,12
very weak activity (Table 1, entries 4 and 7). Further
improvement on the reaction activity could be achieved by
conducting the reaction in DCE (Table 1, entries 6, 8−13). In
in organic synthesis.
However, the application of carbocation
Lewis acid catalysis is still rather limited in terms of the reaction
scopes and catalytic efficiency. Recently, we have developed
latent carbocation with chiral trityl phosphate for Lewis acid
catalysis in the Friedel−Crafts reaction, HDA reaction, and
addition, the catalyst loading of [Ph C][BArF] can be reduced
3
from 10 mol % to 5 mol % while maintaining a similar
performance (Table 1, entry 14). Further lowering the loading to
2
entry 15). The reaction at 50 °C was preferred, and conducting
the reaction at ambient temperature gave only 34% yield (Table
13
carbonyl-ene reaction. Herein, we report that tritylium salt
Ph C][BArF], in situ generated by Ph CBr and NaBArF, could
mol % led to serious reduction of yield (60% yield, Table 1,
[
3
3
effectively promote a Diels−Alder reaction with anthracenes
with broad scopes under mild conditions (Scheme 1B).
The model reaction of anthracenes 1a and β,γ-unsaturated α-
keto ester 2a was investigated with different Lewis acid catalysts
1
, entry 16).
Other metal Lewis acid, such as InBr , FeBr , AlCl , and BF ·
3
3
3
3
OEt , could catalyze the reactions, albeit with lower productivity
2
(
3
Table 1). We were delighted to find that Diels−Alder product
a was obtained in 60% yield as a single stereoisomer when 10%
Ph CClO was used as the catalyst in toluene at 50 °C (Table 1,
Received: February 20, 2018
3
4
entry 2). No reaction was observed in the absence of any catalyst
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b00619
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Optimization of the Reaction Conditions
presented in Scheme 3. A number of β,γ-unsaturated α-keto
esters 2 were examined, and aromatic keto esters bearing either
Scheme 3. Substrate Scope in Diels−Alder Reaction of
a
Anthracenes 1 and β,γ-Unsaturated α-Keto Esters 2
b
entry
catalyst
none
solvent
yield (%)
1
2
3
4
5
6
7
8
9
toluene
toluene
toluene
toluene
toluene
toluene
toluene
p-xylene
PhCl
NR
60
Ph CClO
3
4
Ph CBF
3
34
4
Ph CBr
3
NR
58
Ph CBr/InBr
3
3
Ph CBr/NaBArF
3
67
NaBArF
21
Ph CBr/NaBArF
3
59
Ph CBr/NaBArF
3
61
10
11
12
13
14
15
16
17
18
19
20
21
Ph CBr/NaBArF
DCM
58
3
Ph CBr/NaBArF
3
DCE
91
Ph CBr/NaBArF
3
CHCl3
76
Ph CBr/NaBArF
3
CH CN
trace
90
3
c
Ph CBr/NaBArF
3
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
d
Ph CBr/NaBArF
3
60
c
c
c
c
c
c
,e
Ph CBr/NaBArF
3
34
InBr3
65
FeBr3
77
AlCl3
16
BF •OEt
46
3
2
HBF •OEt
NR
4
2
a
General conditions: 1a (0.2 mmol), 2a (0.1 mmol), and catalyst (10
b
1
mol %) in solvent (0.2 M) at 50 °C, for 24 h. Determined by H
NMR analysis with an internal standard, 1,3,5-trmethyloxylbenzene.
c
d
Ph CBr (5 mol %) and NaBArF (5 mol %). Ph CBr (2 mol %) and
3
3
e
NaBArF (2 mol %). At room temperature. NR = no reaction. BArF =
[
3,5-(CF ) C H ] B. DCM = dichloromethane. DCE = 1,2-dichloro-
3 2 6 3 4
ethane.
a
(
Table 1, entries 17−20). It was also noted that a retro-Diels−
General conditions: 1 (0.6 mmol), 2 (0.3 mmol), Ph CBr (5 mol %),
3
b
Alder process also existed in an non-neglectable portion in metal
Lewis acid catalysis due to the strong aromatization tendency of
the Diels−Alder adducts. In control experiments, when the
purified Diels−Alder adduct 3a was treated with Lewis acid
catalyst at room temperature, significant retro reaction (15−22%
conversion) was observed for all the metal Lewis acids, but not
with the carbocation Lewis acid (Scheme 2), highlighting the
and NaBArF (5 mol %) in DCE (0.2 M) at 50 °C, for 24 h. One
mmol scale of 2a. Diastereoselectivity was determined by H NMR.
1
an electron-withdrawing group (F, Cl, Br, Ph) or electron-
donating group (CH ) at the ortho- or meta-position of the
phenyl group can be equally applied with high yields (Scheme 3,
3
gave a relatively lower yield (Scheme 3, 3f). An ortho-fluoride
substituted group also worked well, providing a much better yield
than its chloride- and bromide-substituted counterparts (Scheme
3
a−e, 3g−k), while a strong electron-withdrawing group (CF )
3
Scheme 2. Retro-Diels−Alder Reaction in the Presence of
Lewis Acid
3
, 3l vs 3m and 3n). Gratifyingly, dichloride and naphthyl-
substituted groups could also react with anthracene 1a, giving
6% and 69% yields, respectively. Different ester groups (Et, i-
7
Pr) on α-keto ester were tolerated to give the Diels−Alder
adducts in excellent yields (Scheme 3, 3q and 3r). In addition,
9
,10-dimethylanthracene has also been examined in the reaction,
providing 99% yields of the Diels−Alder product 3s. When 9-
methylanthracene was used, two regioisomeric 3t and 3t′ (7.7:1)
were obtained in 86% yield at 50 °C, while a single regioisomer
3t′ was obtained in 99% yield at room temperature. When 3t′
was treated with trityl catalyst at 50 °C, its transformation to 3t
was clearly observed accompanying the retro-Diel−Alder
process. This observation indicates 3t′ is kinetically favored,
unique performance of carbocation catalysis. Steric effect would
be a possible reason to account for the irreversible nature of
carbon cation catalysis at room temperature. In addition, when
Brønsted acid such as HBF ·OEt was used, the reaction did not
work (Table 1, entry 21) at all, excluding the possibility of free
acid catalysis.
4
2
7e
while 3t is thermodynamically preferred. In addition, 9-bromo-
anthracene could not react at all as a result of its electron-
deficient nature.
With the optimized reactions in hand, the substrate scope of
[
Ph C][BArF] catalysis was investigated. The results are
3
B
DOI: 10.1021/acs.orglett.8b00619
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
The reactions could also be applied to other α,β-unsaturated
carbonyl compounds 4 (Scheme 3). For Z-configured α,β-
enones such as cyclopent-2-enone and cyclohex-2-enone,
moderate yields of the Diels−Alder products were obtained
Scheme 5. Substrate Scope in Diels−Alder Reaction of
a
Pentacene 6
(Scheme 4, 5a and 5b). Methyl vinyl ketone and methyl styryl
Scheme 4. Substrate Scope in Diels−Alder Reaction of
Anthracenes 1 and α,β-Unsaturated Carbonyl Compounds 4
a
a
General conditions: pentacene 6 (0.6 mmol), 2 or 4 (0.3 mmol),
Ph CBr (5 mol %), and NaBArF (5 mol %) in DCE (0.2 M) at 50 °C,
3
1
for 24 h. Diastereoselectivity was determined by H NMR.
a
General conditions: 1 (0.6 mmol), 4 (0.3 mmol), Ph CBr (5 mol %),
3
b
Scheme 6. Proposed Reaction Pathway for the Carbocation
Lewis Acid-Catalyzed Diels-Alder Reaction
and NaBArF (5 mol %) in DCE (0.2 M) at 50 °C, for 24 h. With
InBr (5 mol %). Diastereoselectivity was determined by 2D-NOESY.
3
ketones worked well in the reactions (Scheme 4, 5c−f).
Heterocycle, e.g., thiophene, can also be incorporated to deliver
the Diels−Alder adduct 5g in 79% yield (Scheme 4, 5g). In
addition, chalcones bearing either an electron-withdrawing or
electron-donating group can be equally applied to give the
desired Diels−Alder adducts in up to 99% yields (Scheme 4, 5h−
14
k). In contrast, the use of a typical metal Lewis acid such as
InBr gave only 36% yield under otherwise identical conditions.
3
Moreover, α,β-unsaturated aldehyde, such as (E)-but-2-enal, also
reacted smoothly with anthracene 1a to give the expected adduct
in 86% yield (Scheme 4, 5l). Unfortunately, the reaction did not
work with acrylate and acrylonitrile.
Furthermore, we also examined the reactions with pentacene 6
Scheme 5). To our delight, β,γ-unsaturated α-keto esters,
enone/enal and the product via coordination (A vs B) makes the
retro-Diels−Alder process unfavorable, thus facilitating the
forward reactions.
In summary, we have developed a carbocation Lewis acid-
catalyzed Diels−Alder reaction of anthracene derivatives and a
number of unsaturated carbonyl compounds under mild
conditions with high to excellent yields. Further studies are
currently underway to disclose the mechanistic details and to
develop asymmetric carbocation catalysis of anthracene Diels−
Alder reactions.
(
methyl styryl ketone, and α,β-unsaturated aldehyde were
tolerated to give the Diels−Alder adducts in good to excellent
yields (Scheme 5, 7a−n).
A proposed reaction pathway of the Diels−Alder is shown in
Scheme 6. The unsaturated carbonyl compounds were activated
by a trityl cation to form the intermediate A, thus lowering the
LUMO of dienophile and enabling the Diels−Alder reaction
with anthracene 2a to give the final product after catalyst release.
The capability of a trityl cation in differentiating the starting
C
DOI: 10.1021/acs.orglett.8b00619
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
R. L.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2012, 51, 10271−10274.
ASSOCIATED CONTENT
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The Supporting Information is available free of charge on the
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AUTHOR INFORMATION
Corresponding Authors
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E-mail: lvjian@iccas.ac.cn.
E-mail: luosz@iccas.ac.cn.
ORCID
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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A.; Vardhanapu, P. K.; Mandal, P. K.; Datta, A.; Mandal, S. K. ACS Catal.
This paper is dedicated to Prof. Jin-Pei Cheng on the occasion of
his 70th birthday. We thank the Natural Science Foundation of
China (21390400, 21521002, and 21472193) and the Chinese
Academy of Sciences (QYZDJ-SSW-SLU023) for financial
support. S.L. is supported by the National Program of Top-
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