Palladium-catalyzed allenylation/intramolecular diels-alder reaction of furans with propargyl carboxylates for the synthesis of polycyclic compounds

Article abstract of DOI:10.1002/ejoc.201402059

A highly efficient palladium-catalyzed cascade reaction of propargyl carboxylates bearing a furanyl group with organoborons was developed. This methodology offers rapid access to polycyclic Diels-Alder cycloadducts in good to high yields. The thus-formed oxygen-bridged products were further converted into anthracene derivatives in a chemoselective manner under mild conditions. Copyright

Full text of DOI:10.1002/ejoc.201402059

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201402059
Palladium-Catalyzed Allenylation/Intramolecular Diels–Alder Reaction of
Furans with Propargyl Carboxylates for the Synthesis of Polycyclic
Compounds
Chengyu Wang,[a] Lingkai Kong,[a] Yanli Li,[a] and Yanzhong Li*[a]
Keywords: Synthetic methods / Cycloaddition / Domino reactions / Chemoselectivity / Polycycles / Palladium
A highly efficient palladium-catalyzed cascade reaction of
propargyl carboxylates bearing a furanyl group with or-
ganoborons was developed. This methodology offers rapid
access to polycyclic Diels–Alder cycloadducts in good to high
yields. The thus-formed oxygen-bridged products were fur-
ther converted into anthracene derivatives in a chemoselec-
tive manner under mild conditions.
ganoborons to afford oxygen-bridged polycyclic com-
pounds in high yields, and we also report the further trans-
formation of the products into anthracene derivatives in a
chemoselective manner (Scheme 1).
Introduction
The Diels–Alder reaction of furans is of great impor-
tance in organic synthesis.[1] The resulting oxygen-bridged
norbornenes or norbornadienes are valuable precursors to
functionalized polycyclic compounds.[2] The intramolecular
Diels–Alder reaction of furans[3] is particularly attractive
because of its many benefits, including the ability to con-
struct two or more rings in one step, rate enhancement, and
better defined regioselectivity. In these reactions, furans
participate as diene components, and a variety of dieno-
philes such as alkenes,[4] alkynes,[5] and allenes[6] are com-
patible. However, if alkynes are employed as dienophiles,
only those with electron-withdrawing groups at the terminal
sp carbon atom or terminal alkynes[7] work well. Very few
studies with alkynes bearing normal alkyl or aryl groups
at their terminus have been reported[8] to the best of our
knowledge. This has greatly curtailed the scope and poten-
tial of this methodology in synthetic organic chemistry. This
is likely due to the low reactivity of the unactivated alkynes.
In contrast, allenes are much more reactive than alkynes as
dienophiles.[3a] It was documented that Pd0-catalyzed cross-
coupling reactions of propargylic compounds with or-
ganoborons afford allene derivatives.[9] We envisioned that
propargyl compounds, such as propargyl carbonates, might
be used as unactivated alkyne components to initiate the
intramolecular Diels–Alder reaction of furans by proper
choice of catalysts and organoborons. Herein, we report a
novel Pd0-catalyzed intramolecular Diels–Alder reaction of
furans with propargyl carboxylates in the presence of or-
Scheme 1. Palladium-catalyzed cascade reactions for the synthesis
of polycyclic compounds.
Results and Discussion
The requisite propargylic carbonates with a furyl group,
that is, 1, were readily prepared from the reaction of 2-
(furan-2-ylmethyl)benzaldehyde with terminal alkynes fol-
lowed by esterification with methyl chloroformate. First, the
reaction of propargyl carbonate 1a possessing a phenyl
group on the triple bond with phenylboronic acid (2a) was
performed by using Pd(OAc)2 (5 mol-%) as the catalyst and
K2CO3 (2 equiv.) as the base in THF at 100 °C. However,
desired cycloadduct 3a was not detected (Table 1, entry 1).
By changing the catalyst to PdCl2(PPh3)2, 3a was obtained
in 52% yield (Table 1, entry 2). Pd(PPh3)4 afforded a higher
yield of 3a (Table 1, entry 4). If the amount of 2a was in-
creased to 4.0 equiv., the yield of 3a increased to 66%
(Table 1, entry 5). Interestingly, if Cs2CO3 was used instead
of K2CO3, the yield of 3a increased to 74% (Table 1,
entry 6). If the reaction was performed at 80 °C, 3a was
produced in 52% yield (Table 1, entry 7). Lowering the cat-
alyst loading to 2 mol-% gave 72% yield of the adduct with
[a] Shanghai Key Laboratory of Green Chemistry and Chemical
Processes, Department of Chemistry, East China Normal
University,
500 Dongchuan Road, Shanghai 200241, P. R. China
E-mail: yzli@chem.ecnu.edu.cn
http://www.chem.ecnu.edu.cn/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402059.
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Pd-Catalyzed Allenylation/Intramolecular Diels–Alder Reaction
prolonged reaction time (Table 1, entry 8). Other bases such tively (Table 2, entries 4 and 5). The reaction of 1e bearing
as Et3N, NaOMe, and KOtBu did not give better results a 3,5-dimethoxylphenyl group with 2a and (3,5-dimeth-
than those obtained with Cs2CO3 (Table 1, entries 9–11). oxylphenyl)boronic acid (2e) gave desired products 3g and
By changing the solvent to EtOH or DMF, 3a was pro- 3h in good yields (Table 2, entries 6 and 7). The structure
duced in a relatively low yield (Table 1, entries 12 and 13). of 3h was further confirmed by X-ray crystallographic
Therefore, the optimized reaction conditions involved the analysis.[10] The substituents on the triple bond could also
use of Pd(PPh3)4 (5 mol-%) as the catalyst, Cs2CO3 be alkyl groups; n-butyl-substituted 1f furnished 3i in 78%
(2.0 equiv.) as the base, and THF as the solvent at 100 °C.
yield (Table 2, entry 8). Cyclopropyl-substituted 1g and ter-
minal alkyne 1h also reacted smoothly with 2a to produce
the Diels–Alder cycloadducts. However, these compounds
were not stable. They were further treated with BF3·OEt2
and converted into anthracene derivatives 4a and 4b,
Table 1. Optimization of the reaction conditions for the synthesis
of 3a.
Table 2. Synthesis of various of polycyclic compounds.
[a] Yield of isolated products. Unless otherwise noted, all reactions
were performed in screw-capped tubes by using PhB(OH)2
(2.0 equiv.). dba = dibenzylideneacetone. [b] PhB(OH)2 (4.0 equiv.).
[c] The reaction was performed at 80 °C. [d] The reaction time was
2 h. [e] The reaction time was 14 h.
With the optimized reaction conditions in hand, we next
examined the substrate scope of this catalytic method for
the synthesis of Diels–Alder cycloadducts by using a variety
of propargylic carbonates and boronic acids; the results are
shown in Table 2. We first investigated the electronic effects
of the aromatic substituents on the triple bond. It was
found that substrate 1b possessing an electron-withdrawing
(–Cl) aryl group reacted with 2a and (4-chlorophenyl)-
boronic acid (2b) to afford corresponding product 3b and
3c in 54 and 78% yield, respectively (Table 2, entries 1 and
2). Substrate 1c with a 4-(trifluoromethyl)phenyl group re-
acted with [4-(trifluoromethyl)phenyl]boronic acid (2c) to
produce 3d in 77% yield (Table 2, entry 3). Substrate 1d
containing an electron-donating (–OMe) aryl group reacted
with 2a and (4-methoxylphenyl)boronic acid (2d) to give
[a] Yield of isolated products. Diastereomeric ratio is given in pa-
rentheses. Unless noted, all the reactions were performed in screw-
capped tubes by using Pd(PPh3)4 (5 mol-%) and Cs2CO3
(2.0 equiv.) in THF at 100 °C. [b] The crude product was further
desired cycloadducts 3e and 3f in 72 and 63% yield, respec- treated with BF3·OEt2 (30 mol-%) in dichloromethane.
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SHORT COMMUNICATION
respectively (Table 2, entries 9 and 10). The structures of 4a corresponding 4c and 4d were obtained in 99 and 94%
and 4b were further confirmed by X-ray diffraction analy- yield, respectively (Scheme 2). Notably, there was selective
sis.[10] Boronic acids both with electron-withdrawing and migration of the aryl group over the alkyl group during the
electron-donating aryl groups, for example, 4-chloro-substi- aromatization. The structure of 4d was further confirmed
tuted 2b, 4-methoxy-substituted 2d, and 3,5-dimeth- by X-ray crystallographic analysis.[10]
oxylphenyl-substituted 2e, were also compatible in the reac-
tion; they afforded corresponding cycloadducts 3b, 3e, and
3g in 73, 70, and 68% yield, respectively (Table 2, en-
tries 11–13). If alkyl-substituted boronic acid 2f was em-
ployed in the reaction, anthracene 4b was produced in 44%
yield after further treatment with BF3·OEt2. The phenyl-
ethyl group of the boronic acid was not incorporated in the
final product; this may be due to β-hydrogen elimination of
Scheme 2. Further conversion into anthracene derivatives.
the allenyl palladium intermediate (Table 2, entry 14). To
To understand the mechanism, we carefully examined the
further broaden the substrate scope of this procedure, we reaction of 3-(3,5-dimethoxyphenyl)-1-[2-(furan-2-ylmeth-
attempted to prepare propargyl carbonates with one more yl)phenyl]prop-2-ynyl methyl carbonate (1e) with phenyl-
substituents at the propargylic position. However, the pro- boronic acid (2a) at room temperature. It was found that
tection of the OH group of the tertiary alcohol by using allenic intermediate 5a was obtained in 58% yield in the
methyl chloroformate was not successful for our substrates. presence of Cs2CO3 after 5 h, along with some of the unre-
Then, we turned our attention to tertiary propargyl acet- acted starting materials [Scheme 3, Equation (1)]. Isolated
ates. Propargyl acetate 1i with a methyl group at the prop- 5a was subjected to basic conditions to afford 3g in 87%
argylic position reacted smoothly with 2a to give desired yield in 3 h [Scheme 3, Equation (2)]. Notably, allenic 5a
cycloadduct 3j in 50% yield (Table 2, entry 15). Substrate 1j was transformed into 3g in 45% yield without the addition
with a 3,5-ditrifluoromethylphenyl group resulted in corre- of a base at 100 °C after 3 h. This indicated that Cs2CO3
sponding 3k in 58% yield (Table 2, entry 16). In these cases, was crucial for a high yield of the desired cycloadduct.
one more substituents were successfully introduced into the What was the role of the added base in the cascade reac-
polycyclic products.
tions? Was it necessary for the cross-coupling step or for
The utility of the oxygen-bridged cycloadducts as useful the Diels–Alder reaction step? To make this point clear, the
synthetic intermediates was investigated by simple treat- reaction of 1e with 2a was performed under neutral condi-
ment with BF3·OEt2, which afforded anthracene derivatives tions at room temperature, and allene 5a was also produced
in high yields as exemplified by 4a and 4b (Table 2, en- in 65% yield [Scheme 3, Equation (1)]. The reaction of 1a
tries 9, 10, 14). Upon treating 3a and 3i with BF3·OEt2, with 2a in the absence of base at 100 °C produced dihy-
Scheme 3. The allenic intermediate and its further transformation.
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Pd-Catalyzed Allenylation/Intramolecular Diels–Alder Reaction
NMR (100.6 MHz, CDCl3, Me4Si): δ = 32.92, 59.71, 85.39, 87.92,
122.37, 125.95, 126.39, 126.58, 126.83, 127.14, 127.98, 128.07,
128.14, 128.32, 128.70, 130.58, 133.55, 136.12, 138.84, 144.81,
145.17, 147.22 ppm. HRMS (EI): calcd. for C26H20O 348.1514;
found 348.1512.
droanthracen-2-ol 8a; no oxygen-bridged cycloadduct was
obtained [Scheme 3, Equation (3)]. Treatment of 5a with a
Lewis acid resulted in the formation of 8b and anthracene
4e; again, no oxygen-bridged cycloadduct was observed
[Scheme 3, Equation (4)]. These results suggested that both
the cross-coupling and the Diels–Alder reaction could oc-
cur without the assistance of base, and the role of the base
might be in stabilizing oxygen-bridged compound 3 for a
high yield of the isolated product.
On the basis of the above observations and the reported
work,[9] a possible reaction mechanism is proposed in
Scheme 4. First, oxidative addition of propargyl carbonate
1 to Pd0 gives allenyl palladium intermediate 6, which un-
dergoes transmetalation with organoborane 2 to afford 7.
Reductive elimination of 7 produces intermediate 5. Then,
intramolecular Diels–Alder reaction furnishes desired prod-
uct 3.
Typical Procedure for the Synthesis of 1,2-Diphenylanthracene (4c):
To a solution of 1,1-diphenyl-2,10-dihydro-1H-2,4a-epoxyanthra-
cene (3a; 174 mg, 0.5 mmol) in CH2Cl2 (5 mL) was added
BF3·OEt2 (19 µL, 0.15 mmol). The resulting solution was stirred at
room temperature for 1 h. Then, the solvent was evaporated under
reduced pressure, and the residue was purified by chromatography
on silica gel (petroleum ether/ethyl acetate = 50:1) to afford the
product (164 mg, 99%) as a yellow solid, m.p. 139–142 °C. 1H
NMR (400 MHz, CDCl3, Me4Si): δ = 7.16–7.19 (m, 5 H), 7.25–
7.39 (m, 7 H), 7.56 (d, J = 9.2 Hz, 1 H), 7.81 (d, J = 8.4 Hz, 1 H),
7.99 (d, J = 8.4 Hz, 1 H), 8.05 (dd, J = 0.4, 8.8 Hz, 1 H), 8.21 (s,
1 H), 8.46 (s, 1 H) ppm. 13C NMR (100.6 MHz, CDCl3, Me4Si): δ
= 125.25, 125.56, 125.85, 126.13, 126.20, 126.82, 127.61, 127.77,
127.87, 127.92, 128.24, 128.64, 130.10, 131.05, 131.34, 131.35,
131.56, 131.86, 137.17, 137.30, 139.10, 142.01 ppm. HRMS (EI):
calcd. for C26H18 330.1409; found 330.1413.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, characterization data, and 1H NMR and
13C NMR spectra of all products.
Acknowledgments
The authors thank the National Natural Science Foundation of
China (NSFC) (grant number 21272074) and Program for Changji-
ang Scholars and Innovative Research Team in University
(PCSIRT) for financial support.
Scheme 4. A proposed reaction pathway.
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Conclusions
In conclusion, we showed that oxygen-bridged Diels–
Alder cycloadducts could be efficiently prepared by Pd-cat-
alyzed cascade reactions by using propargyl carboxylates
bearing a furanyl group with organoborons. Aryl and alkyl
substituents on the acetylene terminus were compatible in
the intramolecular Diels–Alder reaction of furans reaction,
which furnished the desired compounds in good to high
yields. The thus-formed oxygen-bridged products were fur-
ther converted into anthracene derivatives in a chemoselec-
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Experimental Section
Typical Procedure for the Synthesis of 1,1-Diphenyl-2,10-dihydro-
1H-2,4a-epoxyanthracene (3a): To a solution of 1-[2-(furan-2-yl-
methyl)phenyl]-3-phenylprop-2-yn-1-yl methyl carbonate (1a;
69 mg, 0.2 mmol) in THF (2 mL) in a screw-capped tube was added
phenylboronic acid (49 mg, 0.4 mmol), Pd(PPh3)4 (12 mg,
0.01 mmol), and Cs2CO3 (130 mg, 0.4 mmol). The resulting solu-
tion was stirred at 100 °C for 1 h. Then, the solvent was evaporated
under reduced pressure, and the residue was purified by chromatog-
raphy on silica gel (petroleum ether/ethyl acetate = 10:1) to afford
3a (51 mg, 74%) as a yellow solid, m.p. 168–170 °C. 1H NMR
(400 MHz, CDCl3, Me4Si): δ = 3.44 (s, 2 H), 5.53 (d, J = 1.6 Hz,
1 H), 5.92 (dd, J = 1.6, 5.8 Hz, 1 H), 6.41 (s, 1 H), 6.42 (d, J =
5.6 Hz, 1 H), 7.06–7.29 (m, 12 H), 7.43–7.45 (m, 2 H) ppm. 13C
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SHORT COMMUNICATION
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Received: February 12, 2014
Published Online: April 28, 2014
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