Rh(i)-Catalyzed enantioselective and scalable [4 + 2] cycloaddition of 1,3-dienes with dialkyl acetylenedicarboxylates

Article abstract of DOI:10.1039/d0ob00361a

An asymmetric intermolecular [4 + 2] cycloaddition of 1,3-dienes with dialkyl acetylenedicarboxylates, which was catalyzed by a rhodium(i)-chiral phosphoramidite complex, was developed. This protocol provided a highly enantioselective access to prepare carbonyl substituted cyclohexa-1,4-dienes with up to 96% yield and >99% ee. Notably, a cycloaddition on the 10 g scale gave the product in 92% yield and with 99% ee, which showed great potential for the scale-up synthesis of carbonyl substituted cyclohexa-1,4-dienes. In addition, oxidative aromatizations and hydrolysis of the products were also investigated.

Full text of DOI:10.1039/d0ob00361a

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DOI: 10.1039/D0OB00361A
ARTICLE
Rh(I)-catalyzed enantioselective and scalable [4+2] cycloaddition of
1,3-dienes with dialkyl acetylenedicarboxylates
Robert Li-Yuan Bao,ac Junjie Yin,ac Lei Shi,ab* and Limin Zhenga
Received 00th January 20xx,
Accepted 00th January 20xx
An asymmetric intermolecular [4+2] cycloaddition of 1,3-dienes with dialkyl acetylenedicarboxylates, which was catalyzed
by rhodium(I) - chiral phosphoramidite complex, was developed. This protocol provided a highly enantioselective access to
prepare the carbonyl substituted cyclohexa-1,4-dienes with up to 96% yield and > 99% ee. Notably, a cycloaddition on 10 g
scale gave the product in 92% yield and with 99% ee, which showed a great potential in the scale-up synthesis of carbonyl
substituted cyclohexa-1,4-dienes. In addition, the oxidative aromatizations and hydrolysis of the products were also
investigated.
DOI: 10.1039/x0xx00000x
O
R
O
CO2Me
CO2Me
1b
Diene Ligands
Introduction
CO2Me
CO2Me
Dansyl
HN
HN
O
Carbonyl substituted cyclohexa-1,4-dienes have received
increasing attentions due to their extensive applications in
organic chemistry. As versatile functional units, the carbonyl
substituted cyclohexa-1,4-diene derivatives have been utilized
to construct the selective fluorogenic probes for the thiols in
peptides and proteins (Figure 1, 1a),1 chiral diene ligands in the
rhodium catalyzed asymmetric transformations (Figure 1, 1b),2
and hydrogen sources in the palladium-catalyzed
hydrogenation of olefins (Figure 1, 1c).3 More importantly, the
functional groups in the carbonyl substituted cyclohexa-1,4-
dienes can be modified easily to construct other significant
fragments. Inspired by these modifications, a diversity of the
carbonyl substituted cyclohexa-1,4-dienes (Figure 1, 1d - 1i)
have been used as important synthetic intermediates in the
natural product synthesis. 4-10
As promising moieties in organic chemistry, the cyclohexa-
1,4-dienes are mainly prepared through the Birch reductions of
aromatic rings,11 the [4+2] cycloadditions of 1,3-dienes with
alkynes,12 the oxidations of phenols,13 and the
electroreductions of aromatic compounds.14 Among these
methods, the [4+2] cycloaddition reactions might be the
appealing synthetic methods due to their mild conditions, high
functional group tolerance, and good atom economy.
O
1a
Fluorogenic Probe
1c
Hydrogen sources
Intermediates towards the synthesis of natural products:
OBn CO2Me
TBSO
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
Me
OPMB
1d intermediate
for Scalarolide
,
1e, intermediate
for (±) - Cinnamodial,
(±) - Chamobtusin A
1f, intermediate
for Cornexistin
OTBS
Me
O
OMe
OBn
Me
Me
R
Me
Me
H
Me
O
Me
H
Me
CO2Me
S
O
O
O
p-Tol
1g, intermediate
for Hypocrolide A
1h, intermediate
for Caribenol A
1i, intermediate
for (-) - Mitrephorone
Figure 1 Representative compounds containing substituted
cyclohexa-1,4-dienes.
-ethylsilyl substituted cyclohexa-1,4-diene, which suffered from
an intramolecular [4+2] cycloisomerization reaction catalyzed
by Rh(I)-(+)-DIOP complex with giving 87% ee (Scheme 1, A).15
After that, Gilbertson and co-workers realized a similar
cycloisomerization of dieneynes in the present of chiral Rh(I)-
bisphosphine complexes with up to 95% ee (Scheme 1, A).16
Next, Mikami and co-workers disclosed that the chiral diene-
Rh(I)-chiral diphosphine complex was a highly efficient catalyst
for the intramolecular [4+2] cycloaddition with up to 98% ee
(Scheme 1, A).17 Notably, Hayashi and co-workers also
established highly efficient Rh(I)-chiral diene catalysts for the
intramolecular [4+2] cycloaddition with up to > 99% ee (Scheme
Actually, several [4+2] cycloaddition reactions have been
employed for the catalytic asymmetric synthesis of substituted
cyclohexa-1,4-dienes in intramolecular or intermolecular
manners. As a pioneering study, Livinghouse and co-workers
have reported an example of asymmetric synthesis of the trim-
a. School of Science, Harbin institute of Technology, Shenzhen, 518055, China.
b. Beijing National Laboratory for Molecular Sciences, Beijing, 100190, China.
c. These authors contribute equally.
E-mail: lshi@hit.edu.cn. Homepage: http://homepage.hit.edu.cn/shilei.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
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ARTICLE
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Table 1 Optimization of reaction conditionsa
A) Catalytic asymmetric intramolecular [4+2] cycloadditions
View Article Online
n-C H
DOI: 10.1039/1D10OB00361A
5
R1
CO2Me
R1
R2
CO2Me
L
Rh(I), , AgSbF6
Rh(I), Ir(I)
n-C5H11
+
solvent, rt
N2, 24 h
R2
chiral ligands
CO2Me
CO2Me
2a
3a
4a
R =
B) Catalytic asymmetric intermolecular [4+2] cycloadditions
R
R
*
CO2Me
Rh(I)
CO2Me
CO2Me
PPh2
PPh2
O
O
O
O
PPh2
PPh2
chiral ligands
N
+
P
R
R'
R'
CO2Me
L3
L2
L1
L4
Hayashi, chiral diene, up to 72% yield, 87% ee
Shibata, chiral BINAP, up to 69% yield, 94% ee
Ph
Ph
Ph
N
Ph
N
Ph
N
C) This work
N
N
R
R
CO2Me
L5
L6
L7
L8
*
R'
CO2Me
CO2Me
R'
Rh(NBD)2BF4
+
Entry
Rh(I)
L
Solvent Yieldb
%
Ee c
chiral phosphoramidite
CO2Me
%
up to 96% yield
up to > 99% ee
scale up to 10 g
high functional-group tolerance
1
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
[Rh(COD)Cl]2
Rh(COD)2BF4
[Rh(COE)Cl]2
[Rh(NBD)Cl]2
Rh(NBD)2BF4
No Rh(I)
L1
L2
L3
L4
L5
L6
L7
L8
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
L5
Toluene trace
Toluene N.R.
Toluene 16
Toluene 15
Toluene 77
Toluene N.R.
Toluene N.R.
Toluene 67
Toluene 82
Toluene 71
Toluene 30
Toluene 96
Toluene trace
Toluene 59
--
2
--
Scheme 1 Catalytic asymmetric synthesis of substituted
cyclohexa-1,4-dienes.
3
2
4
0
1, A).18 As a breakthrough, his catalytic system could also be
used for two examples in the intermolecular [4+2]
5
98
--
cycloadditions
of
1,3-dienes
and
dimethyl
6
acetylenedicarboxylate with up to 87% ee (Scheme 1, B).
Recently, Shibata and co-workers presented a Rh(I)-BINAP
catalyzed intermolecular [4+2] cycloaddition with good
enantioselectivities, in which one example achieved the high
enantioselectivity (94% ee) (Scheme 1, B).19 Compared with the
intramolecular [4+2] cycloadditions, the intermolecular
cycloadditions constructed the substituted cyclohexa-1,4-
dienes through convergent synthesis, which circumvented extra
synthetic steps to connect the diene and alkyne moieties to
prepare the enynes in the intramolecular cycloadditions. To our
knowledge, only two reports focused on the asymmetric
intermolecular [4+2] cycloadditions, and they have only
achieved moderate to good enantioselectivities with limited
substrates and functional groups. In fact, accessing the practical
and scalable asymmetric intermolecular [4+2] cycloaddition has
remained an unmet challenge. Herein, we report a catalytic
asymmetric cycloaddition of 1,3-dienes and dialkyl
acetylenedicarboxylates catalyzed by Rhodium(I)-chiral
phosphoramidite complex with excellent enantioselectivies and
good functional group compatibility.
7
--
8
54
96
98
98
99
--
9
10
11
12
13
14 d Rh(NBD)2BF4
15 e Rh(NBD)2BF4
99
85
13
95
87
--
Toluene
3
16 f
17
18
19
20
Rh(NBD)2BF4
Rh(NBD)2BF4
Rh(NBD)2BF4
Rh(NBD)2BF4
Rh(NBD)2BF4
Toluene 12
DCE
89
Et2O
THF
7
N.R.
N.R.
CH3CN
--
a
Reaction conditions: 2a (0.2 mmol), 3a (0.6 mmol), Rh(I) (10
mol%), L (12 mmol%) and AgSbF6 (20 mol%) in solvent (3 mL)
b
c
d
under N2 at 25 °C
.
Isolated yields. Determined by HPLC.
Results and discussion
e
f
Open to air. H2O (5 L) was added. No AgSbF6. Rh(I) =
rhodium(I) complexes. DCE = 1,2-Dichloroethane. Et2O = Diethyl
ether. THF = Tetrahydrofuran.
To begin our investigations, we opted for the dimethyl
acetylenedicarboxylate 2a and diene 3a as model substrates for
this [4+2] cycloaddition in toluene at 25 °C (Table 1). We initially
selected the [Rh(COD)Cl]2 as the rhodium catalyst and screened
several chiral ligands (Table 1, entry 1-8). Fortunately, the chiral
phosphoramidite ligand L5, which was reported by Feringa
group,20 has proved to be effective in this asymmetric transfor-
-mation, providing a good yield (77%) with an excellent
enantioselectivity (98% ee) (Table1, entry 5). Although the yield
was a weak point for improvement, the good asymmetric
induction still provided a clue for the further screening. With the
optimal ligand L5 in hand, we investigated the effect of different
2 | J. Name., 2012, 00, 1-3
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ARTICLE
rhodium(I) complexes (Table 1, 9-12). Very pleasingly, we found
that the Rh(NBD)2BF4 was the most effective rhodium(I)
complex for this cycloaddition, affording 4a in 96% yield and
with 99% ee. To get a better understanding of the nature of the
catalytic system, further control experiments were conducted.
As expected, the reaction couldn’t proceed smoothly in the
absence of rhodium(I) complexes (Table 1, entry 13). When the
reaction was carried out under air, the yield would decrease to
59% (Table 1, entry 14). If H2O was added into the reaction, the
reactivity would be depressed sharply (Table 1, entry 15).
Additionally, both the reactivity and enantioselectivity would
decrease dramatically without adding AgSbF6 into the catalytic
system (Table1, entry 16), and this result implied that the
hexafluoroantimonate anion could improve the reaction rate
and enantioselectivity of the cycloaddition, which was
consistent with the remarkable accelerating effect of the
hexafluoroantimonate anion in Livinghouse’s report.21 In the
end, our efforts to evaluate the effect of the solvents revealed
that the toluene was the optimal solvent (Table 1, 17-20). In
summary, the condition of entry 12 in Table 1 was the best
option.
Table
2
Substrate scope of enantioselective
View Article[O4n+li2ne]
cycloadditionsa,b
DOI: 10.1039/D0OB00361A
R1
CO2R
+
L5
Rh(NBD)2BF4,
R2
CO2R
CO2R
AgSbF6, toluene
R1
N2, 25 oC, 24 h
R2
CO2R
2
3
4
CO2Me
n-C5H11
CO2Me
n-C9H19
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
4a
4b
4c
4d
96% yield
99% ee
40% yield
95% ee
85% yield
>99% ee
73% yield
8% ee
O
OTs
OAc
O
O
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
4g d
4e c
4f d
4h d
With the optimized conditions in hand, we screened the
asymmetric [4+2] cycloaddition of 2a with a wide range of 1,3-
dienes (Table 2). In general, the steric effect of substrates was a
critical factor for the reaction both in reactivity and
enantioselectivity. Compared to the model reactions, increasing
the length of linear 1,3-diene depressed the reactivity and
enantioselectivity (Table 2, 4b). In contrast, reducing the length
of linear 1,3-diene resulted in a depressed reactivity due to
the low boiling point of the 1,3-diene although the excellent
enantioselectivity was obtained as well (Table 2, 4c). Next,
investigating the steric effect of substituents in the branched
1,3-dienes leaded to slightly diminished yields and drastically
decreased enantiomeric excesses (Table 2, 4d and 4e).
Subsequently, to evaluate the functional group tolerance, the
masked alcohol moieties, protected amine, esters, and phenyl
group were introduced into the 1,3-dienes (Table 2, 4f - 4p).
Gratifyingly, the catalytic system showed good functional group
tolerance with the -OTs, -OAc, -OCO2CH3, -OTBS, -OMOM, -OBn,
the cyclopropyl, -N (CH3) Ts and -CO2Et. Deserved to be
mentioned, introducing the protected groups with large steric
hindrance would lead to lower reactivity. One strategy to
promote the reactivity was using 1,2-dichloroethane as a co-
solvent, and with employing this strategy, the products 4f, 4g,
4h, 4j, and 4n were obtained in moderate to good yields.
Another way to improve the reactivity was to increase the
reaction temperatures, and the products 4k, 4l and 4o were also
obtained under higher temperatures. As for some dienes
containing oxygen atoms, the reaction systems would turn black
and the dimethyl acetylenedicarboxylate 2a couldn’t convert to
the products 4g, 4h, 4i, 4j, and 4o completely. Moreover, the
reactivity of (E)-buta-1,3-dien-1-ylbenzene was also examined
in the cycloaddition. But the products 4p was not isolated, due
to the complexed reaction systems.
55% yield
99% ee
54% yield
98% ee
32% yield
97% ee
62% yield
70% ee
C6H5
OMOM
O
C6H5
OTBS
O
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
4j e
4k f
73% yield
97% ee
4l f
57% yield
94% ee
4i
44% yield
92% ee
28% yield
98% ee
Ts
O
O
N
C6H5
O
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
4o g
23% yield
17% ee
4m
51% yield
96% ee
4n d
4p
--
73% yield
98% ee
O
n-C5H11
CO2iPr
n-C5H11
O
CO2Et
HN
CO2Me
CO2Me
CO2Me
CO2Me
CO2iPr
CO2Et
4q c
--
4s d
73% yield
97% ee
4t e
25% yield
91% ee
4r
--
Ts
n-C5H11
n-C5H11
CO2Me
n-C5H11
N
COMe
CO2CH3
C6H5
C6H5
4u c
4v
4w
4x
84% yield
7% ee
--
--
--
Apart from the linear and branched dienes, pyridin-2(1H)-
one and 2-methylfuran were attempted to use as cyclic dienes
to construct bridged-ring products 4q and 4r in the
cycloaddition respectively. When the pyridin-2(1H)-one was
subjected to the reaction, the reaction system turned to be
complexed and the product 4q was not isolated. When 2-
methylfuran was utilized in the cyclization, it was found that the
2-methylfuran didn’t reactive with (E)-nona-1,3-diene 3a under
a Reaction conditions: 2 (0.2 mmol), 3 (0.6 mmol), Rh(NBD)2BF4
(10 mol%), L5 (12 mol%), and AgSbF6 (20 mol%), in toluene (3
b
c
mL) under N2, 24 h. Isolated yield. In 1,2-dichloroethane (3
mL) at 25 °C, 24 h d In toluene (2 mL) and 1,2-dichloroethane (1
mL) at 25 °C,72 h. e In toluene (2 mL) and 1,2-dichloroethane (1
mL) at 50 °C,72 h. f in toluene (3 mL) at 50 °C, 72 h. g in toluene
(3 mL) at 110 °C, 72 h. -- Not isolated.
This journal is © The Royal Society of Chemistry 20xx
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ARTICLE
Journal Name
the standard conditions.
-me 2, A). Except for the oxidations, the hydrolyVsiieswoArftic4leaOwnlianes
also performed, resulting in the dicarboxylic acid 6a in 97% yield
with 99% ee (Scheme 2, A), which has a potential to synthesize
the glycosidase inhibitor analogues.26
After screening various dienes, the effect of different
substituted alkynes was investigated. Firstly, two dialkyl
acetylenedicarboxylates were employed in the cycloaddition
and the results implied that larger steric hinderance of the
acetylenedicarboxylate would result in lower reactivity (Table 2,
4s and 4t). Then, methyl 2-butynoate, methyl 3-
phenylpropiolate and 4-phenylbut-3-yn-2-one were utilized as
starting materials in the cycloaddition. Unfortunately, they
didn’t react with (E)-nona-1,3-diene 3a and the corresponding
products 4u, 4v and 4w were not obtained. Additionally, we
attempted to employ this rhodium(I)-chiral phosphoramidite
complex to catalyze the intramolecular [4+2] cycloaddition. But
only a significantly low enantioselectivity was obtained (Table 2,
4x).
Further transformations of the Enantio-enriched products
were performed. Since the construction of the polysubstituted
benzenes has emerged as powerful methods in the total
synthesis of Daphenylline,22 and Clostrubin,23 the dimerization
of Artemisinin,24 and the macrocyclic ring formation of
conjugated macrocycles,25 the oxidative aromatization was
carried out firstly to give the 1,2,3-tri-substituted benzene 5a in
42% yield with using DDQ as an oxidant. Interestingly, 4c could
be converted to 5c in 61% yield just under air for a month (Sche-
DOI: 10.1039/D0OB00361A
To evaluate the practicability and explore the potential of
this synthetic method, the scale-up reactions were conducted
(Scheme 2, B). Initially, 1 g of 2a was subjected to this
cycloaddition, resulting in the product 4a in 95% yield and with
99% ee, in which the yield and enantioselectivity were
successfully maintained. Encouraged by this perfect result, an
increased scale reaction on 10 g of 2a was performed. To our
delight, the larger scale reaction also proceeded smoothly,
affording 4a in 92% yield and with 99% ee. Notably, the
superabundant 3a was recyclable through column
chromatography. Based on the good scalability, this robust
cycloaddition showed a great potential in synthetic chemistry.
A plausible mechanism for this rhodium(I)-catalyzed [4+2]
cycloaddition is showed in Scheme 3.15, 18, 27 Firstly, the pre-
prepared rhodium (I)-complex coordinates with dimethyl
acetyl-enedicarboxylate 2a and 1,3-diene. After an oxidative
cyclization, the rhodacyclopentene species 7a is formed, which
predominates the steric selectivity of this transformation. Next,
a
suprafacial 1,3-allylic migration18 occurs to form
a
rhodacycloheptadiene intermediate 7c through
a
metal-
A)
mediated 3-complex 7b. Finally, the cycloadduct is obtained in
the process of reductive elimination, along with the
regeneration of rhodium (I)-complex.
R
n-C5H11
CO2H
R
CO2Me
CO2Me
CO2Me
CO2Me
4a
4c
DDQ for
air for
NaOH
CO2H
6a
R= n-C5H11
,
, 97% yield
99% ee
Conclusions
In summary, we have developed
5a,
42% yield;
R= n-C5H11
,
.
4a
;
5c
R= CH3, , 61% yield.
4c
R= CH3,
a
rhodium(I)-chiral
phosphoramidite complex catalyzed intermolecular [4+2]
cycloaddition. The reaction was tolerated with a range of
functional groups and performed under mild conditions with up
to 96% yield and > 99% ee, thereby providing a practical method
for direct synthesis of the substituted cyclohexa-1,4-dienes in
an asymmetric fashion. The scale-up reactions and
derivatizations of products were also performed respectively.
Further investigations to extend this protocol into natural
product synthesis are ongoing in our laboratory. The results will
be reported in due course.
B)
n-C5H11
CO2Me
CO2Me
L5
Rh(NBD)2BF4,
3a
AgSbF6,
(3 equiv.)
toluene, 25 o
N2, 72 h
C
CO2Me
CO2Me
2a
1 g
4a
95% yield, 99% ee
92% yield, 99% ee
10 g scale
10 g
Scheme 2 Derivatizations and large-scale experiments.
reductive
CO2Me
CO2Me
Experimental section
General procedure:
coordination
elimination
MeO2C
Rh(III)
*
2a
Rh(I)
Rh(I)
R
A Schlenk tube equipped with a stir bar was charged with
Rh(NBD)2BF4 (3.73 mg, 0.02 mmol), L5 (10.7 mg, 0.024 mmol)
and AgSbF6 (13.7 mg, 0.04 mmol) under nitrogen atmosphere.
Then corresponding solvent was added to the tube via syringe
and the resulting mixture was stirred at 25 °C for 1 h. The
reaction was started by addition of the 1,3-dienes (0.6 mmol)
and substituted alkynes (0.2 mmol) separately via syringe. The
reaction was allowed to stir at the corresponding temperature.
When the reaction was completed, the solvent was
evaporated to give a crude product, which was purified with
column chromatography on silica gel or prepared TLC.
CO2Me
R
7c
R
*
CO2CH3
CO2CH3
oxidative
suprafacial
1,3-allylic
migration
cyclization
CO2Me
MeO2C
CO2Me
Rh(III)
*
MeO2C
Rh(III)
R
7b
7a
R
Scheme 3 A Plausible mechanism for the [4+2] cycloaddition.
4 | J. Name., 2012, 00, 1-3
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12 (a) A. Carbonaro, A. Greco, G. DallAsta, J. Org. Chem., 1968,
Procedure for the [4+2] cycloaddition on 10 g scale:
33, 3948; (b) S.-J. Paiks, S. U. Son, Y. K. Chung, OrVgie.wLeAtrttic.,le1O9n9lin9e,
DOI: 10.1039/D0OB00361A
To a flame-dried 2 L two-necked flask equipped with a stir
bar was charged with the chiral phosphoramidite L5 (3.78 g,
8.44 mmol), Rh(NBD)2BF4 (2.63 g, 7.03 mmol) and AgSbF6 (4.83
g, 14.07 mmol) under N2. After addition of the anhydrous
toluene (50 mL) to the flask, the resulting mixture was stirred
for 4 h at 25°C and then another 950 mL of anhydrous toluene
was added to the flask. The reaction system was cooled to 0 °C,
then the (E)-1,3-nonadiene (26.20 g, 211.11 mmol) and
dimethyl acetylenedicarboxylate (10 g, 70.37 mmol) were
added to the flask via syringe, respectively. The reaction system
was allowed to warm to 25 °C and stir at 25 °C for 72 h. When
the reaction was completed, it was quenched with water. After
purification of the crude product, a light brown liquid was
obtained.
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Conflicts of interest
There are no conflicts to declare.
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We are grateful for the financial support from the National
Natural Science Foundation of China (Grant No.21871067), the
Natural Science Foundation of Guangdong Province (Grant No.
2018A030313038), the Shenzhen Fundamental Research
Projects (Grant No. JCYJ20180306171838187), the Harbin
Institute of Technology (Shenzhen) (Talent Development
Starting Fund from Shenzhen Government) and the Open
Project Program of Beijing National Laboratory for Molecular
Sciences (BNLMS201819).
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Organic & Biomolecular Chemistry
Page 6 of 6
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DOI: 10.1039/D0OB00361A
R
R
CO2Me
R'
CO2Me
CO2Me
*
[Rh(NBD)2]BF4
R'
+
chiral phosphoramidite
CO2Me
up to 96% yield
up to > 99% ee
scale up to 10 g
high functional-group tolerance
A highly enantioselective and scalable intermolecular [4+2] cycloaddition to construct the
substituted cyclohexa-1,4-dienes.