2,3-Dichloro-5,6-dicyano-para-benzoquinone (DDQ)/methanesulfonic acid (MsOH)-mediated intramolecular arene-alkene oxidative coupling

Article abstract of DOI:10.1002/adsc.201301169

An efficient intramolecular arene-alkene oxidative coupling of 1,4-diaryl-1,3-butadienes has been developed involving the use of a 2,3-dichloro-5,6-dicyano-para-benzoquinone (DDQ)/acid catalyst. The reaction involves the generation of a radical cation by abstraction of an electron from the substrate with DDQ, an intramolecular Friedel-Crafts-type reaction, and the loss of hydrogen radical.

Full text of DOI:10.1002/adsc.201301169

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DOI: 10.1002/adsc.201301169
2,3-Dichloro-5,6-dicyano-para-benzoquinone (DDQ)/Methanesul-
fonic Acid (MsOH)-Mediated Intramolecular Arene-Alkene
Oxidative Coupling
Ko Hoon Kim,a Cheol Hee Lim,a Jin Woo Lim,a and Jae Nyoung Kima,*
a
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Korea
Fax : (+82)-62-530-3389; e-mail: kimjn@chonnam.ac.kr
Received: December 24, 2013; Published online: February 20, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201301169.
Abstract: An efficient intramolecular arene-alkene
oxidative coupling of 1,4-diaryl-1,3-butadienes has
been developed involving the use of a 2,3-dichloro-
5,6-dicyano-para-benzoquinone (DDQ)/acid cata-
lyst. The reaction involves the generation of a radi-
cal cation by abstraction of an electron from the
substrate with DDQ, an intramolecular Friedel–
Crafts-type reaction, and the loss of hydrogen radi-
cal.
As a formal intramolecular oxidative coupling be-
tween an arene and an alkene, the intramolecular
Friedel–Crafts (IMFC) alkylation of arylalkenes and
a following aromatization (via oxidation or elimina-
tion) has also been reported.[4] IMFC alkenylation can
provide such annulation products directly; however,
the reaction required arylalkynes instead of arylal-
kenes.[5] As another formal intramolecular oxidative
bond-formation between an arene and an alkene,
a 6p-electrocyclization (thermal or photochemical) of
1-aryl-1,3-butadiene and a following aromatization
has been used effectively in some cases.[6]
Keywords: arene-alkene oxidative coupling; 2,3-di-
chloro-5,6-dicyano-para-benzoquinone (DDQ); in-
tramolecular Friedel–Crafts reaction; radical cat-
ions
DDQ
(2,3-dichloro-5,6-dicyano-para-benzoquin-
AHCTUNGTREGoNNUN ne) is readily available oxidizing reagent and has
been used as an effective dehydrogenation reagent.
Recently, the synthetic applications of DDQ have
been thoroughly investigated for the cross-dehydro-
genative coupling (CDC)[7a–g] and intramolecular de-
Intramolecular oxidative cross-coupling between an hydrogenative coupling (IDC) reactions.[7h,i] In addi-
arene and an alkene is an important transformation. tion, DDQ has been used extensively in intramolecu-
Various aromatic and heteroaromatic compounds lar Scholl-type arene-arene coupling reactions.[8]
could be formed directly from their acyclic precursors
In these contexts, a direct and efficient intramolec-
using oxidative cross-coupling.[1,2] Stoltz and co-work- ular arene-alkene oxidative coupling method is highly
ers reported a palladium-catalyzed oxidative cycliza- required. In addition to the intramolecular oxidative
tion of arylalkenes (intramolecular Fujiwara–Moritani arene-alkene coupling, VOF3 and Pd(II)/oxidant[1k,9]
[3]
reaction) for the synthesis of functionalized benzofur- have also been used for the intramolecular Scholl-
ans from aryl allyl ethers.[1a] Glorius and co-workers type arene-arene coupling reaction as well. However,
developed a palladium-catalyzed oxidative cyclization DDQ has not been applied for the intramolecular oxi-
of N-arylenamines to open an efficient way to indoles dative arene-alkene coupling, to the best of our
from anilines.[1b,c] Such transition metal-catalyzed oxi- knowledge. Thus, we decided to examine the feasibili-
dative annulations of arylalkenes has received con- ty of an intramolecular arene-alkene oxidative cou-
tinuing interest[1d–k] and has also been used for the pling reaction mediated by DDQ.
synthesis of some natural products.[1l–n]
We selected methyl 1,4-diphenyl-1,3-butadiene-2-
Very recently, Niphakis and Georg reported carboxylate 1a as a model compound, which can be
a novel VOF3-mediated arene-alkene oxidative cou- easily prepared from the Morita–Baylis–Hillman
pling during the synthesis of phenanthroindolizi- (MBH) adduct via three steps.[10] We assumed that
dines.[2] They successfully applied vanadium oxytri- the reaction between a styryl moiety of 1a and DDQ
fluoride, which has been widely used for the intramo- would produce a radical cation intermediate I which
lecular Scholl-type arene-arene coupling,[3] to their in- could be converted to naphthalene 2a via an oxidative
tramolecular arene-alkene oxidative coupling.
cyclization, as shown in Scheme 1.
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Thus we reduced the amount of the acid catalyst;
however, the reaction was sluggish at room tempera-
ture (entry 2). When we carried out the reaction at
608C (entry 3), 2a was obtained in high yield
(80%).[11] The reaction in benzene (entry 4) showed
a similar result, while no reaction was observed in tol-
uene (entry 5, vide infra).[12] Without DDQ no reac-
tion was observed (entry 6) and 1a was not decom-
posed as compared to the result of entry 1. The reac-
tion at refluxing temperature (entry 7) or in the pres-
ence of 5 mol% of MsOH (entry 8) did not show
a better result. The use of AcOH was completely inef-
fective (entry 9) and CF3COOH was less effective
than MsOH (entry 10). It is interesting to note that
the use of FeCl3 produced 2a in moderate yields at
608C (entry 11) or even at room temperature
(entry 12). However, the yield of 2a was slightly lower
than that of the entry 3. No reaction was observed
Scheme 1. Rationale of intramolecular arene-alkene oxida-
tive coupling.
The reaction of 1a in the presence of DDQ in 1,2- without DDQ (entry 13) and the use of LiClO4 was
dichloroethane (DCE) did not produce 2a in any not effective (entry 14). Replacement of DDQ with
trace amount at room or even at reflux temperature. other oxidants such as benzoquinone (BQ) and p-
However, when we used an acid catalyst – methane- chloranil was totally ineffective (entries 15 and 16).
sulfonic acid (MsOH) – as in the reported intramolec-
As noted above, the reaction of 1a in the presence
ular Scholl-type reactions,[8] naphthalene 2a was ob- of MsOH did not produce 2a without DDQ (entry 6
tained albeit in low yield. Encouraged by the result, in Table 1). From the result, the following two routes
we examined various conditions for the conversion of for the formation of 2a would be regarded as less
1a to 2a, and the results are summarized in Table 1. A probable; (i) thermal 6p-electrocyclization/oxidation
severe decomposition of 1a was observed in the pres- and (ii) IMFC alkylation/oxidation. In order to check
ence of one equivalent of MsOH even at room tem- the possibility of 6p-electrocyclization of 1a under
perature (entry 1).
more drastic conditions, the reaction was examined in
ortho-dichlorobenzene (ODCB) at reflux temperature
(1808C); however, no reaction was observed as shown
in Scheme 2. The reaction even in the presence of
DDQ did not produce 2a at all. In addition, the reac-
tion of 1a was examined in refluxing benzene (20 h)
Table 1. Optimization of reaction conditions.
Entry Oxidant[a] Additive[b]
Solvent T/t[c] 2a[%][d]
1
2
3
4
5
6
7
8
DDQ
DDQ
DDQ
DDQ
DDQ
none
DDQ
DDQ
DDQ
DDQ
DDQ
DDQ
none
MsOH (1.0) DCE
MsOH (0.1) DCE
MsOH (0.1) DCE
25/5 13[e]
25/20 5[f]
60/5 80
MsOH (0.1) benzene 60/7 74
MsOH (0.1) toluene 60/7 0[g]
MsOH (1.0) DCE
MsOH (0.05) DCE
MsOH (0.05) DCE
AcOH (0.1) DCE
60/5 0[g]
83/4 66
60/7 77
9
83/7
0
10
11
12
13
14
15
16
TFA (0.1)
FeCl3 (0.1)
FeCl3 (0.1)
FeCl3 (0.1)
DCE
DCE
DCE
DCE
60/7 35
60/7 64
25/10 65
83/5
83/5
83/5
83/5
0
0
0
0
DDQ
BQ
LiClO4 (0.1) DCE
MsOH (0.1) DCE
p-chloranil MsOH (0.1) DCE
[a]
[b]
[c]
[d]
[e]
[f]
Oxidant was used in 1.1 equiv.
The equiv. of additive in parenthesis.
Temperature T [oC] and time t [h].
Isolated yield.
Complete decomposition of 1a.
65% of 1a was recovered.
[g]
95% of 1a was recovered.
Scheme 2. Trials of indirect route toward 2a.
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2,3-Dichloro-5,6-dicyano-para-benzoquinone/Methanesulfonic Acid
Table 3. DDQ/MsOH-mediated arene-alkene coupling of
1k–t.
in the presence of H2SO4 (2.0 equiv.) in order to ex-
amine the possibility of IMFC alkylation. However,
no reaction was observed. When we used stronger
acid TfOH (2.0 equiv.), we could obtain 3a in low
yield (33%) by the IMFC alkylation pathway along
with its acid derivative 4a (37%). The acid 4a was not
formed by the hydrolysis of 3a. As also shown in
Scheme 2, 4a must be formed via the lactone inter-
mediate, as in our previous paper.[13] DDQ-mediated
dehydrogenation of 3a afforded 2a in good yield
(95%). From the results, both 6p-electrocyclization
and IMFC alkylation accompanying DDQ-mediated
dehydrogenative aromatization pathway could be ex-
cluded.
Encouraged by the results, various 1,3-diene deriva-
tives 1b–t were prepared from the corresponding
MBH bromides via the Wittig reaction according to
the reported methods.[10] The DDQ/MsOH-mediated
intramolecular arene-alkene oxidative couplings of
1b–t were examined under the standard condition
(entry 3 in Table 1), and the results are summarized in
Table 2 and Table 3. Table 2 summarizes the results of
Table 2. DDQ/MsOH-mediated arene-alkene coupling of
1a–j.
[a]
DDQ (1.1 equiv.), MsOH (0.1 equiv.), DCE, 608C, 5 h.
[b]
1k (R1 =3-MeOC6H4, R2 =Ph), 1l (R1 =3,4-Cl2C6H3, R2 =
Ph), 1m (R1 =3-NO2C6H4, R2 =Ph), 1n (R1 =2-BrC6H4,
R2 =Ph), 1o (R1 =4-MeC6H4, R2 =Ph), 1p (R1 =2-furyl,
R2 =Ph), 1q (R1 =2-naphthyl, R2 =Ph), 1r (R1 =1-naph-
thyl, R2 =Ph), 1s (R1 =1-naphthyl, R2 =1-naphthyl), 1t
(R1 =2-naphthyl, R2 =1-naphthyl).
[c]
Carried out in the presence of 0.05 equiv. of MsOH (7 h),
and the yield of 2o decreased to 47% in the presence of
0.1 equiv. of MsOH (2 h).
1,3-dienes 1a–j, which were prepared by the Wittig re-
action between various aldehydes and the MBH bro-
mide of benzaldehyde. Table 3 includes the results of
1k–t that were prepared from diversely-modified
MBH bromides. As shown in Table 2, the reactions of
4-chlorophenyl derivative 1b and 4-methoxyphenyl
derivative 1c provided 2b and 2c in good yields (81%
and 78%). However, the reaction of 4-nitrophenyl de-
rivative 1d did not produce any trace amount of 2d.
An electron abstraction from 1d by DDQ would be
difficult due to the presence of an electron-withdraw-
ing 4-nitro group, and the corresponding radical
cation cannot be formed. The reactions of 4-biphenyl
derivative 1e and 1-naphthyl derivative 1f afforded 2e
and 2f in good yields (82% and 78%). The acetyl de-
rivative 1g also produced 2g without a problem in
slightly lower yield (75%). Even the styryl derivative
[a]
DDQ (1.1 equiv.), MsOH (0.1 equiv.), DCE, 608C, 5 h.
1a (R=Ph), 1b (R=4-ClC6H4), 1c (R=4-MeOC6H4), 1d
(R=4-NO2C6H4), 1e (R=4-PhC6H4), 1f (R=1-naph-
thyl), 1g (R=Ph, E=COMe), 1h (R=styryl), 1i (R=5-
methyl-2-thienyl), 1j (R=n-pentyl).
[b]
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Ko Hoon Kim et al.
1h provided 2h in moderate yield (72%). Unfortu- time (80 h). To our delight, 6a could be isolated in an
nately, the reaction of 2-thienyl derivative 1i failed, excellent yield (95%) in the presence of 2.0 equiv. of
and many intractable side products were observed.[14] FeCl3 for 16 h. The reaction in the presence of MsOH
The reaction of n-pentyl derivative 1j also failed pre- (2.0 equiv.) gave the best result to give 6a in a quanti-
sumably due to the instability of the alkyl radical tative yield (98%) in a short time (12 h). The result
cation.
clearly implied that the use of an excess amount of
As shown in Table 3, the reactions of 3-methoxy- MsOH is helpful to the electron abstraction by DDQ.
phenyl derivative 1k and 3,4-dichlorophenyl deriva- In order to check the possibility of an acid-catalyzed
tive 1l produced 2k and 2l in good yields (84% and IMFC alkylation pathway, the reaction of 5a was ex-
81%). A single regioisomer was obtained in the reac- amined in the presence of MsOH without DDQ
tions, and the other possible regioisomer was not ob- under an O2 balloon atmosphere. The reaction did
served at all. The reaction of 3-nitrophenyl derivative not show the formation of 6a or its dihydro intermedi-
1m showed no conversion. The failure of 1m strongly ate. It is interesting to note that the reaction in tolu-
suggested that the cyclization would be a cationic ene was completely ineffective as in the case of 1a
mechanism involving either an IMFC alkylation of (vide supra, entry 5 in Table 1).[12]
a radical cation or an IMFC alkenylation of a vinyl
Thus, the reactions of similar 1,4-diaryl-1,3-buta-
cation (vide infra). The reactions of 1n and 1o afford- dienes 5b–f were examined, as shown in Table 4. The
ed 2n and 2o in good yields (79% and 68%), while 2- reaction of 4-methoxyphenyl derivative 5b afforded
furyl derivative 1p was decomposed under the reac- 6b in good yield (86%). The regioisomeric compound
tion condition as in the reaction of 1i (vide supra).[14] 6b’ was not formed at all (vide infra, Scheme 4), and
It is interesting to note that the benzofulvene deriva- the result implied that an electron abstraction by
tive was prepared from 2-bromo derivative 1n under DDQ occurred at the 4-methoxybenzylidene moiety
palladium-catalyzed Mizoroki–Heck reaction condi- selectively. In contrast to 5b, the reaction of 4-chloro-
tions.[10c] Four phenanthrene derivatives 2q–t were phenyl derivative 5c produced an inseparable mixture
synthesized from 1q–t in good to high yields (78– of 6c and 6c’ (ca. 1:1) in an excellent yield (98%). The
86%). For the synthesis of 2q and 2t, bond formations reaction of a symmetrical bis(4-methoxybenzylidene)
proceeded at the 1-position of the naphthalene ring derivative 5d gave 6d in moderate yield (56%) in the
regioselectively.
presence of 0.1 equiv. of MsOH at 608C. The reaction
As a next entry, we examined the reaction of bis- of 5d produced many side products in the presence of
benzylidenesuccinimide 5a,[6b,15] as shown in 2.0 equiv. of MsOH at reflux temperature. The reac-
Scheme 3. The substrate 5a is different with 1a–t in tion of 5e gave 6e in an excellent yield (98%). The re-
that both alkenes of 5a are connected to electron- action of anhydride derivative 5f required a long re-
withdrawing carbonyl groups. The HOMO energy of action time (50 h) for the completion,[16] and com-
the double bond of 5a would be lowered by conjuga- pound 6f was isolated in moderate yield (61%).
tion with a carbonyl group, and the abstraction of an
The selective formation of 6b has proven that a radi-
electron from 5a with DDQ would be difficult as cal cation IV was formed selectively instead of III, as
compared to 1a–t.[16] As expected, the formation of shown in Scheme 4. The cation at the 4-methoxyben-
a trace amount (<5%) of benzo[f]isoindole-1,3-dione zylic position of IV could be stabilized by the me-
6a[15b] was observed under the standard conditions thoxy group to form a resonance-stabilized distonic
employing MsOH (0.1 equiv.) in refluxing DCE even radical cation form VI. In addition, the radical at the
after 20 h. The reaction of 5a in the presence of FeCl3 homobenzylic position of IV could be isomerized to
(0.2 equiv.) also showed a sluggish reactivity, and 6a a benzylic position to make the electrophilic cycliza-
was obtained in low yield (36%) even after a long tion more facile. The results stated that the reaction
would be controlled not by the electronic nature of
attacking arene moiety but by the formation of more
stable radical cation intermediate.
As a next entry, we examined the reaction of 2-styr-
ylbiphenyl derivative 7a, as shown in Scheme 5. The
starting material 7a was prepared by Catellani-type
reaction from 2-iodotoluene and styrene, as report-
AHCTUNGTRENNUNG
ed.[17a] The reaction of 7a did not afford the phenan-
threne derivative 8a in reasonable yield under the
standard condition employing MsOH. No reaction
was observed even at refluxing temperature with
20 mol% of MsOH. Only 5% of 8a was formed with
2.0 equiv. of MsOH accompanied with severe decom-
position. Fortunately, 8a was obtained in moderate
Scheme 3. Synthesis of benzo[f]isoindole-1,3-dione 6a.
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2,3-Dichloro-5,6-dicyano-para-benzoquinone/Methanesulfonic Acid
Table 4. Synthesis of benzo[f]isoindole-1,3-diones.[a]
Scheme 4. Selective formation of 6b.
Scheme 5. The reaction of 2-styrylbiaryls.
Mizoroki–Heck reaction.[17b] However, the reaction of
7c in the presence of 5.0 mol% of FeCl3 afforded 8c
in a similar yield (65%) to that of 8a. The radical
cation intermediates VII and VIII (corresponding to I
[a]
Carried out in DCE in the presence of DDQ (1.1 equiv.).
yield (48%) by using FeCl3 (0.1 equiv.) at 608C for and X in Scheme 6, vide infra) cannot be stabilized by
2 h (vide supra, entry 11 in Table 1). The best yield of delocalization, as shown in Scheme 5. This might be
8a (63%) was obtained under the influence of one of the reasons for the low yields of 8a–c.
5 mol% of FeCl3. Analogously, the synthesis of 8b
Based on the experimental results, we proposed
from 7b was ineffective. Among the many trials, the a plausible reaction mechanism for the formation of
reaction of 7b afforded 8b in reasonable yield (45%) 2a as an example, as shown in Scheme 6. An electron
when we used 20 mol% of FeCl3. Although the abstraction of 1a by DDQ produced a radical cation
reason for the low yield of 8b is not clear at this I. An IMFC-type alkylation of either I or its distonic
stage, there has been reported a similar example for benzylic radical cation IX would produce a cyclic rad-
the failure in FeCl3/DDQ-mediated CDC/benzoannu- ical cation X, which loses a proton and hydrogen radi-
lation between 1,2-diarylpropene and styrene bearing cal to give 2a (a-route). However, another plausible
a methoxy substituent.[7g] In order to eliminate a plau- mechanism cannot be ruled out involving an initial
sible harmful effect of a methyl[12] or methoxy loss of hydrogen radical from I to form a vinyl cation
group[7g] in the reaction, 2-styrylbiphenyl (7c, R=H) XI and a subsequent IMFC-type alkenylation process
was prepared from 2-bromobiphenyl and styrene by (b-route).[5] The role of an acid catalyst is not clear at
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Acknowledgements
This research was supported by Basic Science Research Pro-
gram through the National Research Foundation of Korea
(NRF) funded by the Ministry of Education, Science and
Technology (2012R1A1B3000541). Spectroscopic data were
obtained from the Korea Basic Science Institute, Gwangju
branch.
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Scheme 6. Proposed reaction mechanism.
this stage; however, it might facilitate the electron
transfer process between the substrate and DDQ.[8a–c]
In summary, we have disclosed an efficient intramo-
lecular arene-alkene oxidative coupling of 1,4-diaryl-
1,3-butadienes using DDQ in the presence of an acid
catalyst. The widely-used DDQ/acid-catalyzed intra-
molecular Scholl-type reaction conditions are success-
fully applied to an intramolecular arene-alkene oxida-
tive coupling for the first time. The reaction involved
a generation of radical cation by abstraction of an
electron from the substrate with DDQ, an intramolec-
ular Friedel–Crafts-type cyclization, and a loss of hy-
drogen radical. Further studies on the reaction mech-
anism and scope of the reaction are currently under-
way.
Experimental Section
Typical Procedure for the Synthesis of 2a
To a stirred green solution of 1a (132 mg, 0.5 mmol) and
DDQ (125 mg, 1.1 equiv.) in DCE (1.5 mL) at room temper-
ature was added MsOH (5 mg, 10 mol%). Instantaneously
the green color changed to dark green on addition of
MsOH. The dark green reaction mixture was heated to
608C for 5 h. The color of the reaction mixture slowly
turned to brown. After the usual aqueous extractive work-
up and column chromatographic purification process (hex-
anes/ether, 30:1), product 2a was obtained as a white solid;
yield: 105 mg (80%).
[5] For the IMFC-type alkenylation of arylalkynes, see:
a) S. Gowrisankar, K. Y. Lee, C. G. Lee, J. N. Kim, Tet-
rahedron Lett. 2004, 45, 6141–6146, and further referen-
ces cited therein; b) C. E. Song, D.-u. Jung, S. Y.
Choung, E. J. Roh, S.-g. Lee, Angew. Chem. 2004, 116,
702
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a green color appeared presumably due to the forma-
tion of a charge-transfer complex between 1a and
DDQ. The green color deepened instantaneously by
addition of MsOH presumably due to the formation of
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turned to brown by the reaction progress.
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À
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[15] For the preparation of bisbenzylidenesuccinic anhy-
dride or N-phenylimides and their synthetic applica-
Adv. Synth. Catal. 2014, 356, 697 – 704
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asc.wiley-vch.de
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COMMUNICATIONS
Ko Hoon Kim et al.
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AgCl (in CH2Cl2 containing 0.2M tetra-n-butylammo-
nium hexafluorophosphate at a scan rate 200 mVsÀ1).
According to the reports of Rathore,[8a–c] DDQ (Ered
=
0.6 V) in the presence of an acid catalyst readily oxidiz-
es an electron donor with oxidation potential as high as
about 1.7 V.
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[16] The oxidation potentials of 5a and 5f were 1.9 and
2.0 V, respectively, while that of 1a was 1.7 V vs. Ag/
704
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Adv. Synth. Catal. 2014, 356, 697 – 704