Synthesis of tri- and diaryloxybenzenes by rhodium-catalyzed complete intermolecular [2+2+2] cycloaddition of aryl ethynyl ethers

Article abstract of DOI:10.1055/s-0030-1259064

We have established that a cationic rhodium(I)-H₈-BINAP complex catalyzes the complete intermolecular homo-[2+2+2] cycloaddition of aryl ethynyl ethers and cross-[2+2+2] cycloaddition of aryl ethynyl ethers with electron-deficient monoalkynes,

Full text of DOI:10.1055/s-0030-1259064

3092
LETTER
Synthesis of Tri- and Diaryloxybenzenes by Rhodium-Catalyzed Complete
Intermolecular [2+2+2] Cycloaddition of Aryl Ethynyl Ethers
Synthesis of
Tri-
a
o
nd Diaryloxy
s
benzene
s
hiyuki Komine, Yuta Miyauchi, Masayuki Kobayashi, Ken Tanaka*
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology,
Koganei, Tokyo 184-8588, Japan
Fax +81(42)3887037; E-mail: tanaka-k@cc.tuat.ac.jp
Received 5 October 2010
cross-[2+2+2] cycloaddition of aryl ethynyl ethers with
Abstract: We have established that a cationic rhodium(I)–H8-
BINAP complex catalyzes the complete intermolecular homo-
[2+2+2] cycloaddition of aryl ethynyl ethers and cross-[2+2+2] cy-
cloaddition of aryl ethynyl ethers with electron-deficient
monoalkynes, leading to tri- and diaryloxybenzenes, respectively,
at room temperature.
electron-deficient internal monoalkynes, leading to tri-
and diaryloxybenzenes,10 respectively, at room tempera-
ture (Scheme 1).
We first investigated the homo-[2+2+2] cycloaddition of
ethynyl 2-naphthyl ether (1a)11 in the presence of the cat-
ionic rhodium(I)–BIPHEP complex (10 mol%) as a cata-
lyst. Pleasingly, the desired homo-[2+2+2] cycloaddition
proceeded at room temperature for only 1 hour to give
1,3,5- and 1,2,4-triaryloxybenzenes 2a and 3a in good
yield (Table 1, entry 1). The effect of biaryl bisphosphine
ligands was then examined (entries 1–4), which revealed
that the use of H8-BINAP (Figure 1) furnished 2a and 3a
in the highest yield, and 1,3,5-triaryloxybenzene 2a was
Key words: alkynes, aryl ethynyl ethers, [2+2+2] cycloaddition,
H8-BINAP, rhodium
The transition-metal-catalyzed complete intermolecular
[2+2+2] cycloaddition of monoalkynes has been widely
examined for the atom economical and convergent syn-
thesis of substituted benzenes.1 Electronically and steri-
cally diverse arrays of monoalkynes have been employed
for this reaction, while alkynyl ethers have been scarcely
examined despite of their potential utility for the synthesis
of aryl ethers.2–7 An iron carbonyl complex is able to me-
diate the homo-[2+2+2] cycloaddition of an alkynyl ether,
but a reported substrate is limited to di-tert-butoxyacety-
lene.2 The regioselective cross-[2+2+2] cycloadditions of
cyclohexyl trimethylsilylethynyl ether with ethynyl tolyl
sulfone3 and ethyl ethynyl ether with 3-hexyne4 were re-
ported, but these reactions require a stoichiometric
amount of a titanium or zirconium complex. On the other
hand, our research group recently reported the rhodium-
catalyzed complete intermolecular cross-[2+2+2] cy-
cloaddition of aryl ethynyl ethers with nitriles or isocyan-
ates, leading to substituted diaryloxypyridines or
diaryloxy-2-pyridones, respectively.8,9 In this paper, we
describe the rhodium-catalyzed complete intermolecular
homo-[2+2+2] cycloaddition of aryl ethynyl ethers and
O
O
O
PAr2
PAr2
PPh2
PPh2
O
BIPHEP
Segphos (Ar = Ph)
DTBM-Segphos
(Ar = 4-MeO-3,5-t-Bu2C6H2)
PPh2
PAr2
PAr2
PPh2
BINAP
H8-BINAP (Ar = Ph)
xyl-H8-BINAP
(Ar = 3,5-Me2C6H3)
Figure 1
R1
O
O
O
R1
O
R2
2
r.t.
r.t.
O
O
O
R2
+
Rh(I) catalyst
Scheme 1
SYNLETT 2010, No. 20, pp 3092–3098
x
x
.x
x
.2
0
1
0
Advanced online publication: 24.11.2010
DOI: 10.1055/s-0030-1259064; Art ID: U08910ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Tri- and Diaryloxybenzenes
3093
nyl ethers 1b–e could be employed for this reaction to
give the corresponding triaryloxybenzenes in good to high
yields (entries 2–5). The reaction of sterically demanding
ethynyl 2-methylphenyl ether (1c, entry 3) improved the
regioselectivity of 1,3,5-triaryloxybenzene 2c over 1,2,4-
triaryloxybenzene 3c. Although regioselectivities of the
present homo-[2+2+2] cycloaddition reactions of aryl
ethynyl ethers 1a–e were moderate, two regioisomers
could be readily separated by a silica gel chromatography.
Table 1 Screening of Ligands for Rh-Catalyzed Homo-[2+2+2]
Cycloaddition of Aryl Ethynyl Ether 1a
OAr
[Rh(cod)2]BF4
ligand
ArO
OAr
OAr
OAr
2a
+
(2.5–10 mol%)
CH2Cl2, r.t.
1 h
OAr
Our research group reported that the cationic rhodium(I)–
H8-BINAP complex catalyzes the complete intermolecu-
lar cross-[2+2+2] cycloaddition of electron-rich terminal
monoalkynes with highly electron-deficient internal
monoalkynes (dialkyl acetylenedicarboxylates) to give
3,6-disubstituted phthalates in high yields with excellent
regioselectivity.13,14 In a previous report, we attempted the
complete intermolecular cross-[2+2+2] cycloaddition of
ethynyl 2-naphthyl ether (1a) with diethyl acetylenedicar-
boxylate in the presence of the cationic rhodium(I)–H8-
BINAP catalyst, however, the desired 3,6-diaryloxyph-
thalate was obtained in very low yield.8 Thus moderately
electron-deficient internal monoalkynes [ethyl 2-bu-
tynoate (4a)] was used instead of diethyl acetylenedicar-
boxylate. Pleasingly, the desired cross-[2+2+2]
cycloaddition proceeded at room temperature for one hour
to give diaryloxybenzenes 5aa and 6aa with moderate
yield and regioselectivity (Table 3, entry 1). Importantly,
regioisomeric diaryloxybenzenes 7aa and 8aa were not
detected at all in the crude reaction mixture. In the present
cross-[2+2+2] cycloaddition, the use of H8-BINAP as a
ligand is of critical importance. The use of BINAP, Seg-
phos, and BIPHEP dramatically decreased the yield of di-
aryloxybenzenes 5aa and 6aa due to the rapid homo-
[2+2+2] cycloaddition of 1a (entries 2–4). Increasing the
amount of 4a to 1.0 equivalent significantly increased the
yield of 5aa and 6aa, while further increase the amount of
4a to 2.0 equivalents furnished 5aa and 6aa in only slight
improved yield.
1a
(Ar = 2-naphthyl)
ArO
3a
Entry Ligand
Catalyst (mol%) Yield (%)a 2a/3ab
1
2
3
4
5
6
7
8
BIPHEP
10
10
10
10
10
10
5
75
74
72
92
73
57
85
78
48:52
47:53
58:42
63:37
41:59
44:56
60:40
62:38
Segphos
BINAP
H8-BINAP
xyl-H8-BINAP
DTBM-Segphos
H8-BINAP
H8-BINAP
2.5
a Isolated yield.
b Determined by 1H NMR.
obtained as a major regioisomer (entry 4). The use of ster-
ically demanding biaryl bisphosphine ligands decreased
the product yields (entries 5 and 6). The catalyst loading
could be reduced to 5 mol% or 2.5 mol% with slight loss
of the product yield (entries 7 and 8).
The scope of the triaryloxybenzene synthesis was then ex-
amined under the above optimal reaction conditions
(Table 2).12 Not only ethynyl 2-naphthyl ether (1a, entry
1) but also sterically and electronically diverse aryl ethy-
OAr
6 (minor)
R
OAr
R
CO2Et
R
or
Rh(I)+
OAr
ArO
CO2Et
ArO
2
5 (major)
1
δ–
δ+
δ+
δ–
CO2Et
EtO2C
ArO
R
Rh+
ArO
Rh+
Rh+
ArO
δ–
or
δ–
δ+
δ+
OAr
OAr
C (minor)
OAr
B (major)
A
CO2Et
R
4
Scheme 2
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Y. Komine et al.
LETTER
Table 2 Synthesis of Triaryloxybenzenes 2 and 3 by Rh-Catalyzed Homo-[2+2+2] Cycloaddition of Aryl Ethynyl Ethers 1a–ea
Entry
1
Yield of 2 (%)b
Yield of 3 (%)b
O
O
O
O
1
O
O
O
1a
3a 34
2a 51
O
O
O
2
O
O
O
O
1b
2b 40
3b 26
O
O
O
3
O
O
O
O
1c
3c 16
2c 46
OMe
O
OMe
OMe
MeO
O
O
4
O
O
MeO
O
O
OMe
1d
3d 25
OMe
2d 51
CF3
O
CF3
CF3
F3C
O
O
5
O
O
F3C
O
O
CF3
1e
3e 35
CF3
2e 54
a Reactions were conducted using 1a–e, [Rh(cod)2BF4 (5 mol%), H8-BINAP (5 mol%) in CH2Cl2 at r.t. for 1 h.
b Isolated yield.
Synlett 2010, No. 20, 3092–3098 © Thieme Stuttgart · New York

LETTER
Synthesis of Tri- and Diaryloxybenzenes
3095
Table 3 Screening of Ligands for Rh-Catalyzed Cross-[2+2+2] Cycloaddition of Aryl Ethynyl Ether 1a with Electron-Deficient Internal
Monoalkyne 4a
[Rh(cod)2]BF4/
OAr
CO2Et
ligand
(0.025–0.050 equiv)
+
CH2Cl2, r.t.
1 h
1a
4a
(Ar = 2-naphthyl)
(1.0 equiv)
OAr
OAr
ArO
+
CO2Et
CO2Et
CO2Et
ArO
CO2Et
+
+
ArO
ArO
OAr
OAr
5aa
6aa
7aa
8aa
Entry
Ligand
4a (equiv)
0.5
Rh (equiv)
0.025
Yield (%)a
5aa/6aa/7aa/8aab
73:27:0.0
1
2
3
4
5
6
H8-BINAP
BINAP
40
8
0.5
0.050
76:24:0.0
Segphis
0.5
0.050
3
70:30:0.0
BIPHEP
H8-BINAP
H8-BINAP
0.5
0.050
4
67:33:0.0
1.0
0.025
81
83
74:26:0.0
2.0
0.025
73:27:0.0
a Isolated yield of 5–8.
b Determined by 1H NMR.
Table 4 Synthesis of Diaryloxybenzenes 5 and 6 by Rh-Catalyzed Cross-[2+2+2] Cycloaddition of Aryl Ethynyl Ethers 1a–e with Electron-
Deficient Internal Monoalkynes 4a–ca
Entry
1
4
Yield of 5 and 6 (%)b
CO2Et
O
O
1
1a
CO2Et
O
O
O
CO2Et
4a
O
5aa 60
6aa 21
6ab 10
6ac
CO2Et
O
O
2
3
1a
1a
n-Bu
CO2Et
n-Bu
n-Bu
CO2Et
O
4b
5ab 45
CO2Et
O
O
Ph
CO2Et
Ph
Ph
CO2Et
O
4c
5ac
42c (5ac/6ac = 87:13)
Synlett 2010, No. 20, 3092–3098 © Thieme Stuttgart · New York

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Y. Komine et al.
LETTER
Table 4 Synthesis of Diaryloxybenzenes 5 and 6 by Rh-Catalyzed Cross-[2+2+2] Cycloaddition of Aryl Ethynyl Ethers 1a–e with Electron-
Deficient Internal Monoalkynes 4a–ca (continued)
Entry
1
4
Yield of 5 and 6 (%)b
CO2Et
4
1b
O
CO2Et
4a
O
5ba 37
CO2Et
O
5
6
1c
CO2Et
4a
O
5ca 19
OMe
OMe
CO2Et
O
O
1d
MeO
MeO
CO2Et
4a
O
CO2Et
O
5da 46
6da 24
CF3
CF3
CO2Et
O
O
7
1e
F3C
F3C
CO2Et
4a
O
CO2Et
O
5ea 54
6ea 25
a Reactions were conducted using 1a–e (1.0 equiv), 4a–c (1.0 equiv), [Rh(cod)2BF4 (0.025 equiv), H8-BINAP (0.025 equiv) in CH2Cl2 at r.t.
for 1 h.
b Isolated yield.
c Isolated as a mixture of 5ac and 6ac.
The scope of the diaryloxybenzene synthesis was then ex- pling of two aryl ethynyl ethers 1 with rhodium forms
amined under the above optimal reaction conditions rhodacyclopentadiene intermediate A. Subsequent regio-
(Table 4).15 Not only ethyl 2-butynoate (4a, entry 1) but selective coordination of 4 with intermediate A forms in-
also sterically demanding ethyl 2-heptynoate (4b, entry 2) termediate B over intermediate C, which results in the
and ethyl phenylpropiolate (4c, entry 3) could be em- observed regioselective formation of 5 over 6. Although
ployed for this reaction to give the corresponding diary- the chemoselective [2+2+2] cycloaddition between two
loxybenzenes in moderate to good yields with improved molecules of 1 and one molecule of 4 is not clear, the re-
regioselectivity of 5 over 6 (entries 2 and 3). With respect gioselective formation of 5 over 6 might be electronic
to aryl ethynyl ethers, the use of sterically demanding control. The C–C bond formation between electropositive
ethynyl 1-naphthyl ether (1b, entry 4) and ethynyl 2-me- alkyne carbon of 4 and the electronegative rhodacycle car-
thylphenyl ether (1c, entry 5) furnished the corresponding bon a to rhodium exhibits the observed regioselectivity.
diaryloxybenzenes 5ba and 5ca, respectively, with excel- The homo-[2+2+2] cycloaddition of 1, leading to triaryl-
lent regioselectivity, although the product yields de- oxybenzenes 2 and 3, was the sole side reaction in the
creased. On the other hand, electronic nature of aryl rhodium-catalyzed reaction between 1 and 4, which sup-
ethynyl ethers showed a small impact on both the product ports the initial formation of rhodacyclopentadiene inter-
yields and regioselectivity (entries 6 and 7).
mediate A.
Scheme 2 depicts a possible mechanism for the rhodium- Finally, the monoaryloxybenzene synthesis by the rhodi-
catalyzed complete intermolecular cross-[2+2+2] cy- um-catalyzed [2+2+2] cycloaddition of 1,6-diyne 9 with
cloaddition of aryl ethynyl ethers 1 with electron-deficient aryl ethynyl ether 1a was also examined.16 However, the
internal monoalkynes 4. The regioselective oxidative cou- cationic rhodium(I)–H8-BINAP catalyst was ineffective
Synlett 2010, No. 20, 3092–3098 © Thieme Stuttgart · New York

LETTER
Synthesis of Tri- and Diaryloxybenzenes
3097
Manolache, N. Tetrahedron Lett. 2006, 47, 963.
due to the rapid homo-[2+2+2] cycloaddition of 1a. After
screening phosphine ligands, the best result was obtained
by using dppe [1,2-bis(diphenylphosphino)ethane] as a
ligand, although the yield of the corresponding monoaryl-
oxybenzene 1017 was still low (Scheme 3).
(b) Dudley, G. B.; Takaki, K. S.; Cha, D. D.; Danheiser, R.
L. Org. Lett. 2000, 2, 3407. (c) Gevorgyan, V.; Quan, L. G.;
Yamamoto, Y. J. Org. Chem. 2000, 65, 568. (d) Morris, K.
G.; Saberi, S. P.; Thomas, S. E. J. Chem. Soc., Chem.
Commun. 1993, 209. (e) Danheiser, R. L.; Brisbois, R. G.;
Kowalczyk, J. J.; Miller, R. F. J. Am. Chem. Soc. 1990, 112,
3093. (f) Danheiser, R. L.; Gee, S. K.; Perez, J. J. J. Am.
Chem. Soc. 1986, 108, 806.
TsN
[Rh(nbd)2]BF4/
(6) For the nickel-catalyzed complete intermolecular cross-
[2+2+2] cycloaddition of two ethyl ethynyl ethers and
carbon dioxide, see: (a) Tsuda, T.; Kunisada, K.; Nagahama,
N.; Morikawa, S.; Saegusa, T. Synth. Commun. 1989, 19,
1575. (b) For the rhodium-catalyzed complete
ligand
O
9
(10 mol%)
+
TsN
CH2Cl2, r.t.
1 h
10
8% (ligand: H8-BINAP)
23% (ligand: dppe)
O
intermolecular cross-[2+2+2] cycloaddition of two ethyl
ethynyl ethers with an isocyanate, see: Oberg, K. M.; Lee,
E. E.; Rovis, T. Tetrahedron 2009, 65, 5056.
1a (1.1 equiv)
(7) For the nickel-catalyzed complete intermolecular cross-
[3+2+2] cycloaddition of ethyl cyclopropylideneacetate, an
internal 1,3-diyne, and an alkynyl ether, see: Yamasaki, R.;
Terashima, N.; Sotome, I.; Komagawa, S.; Saito, S. J. Org.
Chem. 2010, 75, 480.
(8) Komine, Y.; Tanaka, K. Org. Lett. 2010, 12, 1312.
(9) For the rhodium-catalyzed [2+2+2] cycloadditions of
phenol-linked 1,6-diynes with alkynes and nitriles, leading
to substituted dibenzofurans and azadibenzofurans, see:
Komine, Y.; Kamisawa, A.; Tanaka, K. Org. Lett. 2009, 11,
2361.
(10) Tri- and diaryloxybenzenes are useful compounds in
material sciences. For selected recent examples, see:
(a) Pei, S.; Chen, X.; Jiang, Z.; Peng, W. J. Appl. Polym. Sci.
2010, 117, 2069. (b) Yamanaka, M.; Fujii, H. J. Org. Chem.
2009, 74, 5390. (c) Chen, X.; Zhang, Y.; Liu, B.; Zhang, J.;
Wang, H.; Zhang, W.; Chen, Q.; Pei, S.; Jiang, Z. J. Mater.
Chem. 2008, 18, 5019. (d) Rao, X.; Dang, G.; Zhou, H.;
Yang, W.; Cui, G.; Chen, C.; Yokota, R. J. Polym. Sci., Part
A: Polym. Chem. 2007, 45, 4844.
(11) Aryl ethynyl ethers are stable compounds and can be readily
handled and purified without any special precautions. For
the synthesis of aryl ethynyl ethers 1a–e, see ref. 8.
(12) Typical Procedure (Table 2, Entry 1)
Scheme 3
In conclusion, we have established that a cationic rhodi-
um(I)–H8-BINAP complex catalyzes the complete inter-
molecular homo-[2+2+2] cycloaddition of aryl ethynyl
ethers and cross-[2+2+2] cycloaddition of aryl ethynyl
ethers with electron-deficient internal monoalkynes, lead-
ing to tri- and diaryloxybenzenes, respectively, at room
temperature. Future studies will focus on the further utili-
zation of aryl ethynyl ethers in rhodium-catalyzed reac-
tions.
Acknowledgment
This work was supported partly by a Grant-in-Aid for Scientific
Research (No. 20675002) from MEXT, Japan. We are grateful to
Takasago International Corporation for the gift of H8-BINAP,
Segphos, xyl-H8-BINAP, and DTBM-Segphos, and Umicore for
generous support in supplying a rhodium complex.
Under an argon atmosphere, H8-BINAP (6.3 mg, 0.010
mmol) and [Rh(cod)2]BF4 (4.1 mg, 0.010 mmol) were
dissolved in CH2Cl2 (1.0 mL), and the mixture was stirred
for 5 min. H2 was introduced to the resulting solution in a
Schlenk tube. After stirring at r.t. for 0.5 h, the resulting
mixture was concentrated to dryness. To a CH2Cl2 (0.5 mL)
solution of the residue was added a CH2Cl2 (1.5 mL) solution
of 1a (67.3 mg, 0.400 mmol). The mixture was stirred at r.t.
for 1 h. The resulting mixture was concentrated and purified
on a preparative TLC (n-hexane–toluene = 4:1), which
furnished 2a (34.2 mg, 0.0678 mmol, 51% yield) and 3a
(23.0 mg, 0.0456 mmol, 34% yield).
References and Notes
(1) For recent reviews of the transition-metal-catalyzed [2+2+2]
cycloaddition reactions, see: (a) Galan, B. R.; Rovis, T.
Angew. Chem. Int. Ed. 2009, 48, 2830. (b) Tanaka, K.
Chem. Asian J. 2009, 4, 508. (c) Varela, J. A.; Saá, C.
Synlett 2008, 2571. (d) Shibata, T.; Tsuchikama, K. Org.
Biomol. Chem. 2008, 1317. (e) Heller, B.; Hapke, M. Chem.
Soc. Rev. 2007, 36, 1085. (f) Agenet, N.; Buisine, O.;
Slowinski, F.; Gandon, V.; Aubert, C.; Malacria, M.
Organic Reactions, Vol. 68; RajanBabu, T. V., Ed.; John
Wiley and Sons: Hoboken, 2007, 1. (g) Chopade, P. R.;
Louie, J. Adv. Synth. Catal. 2006, 348, 2307. (h) Gandon,
V.; Aubert, C.; Malacria, M. Chem. Commun. 2006, 2209.
(i) Kotha, S.; Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem.
2005, 4741. (j) Gandon, V.; Aubert, C.; Malacria, M. Curr.
Org. Chem. 2005, 9, 1699. (k) Yamamoto, Y. Curr. Org.
Chem. 2005, 9, 503.
(2) Semmelhack, M. F.; Park, J. Organometallics 1986, 5, 2550.
(3) Suzuki, D.; Urabe, H.; Sato, F. J. Am. Chem. Soc. 2001, 123,
7925.
(4) Takahashi, T. JP 11263737, 1999; Chem. Abstr. 1999, 131,
228541.
(5) For the transition-metal-mediated intermolecular [4+2]-
benzannulation reactions using alkynyl ethers, see:
(a) Darbasie, N. D.; Schnatter, W. F. K.; Warner, K. F.;
Compound 2a: 1H NMR (300 MHz, CDCl3): d = 7.81–7.76
(m, 6 H), 7.72–7.70 (m, 3 H), 7.47–7.35 (m, 9 H), 7.27–7.23
(m, 3 H), 6.53 (s, 3 H). 13C NMR (75 MHz, CDCl3): d =
159.6, 153.9, 134.2, 130.4, 130.0, 127.7, 127.2, 126.6,
125.0, 119.9, 115.0, 103.9. ESI-HRMS: m/z calcd for
C36H24O3Na [M + Na]+: 527.1618; found: 527.1635.
Compound 3a: 1H NMR (300 MHz, CDCl3): d = 7.84–7.64
(m, 9 H), 7.45–7.33 (m, 7 H), 7.30–7.13 (m, 6 H), 6.93–6.86
(m, 2 H). 13C NMR (75 MHz, CDCl3): d = 155.7, 154.7,
154.6, 154.1, 149.0, 142.9, 134.22, 134.19, 134.10, 130.3,
130.1, 130.0, 129.9, 129.7, 129.6, 127.73, 127.68, 127.66,
127.13, 127.08, 127.00, 126.6, 126.45, 126.43, 124.9, 124.6,
124.4, 123.1, 119.7, 119.1, 118.8, 114.8, 114.1, 113.2,
112.5, 111.7. ESI-HRMS: m/z calcd for C36H24O3Na [M +
Synlett 2010, No. 20, 3092–3098 © Thieme Stuttgart · New York

3098
Y. Komine et al.
LETTER
Na]+: 527.1618; found: 527.1617.
3 H), 1.37 (t, J = 7.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3):
d = 167.1, 155.9, 155.2, 154.5, 134.23, 134.20, 133.6, 130.2,
130.08, 130.04, 129.9, 127.7, 127.1, 127.0, 126.8, 126.6,
124.8, 124.6, 119.5, 118.8, 116.5, 114.6, 113.9, 112.1, 61.2,
14.2, 12.9. ESI-HRMS: m/z calcd for C30H24O4Na [M +
Na]+: 471.1567; found: 471.1567.
Compound 2b: 1H NMR (300 MHz, CDCl3): d = 8.11–8.08
(m, 3 H), 7.84–7.81 (m, 3 H), 7.61–7.58 (m, 3 H), 7.51–7.44
(m, 6 H), 7.38–7.33 (m, 3 H), 7.07–7.05 (m, 3 H), 6.45 (s, 3
H).
Compound 3b: 1H NMR (300 MHz, CDCl3): d = 8.21–8.18
(m, 1 H), 8.00–7.97 (m, 1 H), 7.86–7.83 (m, 2 H), 7.74–7.69
(m, 2 H), 7.61–7.58 (m, 1 H), 7.51–7.49 (m, 4 H), 7.40–7.21
(m, 7 H), 7.16–7.14 (m, 1 H), 7.01–6.97 (m, 2 H), 6.92–6.90
(m, 2 H), 6.82–6.78 (m, 1 H).
Compound 5ab: 1H NMR (300 MHz, CDCl3): d = 7.80–7.77
(m, 4 H), 7.71–7.68 (m, 2 H), 7.46–7.32 (m, 6 H), 7.27–7.17
(m, 2 H), 6.69 (d, J = 1.8 Hz, 1 H), 6.54 (d, J = 1.8 Hz, 1 H),
4.29 (q, J = 7.1 Hz, 2 H), 2.66 (t, J = 7.4 Hz, 2 H), 1.65–1.55
(m, 2 H), 1.43–1.30 (m, 2 H), 1.22 (t, J = 7.1 Hz, 3 H), 0.91
(t, J = 7.4 Hz, 3 H).
Compound 2c: 1H NMR (300 MHz, CDCl3): d = 7.21–7.12
(m, 6 H), 7.07–7.01 (m, 3 H), 6.95–6.92 (m, 3 H), 6.12 (s, 3
H), 2.20 (s, 9 H).
Compound 6ab: 1H NMR (300 MHz, CDCl3): d = 7.83–7.78
(m, 4 H), 7.70–7.68 (m, 2 H), 7.47–7.35 (m, 4 H), 7.31–7.30
(m, 2 H), 7.25–7.19 (m, 3 H), 6.84 (d, J = 2.7 Hz, 1 H), 4.36
(q, J = 7.2 Hz, 2 H), 2.94 (t, J = 7.5 Hz, 2 H), 1.61–1.51 (m,
2 H), 1.47–1.35 (m, 5 H), 0.90 (t, J = 7.5 Hz, 3 H).
Compound 5ac: 1H NMR (300 MHz, CDCl3): d = 7.87–7.61
(m, 6 H), 7.54–7.13 (m, 13 H), 6.81 (d, J = 2.4 Hz, 1 H), 6.70
(d, J = 2.4 Hz, 1 H), 4.06 (q, J = 7.2 Hz, 2 H), 0.93 (t, J = 7.2
Hz, 3 H). An aromatic proton of the tetrasubstituted benzene
moiety of minor isomer 6ac: 6.93 (d, J = 2.4 Hz, 1 H).
Ethoxy protons of minor isomer 6ac: 3.99 (q, J = 7.2 Hz,
2H), 0.89 (t, J = 7.2 Hz, 3 H).
Compound 3c: 1H NMR (300 MHz, CDCl3): d = 7.23–7.18
(m, 1 H), 7.16–6.89 (m, 10 H), 6.81–6.78 (m, 1 H), 6.74–
6.72 (m, 1 H), 6.60–6.56 (m, 2 H), 2.24 (s, 3 H), 2.05 (s, 3
H), 1.98 (s, 3 H).
Compound 2d: 1H NMR (300 MHz, CDCl3): d = 6.98–6.94
(m, 6 H), 6.88–6.82 (m, 6 H), 6.19 (s, 3 H), 3.78 (s, 9 H).
Compound 3d: 1H NMR (300 MHz, CDCl3): d = 6.96–6.80
(m, 13 H), 6.61–6.54 (m, 2 H), 3.78 (s, 3 H), 3.77 (s, 6 H).
Compound 2e: 1H NMR (300 MHz, CDCl3): d = 7.62–7.60
(m, 6 H), 7.12–7.10 (m, 6 H), 6.51 (s, 3 H).
Compound 3e: 1H NMR (300 MHz, CDCl3): d = 7.64–7.61
(m, 2 H), 7.54–7.51 (m, 4 H), 7.23–7.20 (m, 1 H), 7.13–7.10
(m, 2 H), 6.95–6.90 (m, 6 H).
Compound 5ba: 1H NMR (300 MHz, CDCl3): d = 8.23–8.20
(m, 1 H), 8.02–7.99 (m, 1 H), 7.84–7.81 (m, 2 H), 7.62–7.57
(m, 2 H), 7.52–7.41 (m, 4 H), 7.37–7.32 (m, 2 H), 7.01–6.96
(m, 2 H), 6.53 (d, J = 2.4 Hz, 1 H), 6.45 (d, J = 2.4 Hz, 1 H),
4.22 (q, J = 7.1 Hz, 2 H), 2.34 (s, 3 H), 1.14 (t, J = 7.1 Hz, 3
H).
(13) (a) Tanaka, K.; Shirasaka, K. Org. Lett. 2003, 5, 4697.
(b) Tanaka, K.; Toyoda, K.; Wada, A.; Shirasaka, K.;
Hirano, M. Chem. Eur. J. 2005, 11, 1145.
(14) For our account of the cationic rhodium(I)–biaryl
bisphosphine-complex-catalyzed [2+2+2]-cycloaddition
reactions, see: Tanaka, K. Synlett 2007, 1977.
Compound 5ca: 1H NMR (300 MHz, CDCl3): d = 7.24–6.99
(m, 6 H), 6.95–6.85 (m, 2 H), 6.31 (d, J = 2.1 Hz, 1 H), 6.17
(d, J = 2.1 Hz, 1 H), 4.30 (q, J = 7.2 Hz, 2 H), 2.30 (s, 3 H),
2.23 (s, 3 H), 2.15 (s, 3 H), 1.27 (t, J = 7.2 Hz, 3 H).
Compound 5da: 1H NMR (300 MHz, CDCl3): d = 6.98–6.90
(m, 4 H), 6.88–6.83 (m, 4 H), 6.39 (d, J = 2.0 Hz, 1 H), 6.29
(d, J = 2.0 Hz, 1 H), 4.32 (q, J = 7.1 Hz, 2 H), 3.79 (s, 3 H),
3.78 (s, 3 H), 2.30 (s, 3 H), 1.29 (t, J = 7.1 Hz, 3 H).
Compound 6da: 1H NMR (300 MHz, CDCl3): d = 7.11 (d,
J = 2.7 Hz, 1 H), 6.94–6.90 (m, 2 H), 6.87–6.83 (m, 6 H),
6.61 (d, J = 2.7 Hz, 1 H), 4.33 (q, J = 7.1 Hz, 2 H), 3.79 (s,
3 H), 3.78 (s, 3 H), 2.42 (s, 3 H), 1.36 (t, J = 7.1 Hz, 3 H).
Compound 5ea: 1H NMR (300 MHz, CDCl3): d = 7.61–7.56
(m, 4 H), 7.08–7.03 (m, 4 H), 6.72 (d, J = 2.1 Hz, 1 H), 6.52
(d, J = 2.1 Hz, 1 H), 4.26 (q, J = 7.2 Hz, 2 H), 2.39 (s, 3 H),
1.18 (t, J = 7.2 Hz, 3 H).
(15) Typical Procedure (Table 4, Entry 1)
Under an argon atmosphere, H8-BINAP (6.3 mg, 0.010
mmol) and [Rh(cod)2]BF4 (4.1 mg, 0.010 mmol) were
dissolved in CH2Cl2 (1.0 mL), and the mixture was stirred
for 5 min. H2 was introduced to the resulting solution in a
Schlenk tube. After stirring at r.t. for 0.5 h, the resulting
mixture was concentrated to dryness. To a CH2Cl2 (0.5 mL)
solution of the residue and 4a (44.9 mg, 0.400 mmol) was
added a CH2Cl2 (1.5 mL) solution of 1a (67.3 mg, 0.400
mmol). The mixture was stirred at r.t. for 1 h. The resulting
mixture was concentrated and purified on a preparative TLC
(n-hexane–EtOAc = 15:1), which furnished 5aa (53.9 mg,
0.120 mmol, 60% yield) and 6aa (18.5 mg, 0.0412 mmol,
21% yield).
Compound 5aa: 1H NMR (300 MHz, CDCl3): d = 7.81–7.77
(m, 4 H), 7.72–7.69 (m, 2 H), 7.47–7.37 (m, 4 H), 7.34–7.33
(m, 2 H), 7.27–7.23 (m, 1 H), 7.21–7.18 (m, 1 H), 6.66 (d,
J = 1.8 Hz, 1 H), 6.56 (d, J = 1.8 Hz, 1 H), 4.28 (q, J = 7.1
Hz, 2 H), 2.38 (s, 3 H), 1.20 (t, J = 7.1 Hz, 3 H). 13C NMR
(75 MHz, CDCl3): d = 167.1, 158.92, 158.91, 155.6, 154.7,
153.8, 139.40, 139.38, 134.1, 130.4, 130.1, 130.0, 129.8,
127.7, 127.6, 127.1, 126.6, 126.5, 125.0, 124.7, 121.6,
119.8, 119.4, 115.3, 114.9, 113.9, 107.6, 61.2, 19.8, 14.1.
ESI-HRMS: m/z calcd for C30H24O4Na [M + Na]+: 471.1567;
found: 471.1575.
Compound 6ea: 1H NMR (300 MHz, CDCl3): d = 7.60–7.56
(m, 4 H), 7.43 (d, J = 2.4 Hz, 1 H), 7.06–7.03 (m, 2 H), 6.97–
6.94 (m, 2 H), 6.84 (d, J = 2.4 Hz, 1 H), 4.38 (q, J = 7.2 Hz,
2 H), 2.41 (s, 3 H), 1.39 (t, J = 7.2 Hz, 3 H).
(16) For the rhodium(I)-catalyzed [2+2+2] cycloaddition of
diynes with internal alkynyl ethers, see: (a) Alayrac, C.;
Schollmeyer, D.; Witulski, B. Chem. Commun. 2009, 1464.
(b) Clayden, J.; Moran, W. J. Org. Biomol. Chem. 2007, 5,
1028.
(17) Compound 10: 1H NMR (300 MHz, CDCl3): d = 7.89–7.72
(m, 4 H), 7.72–7.63 (m, 1 H), 7.49–7.37 (m, 3 H), 7.37–7.29
(m, 2 H), 7.22–7.17 (m, 1 H), 7.16–7.10 (m, 1 H), 6.98–6.91
(m, 1 H), 6.87–6.81 (m, 1 H), 4.60 (s, 2 H), 4.58 (s, 2 H), 2.42
(s, 3 H).
Compound 6aa: 1H NMR (300 MHz, CDCl3): d = 7.81–7.77
(m, 4 H), 7.70–7.65 (m, 2 H), 7.47–7.34 (m, 5 H), 7.30 (d,
J = 2.4 Hz, 1 H), 7.24–7.20 (m, 2 H), 7.13–7.12 (m, 1 H),
6.90 (d, J = 2.4 Hz, 1 H), 4.36 (q, J = 7.1 Hz, 2 H), 2.48 (s,
Synlett 2010, No. 20, 3092–3098 © Thieme Stuttgart · New York

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