Synthesis of 1H-inden-1-ol derivatives via rhodium-catalyzed annulation of o-acylphenylboronic acids with alkynes

Article abstract of DOI:10.1246/cl.2005.1416

A rhodium-catalyzed annulation reaction of o-formyl-phenylboronic acid with alkynes occurred regioselectively at room temperature to give substituted 1H-inden-1-ol derivatives. o-Acetylphenylboronic acid also underwent the annulation reaction at 80°C to a

Full text of DOI:10.1246/cl.2005.1416

1416
Chemistry Letters Vol.34, No.10 (2005)
Synthesis of 1H-Inden-1-ol Derivatives via Rhodium-catalyzed Annulation
of o-Acylphenylboronic Acids with Alkynes
Takanori Matsuda, Masaomi Makino, and Masahiro Murakamiꢀ
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering,
Kyoto University, Katsura, Kyoto 615-8510
(Received August 4, 2005; CL-051010)
A rhodium-catalyzed annulation reaction of o-formyl-
phenylboronic acid with alkynes occurred regioselectively at
room temperature to give substituted 1H-inden-1-ol derivatives.
o-Acetylphenylboronic acid also underwent the annulation
reaction at 80 ꢁC to afford 1-methyl-1H-inden-1-ols.
OH
Me
E
CHO
2 mol% [Rh(OH)(cod)]2
dioxane, rt, 3 h
+
E
B(OH)2
Me
1 (1.2 equiv.)
2a
3a 94%
(E = CO2Et)
The rhodium-catalyzed addition reactions of organoboron
compounds have rapidly emerged as a new protocol for the for-
mation of carbon–carbon bonds.1 An intermediate organorho-
dium(I) species can add to relatively polar unsaturated function-
alities like carbonyl2 and cyano3 groups as well as carbon–car-
bon double4 and triple5 bonds. Recently, rhodium-catalyzed
processes forming cyclic skeletons through consecutive addi-
tions to different unsaturated functionalities have been devel-
oped.6 We now report a rhodium-catalyzed annulation reaction
of o-acylphenylboronic acids with alkynes forming 1H-inden-
1-ol derivatives.7,8
O
O
O[Rh]
E
[Rh]
[Rh]
E
Me
Me
B
A
C
Scheme 1.
Table 1. Rhodium-catalyzed annulation of o-formylphenylbor-
onic acid (1) with alkyne 2a
Commercially available o-formylphenylboronic acid (1, 1.2
equiv.) was allowed to react with methyl but-2-ynoate (2a, 1.0
R1
OH
9
2 mol% [Rh(OH)(cod)]2
equiv.) in the presence of [Rh(OH)(cod)]2 (4 mol % Rh,
R1
+
1
cod = cycloocta-1,5-diene) in 1,4-dioxane at room tempera-
ture. After 3 h, 1H-inden-1-ol 3a was obtained in 94% yield
(Scheme 1).10 The ester group was exclusively attached to the
2-position of the indenol skeleton. The annulation reaction is
considered to consist of i) transmetalation between rhodium(I)
and arylboronic acid 1 to form A, ii) highly regioselective
(>98:2) 1,2-addition across the carbon–carbon triple bond of
2a to form B, iii) intramolecular addition of the resulting ꢀ-sty-
rylrhodium to the aldehydic carbonyl group to form C, and iv)
protonolysis/transmetalation releasing 3a. Neither benzalde-
hyde nor o-alkenylbenzaldehyde, which might arise from proto-
nolysis of A or B, respectively, was found in the reaction mix-
ture, indicating that the annulation sequence proceeded more
facilely than protonolysis of the Rh–C(sp2) linkages. Unlike
the case with o-cyanophenylboronic acid,7b a seven-membered
ring product through double insertion of 2a was not found in
the reaction mixture. Intermediate B once formed immediately
underwent intramolecular addition to a formyl group, which
should be considerably easier than the addition to a cyano group.
Examples of the rhodium-catalyzed annulation reaction of 1
with other alkynes 2b–2i are shown in Table 1. 3-Trimethylsilyl
acetylenic ester 2b and ketone 2c underwent the annulation reac-
tion with 1 to give the corresponding products in high yield with
excellent regioselectivity (Entries 1 and 2). Similar regioselec-
tivity was achieved with 1-phenylprop-1-yne (2d) (Entry 3).
The regioselectivity observed with 2d was higher than those
with simple phenylboronic acid (3:1)5 and o-cyanophenylboron-
ic acid (10:1),7b indicating effective coordination of the carbonyl
dioxane, rt, 3 h
(1.2 equiv.)
R2
R2
2
3
Entry
2 (R1, R2)
3 (yield/%)b Regioselectivityc
1
2
3
4
5
2b (CO2Et, SiMe3)
2c (COMe, SiMe3)
2d (Ph, Me)
3b (95)
3c (99)
3d (94)
3e (98)
96:4
96:4
97:3
—
—
—
2e (Et, Et)
2f (CH2OAc, CH2OAc) 3f (73)
6d 2g (Ph, Ph)
3g (70)
3h (36)
3i (20)
7
8
2h (i-Bu, H)
2i (Ph, H)
88:12
>98:2
aUnless otherwise noted, all reactions were carried out with bor-
onic acid 1 (0.48 mmol), alkyne 2 (0.40 mmol), and [Rh(OH)-
(cod)]2 (8.0 mmol, 4 mol % Rh) in 1,4-dioxane (2.0 mL) for 3 h.
bIsolated yield. cDetermined by 1H NMR. 10 h.
d
group of 1 as the directing group.6d Whereas the reaction of sym-
metrical alkynes, such as hex-3-yne (2e) and but-2-ynylene di-
acetate (2f), proceeded well (Entries 4 and 5), diphenylacetylene
(2g) required a longer reaction time to attain good yield
(Entry 6). Terminal alkynes could be used as the coupling part-
ner but with far less efficiency (Entries 7 and 8). Oligomerization
of terminal alkynes was unavoidable under the reaction condi-
tions.11 Dimethyl acetylene dicarboxylate and bis(trimethyl-
silyl)acetylene failed to give coupling products 3 in the presence
of the rhodium catalyst. The reaction with alkenes such as ethyl
Copyright ꢀ 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.10 (2005)
1417
References and Notes
1
For reviews, see: a) K. Fagnou and M. Lautens, Chem. Rev.,
103, 169 (2003). b) T. Hayashi and K. Yamasaki, Chem.
Rev., 103, 2829 (2003).
a) M. Pucheault, S. Darses, and J.-P. Genet, J. Am. Chem.
Soc., 126, 15356 (2004). b) T. Matsuda, M. Makino, and
M. Murakami, Org. Lett., 6, 1257 (2004). c) T. Matsuda,
M. Makino, and M. Murakami, Bull. Chem. Soc. Jpn., 78,
1528 (2005), and references cited therein.
R
R
2 mol%
R
OH
R
[Rh(OH)(cod)]2
+
+
1
2
dioxane
r.t., 3 h
(2.4 equiv.)
HO
R
HO
R
4a (R = Et)
4b (R = SiMe3)
5a 23%
5b 90%
6a 66%
6b 0%
3
a) K. Ueura, T. Satoh, and M. Miura, Org. Lett., 7, 2229
(2005). b) T. Miura, H. Nakazawa, and M. Murakami, Chem.
Commun., 2005, 2855.
Scheme 2.
4
5
6
M. Lautens, A. Roy, K. Fukuoka, K. Fagnou, and B.
´
acrylate, phenyl vinyl ketone, and norborna-2,5-diene was also
unsuccessful.
Martın-Matute, J. Am. Chem. Soc., 123, 5358 (2001).
T. Hayashi, K. Inoue, N. Taniguchi, and M. Ogasawara,
J. Am. Chem. Soc., 123, 9918 (2001).
When octa-3,5-diyne (4a) was allowed to react with 2.4
equiv. of 1, doubly annulated 6a (66%, dl/meso = ca. 1:1)
was furnished together with mono-annulated 5a (23%) (Scheme
2). In the case of disilyl-capped diyne 4b, the initial product 5b
was exclusively obtained in high yield. This may be attributed to
severe steric congestion around the remaining CꢂC bond of 5b.
An analogous reaction of o-acetylphenylboronic acid (7)
producing 1-methyl-1H-inden-1-ols 8 required more forcing
conditions (Table 2). More than two equivalents of 7 was used
at an elevated temperature.12 Addition of a small amount of
water was also noted to have a positive effect on the yield. Alky-
noates 2a and 2b worked well to furnish 8a and 8b, respectively,
in good yield with good regioselectivity, like the case of 1
(Entries 1 and 2). Whereas phenyl-substituted alkynes (2d and
2g) gave the products (8d and 8g) in acceptable yield (Entries
3 and 4), a lower yield was observed in the reaction of dialkyl-
acetylene 2j (Enrty 5).
a) M. Lautens and J. Mancuso, J. Org. Chem., 69, 3478
(2004). b) T. Miura, T. Sasaki, H. Nakazawa, and M.
Murakami, J. Am. Chem. Soc., 127, 1390 (2005). c) R.
Shintani, A. Tsurusaki, K. Okamoto, and T. Hayashi, Angew.
Chem., Int. Ed., 44, 3909 (2005). d) T. Matsuda, M. Makino,
and M. Murakami, Angew. Chem., Int. Ed., 44, 4608 (2005),
and references cited therein.
For a related reaction of ortho-functionalized phenylboronic
acids with alkynes, see: a) M. Lautens and T. Marquardt,
J. Org. Chem., 69, 4607 (2004). b) T. Miura and M.
Murakami, Org. Lett., 7, 3339 (2005).
Transition-metal-catalyzed syntheses of 1H-inden-1-ol
derivatives starting from o-halobenzoyl compounds and
alkynes have been reported. Pd: a) J. Vicente, J.-A. Abad,
and J. Gil-Rubio, Organometallics, 15, 3509 (1996). b) V.
Gevorgyan, L. G. Quan, and Y. Yamamoto, Tetrahedron
Lett., 40, 4089 (1999). Ni: c) D. K. Rayabarapu, C.-H. Yang,
and C.-H. Cheng, J. Org. Chem., 68, 6726 (2003). Co: d)
K.-J. Chang, D. K. Rayabarapu, and C.-H. Cheng, J. Org.
Chem., 69, 4781 (2004).
7
8
Table 2. Rhodium-catalyzed annulation of o-acetylphenyl-
boronic acid (7) with alkynes 2a
O
HO
R1
Me
´
R. Uson, L. A. Oro, and J. A. Cabeza, Inorg. Synth., 23, 126
(1985).
9
2 mol% [Rh(OH)(cod)]2
Me
R1
+
dioxane–H2O (40:1)
10 A representative procedure for the rhodium-catalyzed reac-
tion of 1 and 2a (Scheme 1): To a mixture of boronic acid
1 (74.0 mg, 0.49 mmol) and [Rh(OH)(cod)]2 (3.6 mg, 8.0
mmol) were added successively 1,4-dioxane (2.0 mL) and
alkyne 2a (46.7 mg, 0.42 mmol). After stirring the reaction
mixture at room temperature for 3 h, hexane was added.
The mixture was passed through a pad of Florisilꢁ
(hexane:AcOEt = 4:1). Removal of the volatile materials
under reduced pressure gave 3a (85.2 mg, 94%). 3a:
1H NMR (CDCl3, 300 MHz) ꢁ 1.40 (t, J ¼ 7:2 Hz, 3H),
2.49 (d, J ¼ 1:8 Hz, 3H), 3.30 (d, J ¼ 2:4 Hz, 1H), 4.35 (q,
J ¼ 7:2 Hz, 2H), 5.40 (s, 1H), 7.35–7.44 (m, 3H), 7.55–
7.62 (m, 1H); 13C NMR (CDCl3, 75 MHz) ꢁ 12.5, 14.4,
60.4, 75.8, 121.4, 123.9, 128.7, 129.0, 132.3, 142.5, 144.6,
152.7, 165.7. Anal. Calcd for C13H14O3: C, 71.54; H,
6.47%. Found: C, 71.69; H, 6.53%.
11 For rhodium(I)-catalyzed polymerization of alkynes, see: Y.
Misumi, K. Kanki, M. Miyake, and T. Masuda, Macromol.
Chem. Phys., 201, 2239 (2000), and references cited therein.
12 A considerable amount of acetophenone was produced in the
reaction of 2d, 2g, and 2j due to protodeboration of 7 under
the reaction conditions.
13 Note added in proof: A report describing similar results
appeared after acceptance of this paper: R. Shintani, K.
Okamoto, and T. Hayashi, Chem. Lett., 34, 1294 (2005).
B(OH)2
R2
80 °C
R2
7
2
8
Entry 7 (equiv.)
2 (R1, R2)
Time/h 8/%yieldb
1
2
3
4
5
2.4
2.4
4.0
4.0
4.0
2a (CO2Et, Me)
2b (CO2Et, SiMe3)
2d (Ph, Me)
2g (Ph, Ph)
2j (Pr, Pr)
3
3
24
24
24
8ac (80)
8bc (75)
8dc (61)
8g (68)
8j (25)
aBoronic acid 7 (0.96 mmol or 1.60 mmol), alkyne 2 (0.40
mmol), [Rh(OH)(cod)]2 (8.0 mmol, 4 mol % Rh), 1,4-dioxane
(2.0 mL), and water (50 mL) were heated at 80 ꢁC. bIsolated yield
c
by preparative TLC. Good regioselectivities (>95:5) were ob-
1
served by H NMR.
In summary, we developed a simple synthetic route to sub-
stituted 1H-inden-1-ol derivatives through rhodium-catalyzed
annulation of o-acylphenylboronic acids with alkynes.13
We thank H. Fujita for his assistance in the structure deter-
mination by NMR. This work was supported by a Grant-in-Aid
for Young Scientists (B) (Nos. 15750085 and 17750087) from
the Ministry of Education, Culture, Sports, Science and Technol-
ogy, Japan.
Published on the web (Advance View) September 17, 2005; DOI 10.1246/cl.2005.1416