Rhodium-catalyzed synthesis of indenols by regioselective coupling of alkynes with ortho-carbonylated arylboronic acids

Article abstract of DOI:10.1246/cl.2005.1294

A rhodium/diene-catalyzed regioselective synthesis of indenols has been developed through the coupling of alkynes with ortho-carbonylated arylboronic acids. These reactions proceed under mild conditions in uniformly high yield and regioselectivity. The re

Full text of DOI:10.1246/cl.2005.1294

1
294
Chemistry Letters Vol.34, No.9 (2005)
Rhodium-catalyzed Synthesis of Indenols by Regioselective Coupling of Alkynes
with Ortho-carbonylated Arylboronic Acids
ꢀ
Ryo Shintani, Kazuhiro Okamoto, and Tamio Hayashi
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502
(Received July 5, 2005; CL-050872)
A rhodium/diene-catalyzed regioselective synthesis of in-
equiv. of 2-formylphenylboronic acid to give indenol 2a in
81% yield (Table 1, Entry 1). Under these conditions, a variety
of internal alkynes can be coupled with 2-formylphenylboronic
acid to afford the corresponding indenols in high yield as shown
denols has been developed through the coupling of alkynes with
ortho-carbonylated arylboronic acids. These reactions proceed
under mild conditions in uniformly high yield and regioselectiv-
ity. The reaction has also been applied to its asymmetric variant
by the use of chiral diene ligands to achieve high enantioselec-
tivity.
9
in Table 1 (78–94% yield). When unsymmetrical alkynes are
used, they generally exhibit high regioselectivity in the product
formation. For example, aryl or alkenyl groups can be well-dis-
tinguished from alkyl groups (methyl, primary alkyl, and secon-
dary alkyl) in the ratio of ꢂ90:10 (Entries 3–6). Furthermore,
high regioselectivity is also achieved even when two substituents
on the alkyne are both primary alkyl groups as long as one is suf-
ficiently bulkier than the other (>98:2; Entry 7). Esters and silyl
groups on the alkyne are good handles as well to induce high re-
gioselectivity in these coupling reactions (82:18–>98:2; Entries
8 and 9). With respect to the arylboronic acid, 2-acetylphenyl-
boronic acid can also be employed under similar conditions to
give a corresponding indenol with high efficiency as well
(84% yield; Eq 2).
Indenols are an important family of compounds due to their
1
utility as synthetic intermediates in organic chemistry. In addi-
tion, there have been several reports on the biological activity of
2
indenol-containing organic molecules. As a consequence, the
development of efficient methods for the synthesis of indenols,
particularly catalytic enantioselective ones, is a significant ob-
jective. Typical synthetic approaches to these compounds are,
however, based on the use of a preformed indan structure with
3
a manipulation of its oxidation state. In contrast, only a few
methods have provided a catalytic synthesis of indenols in a con-
vergent manner,4 and unfortunately, none of these have been
Table 1. Rhodium-catalyzed regioselective synthesis of
indenols
,5
6
applied to the asymmetric variants so far.
R1
OH
O
[
Rh(OH)(cod)]2
3 mol% Rh)
For the development of a new convergent method for inden-
ol synthesis, we initiated a program focusing on the coupling of
alkynes with ortho-carbonylated arylboronic acids under rhodi-
(
R1
H
+
dioxane/H2O (20/1)
R2
1
35 °C, 4 h
B(OH)2
R2
7
um catalysis. Herein we describe that a rhodium/diene catalyst
1
.2 equiv.
2
is uniquely effective for a regioselective coupling of these com-
ponents under mild conditions, and that the employment of chi-
ral diene ligands leads to the realization of carbon–carbon bond-
forming catalytic asymmetric synthesis of indenols in relatively
high enantioselectivity.
R1
R2
Yield/%a
81
Entry
1
2b
n-Pr
Ph
n-Pr
(1a)
(1b)
(1c)
(1d)
(1e)
Ph
Me
83
92
78
3
4b
5b
Ph
(95:5)
(95:5)
As a starting point, we chose to examine a reaction of 4-oc-
tyne (1a) with 2-formylphenylboronic acid (1.5 equiv.) in the
Ph
n-Bu
Cy
ꢁ
presence of 5 mol % rhodium catalyst at 60 C (Eq 1). Although
Rh/phosphine complexes are known to catalyze a reaction of in-
82c (90:10)
Ph
8
6
7
Me
Et
(1f)
81 (95:5)
ternal alkynes with arylboronic acids, the use of phosphine li-
gands in this reaction failed to produce the desired indenol
MeO2C
(2a). In contrast, the reaction proceeded smoothly in the pres-
(1g)
88 (>98:2)
ence of [Rh(OH)(cod)]2 as a catalyst, furnishing the targeted in-
denol (2a) in 92% yield.
MeO2C Me
8
9d
MeO C
2
Me
Me
(1h)
(1i)
87 (>98:2)
94 (82:18)
OH
O
3
Me Si
n-Pr
5
mol% Rh-catalyst
KOH (0.3 equiv.)
H
+
n-Pr (1)
n-Pr
a
Isolated yield (combined yield of regio isomers unless otherwise
b
dioxane/H2O (10/1)
0 °C, 4 h
noted). Numbers in parentheses describe the regioselectivity. The
ꢁ
B(OH)2 n-Pr
.5 equiv.
1a
2a
c
6
reaction was conducted at 60 C. Isolated yield of the major regio
d
1
Rh-catalyst
Yield/%
isomer. 2.4 equiv. of 2-formylphenylboronic acid was used.
RhCl(PPh3)3
0
<5
92
HO
O
CO2Me
[
Rh(OH)(cod)]2
5 mol% Rh)
Me
CO2Me (2)
[
RhCl((R)-binap)]2
(
[
Rh(OH)(cod)] a
Me
B(OH)2
1.2 equiv.
+
2
dioxane/H2O (20/1)
aNo KOH was added.
60 °C, 4 h
Me
1.0 equiv.
Me
After some investigations, we found that the reaction also
ꢁ
2j: 84% yield
(>98:2 regioselectivity)
proceeds with 3 mol % catalyst loading at 35 C by using 1.2
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.9 (2005)
1295
Support has been provided in part by a Grant-in-Aid for
Scientific Research, the Ministry of Education, Culture, Sports,
Science and Technology, Japan (21 COE on Kyoto University
Alliance for Chemistry).
R1
R2
HO
O
R
R1
R
+
B(OH)2
R2
[
Rh] OH
R1
−
[Rh] OH
References and Notes
H2O
Rh]
1
a) W. M. Clark, A. M. Tickner-Eldridge, G. K. Huang, L. N.
Pridgen, M. A. Olsen, R. J. Mills, I. Lantos, and N. H. Baine,
J. Am. Chem. Soc., 120, 4550 (1998). b) R. J. Mills, C. J. Kowalski,
L. Ping, and K. J. Gombatz, PCT Int. Appl. WO 1996-US18084
O
[
O
R
O
R
R2
R
R1
[
Rh]
1
9961108 (1997). c) A. G. Myers, P. J. Proteau, and T. M. Handel,
[
Rh]
R2
R2
R1
J. Am. Chem. Soc., 110, 7212 (1988). d) D. L. J. Clive and M. Yu,
Chem. Commun., 2002, 2380. e) D. L. J. Clive, M. Yu, and M.
Sannigrah, J. Org. Chem., 69, 4116 (2004).
A
B
C
Scheme 1. Proposed catalytic cycle of the rhodium-catalyzed
coupling of alkynes with ortho-carbonylated arylboronic acids.
2
3
4
a) Kuraray Co. Ltd., Jpn. Kokai Tokkyo Koho, JP 1980-17353
1
9800214 (1981). b) Kuraray Co. Ltd., Jpn. Kokai Tokkyo Koho,
JP 1980-131806 19800922 (1982). c) Y. Ishiguro, K. Okamoto,
F. Ojima, and Y. Sonoda, Chem. Lett., 1993, 1139.
These coupling reactions presumably go through a catalytic
cycle illustrated in Scheme 1. Thus, transmetallation of an aryl-
boronic acid to the hydroxorhodium catalyst forms arylrhodium
species A. An alkyne inserts into this carbon–rhodium bond to
generate alkenylrhodium intermediate B. Insertion of the car-
bonyl group at the ortho-position results in the formation of an
alkoxorhodium species with a five-membered carbocycle (C).
Hydrolysis of this intermediate produces the desired indenol
and regenerates the hydroxorhodium species.
Because the second carbon–carbon bond formation of this
process (i.e., B ! C) creates a stereogenic center, the use of a
proper chiral ligand might be able to show a good control on
the stereochemical outcome. In this regard, because Rh/phos-
phine complexes do not catalyze these reactions as described
in Eq 1, the use of chiral phosphine ligands is not promising
for the development of an asymmetric variant. We therefore
decided to employ chiral diene ligands on the basis of the high
efficiency of Rh/cod catalyst as demonstrated in Table 1. For ex-
ample, in the reaction of alkyne 1g with 2-formylphenylboronic
a) H. H. Szmant and R. Nanjundiah, J. Org. Chem., 43, 1835
(1978). b) H. C. Gibbard, C. J. Moody, and C. W. Rees, J. Chem.
Soc., Perkin Trans. 1, 1985, 723. c) J. A. Pincock and I. S. Young,
Can. J. Chem., 81, 1083 (2003).
Palladium catalysis: a) J. Vincente, J.-A. Abad, and J. Gil-Rubio, J.
Organomet. Chem., 436, C9 (1992). b) L. G. Quan, V. Gevorgyan,
and Y. Yamamoto, J. Am. Chem. Soc., 121, 3545 (1999). c) V.
Gevorgyan, L. G. Quan, and Y. Yamamoto, Tetrahedron Lett.,
40, 4089 (1999). Nickel catalysis: d) D. K. Rayabarapu and C.-H.
Cheng, Chem. Commun., 2002, 942. e) D. K. Rayabarapu, C.-H.
Yang, and C.-H. Cheng, J. Org. Chem., 68, 6726 (2003). Cobalt
catalysis: f) K.-J. Chang, D. K. Rayabarapu, and C.-H. Cheng,
Org. Lett., 5, 3963 (2003). g) K.-J. Chang, D. K. Rayabarapu,
and C.-H. Cheng, J. Org. Chem., 69, 4781 (2004).
5
6
For examples of stoichiometric convergent synthesis of indenols,
see: a) N. P. Robinson, L. Main, and B. K. Nicholsen, J. Organo-
met. Chem., 364, C37 (1989). b) L. S. Liebeskind, J. R. Gasdaska,
and J. S. McCallum, J. Org. Chem., 54, 669 (1989). c) J. Vincente,
J.-A. Abad, B. L o´ pez-Pel a´ ez, and E. Mart ´ı nez-Viviente, Organo-
metallics, 21, 58 (2002).
There have been some scattered examples for the synthesis of enan-
tio-enriched indenols. a) Catalytic asymmetric reduction of an in-
denone: Ref 1a. b) Kinetic resolution by lipase: M. B. Onaran
and C. T. Seto, J. Org. Chem., 68, 8136 (2003). c) Stoichiometric
asymmetric epoxidation followed by a ring-opening: Ref 1c. d)
Ring-closing metathesis of an enantio-enriched substrate: Refs 1d
and 1e.
ꢀ
acid, the use of (R,R)-Ph-bod , a C2-symmetric chiral diene
1
0,11
ligand developed in our group, regioselecitvely furnished
indenol 2g in 97% yield with 70% ee (Eq 3). By changing the
ꢀ
10,12
ligand to (S,S)-Bn-bod ,
to 81% ee with excellent yield and regioselectivity.
the enantioselectivity is improved
[RhCl(C2H4)2]2
7
For examples of the use of ortho-functionalized arylboron reagents
in the rhodium-catalyzed addition cyclization reactions, see: a) M.
Lautens and J. Mancuso, Org. Lett., 4, 2105 (2002). b) M. Lautens
and J. Mancuso, J. Org. Chem., 69, 3478 (2004). c) M. Lautens and
T. Marquardt, J. Org. Chem., 69, 4607 (2004). Very recently,
another example appeared using 2-cyanophenylboronic acid:
d) T. Miura and M. Murakami, Org. Lett., 7, 3339 (2005).
T. Hayashi, K. Inoue, N. Taniguchi, and M. Ogasawara, J. Am.
Chem. Soc., 123, 9918 (2001).
O
R
OH
(
5 mol% Rh)
H
ligand (5.5 mol%)
*
+
(3)
KOH (0.3 equiv.)
dioxane/H2O (10/1)
35 °C, 4 h
B(OH)2
R
Me
1g
Me
1
.5 equiv.
2g
R = C(Me)(CO2Me)2
8
9
1
Ph
Terminal alkynes are not suitable coupling partners under these
conditions.
Ph
Ph
Ph
R,R)-Ph-bod*
(
(S,S)-Bn-bod*
0 a) N. Tokunaga, Y. Otomaru, K. Okamoto, K. Ueyama, R.
Shintani, and T. Hayashi, J. Am. Chem. Soc., 126, 13584 (2004).
b) Y. Otomaru, K. Okamoto, R. Shintani, and T. Hayashi, J. Org.
Chem., 70, 2503 (2005). c) R. Shintani, T. Kimura, and T. Hayashi,
Chem. Commun., 2005, 3213.
9
7% yield, 70% ee
97:3 regioselecitivity)
97% yield, 81% ee
(>98:2 regioselecitivity)
(
In summary, we have developed a rhodium-catalyzed
regioselective synthesis of indenols through the coupling of al-
kynes with ortho-carbonylated arylboronic acids. These reac-
tions proceed under mild conditions in uniformly high yield
and regioselectivity. The reaction has also been applied to its
asymmetric variant by using chiral diene ligands, achieving high
enantioselectivity. Future studies will explore further expansion
of the scope of this and related processes.
1
1 See also: a) T. Hayashi, K. Ueyama, N. Tokunaga, and K. Yoshida,
J. Am. Chem. Soc., 125, 11508 (2003). b) C. Defieber, J.-F. Paquin,
S. Serna, and E. M. Carreira, Org. Lett., 6, 3873 (2004).
2 a) R. Shintani, K. Okamoto, Y. Otomaru, K. Ueyama, and T.
Hayashi, J. Am. Chem. Soc., 127, 54 (2005). b) R. Shintani, A.
Tsurusaki, K. Okamoto, and T. Hayashi, Angew. Chem., Int. Ed.,
44, 3909 (2005).
1
Published on the web (Advance View) August 20, 2005; DOI 10.1246/cl.2005.1294