Rh(I)-catalyzed reaction of 2-(chloromethyl)phenylboronic acids and alkynes leading to indenes

Article abstract of DOI:10.1021/ol8006887

(Chemical Equation Presented) The reaction of 2-(chloromethyl)phenylboronic acid (1) with alkynes in the presence of a Rh(I) complex gave indene derivatives in high yields. The regioselectivity depends on the steric nature of the substituent on the alkynes. A bulky group favors the α-position of indenes.

Full text of DOI:10.1021/ol8006887

ORGANIC
LETTERS
2008
Vol. 10, No. 14
2975-2978
Rh(I)-Catalyzed Reaction of
2-(Chloromethyl)phenylboronic Acids
and Alkynes Leading to Indenes
Masaki Miyamoto,† Yasuyuki Harada,† Mamoru Tobisu,‡ and Naoto Chatani*,†
Department of Applied Chemistry, Faculty of Engineering, Osaka UniVersity, Suita,
Osaka 565-0871, Japan, and Frontier Research Base for Global Young Researchers,
Graduate School of Engineering, Osaka UniVersity, Suita, Osaka 565-0871, Japan,
chatani@chem.eng.osaka-u.ac.jp
Received April 20, 2008
ABSTRACT
The reaction of 2-(chloromethyl)phenylboronic acid (1) with alkynes in the presence of a Rh(I) complex gave indene derivatives in high yields.
The regioselectivity depends on the steric nature of the substituent on the alkynes. A bulky group favors the r-position of indenes.
The development of new reactions that construct carbocycles
through carbon-carbon bond formation continues to be a
Scheme 1
.
Catalysis Triggered by Addition of o-Functionalized
prime issue in synthetic organic chemistry. Recently, the
Rh(I)-catalyzed reaction of alkynes with ortho-functionalized
organoboron reagents leading to carbocycles has been
extensively studied.1 The reactions are triggered by the
addition of arylrhodium(I) species II, which is generated
from the transmetalation of a Rh(I) complex with ortho-
functionalized arylboronic acids I across alkynes to form
vinylrhodium(I) complexes III. Then, the vinylrhodium
moiety in III reacts with the intramolecular functional groups
(FG) attached at the ortho position in the adjacent aryl ring
to give carbocycles (Scheme 1). Various functional groups,
Arylboronic Acids
such as aldehydes and ketones,2,3 esters,3a,4 nitriles,5 R,ꢀ-
unsaturated carbonyl compounds,6 ethers,7 bromides,8 io-
dides,9 and isocyanates,10 have been known to participate
in this and related transformations to construct carbocycles.
(5) (a) Miura, T.; Nakazawa, H.; Murakami, M. Chem. Commun. 2005,
2855–2856. (b) Miura, T.; Murakami, M. Org. Lett. 2005, 7, 3339–3341.
(6) (a) Lautens, M.; Marquardt, T. J. Org. Chem. 2004, 69, 4607–4614.
(b) Shintani, R.; Tsurusaki, A.; Okamoto, K.; Hayashi, T. Angew. Chem.,
Int. Ed. 2005, 44, 3909–3912. (c) Tseng, N.-W.; Mancuso, J.; Lautens, M.
J. Am. Chem. Soc. 2006, 128, 5338–5339. (d) Kurahashi, T.; Shinokubo,
H.; Osuka, A. Angew. Chem., Int. Ed. 2006, 45, 6336–6338.
(7) (a) Miura, T.; Shimada, M.; Murakami, M. J. Am. Chem. Soc. 2005,
127, 1094–1095. (b) Miura, T.; Sasaki, T.; Harumashi, T.; Murakami, M.
J. Am. Chem. Soc. 2006, 128, 2516–2517.
† Faculty of Engineering, Osaka University.
‡ Graduate School of Engineering, Osaka University.
(1) For a recent review, see: Miura, T.; Murakami, M. Chem. Commun.
2007, 217–224.
(2) (a) Shintani, R.; Okamoto, K.; Hayashi, T. Chem. Lett. 2005, 34,
1294–1295. (b) Matsuda, T.; Makino, M.; Murakami, M. Chem. Lett. 2005,
34, 1416–1417. (c) Matsuda, T.; Shigeno, M.; Makino, M.; Murakami, M.
Org. Lett. 2006, 8, 3379–3381.
(3) (a) Shintani, R.; Okamoto, K.; Otomaru, Y.; Ueyama, K.; Hayashi,
T. J. Am. Chem. Soc. 2005, 127, 54–55. (b) Miura, T.; Shimada, M.;
Murakami, M. Synlett 2005, 667–669. (c) Miura, T.; Shimada, M.;
Murakami, M. Angew. Chem., Int. Ed. 2005, 44, 7598–7600. (d) Miura,
T.; Shimada, M.; Murakami, M. Tetrahedron 2007, 63, 6131–6140.
(4) Miura, T.; Sasaki, T.; Nakazawa, H.; Murakami, M. J. Am. Chem.
Soc. 2005, 127, 1390–1391.
(8) Harada, Y.; Nakanishi, J.; Fujihara, H.; Tobisu, M.; Fukumoto, Y.;
Chatani, N. J. Am. Chem. Soc. 2007, 129, 5766–5771.
(9) Shintani, R.; Yamaguchi, T.; Hayashi, T. Org. Lett. 2006, 8, 4799–
4801.
(10) Miura, T.; Takahashi, Y.; Murakami, Y. Org. Lett. 2007, 9, 5075–
5077.
10.1021/ol8006887 CCC: $40.75
Published on Web 06/21/2008
2008 American Chemical Society

Substituted indenes are useful subunits for several ap-
plications, for pharmaceutical compounds possessing inter-
esting biological activities,11 for functional materials,12 and
for indenyl metal complexes as ligands, which are widely
utilized in various catalytic reactions.13 Consequently, much
effort has been devoted to the construction of the indene
ring system.14 Our proposal concerns the reaction of 2-(ha-
lomethyl)phenylboronic acid (FG ) CH2Br or CH2Cl in I)
with alkynes as a possible route for the synthesis of
substituted indenes, which are expected to form by the
oxidative addition of either a CH2Br or a CH2Cl bond to the
generated vinylrhodium III, followed by reductive elimina-
tion. As a result of testing this proposal, we wish to report
a new method for the synthesis of indenes from the Rh(I)-
catalyzed reaction of 2-(chloromethyl)phenylboronic acid (1)
and internal alkynes.
Table 1. Rh(I)-Catalyzed Reaction of Alkynes with
2-(Chloromethyl)phenylboronic Acid (1)a
When the reaction of 2-(bromomethyl)phenylboronic acid
(2, 1.5 mmol) with 4-octyne (1 mmol) was carried out in
dioxane/H2O (100/1, 1 mL) at 80 °C in the presence of
[RhCl(cod)]2 (0.025 mmol) and Na2CO3 (1 mmol) under
nitrogen for 20 h, 2,3-dipropyl-1H-indene (3) was obtained
in 12% isolated yield. The use of a higher catalyst loading
(0.1 mmol) at the reaction temperature of 50 °C increased
the yield to 36%. All attempts to optimize the reaction
conditions failed when using 2 as the substrate. After the
optimization of the reaction conditions, we were pleased to
find that the use of 2-(chloromethyl)phenylboronic acid (1)
gave high yields of indene derivative 3 (Scheme 2). It was
Scheme 2. Rh(I)-Catalyzed Reaction of
2-(Chloromethyl)phenylboronic Acid (1) and 4-Octyne
found that the Ir(I) complex, such as [IrCl(cod)]2 is also
active in the indene synthesis, but the yield was lower than
that in the Rh(I)-catalyzed reaction.
a Reaction conditions: alkyne (1 mmol), 2-(chloromethyl)phenylboronic
acid (1, 1.5 mmol), [RhCl(cod)]2 (0.025 mmol), and Na2CO3 (1.2 mmol)
in dioxane/H20 (10/1, 1.1 mL) at 50 °C for 20 h under N2. b Isolated yields.
The numbers in the parentheses indicate the regioisomeric ratios determined
by GC. c [RhCl(cod)]2 (0.05 mmol) was used. d [RhOH(cod)]2 (0.025 mmol)
was used as the catalyst.
(11) For examples, see: (a) Karaguni, I.-M.; Glusenkamp, K.-H.;
Langerak, A.; Geisen, C.; Ullrich, V.; Winde, G.; Moroy, T.; Muller, O.
Bioorg. Med. Chem. Lett. 2002, 12, 709–713. (b) Mu¨ller, O.; Gourzoulidou,
E.; Carpintero, M.; Karaguni, I.-M.; Langerak, A.; Herrmann, C.; Mo¨ro¨y,
T.; Klein-Hitpaꢀ, L.; Waldmann, H. Angew. Chem., Int. Ed. 2004, 43, 450–
454.
The reaction proceeds as we proposed, as shown in
Scheme 2. Transmetalation of Rh(I) with 2-chlorometh-
ylphenylboronic acid (1) generates a 2-(chloromethyl)phe-
nylrhodium(I) complex IV, to which the insertion of an
(12) For examples, see: (a) Barbera´, J.; Raitin, O. A.; Ros, M. B.;
Torroba, T. Angew. Chem., Int. Ed. 1998, 37, 296–299. (b) Yang, J.;
Lakshmikantham, M. V.; Cava, M. P. J. Org. Chem. 2000, 65, 6739. (c)
Hahn, S. F.; Hillmyer, M. A. Macromolecules 2003, 36, 71–76.
2976
Org. Lett., Vol. 10, No. 14, 2008

alkyne gives the vinylrhodium complex V. Oxidative addition
of C-Cl on the adjacent phenyl ring produces the rhod-
ium(III) species VI, which undergoes reductive elimination
to give indene 3. When the reaction was carried out under
an ambient pressure of CO, no carbonylation products were
obtained, but indene 3 was obtained in low yield, although
the exclusive formation of a carbonylation product was
observed in the case of FG ) Br or Cl.8 This is due to the
unfavorable formation of a seven-membered metalacycle,
which is required for CO insertion.
The results of the reaction using various alkynes are sum-
marized in Table 1.15 Internal alkynes having alkyl and aryl
groups gave the corresponding indenes in high yields. The
reaction of 1-phenylhexyne gave a regioisomeric mixture of 9
with a ratio of 26:1. It was found that the regioselectivity is
affected by the electronic nature of a substituent. Introduction
of an electron-withdrawing group, such as CF3 at the para-
position on the phenyl ring, increased the regioselectivity of
11 to the ratio of 32:1. On the other hand, the regioselectivity
decreased to 13:1 when 1-(4-methoxyphenyl)hexyne was used
as the substrate. The steric effects also dramatically affected
the regioselectivity, as in the case of 1-(2-methylphenyl)hexyne,
The reaction of 2-(chloromethyl)-4-fluorophenylboronic
acids (14) with diphenylacetylene and phenylpropyne gave
the corresponding indenes 15 and 16, respectively, in high
yields (Scheme 3).
Next, we examined the reaction of alkenes with 1, which
would be expected to lead to the formation of indane
derivatives if the reaction proceeds similar to the reaction
with alkynes. However, alkenes were not suitable substrates
for the present reaction. Even with norbornene, the corre-
sponding indane derivative 17 was obtained in a low yield
(Scheme 4), although an arylrhodium species is well-known
to react with norbornene or 7-oxanorbornene.16
Scheme 4. Reaction of Norbornene with 1
The conjugate addition of arylboronic acids to R,ꢀ-
unsaturated carbonyl compounds catalyzed by the Rh(I)
complex, in particular, the asymmetric version, has been
extensively studied.17 Then, we examined the reaction of
electron-deficient olefins with 1. The reaction of 3-buten-2-
one with 1 did not give any cyclized products, but a simple
1,4-addition selectively took place to give 18 in good yield
(Scheme 5). The reaction of acrolein also afforded only a
Scheme 3. Rh(I)-Catalyzed Reaction of
2-(Chloromethyl)-4-fluorophenylboronic Acid (14) and Alkynes
Scheme 5
.
Reaction of R,ꢀ-Unsaturated Carbonyl Compounds
with 1
leading to 12. Alkynes having a silyl group and an ester group
were not suitable for the present indene synthesis. The reaction
of (trimethylsilyl)phenylacetylene gave a complex mixture
involving the corresponding indene derivative in low yield (data
not shown in Table 1). The use of (trimethylsilyl)propyne as
an alkyne partner gave the corresponding indene 13 in low yield.
When the amount of the catalyst loading was increased, the
yield of 13 increased, but the regioselectivity was not so high.
Alkynes having an ester group, such as methyl 2-butynoate and
methyl phenylpropiolate, did not give the corresponding indenes.
(13) For reviews, see: (a) Zargarian, D. Coord. Chem. ReV. 2002, 233,
157–176. (b) Calhorda, M. J.; Felix, V.; Veiros, L. F. Coord. Chem. ReV.
2002, 230, 48–63. See, also: (c) Alt, H. G.; Ko¨ppl, A. Chem. ReV. 2000,
100, 1205–1222.
(15) Notes: (a) The use of terminal alkynes did not produce the
corresponding indenes under these conditions. (b) The regioselectivities
observed in the reactions with unsymmetrical alkynes are mostly parallel
to those observed in our preveous report. See ref 8.
(14) For recent papers on the catalytic synthesis of indenes, see: (a)
Guo, L.-N.; Duan, X.-H.; Bi, H.-P.; Liu, X.-Y.; Liang, Y.-M. J. Org. Chem.
2006, 71, 3325–3327. (b) Dube, P.; Toste, F. D. J. Am. Chem. Soc. 2006,
128, 12062–12063. (c) Zhang, D.; Liu, Z.; Yum, E. K.; Larock, R. C. J.
Org. Chem. 2007, 72, 251–262. (d) Dong, C.-G.; Yeung, P.; Hu, Q.-S. Org.
Lett. 2007, 9, 363–366.
(16) Tseng, N.-W.; Mancuso, J.; Lautens, M. J. Am. Chem. Soc. 2006,
128, 5338–5339. and references cited therein.
(17) For recent reviews, see: (a) Hayashi, T.; Yamasaki, K. Chem. ReV.
2003, 103, 2829–2844. (b) Fagnou, K.; Lautens, M. Chem. ReV. 2003, 103,
169–196.
Org. Lett., Vol. 10, No. 14, 2008
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conjugate addition product 19. These results show that
protonation of the initially generated rhodium enolate 20 is
much faster than intramolecular nucleophilic substitution of
a chloride.
In summary, we reported on the development of a new
synthetic method to access indene derivatives. The reaction
involves the addition of an arylrhodium(I) species to alkynes
and the oxidative addition of a C-Cl on the adjacent phenyl
ring to the resulting vinylrhodium(I), which undergoes
reductive elimination.
Supporting Information Available: Experimental pro-
cedures and spectroscopic data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL8006887
2978
Org. Lett., Vol. 10, No. 14, 2008