Rh(l)-catalyzed CO gas-free carbonylative cyclization reactions of alkynes with 2-bromophenylboronic acids using formaldehyde

Article abstract of DOI:10.1021/ol900327x

The rhodium(l)-catalyzed reaction of alkynes with 2-bromophenylboronic acids in the presence of paraformaldehyde resulted in a CO gas-free carbonylative cyclization, yielding indenone derivatives. [RhCI(BINAP)] ₂ and [RhCI(cod)]₂ wer

Full text of DOI:10.1021/ol900327x

ORGANIC
LETTERS
2009
Vol. 11, No. 8
1777-1780
Rh(I)-Catalyzed CO Gas-Free
Carbonylative Cyclization Reactions of
Alkynes with 2-Bromophenylboronic
Acids Using Formaldehyde
Tsumoru Morimoto,*,† Kae Yamasaki,† Akihisa Hirano,† Ken Tsutsumi,†
Natsuko Kagawa,† Kiyomi Kakiuchi,† Yasuyuki Harada,‡ Yoshiya Fukumoto,‡
Naoto Chatani,*,‡ and Takanori Nishioka§
Graduate School of Materials Science, Nara Institute of Science and Technology
(NAIST), Takayama, Ikoma, Nara 630-0192, Japan, Department of Applied Chemistry,
Faculty of Engineering, Osaka UniVersity, Suita, Osaka 565-0871, Japan, and
Department of Material Science, Graduate School of Science, Osaka City UniVersity,
Sumiyoshi-ku, Osaka, 558-8585, Japan
morimoto@ms.naist.jp; chatani@chem.eng.osaka-u.ac.jp
Received February 13, 2009
ABSTRACT
The rhodium(I)-catalyzed reaction of alkynes with 2-bromophenylboronic acids in the presence of paraformaldehyde resulted in a CO gas-free
carbonylative cyclization, yielding indenone derivatives. [RhCl(BINAP)]2 and [RhCl(cod)]2 were responsible for the decarbonylation of formaldehyde
and the subsequent carbonylation of alkynes with 2-haloboronic acids, respectively, leading to efficient whole carbonylation. Sterically bulky
and electron-withdrawing groups on unsymmetrically substituted alkynes favored the r-position of indenones.
Transition-metal-catalyzed carbonylation has become an
essential, powerful tool for the synthesis of a wide variety
of carbonyl compounds.1 Recent considerable efforts have
focused on its experimental simplification and on the
development of novel carbonylative transformations. Con-
sequently, gaseous carbon monoxide has been replaced by
much easier handling organic and inorganic carbonyl com-
pounds in various carbonylation reactions, as follows:
hydrocarbonylation (hydroesterification, hydroamidation, and
hydrocarboxylation) of alkenes and alkynes;2,3 hydroformy-
lation of alkenes;2 alkoxy-, amino-, and hydroxycarbonyla-
tion of aromatic and alkenyl halides;2,4 the Pauson-Khand
reaction;2,5 hydrocyclocarbonylation of alkynes;2,6 and car-
bonylative ring-expansion of spiropentanes.7 In this paper,
we describe a new utilization of the CO gas-free protocol
consisting of decarbonylation of formaldehyde and sequential
carbonylation;2,4n,5b,6,7 thus, a rhodium(I)-catalyzed carbo-
nylative cyclization reaction of alkynes with 2-haloboronic
acids in the presence of formaldehyde results in carbonylative
cyclization to afford indenones.8,9
Our previous work showed that phosphine-free rhodium
complexes, such as [RhCl(cod)]2 and [RhCl(CO)2]2, show
catalytic activity for the carbonylation reaction using carbon
monoxide, while rhodium-phosphine complexes, such as
† Nara Institute of Science and Technology (NAIST).
‡ Osaka University.
§ Osaka City University.
(1) (a) Kolla´r, L. Modern Carbonylation Methods; Wiley-VCH: Wein-
heim, 2008. (b) Beller, M. Catalytic Carbonylation Reaction; Springer-
Verlag: Berlin, 2006. (c) Colquhoun, H. M.; Thompson, D. J.; Twigg, M. V.
Carbonylation; Plenum Press: New York, 1991.
(3) Kobayashi, Y.; Kamisaki, H.; Yanada, K.; Yanada, R.; Takemoto,
Y. Tetrahedron Lett. 2005, 46, 7549–7552 (intramolecular hydroamidation
of yne-formamides).
(2) For a review, see: Morimoto, T.; Kakiuchi, K. Angew. Chem., Int.
Ed. 2004, 43, 5580–5588
.
10.1021/ol900327x CCC: $40.75
Published on Web 03/20/2009
2009 American Chemical Society

RhCl(PPh3)3 and RhH(CO)(PPh3)3, are catalytically ineffec-
tive.8 This was a significant finding for our study, because
it is generally recognized that rhodium-phosphine com-
plexes more efficiently catalyze the decarbonylation of
aldehydes.10 The key to solving this question was to control
the amount of added phosphine ligand so that rhodium
complexes both with and without phosphine ligands, which
should be responsible for decarbonylation and carbonylation,
respectively, could coexist in one catalyst system.
results encouraged us to verify the synergism between
decarbonylation formaldehyde by [RhCl(BINAP)]2 and car-
bonylative cyclization of alkynes with 2-haloarylboronic
acids by [RhCl(cod)]2.
Under the catalyst consisting of [RhCl(cod)]2 and BINAP
in a molar ratio of 2.5:1, we examined the reaction of
4-octyne with 2-bromophenylboronic acid in the presence
of paraformaldehyde instead of carbon monoxide (Table 1,
First, we pursued a rhodium species generated from the
reaction of [RhCl(cod)]2 with BINAP, the amount of which
was not to cover all of a given rhodium center. The 31P NMR-
experimental treatment of [RhCl(cod)]2 with BINAP ([RhCl-
(cod)]2/BINAP ) 2.5:1) in CD2Cl2 at room temperature
resulted in complete consumption of the BINAP to give
[RhCl(BINAP)]2 as the sole rhodium complex having a
BINAP ligand.11 Furthermore, 103Rh NMR analysis revealed
the existence of two kinds of rhodium species, which can
be assigned to [RhCl(cod)]2 and [RhCl(BINAP)]2. These
Table 1. Effect of BINAP in the Reaction of 4-Octyne with 1
and Paraformaldehydea
(4) For recent papers on use of Mo(CO)6, see: (a) Wu, X.; Mahalingam,
A. K.; Wan, Y.; Alterman, M. Tetrahedron Lett. 2004, 45, 4635–4638. (b)
Herrero, M. A.; Wannberg, J.; Larhed, M. Synlett 2004, 2335–2338. (c)
Wannberg, J.; Dallinger, D.; Kappe, C. O.; Larhed, M. J. Comb. Chem.
2005, 7, 574–583. (d) Wannberg, J.; Kaiser, N.-F. K.; Vrang, L.;
Samuelsson, B.; Larhed, M.; Hallberg, A. J. Comb. Chem. 2005, 7, 611–
617. (e) Wu, X.; Ro¨nn, R.; Gossas, T.; Larhed, M. J. Org. Chem. 2005, 70,
3094–3098. (f) Wu, X.; Larhed, M. Org. Lett. 2005, 7, 3327–3329. (g)
Wu, X.; Ekegren, J. K.; Larhed, M. Organometallics 2006, 25, 1434–1439.
(h) Wu, X.; Wannberg, J.; Larhed, M. Tetrahedron 2006, 62, 4665–4670.
(i) Gold, H.; Ax, A.; Vrang, L.; Samuelsson, B.; Karle´n, A.; Hallberg, A.;
Larhed, M. Tetrahedron 2006, 62, 4671–4675. (j) Wannberg, J.; Sabnis,
Y. A.; Vrang, L.; Samuelsson, B.; Karle´n, A.; Hallberg, A.; Larhed, M.
Bioorg. Med. Chem. 2006, 14, 5303–5315. (k) Letavic, M. A.; Ly, K. S.
Tetrahedron Lett. 2007, 48, 2339–2343. For recent papers on the use of
DMF, see: (l) Ju, J.; Jeong, M.; Moon, J.; Jung, H. M.; Lee, S. Org. Lett.
2007, 9, 4615–4618. (m) Tambade, P. J.; Patil, Y. P.; Bhanushali, M. J.;
Bhanage, B. M. Tetrahedron Lett. 2008, 49, 2221–2224. For a recent paper
on the use of aldehydes, see: (n) Morimoto, T.; Fujioka, M.; Fuji, K.;
Tsutsumi, K.; Kakiuchi, K. J. Organomet. Chem. 2007, 692, 625–634. For
a recent paper on the use of acetic formic anhydride, see: (o) Berger, P.;
Bessmernykh, A.; Caille, J.-C.; Mignonac, S. Synthesis 2006, 3106–3110.
For a recent paper on the use of a carbamoylsilane, see: (p) Cunico, R. F.;
Pandey, R. K. J. Org. Chem. 2005, 70, 9048–9050.
entry
BINAP (mol %)
yield of 2b (%)
yield of 3b (%)
1
2
3
41
75
47
32
83
9
4
3
1
2
5
1
4
trace
4
5c
a Reaction conditions: 4-octyne (1 mmol), 1 (1.5 mmol), paraformal-
dehyde (5 mmol), [RhCl(cod)]2 (0.025 mmol), BINAP, Na2CO3 (2 mmol)
in dioxane/H2O (100/1, 2 mL) at 100 °C for 40 h. b Isolated yield. c 3 mmol
of 1 was used for 30 h.
entry 2). The reaction proceeded efficiently to afford the
desired indenone 2 in 75% yield, along with 4% of
naphthalene derivative 3. The addition of up to 5 mol % of
BINAP led to the formation of 2 in much lower yields
(entries 1 and 4). From these results, we postulated that
[RhCl(BINAP)]2 and [RhCl(cod)]2 are involved mainly in
the decarbonylation and carbonylative cyclization processes,
respectively, as we expected. Among other phosphines tested,
BIPHEP was almost as effective as BINAP: BIPHEP (71%),
dppe (68%), dppp (58%), dppb (62%), dppf (55%), and
2PPh3 (53%). Use of 3 equiv of 2-bromophenylboronic acid
increased the yield of 2 to as high as 83% in even a shorter
reaction time (30 h) (entry 5). Under these conditions,
pentafluorobenzaldehyde and trans-cinnamaldehyde did not
work better than paraformaldehyde (28% and 13% yields).12
The standard conditions established thus constituted 2.5 mol
% of [RhCl(cod)]2, 1 mol % of BINAP, 3 equiv of
2-bromophenylboronic acid, and 2 equiv of Na2CO3, in
dioxane/H2O (100/1) at 100 °C for 30 h.
(5) For recent papers on the use of aldehydes, see: (a) Jeong, N.; Kim,
D. H.; Choi, J. H. Chem. Commun. 2004, 1134–1135. (b) Fuji, K.;
Morimoto, T.; Tsutsumi, K.; Kakiuchi, K. Tetrahedron Lett. 2004, 45, 9163–
9166. (c) Kwong, F. Y.; Li, Y. M.; Lam, W. H.; Qiu, L.; Lee, H. W.; Yeung,
C. H.; Chan, K. S.; Chan, A. S. C. Chem.sEur. J. 2005, 11, 3872–3880.
(d) Shibata, T.; Toshida, N.; Yamasaki, M.; Maekawa, S.; Takagi, K.
Tetrahedron 2005, 61, 9974–9979. (e) Kwong, F. Y.; Lee, H. W.; Qiu, L.;
Lam, W. H.; Li, Y.-M.; Kwong, H. L.; Chan, A. S. C. AdV. Synth. Catal.
2005, 347, 1750–1754. (f) Kwong, F. Y.; Lee, H. W.; Lam, W. H.; Qiu,
L.; Chan, A. S. C. Tetrahedron: Asymmetry 2006, 17, 1238–1252. For a
recent paper on the use of formates, see: (g) Lee, H. W.; Chan, A. S. C.;
Kwong, F. Y. Chem. Commun. 2007, 2633–2635.
(6) Fuji, K.; Morimoto, T.; Tsutsumi, K.; Kakiuchi, K. Chem. Commun.
2005, 3295–3297 (use of formaldehyde).
(7) Matsuda, T.; Tsuboi, T.; Murakami, M. J. Am. Chem. Soc. 2007,
129, 12596–12597 (use of formaldehyde).
(8) Harada, Y.; Nakanishi, J.; Fujihara, H.; Tobisu, M.; Fukumoto, Y.;
Chatani, N. J. Am. Chem. Soc. 2007, 129, 5766–5771.
(9) Recently, Rh(I)-catalyzed carbonylation reactions of alkynes with
phenylboronic acid leading to R,ꢀ-unsaturated γ-lactones were reported.
¨
See: (a) Aksin, O; Dege, N.; Artok, L.; Tu¨rkmen, H.; C¸ etinkaya, B. Chem.
¨
Commun. 2006, 3187–3189. (b) Kus¸, M.; Artok, O. A.; Ziyanak, F.; Artok,
A proposed reaction pathway for the present reaction is
shown in Scheme 1.8 First, addition of BINAP, the amount
L. Synlett 2008, 2587–2592.
(10) Kreis, M.; Palmelund, A; Bunch, L.; Madsen, R. AdV. Synth. Catal.
2006, 348, 2148–2154, and references therein.
(11) [RhCl(BINAP)]2: 31P NMR (CD2Cl2) δ 49.5 ppm (d, JP-Rh ) 199
Hz). [RhCl(cod)]2: 103Rh NMR (CD2Cl2) δ 2438 ppm (s). The mixture of
[RhCl(cod)]2 (2.5 equiv) with BINAP (1 equiv): 31P NMR (CD2Cl2) δ 49.5
ppm (d, JP-Rh ) 199 Hz); 103Rh NMR (CD2Cl2) δ 1620 (t, JRh-P ) 199
Hz), 2438 ppm (s). For details, see the Supporting Information.
(12) For successful uses of other aldehydes on the CO gas-free
carbonylations, see: (a) Morimoto, T.; Fuji, K.; Tsutsumi, K.; Kakiuchi, K.
J. Am. Chem. Soc. 2002, 124, 3806–3807. (b) Morimoto, T.; Fujioka, M.;
Fuji, K.; Tsutsumi, K.; Kakiuchi, K. Chem. Lett. 2003, 32, 154–155. (c)
References 4n, 5a and 5c-f.
1778
Org. Lett., Vol. 11, No. 8, 2009

Scheme 1
.
Reaction Pathway
Table 2. Rh(I)-Catalyzed Reaction of Alkynes with 1 and
Paraformaldehydea
entry
R1
R2
Ph
Me
Bu
Me
Ph
Ph
COOEt
yieldb (%)
1
2
Ph
Ph
Ph
4, 78
5, 80 (16:1)
6, 76 (6:1)
7, 67
8, 75
9, 73 (26:1)
10, 44 (3:1)
3
4c
5
Me3Si
Me3Si
COOMe
Me3Si
6c
7c
a Reaction conditions: alkyne (1 mmol), 1 (3 mmol), paraformaldehyde
(5 mmol), [RhCl(cod)]2 (0.025 mmol), BINAP (0.01 mmol), Na2CO3 (2
mmol) in dioxane/H2O (100/1, 2 mL) at 100 °C for 30 h. b Isolated yields.
The numbers in parentheses are the ratios of regioisomers. c 1.5 mmol of
1 was used.
of which cannot cover all of the given rhodium metal, leads
to the partial formation of [RhCl(BINAP)]2, along with the
intact [RhCl(cod)]2. The former complex would mainly
decarbonylate formaldehyde to yield the carbonyl moiety and
hydrogen. On the other hand, the latter would predominantly
catalyze the actual carbonylation step as shown in Scheme
1b. Thus, transmetalation of Rh-OH with 2-haloarylboronic
acid 1 yields the arylrhodium(I) complex A. The addition,
in a cis-manner, of complex A to an alkyne gives the
vinylrhodium(I) complex B, in which the oxidative addition
of the proximal C-Br bond to the rhodium center produces
the rhodacycle C. The insertion of the carbonyl moiety
abstracted from formaldehyde, followed by reductive elimi-
nation, affords indenone 2 with regeneration of the rhod-
ium(I) catalyst.
to lead to the least steric strain around the forming
carbon-carbon bond, rather than to the longer carbon-
rhodium bond (Scheme 2). For unsymmetrical alkynes with
Scheme 2
Under the aforementioned optimized conditions, various
alkynes having aryl, alkyl, ester, and silyl groups could be
used to give the corresponding indenones in moderate to high
yields, as shown in Table 2. Diphenylacetylene also worked
well. For unsymmetrically substituted alkynes, the reaction
proceeded generally in a regioselective manner, and either
a sterically bulky group or an electron-withdrawing group
on alkynes favored the R-position of indenones. The reaction
of 1-phenyl-1-propyne proceeded regioselectively to afford
mainly an indenone with a phenyl group located at the
R-position (entry 2). The replacement of the methyl group
with a bulkier butyl group led to a decrease in regioselectivity
(entry 3). In the case of the reaction of trimethylsilylacetylene
derivatives, an exclusive R-orientation of the silyl group was
observed (entries 4 and 5). The above results show that the
bulkier group selectively locates at the R-position of the
carbonyl in the product. This tendency could be explained
based on the rational consideration of Larock, who maintains
that the high regioselectivity would probably depend on the
steric hindrance present in the developing carbon-carbon
bond.13 The alkyne insertion to intermediate A occurs so as
an ester group, the electronic factor is involved in the
selectivity in the manner of a 1,4-addition. An ester group
affects the regioselectivity more strongly than a phenyl group
and locates at the R-position (entry 6), while the effect on
R-selectivity is inferior to the steric effect of a silyl group
(entry 7).
Thus, the strength of the effect of substituents on R-se-
lectivity can be summarized as follows: SiMe3 > CO2R .
aryl > alkyl, which is consistent with that observed in the
reaction using carbon monoxide.8
Substituents on the aromatic ring of boronic acid were
tolerant to the carbonylation reaction (Table 3). The reaction
of 4-octyne with 2-bromo-5-methoxyphenylboronic acid gave
indenone 11, where the carbonyl moiety was introduced into
the Br-bound carbon. This implied that the product would
not form via the [2 + 2 + 1] cycloaddition of the in situ
generated benzyne, the alkyne, or the abstracted CO moi-
(14) (a) Retboll, M.; Edwards, A. J.; Rae, A. D.; Willis, A. C.; Bennett,
M. A.; Wenger, E. J. Am. Chem. Soc. 2002, 124, 8348–8360. (b) Chatani,
N.; Kamitani, A.; Oshita, M.; Fukumoto, Y.; Murai, S. J. Am. Chem. Soc.
2001, 123, 12686–12687. For a review, see: (c) Dyke, A. M.; Hester, A. J.;
Lloyd-Jones, G. C. Synthesis 2006, 4093–4112.
(13) Zhang, D.; Liu, Z.; Yum, E. K.; Larock, R. C. J. Org. Chem. 2007,
72, 251–262.
Org. Lett., Vol. 11, No. 8, 2009
1779

Finally, we investigated application of the CO gas-free
method using formaldehyde in the reaction of 2-bromoary-
lacetylenes with nonhalogenated arylboronic acid, in which
intermediate B could be generated by the insertion of the
alkyne to arylrhodium followed by E,Z-isomerization (Scheme
3). Indeed, the reaction of 2-bromophenyl(trimethylsily-
Table 3. Rh(I)-Catalyzed Reaction of Alkynes with
2-Bromoarylboronic Acids and Paraformaldehydea
Scheme 3. Reaction of 2-Bromophenyl(trimethylsilyl)acetylene
(21) with Phenylboronic Acid and Paraformaldehyde
l)acetylene (21) with phenylboronic acid gave indenone 8
in 58% yield, albeit requiring the additional use of 2 equiv
of styrene as the additive. A butyl and phenyl analogue to
21 did not give the corresponding indenones, and complex
mixtures were obtained.
In conclusion, we have reported that the CO gas-free
protocol utilizing the decarbonylation of formaldehyde with
a rhodium(I) catalyst is applicable to the carbonylative
cyclization reaction of alkynes with 2-haloarylboronic acids
leading to indenones. The addition of BINAP, the amount
of which must not cover all the given [RhCl(cod)]2, leads to
the partial formation of [RhCl(BINAP)]2 and intact
[RhCl(cod)]2. These are mainly involved in the decarbony-
lation, and subsequent carbonylation, of formaldehyde,
respectively, leading to efficient carbonylation. The reaction
proceeded generally in a regioselective manner, and sterically
bulky and electron-withdrawing groups favored the R-posi-
tion of the indenones.
a Reaction conditions: alkyne (1 mmol), 2-bromoarylboronic acid (3
mmol), paraformaldehyde (5 mmol), [RhCl(cod)]2 (0.025 mmol), BINAP
(0.01 mmol), Na2CO3 (2 mmol) in dioxane/H2O (100/1, 2 mL) at 100 °C
for 30 h. b Isolated yields. All products were obtained as a single regioisomer.
ety.14 For reactions of silylacetylenes having methyl and
phenyl groups, the corresponding indenones 12 and 13 were
obtained as sole products, respectively. Other substituted
2-bromophenylboronic acids also could be used for the
present carbonylation reaction, being converted into inde-
nones 14-19. Replacement of 2-bromophenylboronic acid
with 2-chloro analogues also gave indenones 2 and 20,
although in lower yields, along with ca. 5% yields of styrene
derivatives as byproducts. The latter was formed by proton-
ation of the generated vinylrhodium species, related to
complex B, probably due to the poorer reactivity of the C-Cl
bond.
Acknowledgment. This work was financially supported,
in part, by a Grant-in-Aid for Scientific Research on Priority
Areas “Advanced Molecular Transformations of Carbon
Resouces” from MEXT.
Supporting Information Available: Experimental details
1
and copies of H, 13C, 31P, and 103Rh NMR spectra. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL900327X
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Org. Lett., Vol. 11, No. 8, 2009