Rhodium-catalyzed aryl- and alkylation-oligomerization of alkynoates with organoboron reagents giving salicylates

Article abstract of DOI:10.1039/c000402b

The reaction of alkynoates with aryl- or alkylboron reagents in the presence of a rhodium/diene catalyst gave high yields of salicylate derivatives with high selectivity, which consist of three or four molecules of the alkynoate and one organic group derived from the organoboron reagents. The Royal Society of Chemistry.

Full text of DOI:10.1039/c000402b

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Rhodium-catalyzed aryl- and alkylation–oligomerization of alkynoates
with organoboron reagents giving salicylatesw
Yuichi Yasuhara, Takahiro Nishimura* and Tamio Hayashi*
Received (in Cambridge, UK) 8th January 2010, Accepted 1st February 2010
First published as an Advance Article on the web 17th February 2010
DOI: 10.1039/c000402b
The reaction of alkynoates with aryl- or alkylboron reagents in
the presence of a rhodium/diene catalyst gave high yields of
salicylate derivatives with high selectivity, which consist of three
or four molecules of the alkynoate and one organic group derived
from the organoboron reagents.
It was found that the addition of aromatic boron reagents to an
alkynoate in the presence of a rhodium/diene catalyst gave the
arylation–oligomerization products incorporated with three mole-
cules of the alkynoates.10,11 Thus, treatment of ethyl 2-heptynoate
(1a) with phenylboroxine (2a, 1 equiv.) in the presence of
[Rh(OH)(cod)]2 (5 mol% of Rh) in 1,4-dioxane and H2O (1 equiv.
to B) at 70 1C gave 77% yield of phenol derivative 3a (Scheme 3). It
should be noted that the use of rhodium catalysts coordinated with
The research area of catalytic conjugate addition of organoboron
reagents to a,b-unsaturated carbonyl compounds has been a
focus of attention as one of the most reliable methods of forming
carbon–carbon bonds.1 For example, the conjugate addition to
alkynoates offers a convenient route to the synthesis of multiply-
substituted alkenoates. There have been reports on the addition of
arylboronic acids to alkynoates giving hydroarylation products,
which is catalyzed by Co,2 Rh,3 Pd,4 and Cu5 complexes
(Scheme 1).6 In this context, we focused on the rhodium-catalyzed
arylation and alkylation of alkynoates by use of organoboron
reagents, and we found that a rhodium complex catalyzes a
unique multi-component reaction of alkynoates with organo-
boron reagents giving salicylate derivatives (Scheme 2). This aryl-
or alkylation–oligomerization is triggered by the addition of an
aryl- or an alkylrhodium intermediate to an alkynoate and is
terminated by the intramolecular carborhodation of an ester
carbonyl,7 via multiple carbon–carbon bond formations.8,9
12
phosphine ligands such as [Rh(OH)((R)-binap)]2 resulted in the
preferential formation of hydrophenylation product 4 as expected.3
Scheme 3 Arylation-trimerization of the alkynoate.
Scheme 1 Hydroarylation of alkynoates.
Scheme 2 Aryl- and alkylation–oligomerization reactions.
Department of Chemistry, Graduate School of Science,
Kyoto University, Sakyo, Kyoto 606-8502, Japan.
E-mail: tnishi@kuchem.kyoto-u.ac.jp, thayashi@kuchem.kyoto-u.ac.jp;
Fax: +81 75 753 3988; Tel: +81 75 753 3983
w Electronic supplementary information (ESI) available: Experimental
procedures and compound characterization data. See DOI: 10.1039/
c000402b
Scheme 4 Proposed catalytic cycle.
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A catalytic cycle proposed for the reaction producing
salicylate 3a from alkynoate 1a and phenylboroxine is shown
in Scheme 4. Transmetalation of phenyl group from boron to
rhodium forms a phenylrhodium species II. Insertion of 1a
into the Rh–Ph bond gives an alkenylrhodium species III. The
carborhodation of 1a is repeated two more times to give a
trienylrhodium species V. The intermediate V does not react
further with the alkynoate but undergoes intramolecular
carborhodation of ester carbonyl to form six-membered ring
VI. b-Elimination of the ethoxy group on VI gives alkylidene
cyclohexa-2,4-dienone VII and regenerates the alkoxo
species I. The phenol 3a is finally formed by tautomerization
of VII.
The salicylate 3a obtained here was readily converted into a
fully substituted benzofuran. Thus, treatment of 3a with
iodine in the presence of K2CO3 gave benzofuran 6 in 93%
yield (Scheme 6).14
Scheme 6 Transformation into a benzofuran derivative.
The catalytic cycle is supported by the reaction of the
alkynoate 1a with alkenyl(trimethyl)tin 5,1,13 which should
generate the alkenylrhodium species III (Scheme 4) by trans-
metalation to the rhodium center. The reaction of 1a with 5
gave 47% yield of 3a (Scheme 5), which is the same product as
that obtained in the reaction of phenylboroxine with 1a
(Scheme 3). These results indicate that the catalytic cycle
involves the alkenylrhodium species III as a key intermediate.
The use of alkylboronic acids in place of arylboroxines
changed the reaction pathway to incorporate four molecules
of alkynoates with high selectivity. Thus, the reaction of
methylboronic acid (7) with ethyl 2-heptynoate (1a) in the
presence of [Rh(OH)(cod)]2 (5 mol% of Rh) in 1,4-dioxane
at 70 1C gave 74% yield of salicylate 8a which is substituted
with a dienyl group (Table 2, entry 1). This methylation–
tetramerization reaction proceeded smoothly for some other
alkynoates 1b–1i (entries 2–9). The selectivity is particularly
high for the siloxy-substituted 2-heptynoate 1g to give the
corresponding dienylsalicylate 8g in 89% yield (entry 7). It is
remarkable that a butyl group was successfully introduced in
the reaction of alkynoate 1e with butylboronic acid (9), which
gave 66% yield of butylation–tetramerization product 10
(entry 10).
Scheme 5 Reaction of the alkenyl(trimethyl)tin reagent.
Table
2 Rhodium-catalyzed addition of alkylboronic acids to
alkynoatesa
The results obtained for the reactions of 1a with several
arylboroxines in dioxane are summarized in Table 1. The reac-
tion of 1a with arylboroxines substituted with electron-donating
and -withdrawing groups on the benzene ring gave the four-
component reaction products in good yields (52–82% yields,
entries 1–8).
Table 1 Rhodium-catalyzed synthesis of phenol derivatives by
addition of arylboroxines to alkynoate 1aa
Entry
R
R1
R2
Yieldb (%) E : Zc
1
2
3
4
5
6
7
Me (7) Pr
Me (7) Pr
Me (7) Pr
Me (7) Me
Me (7) PhCH2
Me (7) 2-NaphthylCH2
Me (7) t-BuPh2SiO(CH2)3 Me (1g) 89 (8g)
Et (1a)
74 (8a)
86 : 14
74 : 26
70 : 30
53 : 47
68 : 32
73 : 27
75 : 25
—
Me (1b) 73 (8b)
i-Pr (1c) 74 (8c)
Me (1d) 75 (8d)
Me (1e) 80 (8e)
Me (1f) 81 (8f)
8
Me (7)
Me (7)
H
H
Me (1h) 54 (8h)
Et (1i) 65 (8i)
Me (1e) 66 (10)
Entry
Ar
Yieldb (%)
E : Zc
9d
10
—
73 : 27
Bu (9) PhCH2
1
2
3
4
5
6
7
8
Ph (2a)
Ph (2a0)
80 (3a)
77 (3a)
80 (3b)
77 (3c)
82 (3d)
81 (3e)
74 (3f)
52 (3g)
10 : 90
9 : 91
8 : 92
10 : 90
7 : 93
6 : 94
a
Reaction conditions: Alkynoate 1 (0.50 mmol), RB(OH)2 (1.25 mmol),
b
[Rh(OH)(cod)]2 (5 mol% of Rh), 1,4-dioxane (1.0 mL). Combined
4-MeC6H4 (2b)
4-MeOC6H4 (2c)
4-ClC6H4 (2d)
3,5-Me2C6H3 (2e)
2-MeC6H4 (2f)
2-Naphthyl (2g)
yield of the isolated (E)- and (Z)-isomers. Determined by 1H NMR
d
analysis. 1i (1.5 mmol), MeB(OH)2 (3.75 mmol), [Rh(OH)(cod)]2
c
(5 mol% of Rh), 1,4-dioxane (3.0 mL).
20 : 80
13 : 87
a
Reaction conditions: Alkynoate 1a (0.30 mmol), arylboroxine (0.30 mmol),
b
[Rh(OH)(cod)]2 (5 mol% of Rh), 1,4-dioxane (0.60 mL). Combined yield
The X-ray crystal structure of the isolated 8e-(Z) shown in
Fig. 1 and its NMR analysis clearly indicate that 8e is produced
by the reaction between one molecule of methylboronic acid
and four molecules of the alkynoate.
of the mixture of (E)- and (Z)-isomers. c Determined by 1H NMR
analysis. d Performed with PhB(OH)2 (0.75 mmol) instead of (PhBO)3.
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7 For an example of rhodium-catalyzed reaction of 2-cyanophenyl-
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benzotropone derivative, see: T. Miura and M. Murakami,
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Fig. 1 ORTEP illustration of product 8e-(Z) with thermal ellipsoids
drawn at 50% probability level (hydrogens are omitted except for
phenol and vinyl hydrogens).
8 For reviews on rhodium-catalyzed sequential multiple C–C bond
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The reaction of alkynoate 1h with alkenyltrifluoroborate
1115 gave 43% yield of 8h (Scheme 7), which is the same
product as that obtained in the reaction of methylboronic acid
with 1h (Table 2, entry 8). This result is consistent with the
catalytic cycle of the methylation of 1h involving the alkenyl-
rhodium species VIII as a key intermediate, which reacts with
alkynoate three times in a manner analogous to the phenyl-
rhodium species II in Scheme 4.
M. Schafer, J. Wolf, K. Peters and H. G. von Schnering, Angew.
¨
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Scheme 7 Reaction of potassium alkenyltrifluoroborate 11.
11 Reviews on transition metal-catalyzed [2 + 2 + 2] cycloaddition
reactions of alkynes, see: (a) S. Kotha, E. Brahmachary and
K. Lahiri, Eur. J. Org. Chem., 2005, 4741; (b) P. R. Chopade
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In summary, we found a new type of rhodium-catalyzed multi-
component reaction where salicylate derivatives are produced
selectively from three or four molecules of the alkynoate and one
organic group derived from organoboron reagents.
12 T. Hayashi, M. Takahashi, Y. Takaya and M. Ogasawara, J. Am.
Chem. Soc., 2002, 124, 5052.
This work was supported by a Grant-in-Aid for Scientific
Research (S) (19105002) from the MEXT, Japan. Y. Y. thanks
the Japan Society for the Promotion of Science for Young
Scientists for a research fellowship.
13 For selected examples of rhodium-catalyzed reactions using aryl-
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Chem. Commun., 1997, 1621; (b) T. Hayashi and M. Ishigedani,
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Chem. Soc., 2000, 122, 9538; (d) T. Koike, M. Takahashi, N. Arai
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This journal is The Royal Society of Chemistry 2010
2132 | Chem. Commun., 2010, 46, 2130–2132