Bismuth-catalyzed intramolecular hydro-oxycarbonylation of alkynes

Article abstract of DOI:10.1246/cl.2008.602

Bi(OTf)₃ was found to be a good catalyst for intramolecular addition of carboxylic acids to alkynes (hydro-oxycarbonylation), which afforded the corresponding 5- and 6-membered lactones in moderate to good yields under mild conditions. Copyrigh

Full text of DOI:10.1246/cl.2008.602

602
Chemistry Letters Vol.37, No.6 (2008)
Bismuth-catalyzed Intramolecular Hydro-oxycarbonylation of Alkynes
Kimihiro Komeyama,ꢀ Keita Takahashi, and Ken Takakiꢀ
Department of Chemistry and Chemical Engineering, Graduate School of Engineering, Hiroshima University,
1-4-1 Kagamiyama, Higashi-Hiroshima 739-8527
(Received March 10, 2008; CL-080264; E-mail: kkome@hiroshima-u.ac.jp)
Bi(OTf)3 was found to be a good catalyst for intramolecular
an early transition metal catalyst like Sc(OTf)3 at room temper-
ature in dichloroethane (DCE), no consumption of the substrate
was observed (Entry 1). Late transition metals such as PdCl2
and PtCl2 were greatly effective for the cyclization (Entries 2
and 3), especially, PtCl2 exclusively afforded 5-membered
vinylidene–lactone 2a0 in excellent yield (Entry 3). Ni(OTf)2
and Cu(OTf)2 showed a sluggish susceptibility for the reaction
to leave most of 1a unchanged (Entries 4 and 5). In sharp
contrast, different behavior was observed when the borderline-
metal catalysts,4 Fe(OTf)3 and Bi(OTf)3, were employed in
the cyclization. Thus, these catalysts exhibited a good to high
catalytic performance and a drastic change of the product struc-
ture: exclusive formation of endo-lactone 2a (Entries 6 and 7).5
Utilization of the bismuth catalyst particularly made the cycliza-
tion complete quickly (0.5 h). The counter ion of the bismuth
catalysts also had effect on the reaction. With ClO4 and
BF4, the reactions were less effective than OTf (Entries 7–9).
Of course, the cyclization did not proceed without these
catalysts.
The catalytic activity strongly depended on the solvent used
(Table 2). In non-polar solvents, the bismuth catalyst showed a
high catalytic performance. That is, 2a was given in high yield
in DCE and toluene, whereas polar solvents such as acetonitrile
and 1,4-dioxane resulted in low or negligible conversions of
the substrate, respectively. Most of the substrate 1a remained
unchanged in hexane solvent because of its insolubility.
Other Bi(OTf)3-catalyzed cyclizations of alkynyl carboxylic
acids to lactones succeeded as shown in eqs 1–3. The acid 1b,
bearing two terminal alkynyl and carboxylic moieties in a mole-
cule, converted directly into spiro-cyclic lactone in 33% yield
(eq 1). Although the transformation of the long chain acid 1c
proceeded smoothly to give 6-membered lactone via exo-cycli-
zation mode in 91% NMR yield, a part of the product was
spontaneously hydrated by a workup procedure to give the keto-
carboxylic acid in 22% isolated yield (eq 2). It is remarkable
that the Bi catalyst took part in the cyclization of alkyne rather
than that of olefin (eq 3).6
addition of carboxylic acids to alkynes (hydro-oxycarbonyla-
tion), which afforded the corresponding 5- and 6-membered
lactones in moderate to good yields under mild conditions.
Heterocycles are common structures of a wide range of
natural and biological active molecules. Therefore, the develop-
ment of new and efficient methodologies for the synthesis of
heterocyclic compounds is of central importance in organic
synthesis.1 Of the attractive process recently developed, transi-
tion-metal-catalyzed addition of the heteroatom–hydrogen
bond (X–H) across the carbon–carbon multiple bond could be
recognized as the most atom-economical method.2 However,
due to a number of inherent factors including low reactivity
of X–H bond and alkyne, effective transition-metal-catalyzed
protocols for the transformation with heteroatom nucleophiles
remain scarce.
Previously, we have demonstrated that environmentally
benign iron salts were effective catalysts for the intramolecular
hetero-functionalization of unactivated olefins with amines,
alcohols, and carboxylic acids to yield the corresponding hetero-
cycles, wherein the iron could activate both the heteroatoms and
the carbon–carbon double bonds in a dual mode.3 However, the
catalyst showed lower activity for the addition to alkynes. Thus,
we searched other catalysts, and then discovered a high activity
of bismuth catalyst for the alkyne-functionalization. Herein, we
report a new method for intramolecular cyclization of alkynyl
carboxylic acids by use of Bi(OTf)3 catalyst.
As an initial investigation, we examined a catalytic ability
of various transition metals for the cyclization of 2,2-diphenyl-
pent-4-ynoic acid (1a) as a model substrate. These results
are summarized in Table 1. When the acid 1a was treated with
Table 1. Screening of catalysts for hydro-oxycarbonylation
of 1a
O
O
O
OH
O
O
2.5 mol% catalyst
DCE (0.1 M), rt
+
Ph
Ph
Ph
Ph
Ph
Ph
Table 2. Solvent effect for Bi(OTf)3-catalyzed hydro-oxycar-
bonylation
1a
2a
2a'
O
OH
O
Yield (2a/2a0)/%a
Conv./%a
2.5 mol% Bi(OTf)3
O
Entry
Catalyst
Time/h
Ph
Ph
Ph
Ph
1
2
3
4
5
6
7
8
9
Sc(OTf)3
PdCl2
24
22
9
no reaction
67 (0/100)
95 (0/100)
10 (0/100)
9 (0/100)
—
67
solvent (0.1 M)
rt, 0.5 h
1a
2a
PtCl2
100
16
Entry
Solvent
Yield/%a
Conv./%a
Ni(OTf)2
Cu(OTf)2
Fe(OTf)3
Bi(OTf)3
24
24
24
0.5
9
1
2
3
4
5
DCE
83
80
35
0
100
100
46
7
45 (100/0)
83 (100/0)
79 (100/0)
52 (100/0)
100
100
100
100
Toluene
MeCN
Bi(ClO4)3
Bi(BF4)3
0.5
0.5
1,4-dioxane
Hexane
0
2
aDetermined by 1H NMR.
aDetermined by 1H NMR.
Copyright ꢀ 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.6 (2008)
603
both carboxylic and alkyne function like our previous finding.3
Studies on scope and limitation of the system and on details
of the reaction mechanism are currently in progress.
O
O
O
O
HO
OH
2.5 mol% Bi(OTf)3
(1)
(2)
(3)
DCE, 80°C, 0.5 h
O
O
1b
33%
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Area no. 18850015 from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
O
O
Ph
Ph
O
O
O
OH
2.5 mol% Bi(OTf)3
OH
OH
+
Ph
Ph
Ph
Ph
O
DCE, 80°C, 0.5 h
References and Notes
1c
69%
22%
1
2
3
a) F. Q. Alali, X.-X. Liu, J. L. McLaughlin, J. Nat. Prod. 1999,
62, 504. b) D. O’Hagan, Nat. Prod. Rep. 2000, 17, 435. c) J. P.
Michael, Nat. Prod. Rep. 2001, 18, 520.
a) F. Alonso, I. P. Beletskaya, M. Yus, Chem. Rev. 2004, 104,
3079. b) I. Nakamura, Y. Yamamoto, Chem. Rev. 2004, 104,
2127.
a) K. Komeyama, T. Morimoto, K. Takaki, Angew. Chem., Int.
Ed. 2006, 45, 2938. b) K. Komeyama, T. Morimoto, Y.
Nakayama, K. Takaki, Tetraheron Lett. 2007, 48, 3259.
c) K. Komeyama, Y. Mieno, S. Yukawa, T. Morimoto, K.
Takaki, Chem. Lett. 2007, 36, 752.
O
Ph
O
5 mol% Bi(OTf)3
DCE, rt, 1.5 h
Ph
1d
40%
Table 3.
O
O
OH
O
O
R
R
O
2.5 mol% Bi(OTf)3
solvent
R
+
R'
R'
R'
R'
R'
R'
1
2'
3
4
5
a) I. Fleming, Frontier Orbitals and Organic Chemical
Reactions, John Wiley & Sons, Ltd., London, 1976. b) T.-L.
Ho, Hard and Soft Acids and Bases Principle in Organic
Chemistry, Academic Press, New York, 1977.
When 2a0 was treated with Bi(OTf)3 catalyst, quantitative
yield of 2a was formed. The result would indicate the
vinylidene–lactone was reconstructed to the endocyclic one
via olefinic isomerization under the conditions.
The same selectivity was accomplished by AuI catalyst. E.
ˆ
Genin, P. Y. Toullec, S. Antoniotti, C. Brancour, J.-P. Genet,
V. Michelet, J. Am. Chem. Soc. 2006, 128, 3112.
The olefinic isomerization, described in Table 1, was not
observed in the reaction of the aromatic alkynes due to thermo-
dynamic stability of benzylidene-form.
a) C. Lambert, K. Utimoto, H. Nozaki, Tetrahedron Lett. 1984,
25, 5323. b) D. M. T. Chan, T. B. Marder, D. Milstein, N.
Taylor, J. Am. Chem. Soc. 1987, 109, 6385. c) P. Pale, J.
Chuche, Tetrahedron Lett. 1987, 28, 6447. d) M. Viciano, E.
Alkynyl carboxylic acid 1
Temp Time Total yield Ratio (20/3)
Entry
R
R0
/ꢁC
/h
/%a
/%b
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
1e
1f
80
rt
3.0
1.5
3.0
0.5
0.5
0.5
8.0
0.5
1.5
95
54
(28/72)
(0/100)
(0/100)
(0/100)
(12/88)
(0/100)
(0/100)
(6/94)
4-MeOC6H4
3-MeC6H4
4-BrC6H4
Ph
Ph
1g
1h
1i
80
80
80
rt
73
Ph
83
Me
Me
Me
Me
Me
92b
100b
93b
98b
99b
4-MeOC6H4
4-MeC6H4
3-MeC6H4
4-BrC6H4
1j
6
7
8
1k
1l
rt
80
80
1m
(24/76)
aIsolated yield. bDetermined by 1H NMR.
Next, under the optimized conditions we investigated the
intramolecular addition of carboxylic acid to aromatic alkyne
moiety. These results are listed in Table 3. The reaction of 1e
with Bi(OTf)3 catalyst mainly afforded 3e in 68% yield with
benzylidene–lactone 2e07 in 27% yield (Entry 1). It is noteworthy
that late transition-metal-catalyzed cyclization of 4-pentynoic
acids generally leads 5-exo-dig manner to furnish mainly the
vinylidene–lactones, except for a few examples.8 Indeed,
exposure of the acid 1e with PtCl2 (2.5 mol %) at 80 ꢁC (DCE)
for 19 h yielded 82% of 2e0 along with 9% of the endocyclic
one 3e, in contrast with the present result. Moreover, replace-
ment of substituent at terminal phenyl group resulted in an
exclusive formation of the 6-membered lactone. Thus, reaction
of 1f with the bismuth catalyst gave 54% yield of 3f without
any other isomers (Entry 2). Similar regiospecificity were also
observed in the case of 1g and 1h, leading to only 3g and 3h
in 73% and 83% yields, respectively (Entries 3 and 4). Similar
predominant formation of 6-membered lactones was achieved
in the reaction of 2,2-dimethyl-4-pentynoic acid derivatives
1i–1m (Entries 5–9).9
´
´
Mas-Marza, M. Sanau, E. Peris, Organometallics 2006, 25,
3063. e) J. H. H. Ho, D. S. C. Black, B. A. Messerle, J. K.
Clegg, P. Turner, Organometallics 2006, 25, 5800. f) H.
Harkat, J.-M. Weibel, P. Pale, Tetrahedron Lett. 2006, 47,
6273. Examples for high selective synthesis of 6-membered
lactones: g) H. Sashida, A. Kawamukai, Synthesis 1999,
1999, 1145. h) F. Bellina, D. Ciucci, P. Vergamini, R. Rossi,
Tetrahedron 2000, 56, 2533.
9
These product yields were determined by NMR measurement
for the crude product with dimethyl terephthalate as an internal
standard because the products 3f–3j were somewhat labile.
10 Representative procedure for the Bi-catalyzed cyclization of
alkynyl carboxylic acid: A solution of 1a (50 mg, 0.20 mmol)
and Bi(OTf)3 (3.3 mg, 5 mmol) in DCE (2 mL) was stirred
under the suitable conditions with TLC monitoring. After
complete, the reaction mixture was passed through a short sili-
ca-gel column with ether. Concentration of the filtrate gave the
crude product, which afforded 82% (41 mg) of 3,3-diphenyl-5-
methyl-2(3H)-furanone (2a) by silica-gel column chromatog-
raphy. 2a: Colorless oil; Rf (Hexane/EtOAc = 5:1) = 0.51;
1H NMR (CDCl3, 270.05 MHz) ꢀ 2.10 (3H, d, J ¼ 1:3 Hz),
5.70 (1H, br s), 7.22–7.38 (10H, m); 13C NMR (CDCl3, 67.8
MHz) ꢀ 14.0, 61.5, 109.6, 127.5, 127.6, 128.7, 140.4, 151.3,
177.6; EI-MS m=z 250 (Mþ), 221 (46), 207 (83), 179 (100).
In summary, we have disclosed a bismuth-catalyzed intra-
molecular hydro-oxycarbonylation of alkynes, giving rise to 5-
and 6-membered lactones in high yields and selectivity under
mild conditions.10 In comparison with other transition-metal
catalysts, the bismuth catalyst is helpful for the transformation
owing to its easy handling and commercial availability. Al-
though the actual role of the bismuth catalyst is not yet clear,
we thought that the bismuth might act as a dual activator of
Published on the web (Advance View) April 26, 2008; doi:10.1246/cl.2008.602