Bismuth-catalyzed intramolecular carbo-oxycarbonylation of 3-alkynyl esters

Article abstract of DOI:10.1021/ol8019567

(Chemical Equation Presented) Borderline metal complexes, especially Bi(OTf)₃, efficiently catalyze the carbo-oxycarbonylation of alkynyl esters to form multisubstituted lactones in moderate to high yields.

Full text of DOI:10.1021/ol8019567

ORGANIC
LETTERS
2008
Vol. 10, No. 22
5119-5122
Bismuth-Catalyzed Intramolecular
Carbo-oxycarbonylation of 3-Alkynyl
Esters
Kimihiro Komeyama,* Keita Takahashi, and Ken Takaki*
Department of Chemistry and Chemical Engineering, Graduate School of Engineering,
Hiroshima UniVersity, 1-4-1 Kagamiyama, Higashi-Hiroshima 739-8527, Japan
kkome@hiroshima-u.ac.jp
Received August 21, 2008
ABSTRACT
Borderline metal complexes, especially Bi(OTf)3, efficiently catalyze the carbo-oxycarbonylation of alkynyl esters to form multisubstituted
lactones in moderate to high yields.
Transition-metal-catalyzed addition of heteroatoms across
carbon-carbon unsaturated bonds has attracted significant
interest, particularly in the intramolecular reaction, because
the heterocycles provide the core and key structures of natural
products and organic materials. Thus, many metal catalysts
have been explored for the efficient transformation. On their
survey, there are two activation modes of the substrates by
the catalysts: σ- and π-activations (A and B in Figure 1,
intermediates like amide, imide, and alkoxide species.2 On
the other hand, soft metals (e.g., Au, Pt, Hg, Ag, and Pd),
with lower LUMO energy, provide π-complexes with
carbon-carbon multiple bonds (acceptor).3 Although these
catalysts reveal excellent capacity in the area, their substitu-
tion by air-stable, inexpensive, and environmentally benign
metal is desired for practical production.
For the development of a new catalyst system, we
investigated the activity of borderline metals,1b based on the
following working hypothesis. Their LUMO energy should
be laid in the middle of those of hard and soft metals, and
therefore, they can interact with both heteroatoms and
carbon-carbon multiple bonds as depicted (C) in Figure 1.
Consequently, dual activation of donor and acceptor, i.e.,
σ- and π-activation, could be expected with the borderline
catalysts, which would guarantee a good catalytic perfor-
mance in the reaction.4 Moreover, the interaction may bring
the two reaction sites close. In spite of these possibilities,
their application to the heteroatom-cyclization had been
Figure 1. Activation modes of heteroatom (X) and Ct C with metal
catalysts ([M]) in the intramolecular heterofunctionalization.
respectively). According to the HSAB theory, the mode is
dependent on the affinity of the reaction site of the substrate
with the metals.1 In the σ-activation, hard metals (e.g., group
3 and 4 metals), having relatively higher LUMO energy,
interact strongly with heteroatoms (donor) followed by the
metalation of heteroatom-hydrogen bonds to yield reactive
(1) (a) Fleming, I. Frontier Orbital and Organic Chemical Reactions;
John Wiley & Sons, Ltd.: London, 1976. (b) Ho, T.-L. Hard and Soft Acids
and Bases Principle in Organic Chemistry; Academic Press: New York,
1977. (c) Woodward, S. Tetrahedron 2002, 58, 1017.
(2) (a) Mu¨ller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675. (b) Alonso,
F.; Beletskaya, I. P.; Yus, M. Chem. ReV. 2004, 104, 3079.
(3) (a) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395. (b) Fu¨rstner,
A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410.
10.1021/ol8019567 CCC: $40.75
Published on Web 10/22/2008
2008 American Chemical Society

scarcely developed. Recently, this idea proved to work well
by our studies on hydroamination, hydroalkoxylation, and
hydro-oxycarboxylation of unactivated alkenes and alkynes
using iron and bismuth as representative borderline catalysts.5
During our investigation along this line, we found that
intramolecular carbo-oxycarbonylation of alkyne6 takes place
readily on treatment of alkynyl benzylic esters with Bi(OTf)3
catalyst7 (Scheme 1). We report herein these results.
Table 1. Optimization of Conditions in Carbo-oxycarbonylation
of Alkynyl Ester 1a in the Presence of Various Catalysts and
MSa
catalyst
(mol %)
MS
(mg)
time
(h)
yield of
2b (%)
conv of
1b (%)
entry
1
2
3
4
5
6
7
8
Bi(OTf)3 (2.5)
Bi(OTf)3 (2.5)
Bi(OTf)3 (2.5)
Bi(OTf)3 (2.5)
Bi(OTf)3 (5.0)
Bi(OTf)3 (10.0)
none
100
none
150
200
100
100
none
100
100
100
100
100
100
100
100
100
100
6
10
24
24
3
69
41
56
57
100
100
82
77
100
100
Scheme 1
61
3
62 (60)
n.r.
n.r.
50
55
51
45
40
20
24
10
10
7
7
7
7
7
24
24
7
none
9
Fe(OTf)2 (10.0)
Fe(OTf)3 (10.0)
Cu(OTf)2 (10.0)
Zn(OTf)2 (10.0)
Ni(OTf)2 (10.0)
PdCl2 (10.0)
PtCl2 (10.0)
Sc(OTf)3 (10.0)
TfOH (10.0)
100
100
100
100
98
21
25
100
100
10
11
12
13
14
15
16
17
When alkynyl ester 1a was treated with 2.5 mol % of
Bi(OTf)3 and molecular sieves in dichloromethane (DCE)
at room temperature for 6 h, 3,4-dihydropyran-2-one 2a was
obtained in 69% yield together with 2,2-dimethyl-5-phenyl-
pent-4-ynoic acid (3) (18%), a hydrolysis product of 1a
(Table 1, entry 1). Molecular sieves played important roles
in repressing the formation of the carboxylic acid 3 and in
reducing reaction time (entry 2). However, its excess use
caused a decrease of the catalytic performance (entries 3 and
4). More loading of the catalyst increased the reaction rate,
although the yield of 2a was almost unchanged (entries 5
and 6). The present reaction did not proceed with molecular
sieves alone or without the bismuth catalyst (entries 7 and
8). Employment of other borderline metals, such as Fe-
(OTf)2or3, Cu(OTf)2, Zn(OTf)2, and Ni(OTf)2, were similarly
effective, albeit with slightly lower yields (entries 9-13).
PtCl2 and PdCl2, soft π-acids, also gave the product 2a, but
the reaction rate was very slow (20-24% yield, 24 h) (entries
14 and 15). In sharp contrast, TfOH and Sc(OTf)3, a hard
Brønsted acid and Lewis acid, exclusively provided the
carboxylic acid 3 as a single product (entries 16 and 17).
Hexane, toluene, and MeNO2 were suitable solvents as well
as DCE, whereas 1,4-dioxane, tetrahydrofuran, and aceto-
nitrile prevented the reaction.
trace
trace
7
a 1a (50 mg, 0.16 mmol) was used at room temperature in DCE (0.1
M). b Determined by 1H NMR with mesitylene as a internal standard. Value
in parentheses indicates isolated yield.
With optimal conditions in hand, we examined the scope
of the Bi(OTf)3-catalyzed carbo-oxycarbonylation with vari-
ous alkynyl esters (Table 2). Lower temperature improved
the product yield of 2a up to 81%, albeit for longer reaction
time (entry 2). With respect to the substituent effect of the
Table 2. Bismuth-Catalyzed Carbo-oxycarbonylation of Various
Alkynyl Esters 1a
alkynyl esters 1
T
time yield of
entry
R1
R2
R3
(°C) (h) 2 (%)b
(4) σ-π Chelation of typical metals was reported by Yamamoto et al.;
see: Asao, N.; Asano, T.; Ohishi, T.; Yamamoto, Y. J. Am. Chem. Soc.
2000, 122, 4817.
1
2
3
4
5
6c
7
8
9
1a, Ph
Me
Me
Et
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
rt
0
rt
rt
3
44
5
60
81
45
70
67
37
87
92
69
34
58
45
78
83
93
95
98
1a, Ph
(5) (a) Komeyama, K.; Morimoto, T.; Takaki, K. Angew. Chem., Int.
Ed. 2006, 45, 2938. (b) Komeyama, K.; Morimoto, T.; Nakayama, Y.;
Takaki, K. Tetrahedron Lett. 2007, 48, 3259. (c) Komeyama, K.; Mieno,
Y.; Yukawa, S.; Morimoto, T.; Takaki, K. Chem. Lett. 2007, 36, 752. (d)
Komeyama, K.; Takahashi, K.; Takaki, K. Chem. Lett. 2008, 37, 602. (e)
Komeyama, K.; Miyagi, M.; Takaki, K. Heteroatom Chem. 2008, 19, 644–
648.
1b, Ph
1c, 4-ClC6H4
1d, 4-MeC6H4 Me
1e, 4-MeOC6H4 Me
1f, Ph
1g, 4-ClC6H4
Me
7
-15 19
rt
rt
rt
0
0
rt
0
1
7
3
2
2
1
7
2
2
1
2
1
Ph
4-ClC6H4
1h, 4-MeC6H4 4-MeC6H4 Ph
(6) Fu¨rstner has reported similar reactions using platinum and gold
catalysts; see ref 3b and: Fu¨rstner, A.; Davies, P. W. J. Am. Chem. Soc.
2005, 127, 15024.
10 1i, 4-MeOC6H4 4-MeOC6H4 Ph
11 1j, Ph
12 1k, Ph
13 1l, Ph
14 1m, Ph
15 1n, Ph
16 1o, Ph
17 1p, Ph
2-naphthyl Ph
cyclpropyl Ph
(7) The behavior of Bi(OTf)3/MPF6 (M ) K or Cu) systems as σ- and
π-acids was postulated by Shibasaki and Matsunaga et al.: Qin, H.;
Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2006, 128,
1611.
Ct CnBu
Ph
Ph
4-BrC6H4
4-MeOC6H4 rt
4-MeC6H4 rt
3-MeC6H4 rt
rt
rt
Ph
Ph
(8) In previous work,5d we found that the iron- and the bismuth-catalyzed
addition of heteroatom to alkynes seems to mainly proceed at the alkynyl
carbon attached with aryl group. Furthermore, treatment of product 2r′ with
NaOH (5 equiv) for 3 h in methanol provided 2-(2-benzhydrylhexanoyl-
)benzoic acid in 47% yield.
Ph
a Conditions: 1 (0.16 mmol), MS (100 mg), Bi(OTf)3 (10 mol %), DCE
(0.1 M). b Isolated yield. c Carried out in MeNO2 solvent.
5120
Org. Lett., Vol. 10, No. 22, 2008

ester moieties (R1), the electron-deficient aryl of 1c provided
a slightly better yield than the electron-rich ones of 1d and
1e (entries 4-6). Moreover, diarylmethyl esters 1f-h were
more reactive than the corresponding monoaryethyl esters
1a, 1c, and 1d, wherein electron-deficient aryls also facili-
tated the reaction (entries 8 vs 9, 10). A bulky naphthyl group
did not prevent the cyclization (entry 11). It is noteworthy
that the present reaction permitted labile substituents like
alkynyl and cyclopropyl groups to take part in the transfor-
mation (entries 12 and 13). However, other alkynyl esters
such as allyl, 2-cyclohexenyl, bezyl, fluorenyl, and 2,2,2-
trifluoro-1-phenylethyl esters were unchanged and did not
provide the desired products. These findings might indicate
that the cleavage of C(O)O-C bond of esters is a key step
of the present carbo-oxycarbonylation. Electronic property
of terminal aryl substituents (R3) did not influence the
reactivity to afford the dihydropyran-2-ones 2m-p in
excellent yields (entries 14-17). Additionally, the procedure
could be applied to the synthesis of multisubstituted isocou-
marin 2q (Scheme 2). In contrast, in the case of terminal
Scheme 4. Inter- vs. Intramolecular Reaction
because the postulated product 4 was not detected under
various conditions. In addition, although bismuth complexes
have been known to catalyze the benzylation of aromatic
rings with benzylic alcohols,10 the compound 4 prepared
separately was recovered unchanged in the reaction with
1-phenylethanol and its acetate using Bi(OTf)3. Furthermore,
evidence to support the intramolecular reaction was obtained
by the crossover experiment (Scheme 5). Treatment of an
Scheme 2
Scheme 5. Crossover Reaction of 1g and 1o
alkyl substituent 1r, exo-type cyclization mainly proceeded
to afford 5-membered lactone 2r′ with two stereoisomers
(Scheme 3).8
Scheme 3
equimolar mixture of 1g and 1o with 10 mol % of Bi(OTf)3
gave 2g and 2o in quantitative yields, respectively, without
any crossover products.
We envisioned two possible reaction paths, inter- and
intramolecular alkyl migrations, for the present cyclization
as illustrated in Scheme 4. In the intermolecular process (path
a), the ester 1a would be converted to the primary product
45d by the fast hydrolysis of the C(O)O-benzyl bond
followed by hydro-oxycarboxylation, which is then benzy-
lated with the [PhCHMe]+ equivalent derived from another
molecule of 1a to afford the product 2a. Alternatively, direct
cyclization of 1a leading to the metalated intermediate and
subsequent intramolecular 1,5-migration of the alkyl group9
would yield 2a (path b). Path a seems to be less likely
On the basis of these results, we propose the reaction
mechanism in Scheme 6. The borderline bismuth would
coordinate not only to the ester moiety but also to the triple
bond of 1, leading to dually activated species D, in which
the activated mode would make two reaction sites (ester and
alkyne) close. Subsequent cyclization of D takes place readily
through nucleophilic addition of the carbonyl oxygen to the
bismuth-coordinated alkyne E to yield the zwitterionic
intermediates F or F′. Then, intramolecular 1,5-migration
of the benzyl group to the metalated sp2-carbon liberates the
products 2 or 2′ and the catalyst.
(9) (a) Ferrier, R. J.; Middleton, S. Chem. ReV. 1993, 93, 2779. (b)
Tayama, E.; Isaka, W. Org. Lett. 2006, 8, 5437.
(10) Rueping, M.; Nachtsheim, B. J.; Ieawsuwan, W. AdV. Synth. Catal.
2006, 348, 1033.
Org. Lett., Vol. 10, No. 22, 2008
5121

conditions. The excellent catalyst activity of the borderline
metals, particularly of bismuth, observed in this cyclization
would be attributable to their unique activation mode.
Furthermore, these results suggest that inexpensive and
tractable bismuth has a good potentiality to substitute a part
of the conventional transition metal catalysts and to provide
new reaction pathways in organic synthesis. We are currently
exploring the detail of mechanism and developing other
functionalizaitons of the carbon-carbon multiple bonds with
the borderline metals.
Scheme 6. Plausible Reaction Mechanism
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research from the Ministry of Educa-
tion, Culture, Sports, Science, and Technology, Japan.
Supporting Information Available: Experimental pro-
cedures and product characterization. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
In conclusion, we have developed a novel bismuth-
catalyzed intramolecular carbo-oxycarbonylation of alkynyl
benzylic esters, which mainly afforded multisubstituted
6-membered lactones 2 in good to high yields under mild
OL8019567
5122
Org. Lett., Vol. 10, No. 22, 2008