Ruthenium-Catalyzed Cyclocarbonylation of Allenyl Alcohols and Amines: Selective Synthesis of Lactones and Lactams

Article abstract of DOI:10.1021/jo0350615

Allenyl alcohols such as 4-hydroxybuta-1,2-dienes and 5-hydroxypenta-1,2-dienes having a variety of substituents undergo cyclocarbonylation in the presence of a ruthenium catalyst under mild conditions selectively to give five- and six-membered lactones in a high yield with 100% atom economy. 5-Aminopenta-1,2-dines are also cyclocarbonylated to give γ-lactams. A possible carbonylation mechanism involving a ruthenium cluster intermediate is proposed on the basis of experimental results.

Full text of DOI:10.1021/jo0350615

Ru th en iu m -Ca ta lyzed Cycloca r bon yla tion of Allen yl Alcoh ols a n d
Am in es: Selective Syn th esis of La cton es a n d La cta m s
Eiji Yoneda, Shi-Wei Zhang, Da-Yang Zhou, Kiyotaka Onitsuka, and Shigetoshi Takahashi*
The Institute of Scientific and Industrial Research, Osaka University, Mihogaoka, Ibaraki,
Osaka 567-0047, J apan
takahashi@sanken.osaka-u.ac.jp
Received J uly 23, 2003
Allenyl alcohols such as 4-hydroxybuta-1,2-dienes and 5-hydroxypenta-1,2-dienes having a variety
of substituents undergo cyclocarbonylation in the presence of a ruthenium catalyst under mild
conditions selectively to give five- and six-membered lactones in a high yield with 100% atom
economy. 5-Aminopenta-1,2-dines are also cyclocarbonylated to give γ-lactams. A possible carbo-
nylation mechanism involving a ruthenium cluster intermediate is proposed on the basis of
experimental results.
In tr od u ction
such as benzofuranones and dihydroindolones. Recently,
we have extended the Rh-catalyzed carbonylation of
alkynes to dienes giving polyketones5 and have now found
a new catalytic system that is effective for the cyclocar-
bonylation of allenes. Although Rh-catalyzed reactions
of allenes with carbon monoxide caused polymerization
to give 1:1 alternating polymers,6 we have now found that
allenyl alcohols undergo cyclocarbonylation by the ca-
talysis of a ruthenium complex to give lactones in
excellent yields. Interestingly, five- and six-membered
lactones can be prepared directly from 4-hydroxybuta-
1,2-diene and 5-hydroxypenta-1,2-diene, respectively. The
present carbonylation may be characterized by high
selectivity and yield with atom economy of 100%. The
preliminary result has already been communicated,7 and
herein full details on the scope and mechanism of the
cyclocarbonylation are described. Application of the car-
bonylation to allenylamines giving lactams is also re-
ported.
Carbonylation reactions have a long history and still
attract much attention in both academic and industrial
fields.1 The innovation of new types of carbonylations has
always provided us new methods for efficient syntheses
of a variety of useful compounds. Carbonylations of
alkenes and alkynes in the presence of nucleophiles such
as alcohols and amines often afford carboxylic acid
derivatives. Carbonylations of such unsaturated sub-
strates bearing hydroxyl and amino groups at a position
neighboring the unsaturated carbon-carbon bond result
in intramolecular cyclization, so-called cyclocarbonyla-
tion, to give lactones and lactams. The cyclocarbonyla-
tions continue to be a challenging area in synthetic
organic chemistry since heterocyclic compounds are
produced directly from such unsaturated compounds.2
Previously, we have shown that alkynes bearing adjacent
functional groups such as ortho-alkynylphenols3 and
ortho-anilines4 undergo cyclocarbonylation by the cataly-
sis of rhodium carbonyls under water-gas shift reaction
conditions to produce various heterocyclic compounds
* Corresponding author. Phone: +81-6-6879-8455. Fax: +81-6-
6879-8459.
(1) (a) New Syntheses with Carbon Monoxide; Falbe, J . Eds.;
Spronger-Verlag: Heidelberg, 1980. (b) Parshall, G. W. Homogeneous
Catalysis; Wiley-Interscience: New York, 1980. (c) Catalysis in C1
Chemistry,; Keim, W., Eds.; D. Reidel Publishig Company: Dordrecht,
1983. (d) Masters, C. Homogeneous Transition-Metal Catalysis;
Wiley: New York, 1993. (e) Applied Homogeneous Catalysis with
Organometallic Compounds; Cornils, B., Herrmann, W. A., Eds.;
VCH: Weinheim, 1996; Vol. 2, Chapter 2.
(2) For review see: (a) Schore N. E. Chem. Rev. 1988, 88, 1081. (b)
Colquhoun, H. M.; Thompson, D. J .; Twigg, M. V. Carbonylation: Direct
Synthesis of Carbonyl Compounds; Plenum Press: New York, 1991.
(c) Stille, J . K. In Comprehensive Organic Synthesis: Trost, B. M.,
Fleming, L, Eds.; Pergamon Press: New York, 1991; Vol. 4, p 913. (d)
Negishi, E.; Coperet, C.; Ma, S.; Lion, S. Y.; Liu, F. Chem. Rev. 1996,
96, 365. (e) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J . Chem.
Rev. 1996, 96, 635. (f) Ungvary, F. Coord. Chem. Rev. 1998, 170, 245.
(3) (a) Yoneda, E.; Sugioka, T.; Hirao, K.; Zhang, S.-W.; Takahashi,
S. J . Chem. Soc., Perkin Trans. 1 1998, 477. (b) Yoneda, E.; Sugioka,
T.; Zhang, S.-W.; Takahashi, S. Tetrahedron Lett. 1998, 39, 5061.
(4) Hirao, K.; Morii, N.; J oh, T.; Takahashi, S. Tetrahedron Lett.
1995, 36, 6243.
Resu lts a n d Discu ssion
Ca r bon yla tion of Allen yl Alcoh ols. Cyclocarbony-
lations of alkenes and alkynes giving lactones have been
extensively studied,8 whereas the carbonylation of allenes
has been directed to the preparation of methacrylates9
and there have been no reports so far on the synthesis
of lactones from allenes in the literature. In the course
(5) Zhang, S.-W.; Kaneko, T.; Takahashi, S. Macromolecules 2000,
33, 6930.
(6) Osakada, K.; Choi, J .-C.; Yamamoto, T. J . Am. Chem. Soc. 1997,
119, 12390. (b) Osakada, K.; Takenaka, T.; Choi, J .-C. J . Polym. Chem.,
A: Polym. Chem. 2000, 38, 1505.
(7) Yoneda, E.; Kaneko, T.; Zhang, S.-W.; Onitsuka, K.; Takahashi,
S. Org. Lett. 2000, 2, 441.
10.1021/jo0350615 CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/09/2003
J . Org. Chem. 2003, 68, 8571-8576
8571

Yoneda et al.
TABLE 1. Cycloca r bon yla tion of Allen esa
of our studies on rhodium-catalyzed cyclocarbonylation
of functionalized alkynes, we have found that ruthenium
carbonyls were not effective for the carbonylation of
alkynes but catalyze a new cyclocarbonylation of allenyl
alcohols exclusively to give lactones. Thus, a simple
reaction of 1-propa-1,2-dienylcyclohexan-1-ol 1a (1 mmol)
with 10 atm of carbon monoxide in the presence of Ru3-
(CO)12 (0.01 mmol) and NEt3 (0.2 mL) in 1,4-dioxane (15
mL) at 100 °C for 8 h gave a single product (2a ), which
showed an M/z of 166 (M+) corresponding to the sum of
the mass number of 138 (1a ) and 28 (CO) and was
identified to be 3-methyl-1-oxaspiro[4.5]dec-3-en-2-one10
by IR and 1H and 13C NMR spectra. Product 2a was
isolated in 95% yield after simple purification by column
chromatography on silica gel.
allenyl
product
yield
(%)b
alcohols 1 R1
R2
R3
R4
(CH2)5
Me Me 2b
R5
2
1a
1b
1c
1d
1e
1f
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
2a 99
95
96
98
98
98
95
2h 98
95
91
H
H
H
Me
iPr
MeO
H
H
H
H
H
Et
Ph 2d
H
H
H
2c
2e
2f
2g
1g
1h
1i
(CH2)5
MeO Me Me 2i
1j
1k
1l
MeO
MeO
H
H
H
H
Et
Ph 2k
2l
2j
93
98
H
1m
Me Me
H
(CH2)5
2m 98
a
Reaction conditions: substrate, 1 mmol; Ru3(CO)12 0.01 mmol;
1,4-dioxane, 15 mL; NEt3, 1.5 mmol; CO pressure, 10 atm; reaction
b
temperature, 100 °C; reaction time, 8 h. Isolated yield.
Carbonylation reactions at lower temperatures of 50
and 80 °C gave 2a in 17 and 75% yields, and 80 and 20%
of starting substrate 1a were recovered, respectively. At
100 °C even under atmospheric pressure of carbon
monoxide, the carbonylation took place to give 2a , though
the yield decreased to 62%.
catalyzed cyclocarbonylation of alkynes proceeded only
in the presence of water.3,4,8d,11
Ca r bon yla tion of Su bstitu ted Allen yl Alcoh ols.
On the basis of the above results, we chose the following
standard reaction conditions to explore the scope of the
present Ru-catalyzed cyclocarbonylation: substrate (1
mmol); catalyst, Ru3(CO)12 (1 mol %); additive, NEt3 (1.5
mmol); solvent, dioxane (15 mL), CO pressure, 10 atm;
reaction temperature, 100 °C. The cyclocarbonylation of
various substituted allenyl alcohols were carried out
under the standard reaction conditions. We consequently
found that the present system is effective for the cyclo-
carbonylation of mono-, di-, and trisubstituted allenyl
alcohols (4-hydroxy-buta-1,2-diene derivatives) 1a -m to
give γ-lactones (furanones) 2a -m in almost quantitative
yields (Table 1), indicating that primary to tertiary
alcohols on the allenic skeleton can take part in the
cyclocarbonylation and that substituents on the allenic
skeleton do not apparently affect the cyclocarbonylation.
To investigate the reactivity of allenyl alcohols, car-
bonylations of 4-hydroxy-4-phenylbuta-1,2-dienes 1n -s
were carried out (Table 2). Benzylallenyl alcohols bearing
chloro, bromo, methoxy, methylthio, and dimethylamino
groups on the phenyl substituent exhibited almost the
same reactivity toward the present cyclocarbonylation
and produced 3-methyl-5-phenylfuranone derivatives
2n -r in good yields (entries 1-5), while allenyl alcohol
1s bearing a nitro group did not give lactone but gave a
complex mixture of products that could not be identified,
although the IR spectrum showed disappearance of the
nitro group (entry 6). 4-Hydroxybuta-1,2-dienes having
a functional group at the 4-position also underwent
smooth cyclocarbonylation (entries 7-9). Ferrocenyl (1t),
vinyl (1u ), and cyclopropyl groups (1v) did not affect the
cyclocarbonylation and remained intact after the cyclo-
carbonylation. The scope suggests that the present cy-
clocarbonylation affords an excellent method for the
We examined catalytic activities of other metal carbo-
nyl complexes such as Co2(CO)8, Fe3(CO)12, Os3(CO)12,
and Rh6(CO)16, which are effective for the carbonylation
of alkenes and alkynes, but all of the complexes were
inactive for the cyclocarbonylation of 1a . Only ruthenium
complexes showed a catalytic activity toward the present
reaction. Ruthenium complexes such as RuCl3 and [RuCl2-
(CO)3]2 showed a definite activity to give 2a in 82 and
92% yield, respectively; however, RuCl2(PPh3)2 and Ru-
ClH(CO)(PPh3)3 are almost inactive. In the absence of
NEt3, 1a was completely consumed; however, the yield
of 2a was reduced to 68%, and an isomer of 2a was
formed as a byproduct (vide infra). As a base, tertiary
amines such as Et3N and tBu3N gave a good effect,
whereas use of secondary and primary amines such as
HNEt2 and H2NBu decreased the selectivity for 2a
(HNEt2, 56; H2NBu, 56% yield) and afforded amido
derivatives as a byproduct. Addition of one equiamount
of water did not affect the carbonylation, although Rh-
(8) (a) Alper, H. Tetrahedron Lett. 1985, 26, 5639. (b) Alper, H.;
Leonard, D. J . Chem. Soc., Chem. Commun. 1985, 511. (c) Alper, H.;
Hamel, N. J . Chem. Soc., Chem. Commun. 1990, 135. (d) J oh, T.;
Doyama, K.; Onitsuka, K.; Shiohara, T.; Takahashi, S. Organnome-
tallics 1991, 10, 2493. (e) Llebaria, A.; Delagado, A.; Camps, F.; Moreto,
J . M. Organometallics 1993, 12, 2825. (f) Kondo, T.; Kodai, K.; Mitsudo,
T. A.; Watanabe, Y. J . Chem. Soc., Chem. Commun. 1994, 755. (g)
Grigg, R.; Khalil, H.; Levett, P.; Viricia, J .; Sridharman, V. Tetrahedron
Lett. 1994, 35, 3197. (h) Coperet, C.; Sugihara, T.; Wu, G.; Shimoyama,
I.; Negishi, E. I. J . Am. Chem. Soc. 1995, 117, 3422. (i) Sugioka, T.;
Zhang, S. W.; Morii, N.; J oh, T.; Takahashi, S. Chem. Lett. 1996, 249.
(j) El Ali, B.; Okuro, K.; Vasapollo, G.; Alper, H. J . Am. Chem. Soc.
1996, 118, 4264. (k) Yu, W.; Alper, H. J . Org. Chem. 1997, 62, 5684.
(l) El Ali, B.; Alper, H. Synlett 2000, 161.
(9) (a) Applied Homogeneous Catalysis with Organometallic Com-
pounds; Cornils, B., Herrmann, W. A., Eds.; VCH: Weinheim, 1996;
Vol. 2, p 1119. (b) Beller, M.; Bolm, C. Transition Metals for Organic
Synthesis; Wiley-VCH: Weinheim, 1998; Vol. 1. (c) Geis, O.; Schmalz,
H.-G. Angew. Chem., Int. Ed. 1998, 37, 911. (d) Sugihara, T.; Yamagu-
chi, M.; Nishizawa, M. Chem. Eur. J . 2001, 7, 1589.
(10) Parker, K. A.; Petraitis, J . J .; Kosley, R. W.; Buchwald, S. L. J .
Org. Chem. 1982, 47, 389.
(11) Zhang, S.-W.; Kaneko, T.; Yoneda, E.; Sugioka, T.; Takahashi,
S. Inorg. Chim. Acta 1999, 296, 195.
8572 J . Org. Chem., Vol. 68, No. 22, 2003

Ruthenium-Catalyzed Cyclocarbonylation
TABLE 2. Cycloca r bon yla tion of Allen yl Alcoh olsa
complexes to give vinylamide and acrylic acid deriva-
tives,12 respectively, but not cyclocarbonylation products,
lactams. We applied the present ruthenium-catalyzed
carbonylation to allenylamines and found that 5-amino-
penta-1,2-dienes were carbonylated to give δ-lactams (eq
5). Thus, 5-aminopenta-1,2-diene (5a ) was reacted with
carbon monoxide in the presence of Ru3(CO)12 (1 mol %)
in triethylamine at 80 °C. Analysis by TLC showed the
products to be a 1:1 mixture of two components 6a and
7a , which were separated by column chromatography on
alumina. By spectral analyses, 6a was identified as
5-methyl-1H,2H,3H-azin-6-one, and 7a was identified as
its isomer, 5-methylenepyperidin-2-one.38 Similarly,
4-methyl-5-aminopenta-1,2-diene 5b gave δ-lactams as
a 1:1 mixture of two isomers 6b and 7b. Recently, Kang
(12) (a) Latthbury, D.; Vernon, P.; Gallagher, T. Tetrahedron Lett.
1986, 27, 6009. (b) Alper, H.; Piotti, M. E J . Org. Chem. 1994, 59, 1956.
(c) Imada, Y.; Vasapollo, G.; Alper, H. J . Org. Chem. 1996, 61, 7982.
(d) Murakami, M.; Itami, K.; Ito, Y. J . Am. Chem. Soc. 1996, 118,
11672.
(13) Kang, S.-K.; Kim, K.-J .; Yu, C.-M.; Hwang, J .-W.; Do, Y.-K. Org.
Lett. 2001, 3, 2851.
(14) Laine, R. M. J . Mol. Catal. 1982, 14, 137.
(15) A first-order reaction rate has been confirmed in a range of 20-
60% coversion of substrate 1a under the reaction conditions: concen-
tration of substrate 1a , 6.7 × 10-2 M; concentration of catalyst
Ru3(CO)12, 6.7 × 10-4 M; solvent, dioxane; additive, Et3N (0.97 M);
CO pressure, 10 atm; 100 °C.
(16) Ben-Shosan, R.; Pettit, R. J . Chem. Soc., Chem. Commun. 1968,
247.
(17) Deeming, A. J .; Arce, A. J .; Sanctis, Y. D.; Bates, P. A.;
Hursthouse, M. B. J . Chem. Soc., Dalton Trans. 1987, 2935.
(18) (a) Brandsma, L.; Verkruijsse, H. D. Synthesis of Acethylenes,
Allenes and Cumullenes; Elsevier: New York; 1981. (b) Crabbe, P.;
Andre, D.; Fillion, H. Tetrahedron Lett. 1979, 893. (c) Hoff, S.;
Brandsma, L.; Arens, J . F. Recl. Trav. Chim. Pays-Bas 1968, 87, 916.
(19) Kimura, M.; Tanaka, S.; Tamaru, Y. Bull. Chim. Soc. J pn. 1995,
68, 1689.
(20) Zimmer, R.; Reissig, H. U. Liebigs Ann. Chem. 1991, 6, 553.
(21) Creary, X. J . Am. Chem. Soc. 1977, 99, 7632.
(22) Masuyama, Y.; Ito, A.; Fukuzawa, M.; Terada, K.; Kurusu, Y.
Chem. Commun. 1998, 2025.
(23) Lautens, M.; Meyer, C.; van Oevern, A. Tetrahedron Lett. 1997,
38, 3833.
(24) Hanack, M.; Heaffner, J . Chem. Ber. 1966, 99, 1077.
(25) Ma, S.; Xie, H.; Wang, G.; Zhang, J .; Shi, Z. Synthesis 2001,
713.
a
Reaction conditions: substrate, 1 mmol; Ru3(CO)12 0.01 mmol;
1,4-dioxane, 15 mL; NEt3, 1.5 mmol; CO pressure, 10 atm; reaction
temperature, 100 °C; reaction time, 8 h. Isolated yield.
b
preparation of furanones having a wide variety of sub-
stituents on the skeleton.
(26) Hong, P.; Mise, T.; Yamazaki, H. J . Organomet. Chem. 1991,
412, 291.
(27) Ma, S.; Yu, Z.; Wu, S. Tetrahedron 2001, 57, 1585.
(28) Ishii, H.; Ishige, M.; Matsushima, Y.; Tohojoh, T.; Ishikawa,
T.; Kawanabe, E. J . Chem. Soc., Perkin Trans. 1 1985, 2353.
(29) Woo, E. P.; Cheng, F. C. W. J . Org. Chem. 1986, 51, 3706.
(30) Kabuss, S. Angew. Chem., Int. Ed. 1968, 7, 64.
(31) Payard, M.; Paris, J .; Tronche, P. J . Heterocycl. Chem. 1978,
15, 1493.
(32) Yamada, T.; Hagiwara, H.; Uda, H. J . Chem. Soc., Chem.
Comm. 1980, 838.
(33) Martin, S. F.; Moore, D. R. Terahedron Lett. 1976, 4459.
(34) Tanabe, Y.; Ohno, N. J . Org. Chem. 1988, 53, 1560.
(35) Canevet, J .-C.; Graff, Y. Helv. Chim. Acta 1979, 62, 1614.
(36) Hofstraat, R. G.; Lange, J .; Scheeren, H. W.; Nivard, R. J . F.
J . Chem. Soc., Perkin Trans. 1 1988, 2315.
The present catalytic system is also effective for the
cyclocarbonylation of allenyl alcohols that contain a
dimethylene spacer between the hydroxyl and allenyl
groups. 5-Hydroxypenta-1,2-dienes 3a -c similarly un-
derwent cyclocarbonylation to give δ-lactones 4a -c,
respectively, in a high yield (eq 4). Substituents on the
methylene spacer do not seem to give undesirable effects
on the formation of six-membered lactones.
Ca r bon yla tion of Allen yla m in es. Amines are well-
known to act as a nucleophile in carbonylation reactions
of alkenes and alkynes giving amides. Allenylamines
such as 4-aminobuta-1,2-diene and 6-aminohexa-1,2-
diene are also carbonylated by the catalysis of palladium
(37) Andrus, M. B.; Li, W.; Keyes, R. F. J . Org. Chem. 1997, 62,
5542.
(38) Campli, E. M.; Chong, J . M.; J ackson, W. R.; Van Der Schoot,
M. Tetrahedron 1994, 50, 2533.
J . Org. Chem, Vol. 68, No. 22, 2003 8573

Yoneda et al.
SCHEME 1
latter carries 50% deuterium content at 4-C, suggesting
migration of one of the two hydrogen atoms at 4-C to the
exo-methylene group in 2′a to form 2a . This deuterium
experiment suggests that amines affect the isomerization
of 2′a to 2a , but not the construction of the furanone
skeleton. Under consideration with the product ratio of
2a /2′a (7/3), deuterium contents of products 2a D-1, 2a D-
2, and 2′a D-2 are consistent with the calculated values
and suggest a transformation of 1a to 2a in the presence
of amines shown in Scheme 1, where the hydrogen of the
OH group in 1 mainly moved to the R-C of allenic group
to give 2, whereas in the minor course the hydrogen
added to the γ-C giving 2′a and then migrated to R-C
finally to yield 2. This transformation route of 1a to 2a
has been confirmed by the carbonylation of γ-deutero 1a
(1a -γD) in the absence of NEt3. The deuterium contents
in the products are shown in eq 9. The lack of deuterium
in the methyl and methylene groups at 3-C in products
2a D-3 and 2′a D-3 undoubtedly indicates simultaneous
formation of 2 and 2′ from 1. These dueterium experi-
ments reveal that the carbonylation of 1 simultaneously
yields 2 and 2′ despite the absence and presence of
amines, followed by transformation of 2′ to 2 in the
presence of amines and the Ru catalyst.
et al. reported that our ruthenium system is also effective
for the cyclocarbonylation of allenyl sulfonamides to give
lactams.13
Ca r bon yla tion of Allen yl Alcoh ols in th e Absen ce
of Am in es. In the course of investigation on the effect
of additives in the present carbonylation, we found that
the carbonylation of allenyl alcohol 1a in the absence of
amine led to the formation of 2a in 68% yield along with
2′a in 27% yield (eq 6).
P ossible Rea ction Mech a n ism . It is known that
propargyl alcohol, which is an isomer of allenyl alcohol,
is carbonylated to produce furanones by the catalysis of
palladium complexes.8k However, when propargyl alcohol
instead of allenyl alcohol was reacted with carbon
monoxide using the ruthenium catalyst, the starting
material was recovered quantitatively, indicating that in
the present carbonylation, allenyl alcohol does not un-
dergo cyclocarbonylation via isomerization to propargyl
alcohol but is directly carbonylated to furanone.
Although product 2′a could not be isolated as a pure
form, the structure was determined by the GC-MASS and
1H and 13C NMR spectra. Interestingly, when a mixture
of 2a and 2′a was heated in the presence of Et3N and
the ruthenium catalyst, complete isomerization of 2′a to
2a was observed, although the isomerization did not
occur in the absence of the amine or the catalyst (Scheme
1). To obtain information on hydrogen migration in the
reaction, we performed the carbonylation of deuterated
allenyl alcohol 1a D in the presence and in the absence
of amine (eqs 7 and 8).
To obtain information on a catalytically active species
in the present carbonylation, we attempted to isolate an
intermediate complex from stoichiometric reactions of the
substrate with the catalyst. The reaction of allenyl alcohol
1a with Ru3(CO)12 in a molar ratio of 1/1 in the presence
of Et3N in benzene at room temperature gave an orange
solution, which formed furanone 2a when heated, but we
could not isolate a definite ruthenium complex from the
reaction mixture. Since the catalytically active species
of the present carbonylation was poorly understood, we
tried to investigate the relation between turnover fre-
quency (TOF) and concentration of catalyst, i.e., Laine’s
kinetic criteria,14 which may tell us whether the active
species is a ruthenium cluster or not. Thus, we chose the
carbonylation reaction of 1a for a mechanistic study and
first confirmed the reaction to be of first order between
the conversion of 1a and the reaction time.15 Then, we
established the relation between TOF and the concentra-
tion of Ru3(CO)12 in the range of 5 × 10-3 to 3 × 10-2
mol % (substrate 1a , 6.6 M), which is shown in Figure 1.
The proportional increase of TFO with increasing the
The carbonylation in the presence of Et3N gave deuter-
ated product 2a D-1 with deuterium contents of 9 and
29% at 4-C and Me, respectively, and in the absence of
the amine afforded deuterated products 2a D-2 and
2′a D-2 with deuterium contents indicated in eq 8. The
former product contains no deuterium at 4-C, while the
8574 J . Org. Chem., Vol. 68, No. 22, 2003

Ruthenium-Catalyzed Cyclocarbonylation
In the presence of NEt3 and the Ru catalyst, 2′ isomerizes
to 2 and finally 2 is obtained as the sole product in this
reaction.
Con clu sion
We have demonstrated that Ru3(CO)12 catalyzes the
cyclocarbonylation of allenyl alcohols to give lactone
derivatives with a high selectivity in a high yield, in
which the hydroxyl group is incorporated in the cycliza-
tion. This carbonylation can be applied to a wide variety
of allenyl alcohols having various functional groups and
provides useful method for the synthesis of a variety of
lactone derivatives directly from allenyl alcohols that may
be easily prepared. On the basis of experimental results,
we propose a possible carbonylation mechanism involving
a ruthenium cluster species as an active intermediate.
F IGURE 1. Relation between TOF and concentration of the
catasyst. Reaction conditions: substrate 1a , 1 mmol; catalyst,
Ru3(CO)12; 1,4-dioxane, 15 mL; NEt3, 1.4 mmol; CO pressure,
10 atm; reaction temperature, 100 °C.
SCHEME 2. P ossible Mech a n ism of th e
Cycloca r bon yla tion
Exp er im en ta l Section
Gen er a l. 1H NMR and 13C NMR were measured at 400 and
100 MHz, respectively, in CDCl3 with tetramethylsilane as an
internal standard. Data are reported as follows: chemical shift
in parts per million (δ), multiplicity (s ) singlet, d ) doublet,
t ) triplet, or m ) multiplet), coupling constant (hertz),
integration, and interpretation. Infrared spectral data (IR)
were reported in reciprocal centimeters.
Ma ter ia ls. Solvents and reagents were dried and purified
prior to use by standard procedures. Allenyl alcohols 1a ,18a,b
1b-g,19 1h ,18a,c 1i,20 1j,18a,c 1k ,20 1l,19 1m ,21 1p ,22 1u ,19 and 3a -
c19,23 were prepared from propargyl alcohol or methoxyallene
with corresponding aldehydes or ketones according to litera-
ture methods.18a,19 New allenyl alcohols 1n -t and 1v were
similarly prepared from 2-prop-2-ynyloxy-tetrahydropyran
with aldehydes via 2-butyn-1-ol derivatives. Allenylamines 5
were prepared by the literature method.24
The preparation and characterization of new allenyl alcohols
1n -t and 1v are provided in Supporting Information.
Typ ica l P r oced u r e of t h e Ca r b on yla t ion of Allen yl
Alcoh ols. A 100 mL stainless steel autoclave was charged
with 1-propa-1,2-dienylcyclohexan-1-ol (1a ) (1 mmol, 138 mg),
1,4-dioxane (15 mL), triethylamine (1.5 mmol), and Ru3(CO)12
(0.01 mmol, 6 mg). The system was flushed three times with
30 atm of CO. Finally, it was pressurized to 10 atm and stirred
at 100 °C. After 8 h, the autoclave was allowed to cool in water,
and then the CO was released. The contents were transferred
to a round-bottomed flask with ether, and the volatiles were
removed in vacuo. The residue was subjected to column
chromatography on silica gel using benzene as an eluent to
give 3-methyl-5,5-pentamethylene-2(5H)-furane (2a )10 (165 mg,
99% yield) as a colorless solid: 1H NMR (CDCl3) δ 1.25-1.89
concentration of Ru3(CO)12 catalyst suggests a trinuclear
ruthenium cluster species to be responsible for the
catalysis.
On the basis of the experimental data described above,
a possible reaction mechanism is proposed in Scheme 2.
Addition of a large amount of MeOH to the reaction
system did not appreciably affect the carbonylation of 1a ,
implying the first step of the reaction to be coordination
of CdCdC, but not of OH, to the Ru catalyst. The initial
step may involve elimination of carbon monoxide from
Ru3(CO)12 giving complex 8. An allenyl alcohol coordi-
nates to a Ru vacant site, followed by transformation to
π-allyl intermediate 10 by interaction with ruthenium
centers. Although we have no experimental results
directly supporting π-allyl species 10, related dinuclear
iron16 and trinucler osmium17 complexes have been
isolated from the reactions of Fe2(CO)9 and Os3(CO)12
with allene, respectively. Nucleophilic attack of the
neighboring hydroxy group may lead to formation of
metallacycle 11, followed by reductive elimination to give
intermediate 12 having a lactone frame. Then, the
hydrogen coordinated to Ru selectively transfers to the
π-allylic moiety, resulting in the formation of 2 and 2′.
(10H, m, CH2 × 5), 1.89 (3H, s, CH3), 5.56 (1H, s, CdCH); 13
C
NMR (CDCl3) δ 10.6, 22.5, 24.7, 34.9, 86.0, 128.4, 153.3, 173.7;
IR (KBr) ν 1770 cm-1 (CdO); MS (EI) m/z 166 (M+). Anal.
Calcd for C10H14O2: C, 72.26; H, 8.49. Found: C, 72.22; H,
8.31.
2(5H)-Furanones 2b,25 2c,26 2d ,27 2e,28 2f,28,29 2g,30 2h ,31 2j,32
2k ,32 2l,33 2n ,34 2p ,35 and 2-pyranones 4a 36 and 4c37 are known
1
compounds and were identified by H and 13C NMR, IR, and
mass spectra. The spectral data are provided in Supporting
Information.
4-Meth oxy-3,5,5-tr im eth yl-2(5H)-fu r a n on e (2i). Pale yel-
low oil; 1H NMR (CDCl3) δ 1.40 (6H, s, CH3), 1.99 (3H, s, CH3),
4.12 (3H, s, OCH3); 13C NMR (CDCl3) δ 8.4, 24.4, 58.9, 80.8,
94.8, 173.9, 177.0; IR (neat) ν 1751 cm-1 (CdO); MS (EI) m/z
156 (M+). Anal. Calcd for C8H12O3: C, 61.52; H, 7.75. Found:
C, 61.80; H, 7.95.
3-Isop r op yl-1-oxa sp ir o[4,5]-3-en -2-on e (2m ). Colorless
1
solid; mp 97-98 °C; H NMR (CDCl3) δ 1.16 (6H, d, J ) 6.8
Hz, CH3 × 2), 1.25-1.75 (10H, m, CH2 × 5), 2.61-2.67 (1H,
J . Org. Chem, Vol. 68, No. 22, 2003 8575

Yoneda et al.
m, CH), 6.96 (1H, s, CdCH); 13C NMR (CDCl3) δ 21.0, 22.5,
24.7, 25.3, 35.0, 85.7, 139.1, 150.5, 172.7; IR (KBr) ν 1748 cm-1
(CdO); MS (EI) m/z 194 (M+). Anal. Calcd for C12H18O2: C,
74.19; H, 9.34. Found: C, 74.44; H, 9.28.
Typ ica l P r oced u r e of th e Ca r bon yla tion of Allen yl-
a m in es. A 100 mL stainless steel autoclave was charged with
penta-3,4-dienylamine (5a )24 (2 mmol, 166 mg), Ru3(CO)12 (0.02
mmol, 13.8 mg), and 30 mL of triethylamine. The system was
flushed three times with 30 atm of CO. Finally it was
pressurized to 10 atm and stirred at 100 °C. After 8 h, the
autoclave was allowed to cool in water, and then the CO was
released. The contents were transferred to a round-bottomed
flask with ether, and the volatiles were removed in vacuo. The
residue was subjected to column chromatography on deacti-
vated alumina using methyl acetate as an eluent to give
3-methyl-5,6-dihydro-1H-pyridin-2-one (6a ) in 37% yield and
3-methylenepiperidin-2-one (7a ) in 37% yield. Similar carbo-
nylation of 2-methylpenta-3,4-dienylamine (5b)24 gave 3,5-
dimethyl-5,6-dihydro-1H-pyridin-2-one (6b) and 3-methylene-
5-methyl-piperidin-2-one (7b) in 41 and 38% yields, respectively.
3-Meth yl-5-(4-br om op h en yl)-2(5H)-fu r a n on e (2o). Col-
1
orless solid; mp 94 °C; H NMR (CDCl3) δ 1.99 (3H, s, CH3),
5.87 (1H, s, CH), 7.09 (1H, s, CdCH), 7.14 (2H, d, J ) 8.3 Hz,
Ar), 7.52 (2H, d, J ) 8.1 Hz, Ar); 13C NMR (CDCl3) δ 10.5,
81.2, 123.0, 128.0, 129.8, 132.0, 134.1, 147.7, 173.9; IR (KBr)
ν 1750 cm-1 (CdO); MS (EI) m/z 253 (M+). Anal. Calcd for
C
11H9BrO2: C, 52.20; H, 3.58; Br, 31.60. Found: C, 52.18; H,
3.37; Br, 31.60.
3-Meth yl-5-(4-m eth ylth iop h en yl)-2(5H)-fu r a n on e (2q).
Colorless solid; mp 57 °C; 1H NMR (CDCl3) δ 1.99 (3H, s, CH3),
2.48 (3H, s, SCH3), 5.82 (1H, s, CH), 7.09 (1H, s, CdCH), 7.16
(2H, d, J ) 8.3 Hz, Ar), 7.25 (2H, d, J ) 8.1 Hz, Ar); 13C NMR
(CDCl3) δ 10.6, 15.5, 81.7, 126.5, 126.9, 129.6, 131.5, 140.0,
148.0, 174.2; IR (KBr) ν 1748 cm-1 (CdO); MS (EI) m/z 220
(M+). Anal. Calcd for C12H12O2S: C, 65.43; H, 5.49; S, 14.56.
Found: C, 65.38; H, 5.32; S, 14.70.
1
Lactam 7a 38 is a known compound and was identified by H
and 13C NMR, IR, and mass spectra.
3-Meth yl-5,6-d ih yd r o-1H-p yr id in -2-on e (6a ). Pale yellow
1
oil; H NMR (CDCl3) δ 1.87 (3H, s, CH3), 2.28-2.32 (2H, m,
CH2), 3.39 (2H, t, J ) 7.8 Hz, NCH2), 6.37 (1H, br, CdCH),
6.64 (1H, br, NH); 13C NMR (CDCl3) δ 16.7, 24.0, 39.8, 130.9,
135.5, 167.8; IR (neat) ν 3257 (NH), 1680 (CdO), 1631 cm-1
(CdC); MS (EI) m/z 111 (M+). Anal. Calcd for C6H9NO: C,
64.84; H, 8.16; N, 12.60. Found: C, 64.58; H, 8.02; N, 12.80.
3,5-Dim eth yl-5,6-d ih yd r o-1H-p yr id in -2-on e (6b). Pale
3-Meth yl-5-(4-(N,N-d im eth yla m in o)p h en yl)-2(5H)-fu r a -
n on e (2r ). Colorless solid; 200 mg (93%), mp 91 °C; 1H NMR
(CDCl3) δ 1.99 (3H, s, CH3), 2.96 (6H, s, CH3 × 2), 5.78 (1H, s,
CH), 6.68 (2H, d, J ) 8.3 Hz, Ar), 7.07 (1H, s, CdCH), 7.10
(2H, d, J ) 8.1 Hz, Ar); 13C NMR (CDCl3) δ 10.5, 40.2, 82.5,
112.1, 121.7, 129.2, 148.4, 150.9, 174.5; IR (KBr) ν 1752 cm-1
(CdO); MS (EI) m/z 217 (M+). Anal. Cacld for C13H15NO2: C,
71.87; H, 6.96; N, 6.45. Found: C, 71.96; H, 6.68; N, 6.30.
3-Meth yl-5-fer r ocen yl-2(5H)-fu r a n on e (2t). Brown solid;
1
yellow oil; H NMR (CDCl3) δ 1.16 (3H, s, CH3), 1.93 (3H, s,
CH3), 2.55-2.58 (1H, m, CH), 2.75-2.77 (1H, m, CH2), 2.81-
2.84 (1H, m, CH2), 5.99 (1H, br, CdCH), 6.80 (1H, br, NH);
13C NMR (CDCl3) δ 17.2, 18.8, 32.1, 48.6, 128.2, 140.4, 165.8;
IR (neat) ν 3255 (NH), 1675 (CdO), 1631 cm-1 (CdC); MS (EI)
m/z 125 (M+). Anal. Calcd for C7H11NO: C, 67.17; H, 8.86; N,
11.19. Found: C, 67.01; H, 8.75; N, 10.89.
1
mp 119 °C; H NMR (CDCl3) δ 1.99 (3H, s, CH3), 4.19-4.24
(4H, m, Cp), 4.21 (5H, s, Cp), 5.85 (1H, s, CH), 7.18 (1H, s,
CdCH); 13C NMR (CDCl3) δ 10.6, 66.6, 67.6, 68.7, 68.9, 79.4,
82.7, 130.0, 147.8, 174.0; IR (KBr) ν 1746 cm-1 (CdO); MS
(FAB) m/z 282 (M+). Anal. Calcd for C15H14O2Fe: C, 63.86; H,
5.00. Found: C, 63.70; H, 4.82.
3-Meth ylen e-5-m eth ylp ip er id in -2-on e (7b). Pale yellow
1
oil; H NMR (CDCl3) δ 1.06 (3H, s, CH3), 1.84-1.90 (2H, m,
CH2), 2.24-2.32 (1H, m, CH), 2.78-2.80 (1H, m, CH2), 2.85-
2.88 (1H, m, CH2), 5.38 (1H, br, CdCH2), 6.35 (1H, br, Cd
CH2), 6.69 (1H, br, NH); 13C NMR (CDCl3) δ 17.3, 33.1, 42.7,
52.2, 120.3, 145.5, 166.5; IR (neat) ν 3248 (NH), 1688 (CdO),
1
3-Meth yl-5-vin yl-2(5H)-fu r a n on e (2u ). Colorless oil; H
NMR (CDCl3) δ 1.88 (3H, s, CH3), 5.23-5.25 (2H, m, CdCH2),
6.01-6.05 (1H, m, CdCH), 6.21 (1H, br, CH), 7.55 (1H, s, Cd
CH); 13C NMR (CDCl3) δ 18.0, 83.1, 115.1, 131.6, 135.6, 137.5,
170.3; IR (neat) ν 1745 cm-1 (CdO); MS (EI) m/z 124 (M+).
Anal. Calcd for C7H8O2: C, 67.73; H, 6.50. Found: C, 67.56;
H, 6.27.
1629 cm-1 (CdC); MS (EI) m/z 125 (M+). Anal. Calcd for C7H11
-
NO: C, 67.17; H, 8.86; N, 11.19. Found: C, 67.02; H, 8.75; N,
11.09.
3-Meth yl-5-cyclop r op yl-2(5H)-fu r a n on e (2v). Colorless
oil; 1H NMR (CDCl3) δ 0.35-0.43 (1H, m, CH2), 0.45-0.51 (1H,
m, CH2), 0.56-0.69 (2H, m, CH2), 0.90-1.01 (1H, m, CH), 1.92
Ack n ow led gm en t. This work was partially sup-
ported by Grant-in-Aid for Scientific Research from the
Ministry of Education, Culture, Sports, Science, and
Technology. The authors are grateful for a J SPS Fel-
lowship for J apan J unior Scientists given to E.N.
(3H, s, CH3), 4.36-4.38 (1H, m, CH), 7.03 (1H, s, CdCH); 13
C
NMR (CDCl3) δ 1.1, 2.7, 10.4, 12.9, 84.3, 129.9, 147.7, 174.0;
IR (neat) ν 1753 cm-1 (CdO); MS (EI) m/z 138 (M+). Anal.
Calcd for C8H10O2: C, 69.54; H, 7.30. Found: C, 69.38; H, 7.34.
3,6,6-Tr im eth yl-2H-p yr a n -2-on e (4b). Pale yellow oil; 1H
NMR (CDCl3) δ 1.43 (6H, s, CH3 × 2), 1.93 (3H, s, CH3), 2.39
(2H, d, J ) 6.0, CH2), 6.46 (1H, d, J ) 5.8, CdCH); 13C NMR
(CDCl3) δ 16.9, 27.6, 35.8, 80.1, 127.6, 137.4, 165.4; IR (neat)
ν 1716 cm-1 (CdO). Anal. Calcd for C8H12O2: C, 68.54; H, 8.63.
Found: C, 68.76; H, 8.41.
Su p p or tin g In for m a tion Ava ila ble: Preparation and
characterization of new allenyl alcohols (1n -t, 1v) and data
for identification of compounds 2b-h , 2j-l, 2n , 2p , 4a , 4c,
and 7a are provided in Supporting Information. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O0350615
8576 J . Org. Chem., Vol. 68, No. 22, 2003