Molybdenum-catalyzed ring-closing metathesis of allenynes

Article abstract of DOI:10.1021/ol0514348

(Chemical Equation Presented) A ring-closing metathesis reaction of allenynes occurred at room temperature in the presence of a molybdenum alkylidene complex to give ring-closed vinylallenes. The vinylallene skeletons were constructed by a metathesis-type

Full text of DOI:10.1021/ol0514348

ORGANIC
LETTERS
2005
Vol. 7, No. 18
3953-3956
Molybdenum-Catalyzed Ring-Closing
Metathesis of Allenynes
Masahiro Murakami,* Sho Kadowaki, and Takanori Matsuda
Department of Synthetic Chemistry and Biological Chemistry, Kyoto UniVersity,
Katsura, Kyoto 615-8510, Japan
murakami@sbchem.kyoto-u.ac.jp
Received June 21, 2005
ABSTRACT
A ring-closing metathesis reaction of allenynes occurred at room temperature in the presence of a molybdenum alkylidene complex to give
ring-closed vinylallenes. The vinylallene skeletons were constructed by a metathesis-type reaction between the alkyne moiety and the proximal
carbon−carbon double bond of the allene moiety.
Ring-closing metathesis (RCM) reactions have rapidly
become one of the most versatile and efficient methods for
constructing carbo- and heterocyclic compounds.1,2 They
have been widely employed as a key step in a number of
natural product syntheses to install cyclic structure. The
molybdenum imido alkylidene complex 1 (Schrock catalyst)3
and the ruthenium benzylidene complex 2 (second-generation
Grubbs catalyst)4 are the most commonly used catalysts
beacuse of their high catalytic activities and their tolerance
of a range of functional groups (Figure 1).
While a variety of cross-metathesis reactions between
alkenes and alkynes (enyne metathesis) have been reported,1,5
there has been only one example of metathesis that involves
allenes; 1,3-disubstituted allenes are formed by a ruthenium-
catalyzed metathesis of monosubstituted allenes.6 Herein, we
report a molybdenum-catalyzed RCM reaction of allenynes7
producing allenyl-substituted cyclic alkenes.
Allenyne 3a was treated with complex 1 (15 mol %) in
(1) Grubbs, R. H., Ed. Handbook of Metathesis; Wiley-VCH: Weinheim,
2003.
(2) (a) Katz, T. J.; Sivavec, T. M. J. Am. Chem. Soc. 1985, 107, 737.
(b) Maifeld, S. V.; Miller, R. L.; Lee, D. J. Am. Chem. Soc. 2004, 126,
12228. For reviews, see: (c) Nakamura, I.; Yamamoto, Y. Chem. ReV. 2004,
104, 2127. (d) Deiters, A.; Martin, S. F. Chem. ReV. 2004, 104, 2199. (e)
McReynolds, M. D.; Dougherty, J. M.; Hanson, P. R. Chem. ReV. 2004,
104, 2239. (f) Wallace, D. J. Angew. Chem., Int. Ed. 2005, 44, 1912.
(3) (a) Schrock, R. R.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2003,
42, 4592. (b) Schrock, R. R. J. Mol. Catal. A 2004, 213, 21.
(4) (a) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.; Wilhelm, T. E.;
Scholl, M.; Choi, T.-L.; Ding, S.; Day, M. W.; Grubbs, R. H. J. Am. Chem.
Soc. 2003, 125, 2546. (b) Grubbs, R. H. Tetrahedron 2004, 60, 7117.
(5) (a) Hansen, E. C.; Lee, D. J. Am. Chem. Soc. 2004, 126, 15074. (b)
Castarlenas, R.; Eckert, M.; Dixneuf, P. H. Angew. Chem., Int. Ed. 2005,
44, 2576. (c) Galan, B. R.; Giessert, A. J.; Keister, J. B.; Diver, S. T. J.
Am. Chem. Soc. 2005, 127, 5762. (d) Kim, M.; Lee, D. Org. Lett. 2005, 7,
1865. For reviews, see: (e) Poulsen, C. S.; Maden, R. Synthesis 2003, 1.
(f) Mori, M. J. Mol. Catal. A 2004, 213, 73. (g) Diver, S. T.; Giessert, A.
J. Chem. ReV. 2004, 104, 1317.
Figure 1.
10.1021/ol0514348 CCC: $30.25
© 2005 American Chemical Society
Published on Web 08/06/2005

toluene8 at room temperature for 3 h. Metathesis between
the alkyne and the proximal carbon-carbon double bond of
the allene moiety took place to afford five-membered ring
product 4a with an allene side chain in 71% yield (eq 1).9
Surprisingly, only the Schrock catalyst 1 successfully medi-
ated the reaction of 3. Grubbs catalyst 2, which has been
most often employed in enyne metathesis reactions,5 gave a
complex mixture of products.10
There are two mechanisms, A and B, conceivable for the
formation of 4 from 3. In mechanism A (Scheme 2), molyb-
Scheme 2. Mechanism A
When allenyne 3a-d with the alkyne terminus deuterated
(>90% D) was used, the deuterium was labeled at the
1-position of the produced allene (>82% D) (eq 2).
Next, a crossover reaction using a mixture of 3b (1.00
equiv) and 3c (1.00 equiv) was carried out in the presence
of complex 1 (0.20 equiv) (Scheme 1). Crossover products
denum vinylidene species D11,12 is initially generated from
the alkylidene complex 1 and allenyne 3; a molybdacyclo-
butene A is formed by [2 + 2] cycloaddition of 1 with the
alkyne moiety of 3.13 Electrocyclic ring-opening affords vin-
ylcarbene species B, which undergoes intramolecular [2 +
2] cycloaddition with the proximal allenic carbon-carbon
double bond. A resulting methylenemolybdacyclobutane C
splits into the molybdenum vinylidene species D and a 1,3-
diene E by retro [2 + 2] cycloaddition. The species D thus
formed turns over the catalytic cycle by following a sequence
analogous to that through A, B, and C, i.e., via [2 + 2] cyclo-
addition forming F, electrocyclic ring-opening giving G,
intramolecular [2 + 2] cycloaddition forming H, and finally
retro [2 + 2] cycloaddition affording the product 4 and D.
Alternatively, mechanism B, which does not involve
molybdenum vinylidene species D, also explains the forma-
Scheme 1. Crossover Experiment with 3b and 3c in the
Presence of Molybdenum Complex 1
(9) Intermolecular cross-metathesis of terminal alkynes with allenes has
so far failed with the catalysis of 1; the alkynes were completely consumed,
whereas the allenes remained unchanged.
(10) No RCM occurred at room temperature when other Ru complexes
such as (PCy3)2Cl2RudCHPh and (PCy3)2Cl2RudCdCHPh were used as
the catalyst.
(11) Mo(VI) vinylidene complexes have not been reported. For a
theoretical study, see: Stegmann, R.; Neuhaus, A.; Frenking, G. J. Am.
Chem. Soc. 1993, 115, 11930.
(12) For vinylidene complexes of Mo in lower oxidation states, see: (a)
Bruce, M. I. Chem. ReV. 1991, 91, 197. (b) McDonald, F. E.; Schultz, C.
C. J. Am. Chem. Soc. 1994, 116, 9363. (c) Lin, Y.-C. J. Organomet. Chem.
2001, 617-618, 141. (d) Ipaktschi, J.; Mohsseni-Ala, J.; Uhlig, S. Eur. J.
Inorg. Chem. 2003, 4313.
(13) For a theoretical study on [2 + 2] cycloaddition of Mo alkylidene
with alkyne and ring-opening of molybdacyclobutene, see: Sheng, Y.; Wu,
Y.-D.; Leszczynski, J. Organometallics 2004, 23, 3189.
4a (0.23 equiv) and 4d (0.22 equiv) were obtained together
with products 4b (0.48 equiv) and 4c (0.72 equiv).
(6) Ahmed, M.; Arnauld, T.; Barrett, A. G. M.; Braddock, D. C.; Flack,
K.; Procopiou, P. A. Org. Lett. 2000, 2, 551.
(7) For cycloisomerization and cyclization of allenynes, see: (a) Hashmi,
A. S. K. In Modern Allene Chemistry; Krause, N., Hashmi, A. S. K., Eds.;
Wiley-VCH: Weinheim, 2004; Vol. 2, p 877. (b) Mandai, T. In Modern
Allene Chemistry; Krause, N., Hashmi, A. S. K., Eds.; Wiley-VCH:
Weinheim, 2004; Vol. 2, p 925.
(8) Unsatisfactory results were obtained with other solvents such as 1,2-
dimethoxyethane (no reaction) and CH2Cl2 (12% yield).
3954
Org. Lett., Vol. 7, No. 18, 2005

Table 1. Molybdenum-Catalyzed RCM of Allenynes 3a
Scheme 3. Mechanism B
allenyne
R1
product
entry
3
Z
R2
R3
4
% yieldb
1
2
3
4
5
6
7
8
9
3a
3b TsN
3e
3f
3g
TsN
H
H
H
H
Me
Me
-(CH2)5-
Me
Et
4a
4b
4e
4f
4g
4h
4i
4c
4j
4k
71c
84
81
76
68
TsN
TsN
TsN
i-Pr
i-Pr
Me
Ph
Me
Me
Me
H
Me Me
3h TsN
H
H
H
H
H
Me
Me
Me
Me
Me
84
73
3i
3c
3j
BnN
(MeO2C)2C
(EtO2C)2C
96 (88d)
95
tion of 4 (Scheme 3). The initial [2 + 2] cycloaddition of
the molybdenum alkylidene complex 1 with the proximal
allenic carbon-carbon double bond of 3 forms molybdenum
alkylidene species J and an allene K. Then, intramolecular
[2 + 2] cycloaddition with the alkyne moiety and ring-
opening follow to give a new Mo alkylidene species M,
which reacts with another allenyne 3 to afford 4.
10
3k TsN
26e
a Allenyne 3 was stirred in toluene (0.02 M) in the presence of 1 (15
mol %) at room temperature for 3 h unless otherwise noted. b Isolated yield
by preparative TLC. c Result with 20 mol % of 1 for 20 min. d Result with
7.5 mol % of 1 for 9 h. e Obtained as a mixture of 4k (26%) and 5 (13%).
We carried out a stoichiometric reaction of 3 with 1 in
order to get further mechanistic insights. Diene 5 was isolated
(9%) in addition to 4a (69%) (eq 3). The formation of the
diene 5, albeit the yield is low, is explained by assuming
mechanism A rather than mechanism B. These product yields
of 5 and 4a suggest that the reaction of vinylidene complex
D with 3 occurs much faster than the reaction of alkylidene
complex 1 with 3. A considerable amount of the catalyst
precursor 1 remained unchanged.14 Thus, we at this stage
with these results favor mechanism A although further
experimental studies are desired for discussion in more detail.
undergo the RCM, presumably because of coordination of
the ether oxygen to the Mo center. Methyl-substituted
allenyne 3n gave a complex mixture that included the desired
product in low yield (<40%), and the phenyl-substituted 3o
was unreactive. Attempts to form a six-membered ring by
RCM of 3p and 3q were also unsuccessful.
Figure 2.
Other examples of the allenyne RCM are listed in Table
1. Allenynes 3a,b,e-h having tosylamine in a tether were
successfully transformed into the corresponding vinylallenes
in a range of 68-84% yields (entries 1-6). N-Benzyl
derivative 3i also afforded the product 4i in 73% yield (entry
7). Malonate derivatives 3c and 3j were excellent substrates
for this reaction and led to nearly quantitative yield (entries
8 and 9). The product 4c was isolated in 88% yield even
with a lower catalyst loading (7.5 mol %), although it
required a longer reaction time. Allenyne 3k with the allenic
terminus monosubstituted also participated in the RCM but
with less efficiency, giving a mixture of vinylallene 4k (26%)
and diene 5 (13%) (entry 10).
Vinylallenes thus obtained can be used as a 1,3-diene in
the Diels-Alder reaction.15 The reaction of vinylallene 4c
with maleic anhydride in toluene at room temperature
furnished cycloadduct 6 as a single diastereomer in 70% yield
presumably via an endo transition state (eq 4).16
The reactions using substrates listed in Figure 2 were
unsuccessful under the conditions described here, showing
the limitations of the metathesis reaction. No reaction
occurred with allenyne 3l with the allenic terminus unsub-
stituted. Allenyne 3m bearing an ether linkage failed to
In conclusion, we have achieved the first RCM of
allenynes producing vinylallenes by the use of molybdenum
imido alkylidene complex 1.
Org. Lett., Vol. 7, No. 18, 2005
3955

Acknowledgment. We gratefully acknowledge the sug-
gestion of mechanism B by one of reviewers, which im-
proved this paper. This work was supported by a Grant-in-
Aid for Scientific Research on Priority Areas (No. 17035044)
from The Ministry of Education, Culture, Sports, Science
and Technology (MEXT). S.K. acknowledges fellowship
support from the Japan Society for the Promotion of Science
for Young Scientists.
Supporting Information Available: Experimental details
and spectral data for new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL0514348
(14) Such a phenomenon is often observed in Ru-catalyzed metathesis
reaction. For a recent example, see ref 5b.
(15) Murakami, M.; Matsuda, T. In Modern Allene Chemistry; Krause,
N., Hashmi, A. S. K., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 2, p 727.
(16) The stereochemistry was assigned by analogy to a similar reaction.
Rega´s, D.; Afonso, M. M.; Rodr´ıguez, M. L.; Palenzuela, J. A. J. Org.
Chem. 2003, 68, 7845.
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Org. Lett., Vol. 7, No. 18, 2005