Ruthenium-catalyzed decarbonylative cyclization of 1,6-diynes

Article abstract of DOI:10.1021/ja0752888

Ruthenium-catalyzed tandem cyclization-decarbonylation of terminal 1,6-diynes give exo-alkylidenecyclopentanes. The starting point of this process is likely to be the formation of an Ru-vinylidene complex. Copyright

Full text of DOI:10.1021/ja0752888

Published on Web 10/10/2007
Ruthenium-Catalyzed Decarbonylative Cyclization of 1,6-Diynes
Carlos Gonza´lez-Rodr´ıguez, Jesu´s A. Varela, Luis Castedo, and Carlos Saa´*
Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica, UniVersidad de Santiago de Compostela,
15782 Santiago de Compostela, Spain
Received July 16, 2007; Email: qocsaa@usc.es
Scheme 1. Ru-Catalyzed Decarbonylative Cyclization of
1,6-diynes 1
Ruthenium-catalyzed transformation is widely recognized as one
of the most efficient means of alkyne functionalization.1 Non-
metathetic ruthenium-catalyzed C-C bond formation between
alkyne partners proceeds via ruthenacycle/bis-carbene2 or vi-
nylidene3 intermediates, depending on the nature of the alkynes
and the reaction conditions. The intramolecular version has recently
been applied to the cycloisomerization of diynols via ruthenacycles4
and the carboxylative cyclization of 1,6-diynes via catalytic Ru-
vinylidenes.5,6 In the course of work on metal-vinylidene-catalyzed
C-C bond-forming reactions,7 we have developed, and report here,
a process that nicely complements the latter transformation, namely
a ruthenium-catalyzed cyclization-decarbonylation of 1,6-terminal
diynes 1 mediated by carboxylic acids8,9 (Scheme 1).
Table 1. Ru-Catalyzed Cyclization of 1a in Acetic Acida
Heating the electron-poor 1,6-diyne 1a (X ) C(CO2Me)2, R )
CO2Me) in a 10 mol % solution of the catalyst [CpRu(CH3CN)3]-
PF6 in AcOH afforded, after 24 h at 90 °C, the exo-methylenecy-
clopentane derivative 2a, with one carbon less than 1a, in good
yield (Table 1, entry 1). Heating at 130 °C for 24 h led to some
decomposition and a lower yield of 2a (entry 2). However, the more
electron-rich, sterically more demanding catalyst [Cp*Ru(CH3CN)3]-
PF6 gave the dienylacetate 3a in quite good yield (entry 3), through
cyclization and intermolecular addition of AcOH.10 The use of other
Ru(II) catalysts, such as CpRu(PPh3)2Cl and (η5-indenyl)Ru(PPh3)2-
Cl, led to lower yields of 2a (entries 4 and 5),11 as did dilution of
1a (entry 6). The reaction was indifferent to the identity of the
carboxylic acid (entry 7).11
entry
catalystb
t
°
C
time
yieldc
product
1
2
3
4
[CpRuL3]PF6
[CpRuL3]PF6
[Cp*RuL3]PF6
CpRu(PPh3)2Cl
(η5-In)Ru(PPh3)2Cl
[CpRuL3]PF6
90
24 h
12 h
2 h
48 h
48 h
24 h
24 h
66%
42%
70%
22%
11%
42%
58%
2a
2a
3ad
2a
2a
2a
2a
130
130
90
5
90
90
90
6e
7f
[CpRuL3]PF6
a [1a] ) 0.1 M except for entry 6. b L ) CH3CN, In) indenyl. c Isolated
yields. d Mixture of Z/E isomers 3:2. e [1a] ) 0.05 M. f Acrylic or propanoic
acid.
Table 2. Ru-Catalyzed Cyclization of 1,6-diynes 1a-l in Acetic
Acida
Other 4-carbon or 4-aza substituted electron-poor 1,6-diynes
1b-d behaved similarly, affording quite good yields of cyclopen-
tylidenes 2b and 2c and pyrrolidine 2d, respectively (Table 2, entries
2-4). Yields were lower without the 1-CO2Me group (Table 2,
entries 5 and 6), but the 1-silylated 1,6-diyne 1g interestingly gave
a slightly better yield of desilylated 2e than its parent, 1e (Table 2,
entries 7 and 5).12 By contrast, ethyl-substituted 1,6-diyne 1h gave
a mixture of 2h and alkyne 4h in 2.5:1 ratio (entry 8).
Interestingly, although the propargyl ether 1i afforded the
corresponding cyclopentylidene 2i at 90 °C (Table 2, entry 9),
heating 1i at 130 °C for 24 h gave a 45% combined yield of dienes
5i and 5i′ (∆2,3) (R ) H) through loss of MeOH (Table 2, entry
10),4 and similar yields of dienes 5j and 5j′ (R ) Me) were obtained
on heating the tertiary alcohol 1j at 90 °C (Table 2, entry 11).4
However, aryl-substituted diynes 1k and 1l gave the corresponding
cyclopentylidenes 2k and 2l in quite good yields even when
[Cp*Ru(CH3CN)3]PF6 was used as catalyst (Table 2, entries 12
and 13).
entry
R
X
diyne
product
yield%b
1
2
3
4
5
CO2Me
CO2Me
CO2Me
CO2Me
H
C(CO2Me)2
C(CO2Et)2
C(CH2OBn)2
NTs
C(CO2Me)2
NTs
C(CO2Me)2
C(CO2Me)2
C(CO2Me)2
C(CO2Me)2
C(CO2Me)2
C(CO2Me)2
C(CO2Me)2
1a
1b
1c
1d
1e
1f
1g
1h
1i
1i
1j
1k
1l
2a
2b
2c
2d
2e
2f
2e
2h
66
74
60
55
50
43
53
36
60
45
40
60f
53
6
7
H
TMS
8c
9d
10e
11
12d
13d
Et
CH2OMe
CH2OMe
C(Me)2OH
Ph
2i
5i + 5i′
5j + 5j′
2k
3-Furyl
2l
a Typical conditions: diyne 1 (0.1 M), 10 mol % [CpRu(CH3CN)3]PF6,
AcOH, 90 °C, 8-24 h. b Isolated yields. c Alkyne 4h (14%) was also
obtained. d Alkynes 4i or alkynes 4k,l were also obtained (<10%).
e Reaction performed at 130 °C. f 2k (55%), catalyst [Cp*Ru(CH3CN)3]PF6.
This afforded dienylacetate 8a or the regioisomeric dienylacetates
7b and 8b in quite good yields (Scheme 3 and Table 3), probably
through formation of ruthenacycle intermediates followed by
addition of AcOH.4,2c
Scheme 4 shows a mechanism that would account for the above
observations.13 Following the formation of ruthenium vinylidene
A,8 nucleophilic addition of AcOH would afford the acyclic vinyl
Ru-hydride B, which through a [3+2]-type cycloaddition would
When 1,7-disubstituted 1,6-diyne 1m was subjected to typical
reaction conditions, dienylacetate 3m was obtained in an excellent
95% yield (Scheme 2).4 This result clearly indicates that only a
terminally unsubstituted yne unit will lose its terminal carbon in
the cyclization process.
Not unexpectedly, carboxylative cyclization occurred when the
reaction was performed with 1- or 8-unsubstituted 1,7-diynes 6.
9
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J. AM. CHEM. SOC. 2007, 129, 12916-12917
10.1021/ja0752888 CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. Ru-Catalyzed Cyclization of 1m in AcOH
give exo-alkylidenecyclopentanes. The starting point of this process
is likely to be the formation of an Ru-vinylidene complex. This
new reaction is expected to open up further opportunities for the
development of catalytic alkyne functionalization.
Scheme 3. Ru-Catalyzed Carboxylative Cyclization of 1,7-diynes
Acknowledgment. This work was supported by the MEC
(Spain) and the E.R.D.F. (Grant CTQ2005-08613), Consolider
Ingenio 2010 (Grant CSD2007-00006), and by the Xunta de Galicia
(Grant PGIDIT06PXIC209041PN). C.G.-R. and J.A.V. thank the
M.E.C. for a predoctoral grant and a Ramo´n y Cajal research
contract, respectively.
Table 3. Ru-Catalyzed Carboxylative Cyclization of 1,7-diynes
6a,ba
entry
diyne
R1
R2
yield%b
7/8
Supporting Information Available: A typical procedure for the
Ru-catalyzed reaction and spectral data for all new compounds. This
material is available free of charge via the Internet at http://pubs.acs.org.
1
6a
6b
6b
H
Et
Et
Me
H
H
85
68
39
0:1
7.5:1
4:1
2
3c
References
a Typical conditions were as in Table 2. b Isolated yields. c Heating 6b
at 130 °C favors formation of the homologue of uncyclized alkyne 4 (R )
Et) in 39% yield. E ) CO2Me.
(1) For a general review, see: (a) Trost, B. M.; Frederiksen, M. U.; Rudd,
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Scheme 4. Proposed Mechanism for the Ru-Catalyzed Tandem
Cyclization-Decarbonylation of 1,6-Terminal Diynes 1
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Ahn, J. A.; Lee, H.; Jun, C. H. J. Am. Chem. Soc. 2004, 126, 13892.
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2006, 12, 6450. (See also ref 1.)
(8) For, an Ru-catalyzed, cyclization-decarbonylation of terminal alkynals,
see: Varela, J. A.; Gonza´lez-Rodr´ıguez, C.; Rub´ın, S. G.; Castedo, L.;
Saa´, C. J. Am. Chem. Soc. 2006, 128, 9576.
(9) For, reductive cyclizations, see: Krische, M. J.; Jang, H.-Y. In Compre-
hensiVe Organometallic Chemistry III; Mingos, D. M. P., Crabtree, R.
H., Eds.; Elsevier: Oxford, England, 2007; Vol. 10, pp 493-536.
(10) This type of nucleophile addition has been observed before: (a) for diynes,
see ref 4b; (b) for alkynes, see ref 2b.
lead to cyclic carbene Ru-hydride C. Reductive loss of AcOH of
C would give the cyclic carbene D, which undergoes another
nucleophilic attack by AcOH to the acyl Ru-hydride E. Reductive
opening of the ruthenacycle of E followed by oxidative addition
of AcOH with concomitant decarbonylation of F led to the Ru-
hydride G.14 Finally, reductive elimination would then afford the
observed cyclopentylidene 2.15 Analogous evolution of B would
give alkyne 4 as a minor product. This mechanism would also
account for 87% of the three hydrogens incorporated in 2a being
deuterium when the reaction of 1a was carried out in AcOD.
In an attempt to insert a second alkyne in the ruthenacycle C,
the reaction of the symmetrical triyne 1n was investigated.
Unfortunately, cyclopentylidene 2n (49%) and uncyclized alkyne
4n (8%) were the only products observed.
(11) For comprehensive screening results, see Supporting Information.
(12) Most likely, desilylation of the putative silylated cyclopentane 2g occurred
under the reaction conditions.
(13) We thank a reviewer for valuable suggestions.
(14) (a) Le Paih, J.; Rodriguez, D. C.; Derien, S.; Dixneuf, P. H. Synlett 2000,
95. (b) No carbonylated product was observed when reaction of 1e was
performed under an atmosphere of CO. See Supporting Information for
details.
(15) The Z geometry of 2 was determined by NOE experiments (see Supporting
Information for details).
In conclusion, we have developed a ruthenium-catalyzed tandem
cyclization-decarbonylation whereby 7-unsubstituted 1,6-diynes
JA0752888
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J. AM. CHEM. SOC. VOL. 129, NO. 43, 2007 12917