A pyridylsilyl group expands the scope of catalytic intermolecular Pauson-Khand reactions

Article abstract of DOI:10.1002/1521-3773(20020916)41:18<3481::AID-ANIE3481>3.0.CO;2-X

Now even unstrained alkenes can be used in catalytic intermolecular Pauson-Khand reactions [Eq. (a)]. This is made possible by the use of the directing group dimethyl(2-pyridyl)silyl, which can be easily removed at the end of the reaction. Furthermore, one observes completely regioselective incorporation of substituents at the 4- and 5-positions of the 2-cyclopentenone structure.

Full text of DOI:10.1002/1521-3773(20020916)41:18<3481::AID-ANIE3481>3.0.CO;2-X

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as a substrate for a catalytic intermolecular PKR. The
oxidative cyclization of alkyne, alkene, and metal can be
regarded as a carbometalation of an (alkyne)metal complex
across an alkene.[9] Therefore, we expected the facile and
regioselective formation of a metallacyclopentene intermedi-
ate owing to the coordination effect of the pyridyl group on
silicon (Scheme 1). We have already established the high
A Pyridylsilyl Group Expands the Scope of
Catalytic Intermolecular Pauson Khand
Reactions**
Kenichiro Itami,* Koichi Mitsudo, and Jun-
ichi Yoshida*
The [2þ2þ1] cycloaddition of alkyne, alkene, and carbon
monoxide mediated or catalyzed by a transition metal M,
which is known as the Pauson Khand reaction (PKR),[1] has
received particular attention in organic synthesis, since it
allows the construction of biologically interesting five-mem-
bered carbocycles in a convergent manner. Although tremen-
dous progress has been seen for the catalytic intramolecular
PKR [Eq. (1)] and many reactions have been reported,[1] the
R4
R3
R4
N
R3
R1
cat. M
+
C
O
O
R2
X
R2
R1
Si
Me2
X = 2-PyMe2Si
X = H, R
desilylation
R4
M
R4
R3
R
R
R3
R1
M
M
N
(1)
X
C
O
O
+
X
N
R2
R1
Si
Me2
R2
R'
Si
R'
+
Me2
Scheme 1. The catalytic intermolecular Pauson Khand reaction directed
by a pyridylsilyl group.
R
R
R
M
(2)
C
O
O
O
+
R'
reactivity of alkenyldimethyl(2-pyridyl)silanes in several
carbometalation processes.[7b,f,10] Moreover, the resultant 2-
PyMe2Si-substituted cyclopentenone should be easily con-
verted into the Si-free derivative by using various desilylation
methods that we developed.[11]
R'
R'
development of an efficient and general procedure for a
catalytic intermolecular PKR [Eq. (2)] lags far behind.[1,2] In
particular, the limitations imposed on the alkene counterpart
are serious: 1) No catalytic intermolecular PKR has been
reported yet for simple alkenes (the reactions are restricted to
ethylene gas and strained alkenes),[2] and 2) in a stoichiomet-
ric PKR, simple alkenes exhibit low reactivity and regio-
selectivity.[1,3] This may be due to the low coordinating ability
of alkenes in comparison with alkynes and carbon monoxide.
Although such problems might be overcome by incorpo-
rating a coordinating heteroatom tethered to the alkenes,[4,5]
the removal of such a directing group after the PKR is
strongly desirable from a synthetic point of view. Therefore,
the utilization of a removable directing group[6] is expected to
enhance the synthetic potential of the catalytic intermolecular
PKR by eliminating the problems associated with reactivity
and regioselectivity issues of the alkene.
We first screened for a catalyst for the intermolecular PKR
using dimethyl(2-pyridyl)(vinyl)silane (1a). Among various
metal complexes (Ti, Fe, Co, Mo, Ru, Rh, Pd, Ir, and Pt),
[Ru3(CO)12] was found to catalyze this process.[12,13] The
reaction of 1a (1.0 equiv), phenylacetylene (2a, 1.5 equiv),
and carbon monoxide (1 atm) at 1008C in toluene in the
presence of [Ru3(CO)12] (5 mol%) gave the desilylated
cyclopentenone 3aa, which was isolated in 55% yield with
virtually complete regioselectivity (Table 1, entry 1).[14] The
trend in regioselectivity (the Ph group is in the position a to
the carbonyl group) is in line with that observed in the
stoichiometric PKR.[1] The realization of a catalytic intermo-
lecular PKR without the need for a high pressure of carbon
monoxide is particularly noteworthy. Under the identical
conditions, no reaction occurred when dimethylphenyl-
(vinyl)silane was used in place of 1a, which clearly implicates
the strong directing effect of the pyridyl group. This is not only
an example of the successful utilization of vinylsilane as an
alkene counterpart in a catalytic intermolecular PKR,[15] but
also a demonstration that 1a could serve as a nongaseous
ethylene equivalent in this reaction.[16]
When the alkyl-substituted alkyne 2b was employed, a
substantial decline in regioselectivity was observed (Table 1,
entry 2). Symmetrical internal alkynes also participate in the
catalytic intermolecular PKR with reasonable efficiency.
When 1-phenylpropyne (2e) was used, cyclopentenone 3ae
was obtained with virtually complete regioselectivity (en-
try 5). However, when the chloro-substituted alkyne 2 f was
allowed to react, there was a substantial decline in the
regioselectivity (entry 6). Since 2e and 2 f are sterically and
Our recent demonstration that the dimethyl(2-pyridyl)silyl
(2-PyMe2Si) group serves as an excellent, removable directing
group in a number of metal-catalyzed reactions[7,8] led us to
investigate the possibility of alkenyldimethyl(2-pyridyl)silane
[*] Assist. Prof. K. Itami, Prof. J. Yoshida, K. Mitsudo
Department of Synthetic Chemistry and Biological Chemistry
Graduate School of Engineering, Kyoto University
Yoshida, Kyoto 606-8501 (Japan)
Fax: ( þ 81)75-753-5911
E-mail: itami@sbchem.kyoto-u.ac.jp
yoshida@sbchem.kyoto-u.ac.jp
[**] This work was supported by a Grant-in-Aid for Scientific Research
from the Japan Society for the Promotion of Science (JSPS). K.M.
thanks JSPS for the Promotion of Science for Young Scientists.
Supporting information for this article is available on the WWW under
http://www.angewandte.org or from the author.
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Table 1. Catalytic intermolecular PKR of 1a and various alkynes 2.[a]
Entry
1
2
Products
Yield [%] (3/4)
2a (R ¼ H, R’ ¼ Ph)
55 (100/0)[b,c]
2
3
4
5
6
2b (R ¼ H, R’ ¼ C6H13)
2c (R ¼ R’ ¼ Ph)
91 (59/41)[b]
88[d]
2d (R ¼ R’ ¼ C3H7)
59[d]
2e (R ¼ CH3, R’ ¼ Ph)
2 f (R ¼ (CH2)4Cl, R’ ¼ Ph)
75 (100/0)[b,c]
67 (87/13)[d]
[a] Reaction conditions: 1a (0.50 mmol), 2 (0.75 mmol), [Ru3(CO)12] (0.025 mmol), CO (1 atm), solvent (1.5 mL). [b] Reaction at 1008C in toluene.
[c] Compound 4 was not detected by NMR spectroscopy and GC analysis. [d] Reaction at 1208C in xylenes.
Table 2. Catalytic intermolecular PKR of substituted vinylsilanes 1 and alkynes 2.[a]
1
2
Products
Yield [%] (3/4)
1b (R1 ¼ C4H9, R2 ¼ H)
2a (R3 ¼ H, R4 ¼ Ph)
41 (100/0)[b,c]
1b (R1 ¼ C4H9, R2 ¼ H)
1b (R1 ¼ C4H9, R2 ¼ H)
1c (R1 ¼ (CH2)4OMe, R2 ¼ H)
2b (R3 ¼ H, R4 ¼ C6H13)
2c (R3 ¼ R4 ¼ Ph)
55 (89/11)[d]
44[b]
2c (R3 ¼ R4 ¼ Ph)
48[b]
1d (R1 ¼ H, R2 ¼ CH3)
2b (R3 ¼ H, R4 ¼ C6H13)
40 (62/38)[e]
[a] Reaction conditions: 1 (0.50 mmol), 2 (0.75 mmol), [Ru3(CO)12] (0.025 mmol), CO (1 atm), solvent (1.5 mL). [b] Reaction at 1408C in xylenes.
[c] Compound 4 was not detected by NMR spectroscopy and GC analysis. [d] Reaction at 1008C in toluene. [e] Reaction at 1208C in xylenes.
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electronically similar, the observed differences in regioselec-
tivity may be due to the directing effect of chloride, which has
been occasionally observed in Ru and other metal com-
plexes.[17]
strategically altered by simply changing the alkyne subunit
to be hydrosilylated prior to the intermolecular PKR;[18] and
4) all the substituents arise from substituents on alkyne
subunits which can be easily altered. Thus, this new strategy
offers a general approach to a diverse range of cyclopentenoid
structures and should find further applications in organic
synthesis.
We next turned our attention to the synthesis of more
highly substituted cyclopentenones by employing substituted
vinylsilanes (Table 2). The advantage of our system is that the
use of a- or b-substituted vinylsilanes (1b d)[18] results in the
regioselective production of substituted cyclopentenones with
the substituent at the 5- or 4-position, respectively. In all cases,
virtually complete regioselectivity with regard to the alkene
subunit was observed. Thus, these substituted vinylsilanes not
only serve as surrogates for terminal alkenes that cannot be
applied in the previously reported catalytic PKR, but also
enable the complete regioselective incorporation of the
alkene subunit into the cyclopentenone skeleton. Although
converting the 2-PyMe2Si group into functional groups other
than a hydrogen atom is not feasible at this stage, the present
observations clearly demonstrate the power and usefulness of
using the 2-PyMe2Si group as a removable directing group in
the catalytic intermolecular PKR.
Our catalytic intermolecular PKR should be a straightfor-
ward approach toward the synthesis of natural and nonnatural
cyclopentanoid products. For example, cyclopentenone 6,
which has emerged as an excellent precursor for the synthesis
of jasmone,[19] methyl jasmonate,[19] and methyl epijasmo-
nate,[19] can be prepared in a single chemical operation from
1a and enyne 5 [Eq. (3); 60% yield, 63% regioselectivity].[20]
Received: May 22, 2002 [Z19338]
[1] Reviews: a) K. M. Brummond, J. L. Kent, Tetrahedron 2000, 56, 3263;
b) N. E. Schore, Org. React. 1991, 40, 1.
[2] Examples of catalytic intermolecular PKR: a) I. U. Khand, G. R.
Knox, P. L. Pauson, W. E. Watts, M. I. Foreman, J. Chem. Soc. Perkin
Trans. 1 1973, 977; b) D. C. Billington, Tetrahedron Lett. 1983, 24,
2905; c) V. Rautenstrauch, P. Mÿgard, J. Conesa, W. K¸ster, Angew.
Chem. 1990, 102, 1441; Angew. Chem. Int. Ed. Engl. 1990, 29, 1413;
d) B. Y. Lee, Y. K. Chung, N. Jeong, Y. Lee, S. E. Hwang, J. Am. Chem.
Soc. 1994, 116, 8793; e) N. Y. Lee, Y. K. Chung, Tetrahedron Lett.
1996, 37, 3145; f) N. Jeong, S. H. Hwang, Y. W. Lee, J. S. Lim, J. Am.
Chem. Soc. 1997, 119, 10549; g) T. Sugihara, M. Yamaguchi, J. Am.
Chem. Soc. 1998, 120, 10782; h) J. W. Kim, Y. K. Chung, Synthesis
1998, 142; i) T. Sugihara, M. Yamaguchi, Synlett 1998, 1384; j) T.
Rajesh, M. Periasamy, Tetrahedron Lett. 1999, 40, 817; k) S. W. Kim,
S. U. Son, S. I. Lee, T. Hyeon, Y. K. Chung, J. Am. Chem. Soc. 2000,
122, 1550; l) M. Hayashi, Y. Hashimoto, Y. Yamamoto, J. Usuki, K.
Saigo, Angew. Chem. 2000, 112, 645; Angew. Chem. Int. Ed. 2000, 39,
631; m) N. Jeong, S. H. Hwang, Angew. Chem. 2000, 112, 650; Angew.
Chem. Int. Ed. 2000, 39, 636; n) M. E. Krafft, L. V. R. BoÊaga, Angew.
Chem. 2000, 112, 3822; Angew. Chem. Int. Ed. 2000, 39, 3676; o) T.
Shibata, K. Takagi, J. Am. Chem. Soc. 2000, 122, 9852.
[3] M. E. Krafft, Tetrahedron Lett. 1988, 29, 999.
[4] Review on directed chemical reactions: A. H. Hoveyda, D. A. Evans,
G. C. Fu, Chem. Rev. 1993, 93, 1307.
[5] In investigating the stoichiometric PKR, several groups have exploit-
ed the directing group strategy for controlling the regio- and
stereoselectivity. For example, see a) M. E. Krafft, C. A. Juliano,
I. L. Scott, C. Wright, M. D. McEachin, J. Am. Chem. Soc. 1991, 113,
1693; b) S. Fonquerna, A. Moyano, M. A. Peric‡s, A. Riera, J. Am.
Chem. Soc. 1997, 119, 10225.
O
5% [Ru3(CO)12
]
1a
+
(3)
CO (1 atm)
toluene, 100 o
C
5
6
jasmones, jasmonates, and epijasmonates
[6] For the use of a removable directing group in metal-catalyzed
reactions, see a) D. A. Evans, G. C. Fu, A. H. Hoveyda, J. Am. Chem.
Soc. 1988, 110, 6917; b) B. Breit, Eur. J. Org. Chem. 1998, 1123;
c) C. H. Jun, H. Lee, J. Am. Chem. Soc. 1999, 121, 880; d) N. D. Buezo,
J. C. de la Rosa, J. Priego, I. Alonso, J. C. Carretero, Chem. Eur. J.
2001, 7, 3890; e) S. Ko, Y. Na, S. Chang, J. Am. Chem. Soc. 2002, 124,
750.
[7] a) J. Yoshida, K. Itami, K. Mitsudo, S. Suga, Tetrahedron Lett. 1999, 40,
3403; b) K. Itami, K. Mitsudo, T. Kamei, T. Koike, T. Nokami, J.
Yoshida, J. Am. Chem. Soc. 2000, 122, 12013; c) K. Itami, T. Nokami,
J. Yoshida, J. Am. Chem. Soc. 2001, 123, 5600; d) K. Itami, T. Koike, J.
Yoshida, J. Am. Chem. Soc. 2001, 123, 6957; e) K. Itami, T. Kamei, J.
Yoshida, J. Am. Chem. Soc. 2001, 123, 8773; f) K. Itami, T. Nokami, Y.
Ishimura, K. Mitsudo, T. Kamei, J. Yoshida, J. Am. Chem. Soc. 2001,
123, 11577; g) K. Itami, K. Mitsudo, A. Nishino, J. Yoshida, Chem.
Lett. 2001, 1088.
[8] Reviews: a) J. Yoshida, K. Itami, J. Synth. Org. Chem. Jpn. 2001, 59,
1086; b) K. Itami, K. Mitsudo, T. Nokami, T. Kamei, T. Koike, J.
Yoshida, J. Organomet. Chem. 2002, 653, 105.
[9] For recent theoretical studies, see a) M. Yamanaka, E. Nakamura, J.
Am. Chem. Soc. 2001, 123, 1703; b) F. Robert, A. Milet, Y. Gimbert, D.
Konya, A. E. Greene, J. Am. Chem. Soc. 2001, 123, 5396; c) T. J. M.
de Bruin, A. Milet, F. Robert, Y. Gimbert, A. E. Greene, J. Am. Chem.
Soc. 2001, 123, 7184.
Moreover, the synthesis of rosaprostol,[21] tetrahydrodicrane-
none B,[21] equilenins,[22] or, more importantly, prostaglan-
dins[23] should be also possible starting from a suitably
substituted 2-cyclopentenone that can, in principle, be pre-
pared by our catalytic intermolecular PKR methodology.
In conclusion, we have developed an efficient procedure for
the catalytic, intermolecular, and regioselective PKR of
unstrained alkenes by utilizing a 2-PyMe2Si group as a
removable directing group. Multisubstituted 2-cyclopente-
nones can now be analyzed retrosynthetically, as in Equa-
tion (4). The advantages of our strategy are that 1) it allows a
R4
R3
R1
R4
R3
[Ru3(CO)12] / CO
O
(4)
R1
R2
Pt / PtBu3
R1
R2
R2
2-PyMe2SiH
2-PyMe2Si
formal catalytic intermolecular PKR using simple alkenes,
which was previously difficult to achieve; 2) it allows a
complete regioselective incorporation of a substituent at the
4- or 5-position of the 2-cyclopentenone skeleton simply by
choosing the position of the substituent in the starting
[10] K. Itami, K. Mitsudo, J. Yoshida, Angew. Chem. 2001, 113, 2399;
Angew. Chem. Int. Ed. 2001, 40, 2337.
[11] a) K. Itami, K. Mitsudo, J. Yoshida, J. Org. Chem. 1999, 64, 8709
(oxidation); b) ref. [7c] (Pd-catalyzed cross-coupling reaction);
c) ref. [7f] (protodesilylation); d) K. Itami, T. Nokami, J. Yoshida,
Tetrahedron 2001, 57, 5045 (electrophile-induced substitution reac-
¼
alkenylsilane; 3) the position of the C C bond can be
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tion); e) ref. [7e] (fluoride-catalyzed reaction with carbonyl com-
pounds).
[15] Very recently, we learned of the results from Pagenkopf and co-
workers on the stoichiometric intramolecular PKR of silicon-tethered
enynes, which include vinylsilane moieties: J. F. Reichwein, S. T.
Iacono, M. C. Patel, B. L. Pagenkopf, Tetrahedron Lett. 2002, 43, 3739.
[16] The development of nongaseous ethylene equivalents has been an
active area of research. For example, see a) W. J. Kerr, M. McLaugh-
lin, P. L. Pauson, S. M. Robertson, Chem. Commun. 1999, 2171;
b) W. J. Kerr, M. McLaughlin, P. L. Pauson, S. M. Robertson, J.
Organomet. Chem. 2001, 630, 104.
[17] D. Huang, J. C. Huffman, J. C. Bollinger, O. Eisenstein, K. G. Caulton,
J. Am. Chem. Soc. 1997, 119, 7398.
[18] The b-substituted vinylsilanes can be prepared with virtually complete
regio- and stereoselectivity by the Pt/PtBu3-catalyzed hydrosilylation
of alkynes with 2-PyMe2SiH: K. Itami, K. Mitsudo, A. Nishino, J.
Yoshida, J. Org. Chem. 2002, 67, 2645.
[19] G. Frµter, J. A. Bajgrowicz, P. Kraft, Tetrahedron 1998, 54, 7633, and
references therein.
[20] Cyclopentenone 6 has been prepared in 25% yield by the stoichio-
metric PKR of the 5 [Co2(CO)6] complexand ethylene gas (35 atm):
D. C. Billington, I. M. Helps, P. L. Pauson, W. Thomson, D. Willison, J.
Organomet. Chem. 1988, 354, 233.
[21] B. M. Trost, A. B. Pinkerton, J. Org. Chem. 2001, 66, 7714.
[22] G. H. Posner, M. J. Chapdelaine, C. M. Lentz, J. Org. Chem. 1979, 44,
3661.
[12] [Co2(CO)8] also catalyzed this process, albeit in lower yield.
[13] For the use of [Ru3(CO)12] as a catalyst in the intramolecular PKR and
related reactions, see a) T. Morimoto, N. Chatani, Y. Fukumoto, S.
Murai, J. Org. Chem. 1997, 62, 3762; b) T. Kondo, N. Suzuki, T. Okada,
T. Mitsudo, J. Am. Chem. Soc. 1997, 119, 6187; c) N. Chatani, T.
Morimoto, Y. Fukumoto, S. Murai, J. Am. Chem. Soc. 1998, 120, 5335;
d) S. K. Kang, K. J. Kim, Y. T. Hong, Angew. Chem. 2002, 114, 1654;
Angew. Chem. Int. Ed. 2002, 41, 1584.
[14] The silylated cyclopentenone was not observed in the reaction
mixture. We assume that desilylation might occur by hydrolysis of
the enolsilane, which is produced by the [1,3]-silyl migration of 5-silyl-
2-cyclopentenone. Similar desilylation was observed during the course
of our investigation of Stille coupling reactions using 2-PyMe2-
SiCH2SnBu3.[7e] The Pd-catalyzed coupling reaction of 2-PyMe2-
SiCH2SnBu3 with acid chloride produced the corresponding methyl
ketone [Eq. (5), unpublished results]. Moreover, we have also
O
O
O
cat. Pd
+
PySi
SnBu3
(5)
SiPy
R
Cl
R
R
[23] R. Noyori, M. Suzuki, Angew. Chem. 1984, 96, 854; Angew. Chem. Int.
Ed. Engl. 1984, 23, 847.
observed that the oxophilicity of the 2-PyMe2Si group was substan-
tially higher than that of the PhMe2Si group.[11d]
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