The Phenylsulfonyl Group as an endo stereochemical controller in intramolecular Pauson-Khand reactions of 3-oxygenated 1,6-enynes

Full text of DOI:10.1002/1521-3773(20000818)39:16<2906::AID-ANIE2906>3.0.CO;2-8

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[22] a) W. E. Crowe, J. P. Mitchell, V. C. Gibson, R. R. Schrock, Macro-
molecules 1990, 23, 3534 ± 3536; b) V. C. Gibson, T. Okada, Macro-
molecules 2000, 33, 655 ± 656.
[23] The 1,5-dimethyl-1,5-cyclooctadiene (6) employed in this study
contained 1,6-dimethyl-1,5-cyclooctadiene (20%) as an inseparable
mixture.
[24] The ethylene ± propylene copolymer obtained was not ªperfectlyº
alternating because of the impurity in 1,5-dimethyl-1,5-cyclooctadiene
(6).[25] We believe that if pure 6 was polymerized, the poly(isoprene)
obtained would have perfectly alternating head-to-tail microstructure,
since trisubstituted alkylidenes have not been observed to form. Thus,
a perfectly alternating ethylene ± propylene would be obtained after
hydrogenation.
only excellent substrates in intramolecular PK reactions, but
also that cyclization takes place with a reversal selectivity, that
is, endo instead of exo selectivity.[7]
Following our usual method of synthesis of (E)-g-hydroxy-
a,b-unsaturated phenyl sulfones,[8] several differently substi-
tuted 1-phenylsulfonyl-3-hydroxy-1,6-enynes (substrates 1a,
3a, 5a, and 7a[9]) were prepared in one step by the piperidine-
promoted condensation of the corresponding aldehydes with
phenylsulfonyl p-tolylsulfinylmethane in acetonitrile at 08C
(78 ± 84% yield, Scheme 1). Next, to study the effect of
[25] Z. Wu, R. H. Grubbs, Macromolecules 1995, 28, 3502 ± 3508.
Enynes b (R3 = TIPS)
Enynes c (R3 = CH2OEt)
Enynes a
O
R3O
HO
R2
R2
R2
R2
R2
R2
a
SO2Ph
R1
H
SO2Ph
R1
b or c
R1
78-84%
90-96%
1, 3, 5, 7
The Phenylsulfonyl Group as an endo
Stereochemical Controller in Intramolecular
Pauson ± Khand Reactions of 3-Oxygenated
1,6-Enynes**
R3O
R2
R2
HO
2, 4, 6, 8
O
R2
R2
d
b or c
R2
R2
H
R1
R1 80-85%
R1
60-73%
Scheme 1. Synthesis of the starting 1,6-enynes 1 ± 8. a) PhSO2CH2SOTol,
piperidine, CH3CN, 08C; b) TIPSOTf, 2,6-lutidine, CH2Cl2, RT;
c) ClCH2OEt, DIPEA, CH2Cl2, RT; d) vinylmagnesium bromide, THF,
À78 8C. TIPSOTfˆ triisopropylsilyl trifluoromethanesulfonate; DIPEAˆ
N,N-diisopropylethylamine.
Javier Adrio, Marta Rodríguez Rivero, and
Juan C. Carretero*
Â
Dedicated to Prof. Jose Barluenga
on the occasion of his 60th birthday
substitution at the g-position, the hydroxy group of these
enynes was protected as the triisopropylsilyl (TIPS) ether
(substrates b) and ethoxymethyl ketal derivatives (substrates
c). To evaluate precisely the effect of the sulfonyl group on the
reactivity and stereoselectivity of the PK reaction, the
corresponding 1-unsubstituted 3-oxygenated 1,6-enynes were
readily prepared by addition of vinylmagnesium bromide to
the appropriate aldehyde (synthesis of alcohols 2a, 4a, 6a,
and 8a[9]) followed by protection of the hydroxy group
(substrates 2b ± c, 4b ± c, 6b ± c, and 8b ± c) (Scheme 1).
Table 1 summarizes the results of the PK cyclizations of
enynes 1 ± 8 under the usual conditions with an amine N-oxide
promoter:[10] initial formation of the alkyne dicobalt complex
by reaction with [Co2(CO)8] in CH2Cl2 at room temperature
followed by addition of 6 equiv of trimethylamine N-oxide
(TMANO). Incomplete conversion was observed under these
standard conditions with enynes 7, and so the reaction was
performed in the presence of TMANO and molecular
sieves[11] (entries 15, 17, and 19).
The intramolecular Pauson ± Khand (PK) reaction of
enynes has become one of the most powerful tools for the
construction of cyclopentenone-fused bicyclic compounds. In
particular, due to the reliability and efficiency of the cycliza-
tion of 1,6-enynes, this reaction has been widely applied to the
synthesis of complex products with bicyclo[3.3.0]octane
skeletons.[1] In the case of 3-substituted 1,6-enynes, it is well
known since the pioneering work of Magnus et al.[2] that the
reaction occurs with moderate to high exo stereoselectivity[3]
(the substituent at the allylic position on the starting enyne
ends up on the less sterically crowded exo face of the bicyclic
product).
Although it is generally assumed that electron-poor alkenes
are unsuitable substrates for PK reactions,[1, 4] we recently
reported that certain 1-sulfinyl-1,6-enynes undergo intramo-
lecular PK cyclizations in acceptable yields and in a highly
stereoselective manner.[5] Encouraged by these results, we
envisioned the use of other electron-poor sulfur-substituted
olefins, such as vinyl sulfones.[6] Here we report that the
readily available racemic or enantiopure 1,6-enynes with g-
oxygenated a,b-unsaturated phenylsulfone structures are not
Remarkably, in spite of the electron-poor character of the
À
C C double bond of the vinyl sulfones 1, 3, 5, and 7, these
compounds reacted completely after 2 ± 3 h to give the
corresponding bicyclic PK adducts, in most cases as the only
detectable compounds (1H NMR) after removal of the cobalt
by-products by filtration through Celite. From a synthetic
viewpoint, it is noteworthy that the yields of PK products from
1-sulfonylated 1,6-enynes (70 ± 79% yields for cyclopente-
nones 9, 11, 13, and 15) are generally higher than those
obtained from the corresponding 1-unsubstituted enynes
(cyclopentenones 10, 12, 14, and 16; 38 ± 79% yield), and
that there is no significant decrease in efficiency on going
from the 4,4-dimethyl series 5 and 7 (Thorpe ± Ingold effect)
to the 4-unsubstituted series 1 and 3.[12]
[*] Prof. J. C. Carretero, J. Adrio, M. Rodríguez Rivero
Â
Departamento de Química Organica
Facultad de Ciencias
Â
Universidad Autonoma de Madrid, 28049 Madrid (Spain)
Fax : (‡34)913-973-966.
E-mail: juancarlos.carretero@uam.es
Â
[**] Financial support of this work by the Ministerio de Educacion y
Cultura (DGES, project PB96-0021) and Comunidad de Madrid
(project 07B/28/1999) is gratefully acknowledged.
Supporting information for this article is available on the WWW under
http://www/wiley-vch.de/home/angewandte/ or from the author.
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Table 1. Pauson ± Khand reactions of enynes 1 ± 8.
reductive desulfonylation of en-
do-9b, endo-9c, and endo-13b
with activated zinc (NH4Cl,
THF/H2O, RT) furnished in
R3O
R2
X
R3O
R3O
R2
X
H
H
a) [Co2(CO)8]
CH2Cl2, RT
R2
R2
X
O
+
O
R1
R2
R2
b) Me3NO
CH2Cl2, RT
R1
excellent
yields
endo-10b
R1
endo
exo
(93%), endo-10c (94%), and
endo-14b (91%), respectively.
In addition, the structure of
endo-9b was unequivocally
proved by X-ray diffraction.[14]
Although the assumed multi-
step mechanism of the PK re-
action makes rationalization of
the stereochemical outcome
difficult, two main factors are
usually invoked in diastereose-
lective PK cyclizations: the con-
formational preferences of the
starting complex prior to metal-
lacycle formation[7, 15] and the
thermodynamic stability of the
putative key cis-cobaltacycle
intermediates.[2, 16] In the case
Entry
Enyne
X
R1
R2
R3
Product
endo/exo[a]
Yield[b] [%] (endo[c] [%])
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15[e]
16
17[e]
18
19[e]
20
1b
2b
1c
2c
3b
4b
3c
4c
5a
6a
5b
6b
5c
6c
7a
8a
7b
8b
7c
8c
SO2Ph
H
SO2Ph
H
SO2Ph
H
SO2Ph
H
SO2Ph
H
SO2Ph
H
SO2Ph
H
SO2Ph
H
H
H
H
H
Me
Me
Me
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
TIPS
TIPS
CH2OEt
CH2OEt
TIPS
9b
10b
9c
92/8
46/54
> 98/ < 2
28/72
91/9
74 (66)
54
76 (76)
72
73 (63)
46
77 (71)
38
60[d]
50
71 (25)
63
10c
11b
12b
11c
12c
13a
14a
13b
14b
13c
14c
15a
16a
15b
16b
15c
16c
TIPS
32/68
93/7
CH2OEt
CH2OEt
H
H
TIPS
25/75
80/20
36/64
39/61
10/90
67/33
20/80
76/24
17/83
94/6
TIPS
CH2OEt
CH2OEt
H
H
TIPS
TIPS
CH2OEt
CH2OEt
74 (47)
79
H
Ph
Ph
Ph
Ph
Ph
Ph
75[d]
42
SO2Ph
H
SO2Ph
H
78[d]
45
< 2/ > 98
87/13
16/84
79[d]
46
of
the
1-sulfonylated-1,6-
[a] Determined by 1H NMR spectroscopy after removal of the cobalt by-products by filtration. [b] Of pure exo ‡
endo adducts after chromatography on silica gel. [c] In parentheses: yield of pure endo-4-sulfonylcyclopentenone
after chromatography. [d] The endo ‡ exo adducts could not be separated by chromatography on silica gel.
[e] Reaction conditions: Me3NO (6 equiv), molecular sieves (4 Š), toluene, RT.
enynes, both effects could oper-
ate in the same direction, pro-
viding a reasonable explanation
for the observed major forma-
tion of the endo isomer
(Scheme 2). Thus, as we had
However, the most outstanding result concerns the stereo-
selectivity of the cyclization. As expected for allylically
substituted 1,6-enynes, the PK reactions of enynes 2 and 6
were moderately exo selective, and, in agreement with the
model proposed by Magnus et al.,[2] which predicts a higher
exo selectivity with increasing size of the substituent at the
alkyne terminus, the PK reactions of the alkyne-substituted
series 4 and 8 were somewhat more exo selective than those of
2 and 6, respectively. Interestingly, the PK reactions of the
sulfonylated enynes 1, 3, 5, and 7 were endo selective in most
cases (values in bold in Table 1), even in the alkyne-
substituted series 3 and 7, which proves the strong capacity
of the phenylsulfonyl group to reverse the ªnaturalº exo
selectivity of the process. Thus, in the four sulfonylated series
the endo-bicyclo[3.3.0]oct-1-en-3-one was obtained with high
(entries 7, 9, and 17) or complete stereoselectivity (entry 3),
whereby the pronounced reversal of stereoselectivity in the
Scheme 2. Proposed mechanism for the observed endo-selective reaction.
case of the pairs of enynes 1c/2c (entries 3 and 4), 3c/4c
(entries 7and 8) and 7b/8b (entries 17and 18) is especially
remarkable. Furthermore, apart from the adducts 15, the rest
of endo/exo mixtures of 4-sulfonylcyclopentenones (adducts
9, 11, and 13) were readily separated by simple chromatog-
raphy on silica gel.
The exo/endo configuration of the sulfonylated cyclopente-
nones 9, 11, 13, and 15 was evident from spectroscopic data.[13]
In addition, the homogeneity of the stereochemical assign-
ments was confirmed in several cases by hydrolysis of the O-
protected PK adducts (products b,c) to the corresponding
alcohols (products a), and by chemical correlation between
sulfonylated and unsulfonylated cyclopentenones. Thus, the
noticed in other g-oxygenated a,b-unsaturated phenyl sul-
fones,[17] the conformation A (OR and Ha in 1,3-parallel
arrangement) would probably be more stable than conforma-
tion B (Ha and Hg in 1,3-parallel arrangement), as is deduced
from the low value of Jb,g (3.5 ± 5.0 Hz, CDCl3) in the starting
enynes 1 and 3. This leads to the cis-cobaltacycle C, in which
the OR and SO2Ph groups are located on opposite faces of the
bicyclic structure, which finally affords the endo adduct. In
contrast, the less stable conformation B (Hb and Hg in anti
relationship) would produce the presumably less stable cis-
cobaltacycle D (intermediate in the formation of the exo
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4.23 (d, J ˆ 4.4 Hz, 1H), 3.59 (m, 1H), 3.51 (m, 2H), 2.71 (m, 2H), 2.24 (m,
2H), 1.21 (t, J ˆ 7.0 Hz, 3H); 13C NMR (CDCl3) d ˆ 198.1, 185.0, 138.6,
134.0, 129.2, 129.1, 125.0, 93.8, 76.3, 68.3, 63.7, 53.2, 32.5, 24.3, 15.1; analysis
calcd for C17H20O5S: C 60.70, H 5.99, S 9.53; found: C 60.46, H 6.42, S 9.92.
adduct), which is likely destabilized with respect to C due to
the 1,3-parallel steric interaction between the OR and SO2Ph
groups (Scheme 2).
For the application of the results shown in Table 1 to the
synthesis of enantiopure 6-oxygenated endo-bicyclo[3.3.0]oct-
1-en-3-ones, optically pure 1-sulfonyl-1,6-enynes were re-
quired. Some years ago we described a practical lipase-
mediated kinetic resolution of a wide structural variety of (Æ)-
g-hydroxy-a,b-unsaturated sulfones based on their highly
enantioselective acetylation with lipase PS (Pseudomonas
cepacia lipase) as catalyst in an organic solvent.[18] Pleasingly,
under these conditions the reaction of (Æ)-1a stopped at 50%
conversion (48 h in toluene as solvent) and afforded 49% of
the alcohol (S)-1a[19] and 46% of the acetate (R)-1d[19] after
flash chromatography, both in very high optical purity (98.5%
ee for (S)-1a (HPLC, Chiralpak AS) and >96% ee for (R)-1d
(1H NMR, [Pr(hfc)3]). Protection of (S)-1a as ketal (S)-1c[19]
and subsequent PK cyclization afforded (4R,5R,6S)-9c[19] as
the only isolated product (72% yield). Finally, zinc-mediated
reductive desulfonylation furnished the enantiomerically pure
endo-substituted cyclopentenone (5R,6S)-10c[19] (94% yield,
98.5% ee (HPLC, Chiralcel OD); Scheme 3).
Received: March 22, 2000 [Z14884]
[1] Recent reviews: a) Y. K. Chung, Coord. Chem. Rev. 1999, 188, 297;
b) O. Geis, H.-G. Schmalz, Angew. Chem. 1998, 110, 955; Angew.
Chem. Int. Ed. 1998, 37, 911; c) J. Marco-Contelles, S. T. Ingate, Org.
Prep. Proced. Int. 1998, 30, 121; d) N. E. Schore in Comprehensive
Organometallic Chemistry II (Eds.: E. W. Abel, F. G. A. Stone, G.
Wilkinson), Elsevier, New York, 1995, Vol. 12, p. 703; d) N. E. Schore,
Org. React. 1991, 40, 1.
[2] The exo selectivity of the intramolecular PK reaction of allylic
substituted 1,6-enynes has been explained by invoking steric repulsion
between the endo allylic group and the substituent at the alkyne
terminus in the cis-cobaltacycle intermediate: a) P. Magnus, D. P.
Becker, J. Am. Chem. Soc. 1987, 109, 7495; b) P. Magnus, L. M.
Principe, M. J. Slater, J. Org. Chem. 1987, 52, 1483; c) P. Magnus, L. M.
Principe, Tetrahedron Lett. 1985, 26, 4851; d) P. Magnus, C. Exon, P.
Albaugh-Robertson, Tetrahedron 1985, 41, 5861.
[3] For other examples of exo selectivity in PK cyclizations of enynes
substituted at allylic or propargylic positions, see a) C. Mukai, J. S.
Kim, M. Uchiyama, S. Sakamoto, M. Hanoka, J. Chem. Soc. Perkin
Trans 1 1998, 2903; b) C. Mukai, M. Uchiyama, S. Sakamoto, M.
Hanaoka, Tetrahedron Lett. 1995, 36, 5761; c) N. Jeong, S. Hwang, Y.
Lee, Y. K. Chung, J. Am. Chem. Soc. 1994, 116, 3159; d) Y. K. Chung,
B. Y. Lee, N. Jeong, M. Hudecek, P. L. Pauson, Organometallics 1993,
12, 220; e) N. Jeong, B. Y. Lee, S. M. Lee, Y. K. Chung, S.-G. Lee,
Tetrahedron Lett. 1993, 34, 4023; f) S. Yoo, S. H. Lee, N. Jeong, I. Cho,
Tetrahedron Lett. 1993, 34, 3425. g) W. R. Roush, J. C. Park, Tetrahe-
dron Lett. 1991, 32, 6285; h) N. Jeong, S. Yoo, S. J. Lee, S. H. Lee, Y. K.
Chung, Tetrahedron Lett. 1991, 32, 2137; i) J. Mulzer, K.-D. Graske, B.
Kirste, Liebigs Ann. Chem. 1988, 891.
[4] One of the most important limitations of the cyclopentenone synthesis
by the PK reaction is that in the reaction of alkyne dicobalt
hexacarbonyl complexes with alkenes bearing electron-withdrawing
groups (for example, ketone, ester, or cyano), after the olefin insertion
step leading to the cobaltacycle intermediate, the reaction proceeds
preferentially by b-H elimination rather than by carbonyl insertion,
furnishing finally 1,3-dienes instead of cyclopentenones; see a) W. A.
Smit, A. S. Gybin, A. S. Shashkov, Y. T. Strychkov, L. G. Kizmina,
G. S. Mikaelian, R. Caple, E. D. Swanson, Tetrahedron Lett. 1986, 27,
1241; b) P. L. Pauson, Tetrahedron 1985, 41, 5855; c) I. U. Khand, P. L.
Pauson, J. Chem. Soc. Chem. Commun. 1974, 379. Only some specific
alkynyl enones led to cyclopentenones in cobalt-catalyzed PK
reactions: A. L. Veretenov, W. A. Smit, L. G. Vorontsova, M. G.
Kurella, R. Caple, A. S. Gibin, Tetrahedron Lett. 1991, 32, 2109. See
also M. Costa, A. Mor, Tetrahedron Lett. 1995, 36, 2867.
EtOCH2O
SO2Ph EtOCH2O
HO
H
H
SO2Ph
a
b, c
d
O
O
(±)-1a
94%
72%
(S)-1a, 49%, 98.5% ee
+ (R)-1d, 46%, > 96% ee
(5R, 6S)-10c
98.5% ee
(4R, 5R, 6S)-9c
Scheme 3. Enantioselective synthesis of 6-oxygenated endo-bicyclo-
[3.3.0]oct-1-en-3-ones. a) Lipase PS, vinyl acetate, molecular sieves, tol-
uene, RT; b) ClCH2OEt, DIPEA, CH2Cl2, RT; c) [Co2(CO)8], CH2Cl2, RT;
TMANO, RT; d) Zn, NH4Cl, THF/H2O, RT.
In summary, we have demonstrated that a,b-unsaturated
sulfones can be useful substrates in intramolecular PK
reactions. Interestingly, unlike the usual stereochemical
behavior of allylic substituted 1,6-enynes, the intramolecular
PK cyclizations of differently substituted (E)-1-phenylsulfon-
yl-3-oxygenated-1,6-enynes occur with moderate to high endo
selectivity. As these sulfonylated enynes are readily available
in both racemic and enantiopure forms, and the sulfonyl group
can be easily removed from the cyclopentenone products, this
overall procedure represents an efficient stereocomplemen-
tary Pauson ± Khand approach to the asymmetric synthesis of
6-substituted bicyclo[3.3.0]oct-1-en-3-ones. The application of
this procedure to the stereoselective synthesis of triquinanes is
underway.
[5] J. Adrio, J. C. Carretero, J. Am. Chem. Soc. 1999, 121, 7411.
[6] Vinyl sulfones had never been successfully used in PK reactions. As a
related reported precedent, the treatment of divinyl sulfone with
alkyne dicobalt complexes did not give the cyclopentenone PK
product (I. U. Khand, P. L. Pauson, Heterocycles 1978, 11, 59) in
accordance with the accepted behavior of alkenes with electron-
withdrawing substituents (see ref. [4]).
[7] To the best of our knowledge, the only reported case of endo
selectivity in a PK reaction of an allylic substituted 1,6-enyne concerns
a specific 3,4-disubstituted enyne: J. A. Casalnuovo, R. W. Scott, E. A.
Harwood, N. E. Schore, Tetrahedron Lett. 1994, 35, 1153. Similarly, for
a study of the endo/exo selectivity in 3,4-disubstituted-1,7-enynes, see
C. Mukai, J. S. Kim, H. Sonobe, M. Hanaoka, J. Org. Chem. 1999, 64,
6822.
Experimental Section
(4R,5R,6S)-9c: A solution of enyne (S)-1c (187mg, 0.61 mmol) in CH 2Cl2
(5 mL) was added dropwise to a stirred solution of [Co2(CO)8] (250 mg,
0.73 mmol) in CH2Cl2 (5 mL) under argon atmosphere at room temper-
ature (RT). The solution was stirred for 10 min, and TMANO (407mg,
3.66 mmol) was added in one portion. The resulting solution was stirred for
3 h at RT and filtered through a pad of Celite, which was washed with
diethyl ether (30 mL). The combined solvents were evaporated and the
residue was purified by flash chromatography (hexane/ethyl acetate 5/1) to
afford 155 mg of (4R,5R,6S)-9c (76%) as a white solid. M.p. 73 ± 748C;
[a]2D0 ˆ ‡241 (c ˆ 0.4, CHCl3); 1H NMR (CDCl3): d ˆ 7.99 ± 7.96 (m, 2H),
7.70 ± 7.55 (m, 3H), 5.92 (m, 1H), 4.65 (m, AB, 2H), 4.28 (t,J ˆ 4.1 Hz, 1H),
[8] a) B. M. Trost, T. A. Greese, J. Org. Chem. 1991, 56, 3189; b) E.
Domínguez, J. C. Carretero, Tetrahedron 1990, 46, 7197.
[9] Alternatively, the phenyl-substituted alkynes 7a and 8a were readily
prepared by Sonogashira reaction of the corresponding terminal
alkynes 5a and 6a with phenyl iodide (Pd(OAc)2 10 mol%, CuI
10 mol%; PPh3 20 mol%, Et3N 200 mol% in benzene at RT; 81 and
75% yield, respectively).
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[10] Very similar yields and diastereoselectivities were obtained in the
thermal PK reaction (CH3CN, 808C) of the dicobalt complexes of the
enynes 1 and 3.
Cyclization of Terminal Diynes Catalyzed by
Thiolate-Bridged Diruthenium Complexes:
A Simple Synthetic Route to endo-Macrocyclic
(Z)-1-En-3-ynes**
[11] The combination TMANO/molecular sieves has been recently
Â
reported as an efficient promoter in PK reactions: L. Perez-Serrano,
Â
L. Casarrubios, G. Domínguez, J. Perez-Castells, Org. Lett. 1999, 1,
1187.
Yoshiaki Nishibayashi, Masashi Yamanashi,
Issei Wakiji, and Masanobu Hidai*
[12] Except for the free alcohols 1a and 3a, which proved to be rather
unreactive in PK reactions. For instance, the alkyne dicobalt
hexacarbonyl complex of 1a did not react at all under thermal
(CH3CN, 808C) or TMANO-promoted conditions (CH2Cl2, RT). A
very low yield of PK products 9a (25% yield, endo/exo ˆ 85/15) was
obtained when the reaction was performed in the presence of
TMANO and molecular sieves. In this case, instead of the PK
cyclopentenone, the main product was the corresponding exocyclic
1,3-diene (see ref. [4]).
Homogeneous catalysis by polynuclear transition metal
complexes has been receiving much attention because the
multimetallic sites are expected to provide unique reaction
sites for activation and transformation of substrate molecules.
These sites are anticipated to differ significantly from those of
conventional monometallic centers coordinated by ancillary
ligands.[1] Toward this end, our studies have long been focused
on the synthesis and reactivity of polynuclear noble-metal
complexes with bridging sulfur ligands.[2] Recently, we
found that the thiolate-bridged diruthenium complexes
[Cp*RuCl(m2-SR)2RuCp*Cl] (1 ± 3)(Cp* ˆ h5-C5Me5; R ˆ
Me, Et, nPr) catalyze the head-to-head Z dimerization of
terminal alkynes containing straight-chain aliphatic and func-
tional groups.[3] Although mononuclear ruthenium complexes
such as [Cp*Ru(L)H3] (L ˆ phosphane) also catalyze the
dimerization of terminal alkynes, such a highly regio- and
stereoselective dimerization of a wide range of terminal
alkynes has never been realized.[4] We
[13] As is usual in other 6-substituted bicyclo[3.3.0]octen-3-ones (for
example, ref. [2c]), the coupling constant between H5 and H6 is a very
simple and excellent criterion for stereochemical diagnosis. Thus, J5,6 is
much smaller in the endo isomers (J5,6 ˆ 3.6 ± 4.8 Hz, H5/H6 in cis
relationship) than in the exo isomers (J5,6 ˆ 7.5 ± 10.5 Hz, H /H6 in trans
5
arrangement). Also, a characteristic trend was observed for the
chemical shift of H6 in the C-4 sulfonylated adducts: H6 is significantly
more deshielded in the endo isomer than in the exo isomer (see
below), in accordance with the strong deshielding effect of the
phenylsulfonyl group on the hydrogen atom in the 1,3-parallel
arrangement. Additionally, these stereochemical assignments have
been confirmed by NOESY experiments on the pairs of isomers endo/
exo 9b and endo/exo 13c.
Cp*
Cp*
have now extended our study of the
catalytic activity of the diruthenium
complexes to include the cyclization of
terminal diynes. Preliminary results are
described here.
Ru Ru
RS
SR
Cl
Cl
1; R = Me
2; R = Et
3; R = nPr
4; R = iPr
Trost and co-workers have reported
the palladium-catalyzed cyclization of
a,w-diynes to give the corresponding exo-macrocyclic 1-en-
3-ynes in moderate yields and high regio- and stereoselectiv-
ities.[5] In sharp contrast, synthetic routes to endo-macrocyclic
1-en-3-ynes are extremely limited.[6] Actually, six steps are
necessary to prepare (Z)-1-cyclododecen-3-yne from cyclo-
dodecanone and the total yield is less than 5%.[6] To the best
of our knowledge, there is no report of a synthetic method for
endo-macrocyclic (Z)-1-en-3-ynes from a,w-diynes.[7]
[14] Crystallographic data (excluding structure factors) for the structures
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC-141942. Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax:
(‡44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
Á
[15] Recent examples: S. Fonquerna, R. Rios, A. Moyano, M. A. Pericas,
A. Riera, Eur. J. Org. Chem. 1999, 3459, and references therein.
[16] For instance, see a) P. M. Breczinski, A. Stumpf, H. Hope, M. E.
Krafft, J. A. Casalnuovo, N. E. Schore, Tetrahedron 1999, 55, 6797;
Treatment of 1,15-hexadecadiyne[8] (6a) in methanol in the
presence of [Cp*RuCl(m2-SMe)2RuCp*Cl] (1) (10 mol%) at
Á
b) J. Castro, A. Moyano, M. A. Pericas, A. Riera, Tetrahedron 1995,
51, 6541.
[*] Prof. Dr. M. Hidai,[‡] Dr. Y. Nishibayashi, M. Yamanashi,
I. Wakiji
Â
Â
[17] a) J. C. Carretero, R. Gomez Arrayas, J. Org. Chem. 1998, 63, 2993;
Department of Chemistry and Biotechnology
Graduate School of Engineering
The University of Tokyo
Â
Â
b) J. Adrio, J. C. Carretero, R. Gomez Arrayas, Synlett 1996, 640.
Similar conformational preferences have been reported for g-oxy-
genated a,b-unsaturated esters, see: c) B. W. Gung, M. B. Francis,
Tetrahedron Lett. 1995, 36, 2579; d) B. W. Gung, M. B. Francis, J. Org.
Chem. 1993, 58, 6177.
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
Fax : (‡81)3-5841-7265
‡
[ ] Current address:
[18] In all the studied cases, only the R enantiomer of the (Æ)-(E)-g-
hydroxy-a,b-unsaturated sulfone was acetylated (J. C. Carretero, E.
Domínguez, J. Org. Chem. 1992, 57, 3867).
Department of Material Science and Technology
Faculty of Industrial Science and Technology
Science University of Tokyo, Noda, Chiba 278-8510 (Japan)
Fax : (‡81)471-24-1699
[19] Specific rotations: (S)-1a: [a]2D0 ˆ ‡28.0 (c ˆ 1, CHCl3); (R)-1d:
[a]2D0 ˆ ‡5.1 (c ˆ 1, CHCl3); (S)-1c: [a]D20 ˆ À25.1 (c ˆ 1.8, CHCl3);
(4R,5R,6S)-9c: [a]D20 ˆ ‡241 (c ˆ 0.4, CHCl3); (5R,6S)-10c: [a]D20
‡90.2 (c ˆ 0.2, CHCl3).
ˆ
E-mail: hidai@rs.noda.sut.ac.jp
[**] This work was supported by a Grant-in-Aid for Specially Promoted
Research (09102004) from the Ministry of Education, Science, Sports,
and Culture, Japan.
Supporting information for this article is available on the WWW under
http://www.wiley-vch.de/home/angewandte/ or from the author.
Angew. Chem. Int. Ed. 2000, 39, No. 16
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