Selective ruthenium-catalyzed transformations of enynes with diazoalkanes into alkenylbicyclo[3.1.0]hexanes

Article abstract of DOI:10.1021/ja0700146

Reaction of a variety of C≡CH bond-containing 1,6-enynes with N ₂CHSiMe₃ in the presence of RuCl(COD)Cp* as catalyst precursor leads, at room temperature, to the general formation of alkenylbicyclo[3.1.0]hexanes with high Z-stereosel

Full text of DOI:10.1021/ja0700146

Published on Web 04/13/2007
Selective Ruthenium-Catalyzed Transformations of Enynes
with Diazoalkanes into Alkenylbicyclo[3.1.0]hexanes
†
†
†
†
Florian Monnier, Chlo e´ Vovard-Le Bray, Dante Castillo, Vincent Aubert,
Sylvie D e´ rien,*,† Pierre H. Dixneuf,* Loic Toupet, Andrea Ienco, and Carlo Mealli
,†
‡
§
§
Contribution from the Laboratoire “catalyse et organom e´ talliques”, Institut Sciences Chimiques
de Rennes, UMR 6226 CNRS-UniVersit e´ de Rennes 1, and Groupe Mati e` re Condens e´ e et
Mat e´ riaux, UMR 6626 CNRS-UniVersit e´ de Rennes 1, Campus de Beaulieu,
3
5042 Rennes Cedex, France, and ICCOM-CNR, Via Madonna del Piano 10,
0019 Sesto Fiorentino, Firenze, Italy
5
Received January 2, 2007; E-mail: pierre.dixneuf@univ-rennes1.fr
Abstract: Reaction of a variety of CtCH bond-containing 1,6-enynes with N
RuCl(COD)Cp* as catalyst precursor leads, at room temperature, to the general formation of alkenylbicyclo-
3.1.0]hexanes with high Z-stereoselectivity of the alkenyl group and cis arrangement of the alkenyl group
2 3
CHSiMe in the presence of
[
and an initial double-bond substituent, for an E-configuration of this double bond. The stereochemistry is
established by determining the X-ray structures of three bicyclic products. The same reaction with 1,6-
enynes bearing an R substituent on the C
the double bond with bulky R groups (SiMe
heterocycles, resulting from a â elimination process, with less bulky R groups (R ) Me, CH
1
carbon of the triple bond results in either cyclopropanation of
, Ph) or formation of alkylidene-alkenyl five-membered
CHdCH ).
3
2
2
The reaction can be applied to in situ desilylation in methanol and direct formation of vinylbicyclo[3.1.0]-
hexanes and to the formation of some alkenylbicyclo[4.1.0]heptanes from 1,7-enynes. The catalytic formation
of alkenylbicyclo[3.1.0]hexanes also takes place with enynes and N
2
CHCO
2
Et or N
2
CHPh. The reaction
can be understood to proceed by an initial [2+2] addition of the RudCHSiMe
3
bond with the enyne CtCH
bond, successively leading to an alkenylruthenium-carbene and a key alkenyl bicyclic ruthenacyclobutane,
which promotes the cyclopropanation, rather than metathesis, into bicyclo[3.1.0]hexanes. Density functional
2 2 5 5
theory calculations performed starting from the model system Ru(HCtCH)(CH dCH )Cl(C H ) show that
3
the transformation into a ruthenacyclobutane intermediate occurs with a temporary η -coordination of the
cyclopentadienyl ligand. This step is followed by coordination of the alkenyl group, which leads to a mixed
alkyl-allyl ligand. Because of the non-equivalence of the terminal allylic carbon atoms, their coupling favors
cyclopropanation rather than the expected metathesis process. A direct comparison of the energy profiles
with respect to those involving the Grubbs catalyst is presented, showing that cyclopropanation is favored
with respect to enyne metathesis.
economy.1,2 Enyne metathesis2,3 and cycloisomerization are
among the most general and useful transformations of enynes,
and the catalytic Pauson-Kand reaction has now been applied
4
Introduction
Enynes have become crucial keys giving access to a variety
of complex architectures, promoted by metal catalysts with atom
5
to enynes. Enynes constitute key building blocks for a variety
of functionalized cycles via cycloadditions. Recently, elec-
trophilic activations of enynes with ruthenium(II), platinum(II),
gold, and gallium(III) catalysts have opened new and efficient
routes for the selective formation of bicyclic compounds, and
the use of suitable dienynes leads to catalytic tricyclization with
6
,7
†
Laboratoire “catalyse et organom e´ talliques”, Institut Sciences Chimiques
8
9
de Rennes.
10
11
‡
Groupe Mati e` re Condens e´ e et Mat e´ riaux.
ICCOM-CNR.
§
(
1) For reviews, see (a) Bruneau, C. Angew. Chem., Int. Ed. 2005, 44, 2328.
(b) Aubert, C.; Buisine, O.; Malacria, M. Chem. ReV. 2002, 102, 813.
1
2
(
2) For enyne metathesis reviews, see: (a) Lloyd-Jones, G. C. Org. Biomol.
Chem. 2003, 1, 215. (b) Mori, M. J. Mol. Catal. A: Chem. 2004, 213, 73.
a vinylcyclopropane unit.
The search for alkene metathesis catalysts arising from RuCl-
L)2Cp* precursors (Cp* ) C5Me5) and diazoalkane as a carbene
(c) Villar, H.; Frings, M.; Bolm, C. Chem. Soc. ReV. 2007, 36, 55.
(
3) For enyne metathesis, see: (a) Mori, M.; Saito, N.; Tanaka, D.; Takimoto,
M.; Sato, Y. J. Am. Chem. Soc. 2003, 125, 5606. (b) Kinoshita, A.; Mori,
M. Synlett 1994, 1020. (c) Kim, S-H.; Zuercher, W. J.; Grubbs, R. H. J.
Org. Chem. 1996, 61, 1073.
(
(5) (a) Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J. Org. Chem.
1997, 62, 3762. (b) Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T. J. Am.
Chem. Soc. 1997, 119, 6187. (c) Tang, Y.; Deng, L.; Zhang, Y.; Dong, G.;
Chen, J.; Yang, Z. Org. Lett. 2005, 7, 1657.
(6) (a) Shibata, T.; Arai, Y.; Tahara, Y-K. Org. Lett. 2005, 7, 4955. (b) Evans,
P. A.; Robinson, J. E.; Baum, E. W.; Fazal, A. N. J. Am. Chem. Soc. 2002,
124, 8782.
(
4) (a) Trost, B. M.; Surivet, J-P.; Toste, F. D. J. Am. Chem. Soc. 2004, 126,
1
5592. (b) Le Paih, J.; Cuervo Rodriguez, D.; D e´ rien, S.; Dixneuf, P. H.
Synlett 2000, 1, 95. (c) Trost, B. M. Acc. Chem. Res. 1990, 23, 34. (d)
Trost, B. M.; Haffner, C. D.; Jebaratnam, D. J.; Krische, M. J.; Thomas,
A. P. J. Am. Chem. Soc. 1999, 121, 6183. (e) Trost, B. M.; Krische, M. J.
J. Am. Chem. Soc. 1999, 121, 6131.
10.1021/ja0700146 CCC: $37.00 © 2007 American Chemical Society
J. AM. CHEM. SOC. 2007, 129, 6037-6049
9
6037

A R T I C L E S
Monnier et al.
source has actually led to the discovery of a new catalytic
to develop their ruthenium-catalyzed formation and to explore
the generality of the reaction.
13
bicyclization of enynes, forming alkenylbicyclo[3.1.0]hexanes
eq 1). This reaction, which tolerates functional groups, has been
(
We report here that the catalytic transformation of 1,6-enynes
and diazoalkanes into alkenylbicyclo[3.1.0]hexane derivatives,
with RuCl(COD)Cp* as catalyst precursor, constitutes a general
reaction, including CdC bond substituted enynes, and shows
high stereoselectivity. By contrast, triple-bond disubstituted
enynes offer competitive reactions with a simple cyclopropa-
nation of the enyne CdC bond or a new monocyclization
reaction leading to alkenyl-alkylidene cyclopentane derivatives.
Actually, we show that the RuCl(dCHY)Cp* catalytic inter-
mediate behaves as an enyne metathesis catalyst inhibitor but
favors cyclopropanation. Density functional theory (DFT)
calculations on a RuCl(HCtCH)(CH2CH2)C5H5 model show
that the formation of an alkenylruthenacyclobutane intermediate
used for the controlled synthesis of bicyclic amino acid
derivatives,14 whereas a similar reaction in the additional
presence of ethylene was successfully orientated toward the
1
5
formation of a cycloalkenylcyclopropane derivative. It was
shown recently that this reaction of a functional enyne with
diazoalkanes, but with the Ni(COD)2 catalyst (COD ) 1,5-cyclo-
16
octadiene), also led to alkenylbicyclo[3.1.0]hexane derivatives.
5
3
Alkenylbicyclo[3.1.0]hexane intermediates have recently been
shown to be powerful for building cyclopentenes with NHC-
Ni(0) catalyst,17 and especially larger cycles via catalyzed
is favored by an η -to-η shift of the cyclopentadienyl ring and
that the large stabilization of the metallacyclobutane intermediate
is due to coordination of the alkenyl bond, leading to an alkyl-
allyl ligand, which favors reductive elimination rather than
metathesis.
[
4+2+1] cycloadditions with Ni(COD)2 and [5+2] cycloaddi-
7
tions with rhodium(I) catalyst.
As the vinylcyclopropane syntheses are not straightforward,18
the interest in alkenylcyclopropanes and bicyclic[3.1.0]hexane
derivatives for controlled building of larger cycles has led us
Results and Discussion
The reaction of the diazoalkane N2CHSiMe3 with alkynes in
the presence of RuCl(COD)Cp* (I) as catalyst precursor leads
to the double addition of a related carbene to the triple bond to
selectively generate silylated 1,3-dienes (eq 2). This reaction
reveals the potential biscarbene character of a triple bond for
coupling with external carbene. It also suggests the intermediate
formation of RuCl(dCHSiMe3)Cp* from RuCl(COD)Cp* and
N2CHSiMe3.
(
7) For cycloaddition involving vinylcyclopropane precursors, see: (a) Wender,
P. A.; Haustedt, L. O.; Lim, J.; Love, J. A.; Williams, T. J.; Yoon, J-Y. J.
Am. Chem. Soc. 2006, 128, 6302. (b) Wegner, H. A.; De Meijere, A.;
Wender, P. A. J. Am. Chem. Soc. 2005, 127, 6530. (c) Wender, P. A.;
Gamber, G. G.; Hubbard, R. D.; Pham, S. M.; Zhang, L. J. Am. Chem.
Soc. 2005, 127, 2836. (d) Yu, Z.-X.; Wender, P. A.; Houk, K. N. J. Am.
Chem. Soc. 2004, 126, 9154. (e) Wender, P. A.; Barzilay, C. M.; Dyckman,
A. J. J. Am. Chem. Soc. 2001, 123, 179. (f) Wender, P. A.; Dyckman, A.
J.; Husfeld, C. O.; Scanio, M. J. C. Org. Lett. 2000, 2, 1609. (g) Wender,
P. A.; Dyckman, A. J. Org. Lett. 1999, 1, 2089. (h) Wender, P. A.;
Dyckman, A. J.; Husfeld, C. O.; Kadereit, D.; Love, J. A.; Rieck, H. J.
Am. Chem. Soc. 1999, 121, 10442. (i) Trost, B. M.; Shen, H. C.; Schulz,
T.; Koradin, C.; Schirok, H. Org. Lett. 2003, 5, 4149. (j) Trost, B. M.;
Shen, H. C.; Horne, D. B.; Toste, F. D.; Steinmetz, B. G.; Koradin, C.
Chem. Eur. J. 2005, 11, 2577.
1
9
(8) (a) Chatani, N.; Kataoka, K.; Murai, S. J. Am. Chem. Soc. 1998, 120, 9104.
(
b) Peppers, B. P.; Diver, S. T. J. Am. Chem. Soc. 2004, 126, 9524. (c)
As the neutral 16-electron ruthenium(II)-carbene intermedi-
ate RuCl(dCHY)Cp* is isoelectronic with the Grubbs catalysts
RuCl2(dCHR)(PCy3)L (L ) PCy3 or imidazolinylidene, IMes),
one might expect that the intermediate RuCl(dCHY)Cp* would
catalyze the enyne metathesis to give the corresponding alk-
Tanaka, D.; Sato, Y.; Mori, M. Organometallics 2006, 25, 799.
(9) (a) F u¨ rstner, A.; Stelzer, F.; Szillat, H. J. Am. Chem. Soc. 2001, 123, 11863.
(
b) Mamane, V.; Gress, T.; Krause, H.; F u¨ rstner, A. J. Am. Chem. Soc.
2
004, 126, 8654. (c) F u¨ rstner, A.; Davies, P. W.; Gress, T. J. Am. Chem.
Soc. 2005, 127, 8244.
(
10) (a) Nieto-Oberhuber, C.; Munoz, M. P.; Lopez, S.; Jim e´ nez-Nunez, E.;
Nevado, C.; Herrero-Gomez, E.; Raducan, M.; Echavarren, A. M. Chem.
Eur. J. 2006, 12, 1677. (b) Nieto-Oberhuber, C.; Lopez, S.; Echavarren,
A. M. J. Am. Chem. Soc. 2005, 127, 6178. (c) Nieto-Oberhuber, C.; Munoz,
M. P.; Bunuel, E.; Nevado, C.; Cardenas, D. J.; Echavarren, A. M. Angew.
Chem., Int. Ed. 2004, 43, 2402. (d) Nieto-Oberhuber, C.; Lopez, S.; Munoz,
M. P.; Cardena, D. J.; Bunuel, E.; Nevado, C.; Echavarren, A. M. Angew.
Chem., Int. Ed. 2005, 44, 6146. (e) Marion, N.; De Fr e´ mont, P.; Lemi e` re,
G.; Stevens, E. D.; Fensterbank, L.; Malacria, M.; Nolan, S. P. Chem.
Commun. 2006, 2048. (f) Lopez, S.; Herrero-Gomez, E.; P e´ rez-Galan, P.;
Nieto-Oberhuber, C.; Echavarren, A. M. Angew. Chem., Int. Ed. 2006, 45,
3
enylcycloalkene. Thus, the enyne 1a would lead to the 1,3-
diene 2a (path (a), eq 3).
6
2
1
2
029. (g) Luzung, M. R.; Matkham, J. P.; Toste, F. D. J. Am. Chem. Soc.
004, 126, 10858. (h) Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128,
4274. (i) Ma, S.; Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006, 45,
00.
(
11) (a) Chatani, N.; Inoue, H.; Kotsuma, T.; Murai, S. J. Am. Chem. Soc. 2002,
1
24, 10294. (b) Kim, S. M.; Lee, S. I.; Chung, Y. K. Org. Lett. 2006, 8,
425.
5
(
12) (a) Peppers, B. P.; Diver, S. T. J. Am. Chem. Soc. 2004, 126, 9524. (b)
Galan, B. R.; Giessert, A. J.; Keister, J. B.; Diver, S. T. J. Am. Chem. Soc.
2
005, 127, 5762.
(
13) Monnier, F.; Castillo, D.; D e´ rien, S.; Toupet, L.; Dixneuf, P. H. Angew.
Chem., Int. Ed. 2003, 42, 5474.
(
14) Eckert, M.; Monnier, F.; Shchetnikov, G. T.; Titanyuk, I. D.; Osipov, S.
N.; Toupet, L.; D e´ rien, S.; Dixneuf, P. H. Org. Lett. 2005, 7, 3741.
15) Kim, B. G.; Snapper, M. L. J. Am. Chem. Soc. 2006, 128, 52.
16) Ni, Y.; Montgomery, J. J. Am. Chem. Soc. 2006, 128, 2609.
17) Zuo, G.; Louie, J. Angew. Chem., Int. Ed. 2004, 43, 2277.
18) As representative synthesis examples, see: (a) Wender, P. A.; Dyckman,
A. J.; Husfeld, C. O.; Scanio, M. J. C. Org. Lett. 2000, 2, 1609. (b)
Wasserman, H. H.; Hearn, M. J.; Cochoy, R. E. J. Org. Chem. 1980, 45,
(
(
(
(
Actually, the initial attempt at transformation13 of the enyne
1
a with 2.4 equiv of N2CHSiMe3 (2 M in hexane) and 5 mol
2
874. (c) Sala u¨ n, J.; Marguerite, J. Org. Synth. 1985, 63, 147. (d)
Schaumann, E.; Kirschning, A.; Narjes, F. J. Org. Chem. 1991, 56,
17.
(19) Le Paih, J.; D e´ rien, S.; O¨ zdemir, I.; Dixneuf, P. H. J. Am. Chem. Soc.
2000, 122, 7400.
7
6038 J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007

Ru-Catalyzed Formation of Alkenylbicyclo[3.1.0]hexanes
A R T I C L E S
Table 1. Catalytic Transformation of Substituted-CdC-Bond
%
of RuCl(COD)Cp*, after 1 h at 60 °C in dioxane (reaction
Enynes 1 with N2CHSiMe3
conditions A), to allow for complete conversion of 1a, did not
lead to the enyne metathesis product 2a but instead gave a 95%
yield of 3a with a Z/E ratio of 4/1 (path (b), eq 3).
The effect of reaction conditions on the reaction efficiency
and yields led us to choose instead N2CHSiMe3 2 M in diethyl
ether, as the reaction takes place more rapidly at room
temperature (complete conversion in 5 min) and uses only 1.1
equiv of N2CHSiMe3 (reaction conditions B). Furthermore,
complete conversion of the enyne can be carried out in various
polar and nonpolar solvents (dioxane, diethyl ether, methylene
chloride, pentane, toluene, and even water), diethyl ether and
dioxane giving the best solubility. The catalyst is used in 5 mol
%
rather than in 3 and 1 mol %, as the reaction conversion is
respectively 100% (5 min), 100% (35 min), and 30% (24 h).
The reaction can take place at 0 °C with 5 mol % of catalyst
but leads to only 76% conversion of 1a after 5 min.
The best conditions for the transformation of 1a into 3a, with
5
mol % of RuCl(COD)Cp* and 1.1 equiv of N2CHSiMe3 in
diethyl ether at room temperature, have been used to study the
generality of the reaction with a variety of terminal triple-bond-
containing enynes (eq 4). These results are summarized in Table
1
.
The results show that the reaction takes place with good
yields, except in the case of 1i, containing an electron-
withdrawing group at the double bond. The nature of the
protecting group (Ts or Cbz) seems to have no influence on
reaching good yields (entries 1 and 2). The alkene chain of 3
possesses preferentially the Z-configuration regardless of the
reaction temperature (entries 1-3). However, only the Z-isomer
is obtained with enynes 1 containing a substituent on the CdC
bond terminal carbon (entries 4-6).
Enynes containing a terminal allylic alcohol function also lead
to bicyclic products (entries 7 and 8), although the reaction is
much slower than with other substituted CdC bond enynes 1d-
f. Only the R-disubstituted product 1h leads to a good yield of
3
h (95%; Z/E ) 90/10).
It is noteworthy that the disubstitution on the terminal carbon
of the alkene bond in 1j disfavored the formation of the bicyclic
compound 3j (11%; Z/E ) 30/70) (entry 10) to the profit of
the “alkene metathesis” products 4 (20%) and 5 (20%). This
observation suggests that this disubstitution disfavors the
reductive elimination step (cyclopropanation) to the profit of
metathesis with equal formation of CHdCHSiMe3 (4) and CHd
CMe2 (5) groups. This also means that, after each metathesis
step giving 4, the released RudCMe2 moiety is efficient only
to perform the metathesis reaction leading to 5, not the
bicyclization.
a
Reaction conditions: A, 2.4 equiv of N2CHSiMe3 (2 M in hexane) in
dioxane (1 mL), 60 °C, 5 mol % RuCl(COD)Cp*; B, 1.1 equiv of
N2CHSiMe3 (2 M in ether) in diethyl ether (1 mL), room temperature, 5
mol % RuCl(COD)Cp*. b Isolated product yields obtained after complete
The diastereoselectivity of the reaction depends on the alkene
stereochemistry. The transformation of 1d (E/Z ) 85/15) gives
two diastereoisomers of 3d (85/15). The X-ray structure of the
isolated major diastereoisomer establishes the cis arrangement
conversion and purification by silica gel chromatography.
of the alkenyl and methyl groups in 3d. Thus, the double-bond
E-configuration favors the selective formation of the diastere-
J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007 6039

A R T I C L E S
Monnier et al.
Table 3. Catalytic Transformation of Carbon-Chain Enynesa
Table 2. Catalytic Transformation of Propargyl Allyl Ethers with
N2CHSiMe3
a
Reaction conditions: 1.1 equiv of N2CHSiMe3 (2 M in ether) in diethyl
b
ether (1 mL), room temperature, 1 h, 5 mol % RuCl(COD)Cp*. Isolated
product yields obtained after complete conversion and purification by silica
gel chromatography.
Table 4. Catalytic Transformation of 1,7-Enynes
a
Reaction conditions: A, 2.4 equiv of N2CHSiMe3 (2 M in hexane) in
dioxane (1 mL), 60 °C, 5 mol % RuCl(COD)Cp*; B, 1.1 equiv of
N2CHSiMe3 (2 M in ether) in diethyl ether (1 mL), room temperature, 5
mol % RuCl(COD)Cp*. Isolated product yields obtained after complete
conversion and purification by silica gel chromatography.
a
b
Reaction conditions: 1.1 equiv of N2CHSiMe3 (2 M in ether) in diethyl
b
ether (1 mL), room temperature, 5 mol % RuCl(COD)Cp*. Isolated
product yields obtained after complete conversion and purification by silica
gel chromatography.
oisomer with cis alkenyl and R2 groups (1d f 3d). The
Z-configuration favors the formation of the diastereoisomer with
trans alkenyl and alkyl (R ) groups in the transformation of 1f
results are shown in Table 4. The transformation of 1,7-enynes
12a,b takes place and 14a,b are obtained. However, under
similar conditions, the 1,8-enyne 13 did not lead to the formation
of eight-membered cycle and was recovered (Table 4).
Enynes with a disubstituted triple bond or a disubstituted
propargylic carbon disfavor the previous catalytic reaction, to
the profit of two reactions leading to either derivative 17 or 18
2
into 3f. This was established by the X-ray structure of 3f.
The catalytic transformation of easily accessible enynes
arising from terminal propargylic alcohols and allyl bromides
was performed, and the results obtained with both types of
conditions, A and B, are presented in Table 2.
(eq 5, Table 5).
It first appears that the bicyclization of oxygenated enynes 6
into derivatives 7 is more difficult to perform than that of enynes
1
, in either conditions A or B. The best results are obtained for
R-disubstituted propargyl ethers (entries 3 and 4).
It is noteworthy that, from the enyne 6b, only a small amount
of the product 8b, corresponding to the double carbene addition
to the triple bond, was observed (entry 2) and that from 6d,
besides the bicyclo[3.1.0.]hexane 7d (20%), the bicyclo[4.1.0]-
heptane derivative 9d (35%) was obtained.
The reaction applied to 1,6-enynes 10, containing only a
carbon chain, led at room temperature to alkenylbicyclo[3.1.0]-
hexanes 11a (62%) and 11b (70%) with high Z-stereoselectivity
of the alkenyl chain (Table 3).
When the alkyne C(1) carbon atom is linked to a bulky
Attempts were then made to apply the previous bicyclization
reaction to 1,7- and 1,8-enynes in order to produce larger rings
and bicyclo[4.1.0]heptane and -[5.1.0]octane derivatives. The
substituent, such as a phenyl (6e) or a trimethylsilyl (15a) group,
the interaction with the triple bond is obviously disfavored and
classical cyclopropanation of the double bond takes place,
6040 J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007

Ru-Catalyzed Formation of Alkenylbicyclo[3.1.0]hexanes
A R T I C L E S
Table 5. Catalytic Transformation of Enynes with Substituted Triple Bonds or Disubstituted Propargylic Carbon
a
Reaction conditions: A, 2.4 equiv of N2CHSiMe3 (2 M in hexane) in dioxane (1 mL), 60 °C, 5 mol % RuCl(COD)Cp*; B, 1.1 equiv of N2CHSiMe3
(
2 M in ether) in diethyl ether (1 mL), room temperature, 5 mol % RuCl(COD)Cp*. b Isolated product yields obtained after complete conversion and
purification by silica gel chromatography.
leading to derivatives 17 (Table 5, entries 1 and 2). For other
alkyne substituents, R ) Me (15b) and CH2CHdCH2 (15c),
besides the expected derivative 16, which is obtained only in
low yield, formation of derivative 18 as the major product is
observed (Table 5, entries 3 and 4). Derivatives 18, at first,
appear to result from an inhibited cyclopropanation reaction
vinylbicyclo[3.1.0]hexanes (eq 6, Table 6). This reaction avoids
the preliminary diazomethane preparation.
(reductive elimination process), to the profit of a â-elimination
process. When the enyne possesses propargylic R,R-disubstitu-
ents and a terminal triple bond (15d,e, entries 5 and 6), the
derivatives 18 or the bicyclo[4.1.0]heptane 9e (entry 6),
analogous to 9d (Table 2, entry 4), are obtained as minor
products, in addition to the formation of the expected bicyclic
products 16.
The direct desilylation of 2-trimethylsilylvinylbicyclo[3.1.0]-
hexanes appeared not to take place under classical conditions.
The treatment of 3a with either KOH in methanol or KF in
tetrahydrofuran did not lead to desilylation.
Reaction of the enynes 1a-e and 10b with a slight excess of
N2CHSiMe3 in methanol at room temperature for only 30 min
led to the vinyl derivatives 19a-f in 60-80% yield (Table 6).
As the double bond of the enyne major isomer has E-
configuration, the major products contained the vinyl group and
the cyclopropane substituent in the cis arrangement (19d,e).
It is noteworthy that the catalytic enyne bicyclization can be
performed in water. Thus, the enyne 1a was reacted with N2-
CHSiMe3 (1.2 equiv, 2 M in ether) and RuCl(Cp*)COD in 2
mL of water for only 5 min at room temperature to reach 100%
conversion and avoid desilylation or decomposition. The deriva-
The in situ formation of diazomethane from N2CHSiMe3 in
methanol was performed and gave much more easily the
J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007 6041

A R T I C L E S
Monnier et al.
Table 7. Catalytic Transformation of Enynes with Diazoacetate
Table 6. Synthesis of Non-silylated Vinylbicyclo[3.1.0]hexanes
a
Reaction conditions: 1.1 equiv of N2CHSiMe3 (2 M in ether) in
methanol (1 mL), room temperature, 5 mol % RuCl(COD)Cp*, 30 min.
b
Isolated product yields obtained after complete conversion and purification
c
by silica gel chromatography. 15 mol % of RuCl(COD)Cp* (with 5 mol
%, the conversion never reached completion).
tive 3a was obtained in 78% yield (eq 7). This result shows
that the catalyst precursor and the intermediate catalytic species
are stable in water and that the reaction in water of diazoalkane
is possible on the condition that the related catalytic reactions
are fast.
a
Reaction conditions: 1.1 equiv of N2CHCO2Et in dioxane (1 mL), 5
mol % RuCl(COD)Cp*, at 100 °C. b Isolated product yields obtained after
complete conversion and purification by silica gel chromatography.
Table 8. Catalytic Transformation of Enynes with
Phenyldiazomethane
The catalytic transformation of enynes with other diazoal-
kanes (eq 8), such as N2CHCO2Et (Table 7) and N2CHPh (Table
8
), was performed and shows that the reaction proceeds as for
N2CHSiMe3. More drastic conditions are required with N2-
CHCO2Et, 100 °C in dioxane for 1-24 h, to obtain complete
conversion and good yield. No conversion takes place under
6
0 °C for N2CHCO2Et.
a
Reaction conditions: 1.1 equiv of N2CHPh, conditionned in toluene
(
2 mL), room temperature, 60 °C, or 100 °C, 5 mol % RuCl(COD)Cp*.
Isolated product yields obtained after complete conversion and purification
b
by silica gel chromatography.
established the cis arrangement of the alkenyl and phenyl groups.
With N2CHPh, the reaction takes place at lower temperature
than with N2CHCO2Et, from room temperature to 100 °C (Table
8). This transformation with 1a allows us to monitor the
variations in Z/E ratio for formation of compound 23 according
The E-configuration of the double bond is always observed
for the derivatives 20-22 formed from enynes 1a-h, 10b, and
d with N2CHCO2Et (Table 7). This was shown by the X-ray
structure of 20e obtained from the E-enyne 1e, which also
6
6042 J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007

Ru-Catalyzed Formation of Alkenylbicyclo[3.1.0]hexanes
A R T I C L E S
Figure 1. ORTEP drawing of the molecular structure of 3d. Thermal
ellipsoids are set at the 50% probability level.
Figure 2. ORTEP drawing of the molecular structure of 3f. Thermal
ellipsoids are set at the 50% probability level.
to temperature. By increasing the reaction temperature from
room temperature (Z/E ) 30/70) to 60 °C (Z/E ) 20/80), only
a slight increase in the formation of the E-isomer is observed.
Comparison of the reaction of 1a at room temperature with N2-
CHSiMe3 and N2CHPh shows that the nature of the diazoalkane
does influence the configuration of the alkenyl bond. From the
N2CHSiMe3 product, an hypervalence interaction between the
silicon and the (Ru)chlorine atoms can occur.
X-ray Diffraction Study of the Alkenylbicyclo[3.1.0]-
hexanes 3d, 3f, and 20e
To elucidate the nature of diastereoisomers arising from the
bicyclization of enynes, the relative positions of substituents
on the cyclopropane moiety were confirmed by X-ray structure
analysis of compounds 3d (isolated major diastereoisomer), 3f,
and 20e. Each compound was purified by chromatography on
silica gel, and crystals were obtained in a mixture of pentane
and diethyl ether. These structures are presented in Figures 1-3.
The ORTEP drawing of the major diastereoisomer of the
compound 3d (Figure 1) shows the Z-stereochemistry (C7-C8
bond) of the double bond with a SiMe3 group and the cis arrange-
ment of the alkenyl and methyl groups on C2 and C3 of the
cyclopropane moiety, respectively. This major diastereoisomer
was isolated from a mixture of compounds 3d obtained in an
Figure 3. ORTEP drawing of the molecular structure of 20e. Thermal
ellipsoids are set at the 50% probability level.
20
demonstrates the cis arrangement on the cyclopropane moiety
(C2-C3-C4) of the phenyl group (on C3) and the alkenyl group
(on C4) of the obtained product. This diastereoselectivity results
from the E-stereoselectivity of the starting enyne. It confirms
that, whatever the diazoalkane derivative, an E-configuration
of the enyne-substituted (R) alkene bond favors the formation
of the diastereoisomer with cis alkenyl and R groups.
Proposed Mechanism
8
5:15 ratio, arising from an E/Z-enyne 1d mixture (E/Z : 85/
Related Stoichiometric Reactions. This catalytic reaction
of enyne bicyclization has some resonance with stoichiometric
reactions of metal-carbene complexes containing an unsaturated
chain. The first related reaction involved the interaction of an
alkene chain containing a stabilized alkoxycarbene-tungsten
15) (Table 1). The X-ray-established stereochemistry shows that
the enyne with E-configuration leads to the diastereoisomer with
cis alkenyl and methyl (at C3 of the initial double bond) groups.
The structure of compound 3f (Figure 2) clearly shows the
three rings at the core of the molecule: a cyclopropane ring
21
complex with an alkyne to give a bicyclo[4.1.0]heptene deriva-
(C5-C6-C8), a heterocycle (N1-C1-C8-C6-C7), and a cy-
22
tive (eq 9).
clohexyl ring (C1-C2-C3-C4-C5-C8). It confirms the Z-
stereochemistry (C9-C10 bond) of the double bond with the
SiMe3 group and shows the trans relative positions between
the alkenyl group on the cyclopropane linked at the C6 carbon
atom and the substituent on the cyclopropane linked at C5. This
diastereoselectivity is imposed by the Z-stereochemistry of the
cyclohexenyl substitutent of the enyne 1f (Z-C5-C8 bond).
The structure of compound 20e (Figure 3) was determined
to show the structural variation with a N2CHCO2Et reaction
product. It shows the E-stereochemistry (C13-C14 bond) of the
double bond with the CO2Et group. The ORTEP drawing
(
20) Crystal structure analysis of 3d, 3f, and 20e is presented in the Supporting
Information. Crystallographic data (excluding structure factors) for 3d, 3f,
and 20e have also been deposited with the Cambridge Crystallographic
Data Center as CCDC 215613, 239959, and 634214. Copies of the data
can be obtained free of charge on application to CCDC, 12 Union Rd.,
Cambridge CB2 1EZ, UK (fax (+44) 1223-336-033; E-mail deposit@
ccdc.cam.ac.uk).
This reaction involved the coupling of the alkyne and MdC
bonds to give the alkenylcarbene intermediate, followed by
(21) Harvey, D. F.; Sigano, D. M. Chem. ReV. 1996, 96, 271.
(22) Parlier, A.; Rudler, H.; Platzer, N.; Fontanille, M.; Soum, A. J. Organomet.
Chem. 1985, 287, C7-C8.
J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007 6043

A R T I C L E S
Monnier et al.
internal [2+2] coupling of the metal-carbene with the CdC
bond and reductive elimination. This stoichiometric reaction has
been developed by Hoye et al.23 and was revealed to be useful
for natural product synthesis. Actually, Hoye was the first to
react an enyne with a manganese-carbene complex and
obtained the stoichiometric version of the present catalytic
reaction.24 This reaction was transferred to Cr, Mo, and W
metal-carbene derivatives and was shown to give, on reaction
with 1,6-enynes, alkenylbicyclo[3.1.0]hexanes.25 At the same
time, Mori et al. demonstrated that the reaction of (OC)5Crd
C(OMe)Me with 1,6-enynes led to bicyclization of the enyne
and/or metathesis reaction products, depending on the nature
of the C(1) double-bond substituent26 (eq 10), via the same
metallacyclobutane intermediate, for which the nature of the R
group favored either reductive elimination with an electron-
withdrawing substituent (R ) p-O2NC6H4-) or metathesis
reaction ([2+2] retrocycloaddition) with an electron-donating
group (R ) p-MeC6H4-).
Scheme 1. Proposed Mechanism for the Selective Transformation
of Enynes and Diazoalkanes into Alkenylbicyclo[3.1.0]hexanes
CHY ) (L)Cl2RudCHPh (L ) Cy3P, IMes), except for the last
step. In this latter case, the intermediate C exclusively leads to
the metathesis process and alkenylcycloalkene and ruthenium-
carbene formation (Scheme 1, step f). Thus, the present reaction
differs from enyne metathesis only by the ability of the RuClCp*
moiety to favor reductive elimination (step d).
Proposed Mechanism with Initial Interaction with the Ct
CH Bond. Our reaction performed with 1a containing a
deuterium atom at the alkyne bond CtCD shows that the
terminal alkyne carbon is involved in the CDdCHSiMe3 bond
formation (eq 11).
This may result from both the electronic influence and the
geometry of the RuClCp* moiety with respect to those of the
(L)Cl2Ru moiety, with no obvious answer. Thus, a computa-
tional study has been undertaken from intermediate B (see the
discussion on DFT calculations below).
The RuCl(dCHSiMe3)Cp* intermediate was proposed in the
1
9
double carbene addition to alkyne (eq 2). Thus, in the
bicyclization reaction, the intramolecular reaction (step c) should
be faster than step e, which was observed only with one enyne
6b, giving 8b in low yield (Table 2 and Scheme 1).
The catalytic transformation of enynes with diazoalkane in
the presence of the catalyst precursor RuClCp*(COD) can be
understood by the initial formation of RuCl(dCHY)Cp* as the
catalytic species, which first reacts with the terminal triple bond
to give the intermediate A, leading to the ruthenium vinylcarbene
B. The intramolecular interaction of the RudC bond with the
CdC bond of B gives back A or produces the metallacyclobu-
tane C, which is subject to reductive elimination to give the
bicyclic products 3 and 7 (Scheme 1).
The catalytic enyne metathesis has been shown by Mori3b to
easily proceed with Grubbs catalyst, and the proposed mecha-
nism involves the interaction of the RudC bond with the triple
bond via a mechanism similar to that in Scheme 1, with [Ru]d
Actually, enyne metathesis with the Grubbs catalyst has led
in a specific case to a parallel minor stoichiometric cyclopropana-
3
b
tion, generating a non-carbene ruthenium system. Alterna-
tively, Diver et al., using the Grubbs II catalyst with a dienyne,
leading to ring constraint, have shown the formation of a
tricyclic compound via a vinylcyclopropane intermediate.12
In some specific cases, enyne metathesis can take place by
an initial interaction of the (carbene)CdRu bond with an enyne
27
double bond. However, according to the product nature arising
from the RuCl(COD)Cp*/N2CHY system, for which the enyne
double bond is incorporated in the cyclopropane, this initial
(23) Hoye, T. R.; Vyvyan, J. R. J. Org. Chem. 1995, 60, 4184.
(24) Hoye, T. R.; Rehberg, G. M. Organometallics 1990, 9, 3014.
(25) Hoye, T. R.; Suriano, J. A. Organometallics 1992, 11, 2044.
(26) Mori, M.; Watanuki, S. J. Chem. Soc., Chem. Commun. 1992, 1082.
(27) Lloyd-Jones, G. C.; Margue, R. G.; De Vries, J. G. Angew. Chem., Int.
Ed. 2005, 44, 7442.
6044 J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007

Ru-Catalyzed Formation of Alkenylbicyclo[3.1.0]hexanes
A R T I C L E S
Scheme 2. Stereochemichal Aspects of Intermediate A
Scheme 3. Proposed Mechanism for the Selective Transformation
of Enynes and Diazoalkanes into Alkenyl Alkylidene
Cyclopentanes
CdC bond interaction does not take place, at least for enynes
containing a terminal alkyne bond (Scheme 1 and Table 1). It
takes place only with disubstituted triple bonds (Scheme 3,
below).
Another initial process could be considered. The electrophilic
12
10
activation of the enyne by ruthenium(II) or by platinum(II)
has been proposed to generate a bicyclo[3.1.0]carbene-metal
intermediate. This process does not take place with the RuClCp*
system, as the stoichiometric reaction of enyne 1a with RuCl-
(COD)Cp* rather leads to enyne oxidative addition and further
addition of N2CHSiMe3 does not lead to the bicyclic product.
Stereochemistry of the Alkenyl Chain. The stereochemistry
in the intermediate B (Scheme 1) depends on the nature of the
substituent of diazoalkane. When Y ) SiMe3, a Z-stereochem-
istry is obtained, while Y ) CO2Et produces an E-stereochem-
istry. Phenyldiazomethane leads to a mixture of Z and E double
bonds.
Simple models show that the formation of intermediate A
requires the anti-positioned Cp* and Y groups to decrease steric
interactions (Scheme 2). Thus, the stereochemistry of the double
bond results from the opening of the metallacyclobutene A. With
Y ) CO2Et, electronic repulsion between Cl and CO2Et groups
alkylidene group, arising from the CtCR group, takes place
(18b,c). Scheme 3 accounts for the catalytic cycle. Initial double-
bond coordination can lead to metallacyclobutane II. With a
bulky triple bond (R ) Ph, SiMe3), in the absence of its
coordination, reductive elimination takes place (step e), giving
the products 17. With a smaller substituent (R ) Me, CHCHd
CH2), the triple bond can be coordinated, and its insertion into
the metallacyclobutane Ru-C bond can lead to the intermediate
III. â-Elimination (step c), formation of intermediate IV, and
reductive elimination (step d) are expected to generate the
observed cyclic products 18 and [RuClCp*], the RuClCp*(d
CHY) precursor.
(A1), or at least the absence of attraction, favors the opening,
such that these groups are pushed away, lowering steric
hindrance and offering alkenyl E-configuration. For Y ) SiMe3,
a strong (hypervalence) interaction between SiMe3 and Cl groups
is expected and can be responsible for the opposite opening in
spite of steric interactions (A2).
However, in this latter case, the stereoselectivity depends also
on the double-bond substitution (R) of the A-allyl arm. The
enynes bearing an alkyl or aryl substituent on the C(1) of the
double bond (R * H) induced in all cases a total Z-stereose-
lectivity (see Table 1, entries 4-6), whereas with R ) H the
Z-isomer was the major one (see Table 1, entries 1-3). The
allyl double bond can coordinate to ruthenium in A only if it is
a terminal double bond (R ) H). The opening bringing the
SiMe3 group near the Cl group can then be disturbed by the
presence of the allyl arm and leads to a Z/E mixture with a Z
Theoretical Study of the Selective Transformation of
Enynes and Diazoalkanes into Alkenylbicyclo[3.1.0]-
hexanes
Since the RuClCp* moiety favors reductive elimination from
the metallacyclobutane C (step d in Scheme 1) rather than
metathesis (step f), DFT calculations were performed in order
to rationalize such a different behavior. The analysis proceeds
from the intermediate B, since an initial interaction of the Ru-
carbene unit with the enyne double bond, rather than with the
enyne alkyne bond, would not lead to the main compounds 3
>
E stereochemistry. If R * H, steric hindrance does not allow
the coordination of the double bond, and thus only the expected
Z-stereochemistry is obtained. Finally, the study with phenyl-
diazomethane shows an E/Z mixture for all reaction tempera-
tures, suggesting that the phenyl substituent has no real
interactions with the Cl group.
28
and 7. Both possibilities have already been analyzed by Straub
and Lloyd-Jones and do not represent our main goal here.
27
Alternative Mechanism with CtCR-Containing Enynes.
When the triple-bond substituent is bulky, such as Ph (6e) or
SiMe3 (15a), interactions with the triple bond are likely
disfavored, and in that case the [2+2] cycloaddition of the Rud
C bond to the CHdCH2 bond takes place, with the unique
formation of cyclopropanes 17 (Table 5). When this alkyne
substituent is smaller, R ) CH3 (15b) and CH2CHdCH2 (15c),
the prefered formation of five-membered cycles with an
For the sake of simplicity, the Cp* ligand was replaced by
the unsubstituted Cp precursor, while the alkyne and alkene
functions of the enyne have been considered as separate HCt
CH and H2CdCH2 units, always in cis positions in the starting
model RuCl(HCtCH)(H2CdCH2)(C5H5). A number species
were optimized by DFT calculations, including various transition
(28) Lippstreu, J. J.; Straub, B. F. J. Am. Chem. Soc. 2005, 127, 7444.
J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007 6045

A R T I C L E S
Monnier et al.
Figure 4. Stationary points on the potential energy surface relative to the possible evolution of the cis carbene/ethylene model B, which corresponds to the
analogous intermediate B in Scheme 1.
metal is far from being pseudo-octahedral. In this case, a small
splitting of the t2g level would correspond to a small highest
occupied molecular orbital-lowest unoccupied molecular orbital
(HOMO-LUMO) gap, while in C the gap is >1 eV. This is
most likely the consequence of a significant Jahn-Teller
distortion. In particular, two features must be underlined. First,
5
3
the Cp ring has no regular η coordination, but it is closer to η
allylic type), since two adjacent Ru-C distances are as long
Figure 5. Coplanarity of critical orbitals at the transition state TSBC.
(
as 2.41 and 2.51 Å. Interestingly, a Walsh diagram based on
states. Figure 4 provides a diagram of the energies and the
stereochemical features of the various stationary points. The
precise nature of each transition state has been validated by
intrinsic reaction coordinate (IRC) calculations.
extended H u¨ ckel molecular orbital (EHMO) calculations shows
3
that the rearrangement of the Cp ligand from the observed η
5
to the more regular η coordination causes a significant decrease
6
of the HOMO-LUMO gap, associated with a decrease of the
thermodynamical stability. The second distortional effect is
highlighted by the direction of the Ru-Cl bond, which is not
symmetrically displaced with respect to the MC1C2C3 ring.
The starting species B is a d pseudo-octahedral complex
which contains two cis-coordinated carbene and ethylene units
and has the formal 18-electron configuration. The relative
orientation of the carbene and ethylene units (the dihedral angle
RuC1C2/RuC3C4 is 50°) indicates that two filled “t2g” orbitals
ensure sufficient back-donation to both ethylene and carbene.
The reorientation of the latter ligands in two orthogonal planes,
already at the transition state TSBC, forces key orbitals to lie
coplanar (Figure 5) and promotes C-C coupling. The energy
4
Essentially, the geometry of C is similar to that of a d -L4MCp
piano-stool species, with one missing leg in this case.
Importantly, the metal unsaturation, implicit in C, appears
mitigated in the optimized model RuCl(HCtC-CH2CH2CH2-
CHdCH2)(C5H5) (C′), which contains the enyne unit. In fact,
the latter (see Figure 6) features an evident agostic interaction
-
1
barrier is not very high (only 9.8 kcal‚mol ), while the
-
1
metallacyclobutane derivative C lies only 4 kcal‚mol above
between the metal and one CH group of the chain which cannot
2
B.
exist in the simplest model C. The involved C-H bond
Surprisingly, the transformation B f C affects the structure
of the ancillary fragment CpClRu, while the now oxidized d
approximately occupies the position of the missing piano-stool
ligand.
4
6046 J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007

Ru-Catalyzed Formation of Alkenylbicyclo[3.1.0]hexanes
A R T I C L E S
Figure 6. Geometry of the model RuCl(HCtCsCH2CH2CH2sCHdCH2)-
(C5H5) (C′), derived from a complete enyne unit.
In any case, the metal has significant electrophilicity in C
and C′, which can be quenched by the donor capabilities of the
Figure 7. Comparison of key reaction steps in the present system and in
the Grubbs one. For the latter, the nomenclature used is that originally
reported in ref 28. The ∆E values are relative to the metallacyclobutane
intermediate in each case.
free dangling olefin group (C4 and C5 atoms) and the return of
5
the Cp ligand to the classic η coordination. The resulting
product E can be considered as a stable 18-electron epta-
coordinated species of the type L4MCp, where two adjacent L
ligands correspond to an in situ-formed allyl moiety. Model E
lies at zero energy in the diagram in Figure 4, being 17.7
-
1
kcal‚mol more stable than the precursor C. Moreover, there
is a very small barrier for the conversion of C into E (2.5
-
1
kcal‚mol ), as indicated by the optimization of the transition
state TSCE. Complex E is also the most immediate precursor
of the final vinyl-substituted cyclopropane product D. The
attainment of the latter implies a reductive elimination step and
the restoring of the d6 metal configuration, but it seems
Figure 8. Dative orbital interactions which stabilize the 14-electron
metallacyclobutane intermediate in the Grubbs-type mechanism.
energetically facile. In fact, the barrier (TSED) is small (5.8
the zero point on the common ∆E scale refers to the metalla-
cyclobutane intermediate (C and 13, respectively).
-
1
kcal‚mol ), and although D is less stable than E by 3.1
-1
kcal‚mol , its formation may be favored if the organic alkene-
cyclopropane derivative behaves as a good leaving molecule.
Concerning the mechanism leading to cyclopropane, the
calculations show that the C1-C3 bond is not formed in one
step from the two equivalent C atoms of the metallacyclobutane
unit (complex C). Rather, at the intermediate E, the atoms C1
and C3 have different electronic natures, being alkylic and
allylic, respectively. Their non-equivalence is also reflected by
the transition state TSED, where the elongation of the Ru-C1
bond (2.49 Å) proceeds faster that that of the Ru-C3 one (2.42
Å). The difference is not sufficiently large to exclude a concerted
electron transfer between the carbon atoms and the metal, but
still it suggests that separation of the carbon charges can
facilitate the reductive elimination process. In the final product
D, the electron count is 16, which is not unusual for classic
We first observe that, with respect to the metallacyclobutane
precursor, the model E is much more stabilized than the
-1
analogous species 22 (by about 18 kcal‚mol ). Also, the barrier
at the transition state 23 is much higher than that at TSCE (18.1
-
1
vs 2.6 kcal‚mol ). On the other hand, the energies involved in
the metathesis process are rather similar in the two cases,
although this route is followed only by the Grubbs system. In
fact, for the latter, the formation of cyclopropane is difficult
due to both the high barrier to the allylic coordinated species
and the scarce stabilization of the latter. The situation is reversed
in the present system.
Given the significantly different energy profiles, it is interest-
ing to explore their electronic causes. The latter are found in
the MO structures of the intermediate metallacyclobutane species
13 and C, which contain different ancillary fragments (i.e.,
T-shaped LCl2Ru and CpClRu, respectively). In the former case,
6
and stable L2MCp complexes (M ) d ).
2
-
Figure 4 also shows the alternative metathesis route, which
leads from B to F through C. The last barrier toward F (TSCF)
implies the cleavage of the olefinic C1-C2 linkage and the
the dialkyl chelate [RHC-CH2-CH2] completes a trigonal
bypiramidal structure, which is rather stable in spite of its
electron count of 14. This is because the symmetrical environ-
ment allows the two coordinated alkyl groups to donate electron
density into four different and empty metal orbitals. As shown
in Figure 8, the in-phase combination of carbon lone pairs is
2
formation of RudC1 and Ru-(η -C2dC3) bonds, but it is not
-
1
particularly high (6.6 kcal‚mol ). The most remarkable result
is that F is definitely less stable than the alternative product E
-1
2
2
(
by 20.2 kcal‚mol ). This was not the case with the Grubbs
dative toward both a σ hybrid and the x -y d orbital, while
the out-of-phase combination donates into one pπ orbital and
one dπ orbital. The orbital interactions are not equally efficient
in C, which also has 14 electrons (by assuming that Cp is only
a four-electron donor) but is much less “organized”. The great
difference in the strengths of the orbital interactions is high-
lighted by the Ru-C distances at the metallacyclobutane rings.
catalyst (LCl2(PMe3)Ru, L ) N-heterocyclic carbene), which
2
8
was previously analyzed by Lippstreu and Straub. These
authors calculated reaction steps analogous to those of Figure
4
, so we highlight in Figure 7 the most relevant differences
between the two systems. For convenience, the species of the
2
8
Grubbs system are named as in the original publication, and
J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007 6047

A R T I C L E S
Monnier et al.
In fact, the values of 2.14 Å (average), optimized for C, are
much longer than those in 13 (2.00 Å),28 where bonding is
definitely stronger.
promotes their coupling and the easy formation of the cyclo-
propane unit.
Experimental Section
Under these circumstances, it is also reasonable that, in the
Grubbs system, any distortion from the stable trigonal bipyramid-
All catalytic reactions were carried out under inert atmosphere in
Schlenk tubes. The complex RuCl(COD)Cp* was prepared according
28
al species “13” has a significant energy cost. For instance, the
transformation into a square pyramid, which characterizes the
transition state toward “22”,28 frees a coordination site at which
the nucleophilic attack of the free olefin arm may be directed
29
1
13
to the reported method. H and C NMR spectra were recorded on
Bruker AM 3000 WB and DPX 200 spectrometers in deuterated
n
chloroform solutions at 298 K. ∆CH refers to cyclopropane nuclei.
(
as occurs between C and E), but the barrier is large (18
IR spectra were recorded on a Bruker IFS28 instrument. Mass spectra
were obtained on a Varian MATT 311 high-resolution spectrometer at
the Centre Regional de Mesures de l’Ouest (CRMPO) of the University
of Rennes 1. Characterization data are presented in the Supporting
Information.
-1
kcal‚mol ). Also, the formation of a coordinated allyl group in
“
this case, there is no possibility of restoring the full donor capa-
bilities of the Cp ligand, and in the hexacoordinated product,
the d metal reaches at most the 16- and not the 18-electron
22” 28 does not produce the same stabilization found in E. In
4
Computational Details. All the calculations were performed using
the hybrid density functional theory with Becke’s three-parameter hybrid
exchange-correlation functional,30 containing the non-local gradient
2
8
configuration. A closer inspection at the geometry of “22”
shows that the coordination geometry is not even pseudo-
octahedral and that, trans to the alkylic carbon atom, there
remains a free coordination site. Most likely, this is protected
by the bulky substituent at one of the N atoms of the heterocyclic
carbene ligand.
31
correction of Lee, Yang, and Parr (B3LYP), using the Gaussian03
32
suite of programs. All the structures were fully optimized, and the
vibrational frequencies were calculated to confirm their nature as
stationary points or as transition states. The reaction pathways were
followed using the IRC method.33 For the ruthenium metal, the effective
core potential of Stuttgart/Dresden34 was used, and the basis set used
for the remaing atomic species was the 6-31G(d,p).35 The qualitative
In conclusion, the present theoretical analysis has quantita-
tively confirmed that the catalyst, based on the CpClRu
fragment, favors the formation of a cyclopropanation product
and inhibits the enyne metathesis. This is mainly due to the
large stabilization of a d heptacoordinated allyl/alkyl intermedi-
ate (E), which is the precursor for the reductive elimination
process and the formation of a cyclopropane unit. Conversely,
the analogous intermediate in the Grubbs process “22”
remains unsaturated at the metal center and does not attain an
equivalent amount of stabilization.
3
6
MO arguments have been developed with the EHMO method using
the CACAO package.37
4
Typical Procedure for Enynes Synthesis. Enynes 1g and 1h were
prepared according to the reported method.38 For the others, a typical
procedure was used. In a Schlenk tube under an inert atmosphere, a
solution of tosyl aminoethynyl (1 equiv) in distilled dimethylformamide
was brought to 0 °C, and 60 wt % of sodium hydride was added (1.2
equiv). The reaction mixture was stirred for 1 h at 0 °C, and the
substituted allyl bromide was added (1.2 equiv). After coming to room
temperature, the reaction mixture was stirred for 16 h and hydrolyzed
by addition of 1 N chloridric acid. The organic phase was washed two
times with brine, dried under magnesium sulfate, and concentrated under
reduced pressure to give an oil, which was purified by silica gel
chromatography (eluent, pentane-diethyl ether mixture) to give the
enyne as a solid.
2
8
General Conclusion
The RuCl(COD)Cp*-catalyzed transformation of CtCH-
containing 1,6-enynes with N2CHSiMe3 into alkenylbicyclo-
[
3.1.0]hexanes appears to be a general reaction for which a
Z-stereoselectivity of the alkenyl chain and a cis arrangement
of cyclopropane alkenyl and R groups are observed for an
E-configuration of the initial double bond. For CtCR-contain-
ing enynes, with bulky R groups simple cyclopropanation of
the enyne double bond takes place, and with less hindered R
groups mixed 1-alkenyl-2-alkylidene five-membered hetero-
cycles are selectively produced. By contrast, with N2CHCO2-
Et, the analogous alkenylbicyclo[3.1.0]hexanes are produced
under slightly more drastic conditions with an E-configuration
of the alkenyl group.
Typical Procedure for Method A. In a Schlenk tube under an inert
atmosphere, to a solution of the enyne in degassed dioxane (1.5 mL)
was added 2.4 equiv of the 2.0 M (trimethylsilyl)diazomethane solution
in hexane. Next, 5 mol % of the precatalyst RuCl(COD)Cp* was
introduced. The mixture was stirred at 60 °C. Reaction completion was
monitored using gas chromatography (GC) or thin-layer chromatog-
raphy (TLC) techniques. The products were obtained after purification
by silica gel chromatography with an ether/pentane eluting mix-
ture.
Typical Procedure for Method B. In a Schlenk tube under an inert
atmosphere, to a solution of the enyne in distilled diethyl ether (1.5
mL) was added 1.1 equiv of the 2.0 M (trimethylsilyl)diazomethane
DFT analysis of a simplified model system, RuCl(HCtCH)-
(CH2dCH2)(C5H5), in which the alkene and alkyne groups of
the enyne reactant are kept separated, has provided some
satisfactory answers to the question of the difference between
the catalytic enyne transformations performed either by the
present CpRuCl-based catalyst (favoring cyclopropanation) or
the Grubbs catalyst (favoring metathesis). In the present case,
a rearrangement of the η -C5H5 ligand toward the allylic η -
type coordination mode is observed, which confers extra
electrophilicity to the metal. From the latter ruthenacyclobutane
species C, a rather stable allyl/alkyl key intermediate (E) is
formed through a barrier, which is quantitatively smaller with
respect to that of the analogous Grubbs catalyst. Eventually,
the non-equivalence of the allylic C1,C3 carbon atoms in E
(
29) Fagan, P. J.; Mahoney, W. S.; Calabrese, J. C.; Williams, I. D. Organo-
metallics 1990, 9, 1843.
(30) Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
(
31) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785.
32) Frisch, M. J.; et al. Gaussian 03, Revision C.02: Gaussian, Inc.:
Wallingford, CT, 2004.
(
(
(
33) Gonzalez, C.; Schlegel, H. B. J. Phys. Chem. 1990, 94, 5523.
34) Dolg, M.; Stoll, H.; Preuss, H.; Pitzer, R. M. J. Phys. Chem. 1993, 97,
5
3
5852.
(
35) Hariharan, P. C.; Pople, J. A. Theor. Chim. Acta 1973, 28, 213.
(36) (a) Hoffmann, R.; Lipscomb, W. N. J. Chem. Phys. 1962, 36, 2872. (b)
Hoffmann, R.; Lipscomb, W. N. J. Chem. Phys. 1962, 37, 3489.
(
37) (a) Mealli, C.; Ienco, A.; Proserpio, D. M. Book of Abstracts of the XXXIII
International Conference on Coordination Chemistry, Florence, Italy, 1998;
p 510. (b) Mealli, C.; Proserpio, D. J. Chem. Educ. 1990, 67, 399.
38) Trost, B. M.; Romero, D. L.; Rise, F. J. Am. Chem. Soc. 1994, 116,
4268.
(
6048 J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007

Ru-Catalyzed Formation of Alkenylbicyclo[3.1.0]hexanes
A R T I C L E S
solution in diethyl ether. Next, 5 mol % of the precatalyst RuCl(COD)-
Cp* was introduced. The mixture was stirred at room temperature.
Reaction completion was monitored using GC or TLC techniques. The
products were obtained after purification by silica gel chromatography
with an ether/pentane eluting mixture.
(Sacconi medal to P.H.D.), which was the initiator of this
cooperative work.
Supporting Information Available: Complete ref 32, Car-
tesian coordinates of the optimized structures, characterization
data for 3a-j, 4, 5, 7a-d, 8b, 9d,e, 11a,b, 14a,b, 16b-e, 17a,e,
Acknowledgment. The authors are grateful to the CNRS and
the Minist e` re de la recherche for support, the latter for Ph.D.
grants to F.M. and C.V., the European Union through the Cost
Program D17 and network IDECAT, the Region Bretagne,
through a PRIR program (169AOC), the Institut Universitaire
de France for membership (P.H.D.), and the Sacconi Foundation
1
8b-e, 19a,c-f, 20a,c,e,g,h, 21-24, and crystal structure
analysis of 3d, 3f, and 20e (PDF); X-ray crystallographic files
for 3d, 3f, and 20e (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
JA0700146
J. AM. CHEM. SOC.
9
VOL. 129, NO. 18, 2007 6049