Cobalt(I)-mediated cycloisomerization of enynes: Mechanistic insights

Article abstract of DOI:10.1002/1521-3765(20010817)7:16<3517::AID-CHEM3517>3.0.CO;2-V

[CpCo(CO)₂] catalyzes the cycloisomerization of 1,n-enynes to afford selectively five- and six-membered ring systems in high yields. The factors governing the cyclization have been explored and we have discovered that the reaction associates tw

Full text of DOI:10.1002/1521-3765(20010817)7:16<3517::AID-CHEM3517>3.0.CO;2-V

FULL PAPER
Cobalt(i)-Mediated Cycloisomerization of Enynes: Mechanistic Insights
Olivier Buisine, Corinne Aubert,* and Max Malacria*[a]
Dedicated to Professor Jean Normant on the occasion of his 65th birthday
Abstract: [CpCo(CO)2] catalyzes the cycloisomerization of 1,n-enynes to afford
selectively five- and six-membered ring systems in high yields. The factors governing
the cyclization have been explored and we have discovered that the reaction
associates two different, but complementary, reactivities of the cobalt(i) complexes.
By a judicious choice of the substitution of the enyne, it was also possible to isolate a
cyclobutene that arises from a cobaltcyclopentene
Keywords: allyl ligands ´ cobalt ´
cobaltacyclopentene ´ cyclization ´
enynes
Introduction
a
M
Transition-metal-induced cycloisomerizations of 1,n-enynes
have emerged as extremely attractive and unique tools for the
synthesis of various type of cyclic compounds in a very easy
one-pot process. Indeed, the rate accelerations provided by
catalysis expand the scope of reactions such as the Alder ene
reactions that normally require harsh conditions.[1] On the
other hand, these cyclizations which generate 1,3- or 1,4-
dienes provide clean chemical processes without any wasteful
by-products. Cyclization of 1,n-enynes has been achieved with
a wide range of transition metal complexes either in a catalytic
or stoichiometric manner[2±6] and represent a versatile ap-
proach to a variety of products by a simple manipulation of
Ia
b
c
M
Ib
X
M
Ic
Scheme 1. Possible pathways for the cycloisomerization of 1,n-enynes.
the catalyst. Excellent reviews which have compiled differents
aspects of the advances in these cyclization reactions have
been published.[7]
The presence of a functional group in the allylic position
allows the formation of a p-allyl complex Ib (path b), which
could further react with the triple bond. Finally, hydridome-
tallation of the alkyne leads to the corresponding vinylmetal
Ic (path c), which is reactive enough to allow the carbome-
tallation of the olefin.
Cobalt catalyst species are particularly useful mediators for
effecting [2‡2‡2] cycloadditions,[8] Pauson ± Khand reac-
tions,[9] homo Diels ± Alder, and [4‡2‡2] cyclizations.[10] More
recently, it has been shown that the cobalt catalysts are also
efficient in ene type reactions of w-acetylenic-b-ketoesters[11]
and reductive carbocyclization of enedienes.[12] To our knowl-
edge, few examples of the cobalt-mediated cycloisomeriza-
tions of 1,n-enynes have been reported. Indeed, monocyclic
1,3-dienes were obtained by thermolysis of the hexacarbo-
nyldicobalt complex of 1,6- and 1,7-enynes[13] and it was also
found that dicobalt octacarbonyl could catalyze a new cyclo-
isomerization reaction of 3-sila-1,7-enynes to eight-membered
cyclic dienylsilanes.[14] In connection with our studies on
cobalt-mediated [2‡2‡2] cycloaddition of allenediynes,[15] we
Considering the mechanistic rationales of the transition-
metal-catalyzed cycloisomerization of enynes, different path-
ways can be considered depending on the reaction conditions
and on the choice of the precatalyst. Generally, the complex-
ation of the metal to an alkene or alkyne allows the activation
either of one or both moities. Depending on which unsatu-
rated bond will react first, three main mechanisms can be
proposed (Scheme 1).
The simultaneous complexation of both unsaturation bonds
(path a) leads preferentially to the metallacycle Ia. Almost all
the transition metal complexes could react to generate such
intermediates; however, their reactivity can be quite different.
[a] Prof. Dr. M. Malacria, Dr. C. Aubert, Dr. O. Buisine
Â
Universite Pierre et Marie Curie (Paris 6)
Á
Â
Laboratoire de Chmie Organique de Synthese associe au CNRS
Tour 44-54, Case 229, 4 place Jussieu
75252 Paris cedex 05 (France)
Fax : (‡33)1-44-27-73-60
E-mail: malacria@ccr.jussieu.fr, aubert@ccr.jussieu.fr
Chem. Eur. J. 2001, 7, No. 16
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0947-6539/01/0716-3517 $ 17.50+.50/0
3517

M. Malacria, C. Aubert, and O. Buisine
FULL PAPER
have disclosed a new cobalt-mediated formal Alder ene
reaction of allenynes.[16] While we focused on this reaction, we
have found that (h5-cyclopentadienyl)cobalt dicarbonyl
[CpCo(CO)2] is able to induce the cyclization of 1,n-enynes
as well.[17] A mechanism involving selective cobalt allylic C H
activation was suggested.
Here, we present the full details of the scope and the
limitations of such a new cobalt(i)-mediated cycloisomeriza-
tion and particularly the investigations into the mechanism.
E
R1
c
a
E
E
E
R1
1 : R1 = SiMe3
E
E
( )n
R2
1 = SiMe3, R2 = H
1 = SiMe3, R2 = Me
E
E
3 : n = 1
4 : n = 2
5 : n = 3
6 : n = 1
7 : n = 1, R1 = Ph
8 : n = 1, R1 = tBu
b
d
R
R2
R
2 : R2 = Me
R2 = Me
E
E
E
E
Ph
Results and Discussion
d
In order to gain a better understanding of the factors (steric,
electronic, etc.) that govern cyclization, we checked the
influence of several important features: the length of the
carbon chain between the two unsaturated bonds, the nature
of the substituent (SiMe3, Ph, tBu) at the triple bond, the
degree of the substitution at the allylic position, and the
substitution of the double bond. Thus, series of 1,n-enynes
which fulfil these criteria were prepared as described in the
following section.
9
ꢀ
Scheme 2. Preparation of 1,n-enynes 3 ± 9. a) NaH (0.6 equiv), BrCH2C
CSiMe3, THF, RT, 70%. b) NaH (0.66 equiv), THF, 0 8C, BrCH2CH
CHCH3, 76%. c) NaH (1.1 equiv), THF, 0 8C, BrCH2CH CH2, 3: 86% or
Br(CH2)2CH CH2, 4: 98% or Br(CH2)3CH CH2, 5: 90% or BrCH2CH
CHCH3, 6: 93%. d) NaH (1.1 equiv), THF, MsOCH2C CPh or
MsOCH2C CtBu, 7: 66%; 8: 70%; 9: 81%.
ˆ
ˆ
ˆ
ˆ
ˆ
ꢀ
ꢀ
Ph
a
c
RO
BnO
O
Preparation of the 1,n-enynes: Almost all 1,n-enynes were
obtained by malonic synthesis. Double alkylation of the
sodium derivative of the dimethylmalonate with silylproparg-
yl bromide to give compound 1 and then with allyl bromide,
4-bromobut-1-ene, 5-bromopent-1-ene, and trans-crotyl bro-
mide furnished the enynes 3 ± 6 in 86%, 98%, 90%, and 93%
yields, respectively. Enynes 7 ± 9 were obtained by the same
procedure of double alkylations: first, with the trans-crotyl
bromide (to give 2) or methallylchloride[18] and then, with the
mesylates derived from 3-phenylprop-2-yn-1-ol and 4,4-di-
methylpent-2-yn-1-ol, generated from the alkylation of the
lithium acetylide derived from the phenyl- and tert-butylace-
tylene with para-formaldehyde in 83% and 96% yields,
respectively (Scheme 2).
R = H 10
R = Bn 11
12
b
E
E
R
E
E
E
E
R
d
e
f
O
O
O
R = SiMe3
R = H
R = SiMe3 18
16
17
O
g
13
R = H
R = Ph
ꢀ
19
20
Scheme 3. Preparation of the enynes 12, 18, and 20. a) BrMgCH2C CH
(1 equiv), Et2O, 0 8C, quant. b) NaH (1.2 equiv), THF, cat. nBu4NI, BnBr
(1.1 equiv), quant. c) 10% [Pd(PPh3)4], 15% CuI, PhI, BuNH2, RT,
benzene, 50%. d) 1. NaI, TMSCl, CH3CN, RT, HO(CH2)2OH, 81%; 2.
The preparation of the enynes 12, and 18 ± 20, which bear
one or two substituents at the allylic position, is outlined on
Scheme 3.
ꢀ
NaH, (MeO2C)2CH2, THF, 51%. e) 1. NaH, BrCH2C CSiMe3, THF, RT,
ꢀ
14: 75% or BrCH2C CH, 15: 80%; 2. HCO2H (15 equiv), petroleum ether,
overnight, 16: quant.; 17: 60%. f) Ph3P(CH3)Br, nBuLi, THF, 78 8C to
RT, 18: 75%. g) 5% Pd(OAc)2, 5% CuI, 10% NEt3, PhI (1 equiv), DMF,
20: 37% from 17.
Condensation of the 3,3-dimethylpent-4-enal[19] with prop-
argylic Grignard led to the alcohol 10 in quantitative yield.
After protection[20] of 10, the Pd Cu coupling reaction[21]
between 11 and iodobenzene led to the formation of the
enyne 12. Alkylation of the dimethylmalonate with 3-iodo-2-
methylpropanal ethylene acetal[22] provided compound 13 in
80% yield. A second alkylation with silylpropargyl or
propargyl bromide followed by a formic acid hydrolysis[23]
gave the aldehydes 16 and 17. Wittig olefination furnished the
enynes 18 and 19. The coupling[20] of the latter with
iodobenzene gave enyne of 20.
Cyclization of the enynes and discussion: When the enynes
3 ± 6 were exposed to a stoichiometric amount of [CpCo-
(CO)2] in boiling xylenes under irradiation, the starting
materials were consumed after 3 ± 5 h. This led to the
formation of six compounds: the 1,2-dimethylenecyclopen-
tanes 21 and 24, their complexed forms 22 and 25, and the (h4-
cyclopentadiene) cobalt complexes 23 and 26.[24] In contrast to
our preliminary communication,[17] we were able to isolate the
cycloadducts 27 and 28 from 3 in 62% yield, but only if the
crude product is directly submitted to an oxidative treat-
ment[25] with copper(ii) chloride (Scheme 4).
Â
Â
Abstract in French: La cycloisomerisation dꢀenynes 1,n
Â
Á
Â
catalysee par CpCo(CO)2 est tres efficace pour la preparation
Â
Â
Á
Á
regioselective de systemes cycliques a cinq et six chaînons. Les
 Â
Â
Â
facteurs gouvernant la cyclisation ont ete apprehendes et nous
Â
Â
avons mis en evidence que cette reaction mettait en jeu des
Â
Â
Â
Â
reactivites differentes, mais complementaires des complexes du
Â
cobalt(i). Par un choix judicieux de la substitution de lꢀenyne, il
 Â
Control experiments showed that enynes 3 ± 6 were totally
recovered in the absence of [CpCo(CO)2] in boiling xylenes
with or without irradiation, indicating the crucial role of the
Á
Â
a ete possible dꢀisoler un cyclobutene resultant dꢀun cobaltacy-
Á
Â
clopentene intermediaire.
3518
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Chem. Eur. J. 2001, 7, No. 16

Cycloisomerization of 1,n-Enynes
3517±3525
voked to rationalize the migration of a dienic system.[26] Thus,
we anticipated that the cyclization furnished first the exo-
dienic complex and that the formation of the (h4-cyclopenta-
diene) cobalt complexes 23 and 26 could be the result of an
assisted migration of the double bonds of 22 and 25. The
cyclization of the enynes 7 and 8 contributes to the under-
standing of this proposal (Scheme 6).
SiMe3
SiMe3
SiMe3
CoCp +
E
E
R1
E
E
E
E
E
a
CoCp
+
E
( )n
R2
n-1( )
n-1( )
n-1( )
R2
R2
R2
R1 = SiMe3 ; R2 = H, Me
inseparable
0%
n = 1-3
0%
3
4
5
6
20% (21+22)
16% (23)
40% (26)
40% (23)
44% (24+25)
26% (21+22)
SiMe3
SiMe3
E
SiMe3
E
E
E
b
+
E
E
3
21% (27)
52% (28)
Scheme 4. Cyclization of the enynes 3 ± 6. a) [CpCo(CO)2], xylenes, hn, D.
b) 1. [CpCo(CO)2], xylenes, hn, D; 2. CuCl2 ´ 2 H2O, MeCN.
Scheme 6. Cyclization of the enynes 6 ± 8.
cobalt mediator. We noticed that decreasing the power and
time of the irradiation, and the use of lower boiling solvents
had negative effects. Thus, longer reaction times were
required and, therefore, some decomposition was observed.
In addition, when the triple bond is monosubstituted (R1 ˆ
H), the cyclization led to a complex mixture of cyclohexa-
dienes and their metallated forms arising from an intermo-
lecular [2‡2‡2] cyclization. Under the conditions of the
reaction, the intermolecular complexation of two terminal
alkynes occured in competition with the intramolecular
complexation of the enyne (Scheme 5). However, by increas-
Indeed, the cyclization of 7, which bears a phenyl group on
the triple bond, led exclusively to the corresponding 1,2-
dimethylenecyclopentane 30 in 77% yield, whereas 8, which
has a tert-butyl substituent on the alkyne gave the endo-dienic
system in 66% yield. These results showed that the migration
of the double bonds is under steric control. Indeed, in all cases,
the complexed cyclopentadiene exo is the compound resulting
from the cyclization. However, when the triple bond is
substituted by a bulky group such as tBu, a strong allylic 1,3-
strain is developed and, consequently, the formation of a
cobalt h3-allyl hydride complex A partially releases this strain
(Scheme 7). The reductive elimination of the cobalt leads to
the isomer in which one of the double bonds is in the endo-
cyclic position. The resulting s-trans diene B was never
isolated and the migration of the second double bond via a p-
allyl cobalt intermediate furnished the complexed endo-cyclic
diene CpCo-31. This isomerization is probably assisted by the
metal and is a very fast process. Thus, the driving force of the
reaction is the synergy of the release of the allylic strain and
the complexation of the endo-cyclic s-cis diene with the
cobalt.
E
E
E
E
R
CoCp
R
E
R = H
E
CoCp
R
H
R
[2+2+2]
Scheme 5. Intra- versus intermolecular complexation of the enyne.
Ene
ing the steric hindrance of the alkyne this competitive process
can be completely suppressed. Thus, in harsh conditions
(boiling xylenes) the use of disubstituted triple bonds allows
this intramolecular complexation of the enyne and the unique
course towards the ene reaction.
The assigned structure of 26 has been unambiguously
confirmed by a single-crystal X-ray analysis.[17] Thus, whatever
the length of the tether between the two unsaturated bonds,
the cyclization leads only to five-membered ring compounds.
The formation of these rings involves the isomerization of the
terminal double bond of the
In the case of the cyclization of 7, as we already observ-
ed,[15b] the strong allylic strain of the styrene moiety evidently
forces an out-of-plane rotation of the phenyl group. In
addition, in the case of a metal-complexed dienic system,
the influence of the conjugation of an aryl substituent is
without efficiency. Therefore, the strain is minimized in the
resulting system and allows the unique formation of the
complexed exo-cyclic system, which after the oxidative treat-
ment leads to the exo-diene 30 in 77% yield. Finally, the
cycloadduct with a SiMe3 group has an intermediate behavior.
starting enyne; this probably
results from the oxidative for-
H
Cp
Co
CoCp
H
H
H
H
mation of a cobalt h3-allyl
hydride through a C H acti-
vation process. As far as we
are aware, such intermediates
with cobalt(i) are quite rare;
however, they have been in-
E
E
E
E
E
E
E
E
CoCp
CpCo
A
B
CpCo-η4- 31
Scheme 7. Isomerization of exocyclic double bonds via a p-allyl hydride complex.
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3519

M. Malacria, C. Aubert, and O. Buisine
FULL PAPER
As the carbon ± silicon bond is longer than a carbon ± carbon
bond,[27] the silylated substituent is less hindered than the tBu
group, the allylic strain is weaker, and the cyclization afforded
a mixture of both endo- and exo-cyclic isomers.
72 h in heating under reflux in xylenes. To our knowledge, the
formation of such a cyclobutene from metallacyclopentene
has never been reported with cobalt. They have been already
involved, but not isolated, as intermediates in palladium-
mediated cyclizations.[28]
In order to more fully explore the competition of the
different pathways, we checked the behavior of the enynes 18
and 20. Similarly to 12, two cyclohexadienes 37/38 and 39/40
were isolated in 89% and 77% yields respectively
(Scheme 9). The proportion of the cyclohexadiene resulting
from the opening of the cyclobutene is still around 20% in
each case.
Having speculated the existence of a p-allyl cobalt complex
in the process of the cyclization, the question concerning the
cyclizing moietyÐp-allyl cobalt versus cobaltacyclopen-
teneÐwas still open. Both pathways can be involved and be
competitive. The cyclization of 3 is the only one which
implicates a cobaltacyclopentene; actually, if one considers
the initial formation of the p-allyl hydride intermediate with a
syn configuration, a 6-endo-trig cyclization process is forbid-
den because it would lead to a E-cyclohexene derivative. The
competitive 4-exo-trig process is totally disfavored in view of
the formation of a highly constrained exo-methylenecyclobu-
tane derivative.
To further probe the nature of the cobalt intermediates in
this reaction, we carried out the cyclization with enyne 12
which has a disubstituted allylic position; this means that the
formation of an h3-allyl hydride is impossible. The reaction
furnished, after oxidative decomplexation, two cyclohexa-
dienes 32 and 33 (Scheme 8). The presence of the phenyl
group avoids the migration of the double bond as in the case
of 30.
R
R
E
E
E
R
E
E
R
a
+
+
E
E
E
18 R = SiMe3
20 R = Ph
-
37
39 57%
38
67%
22%
traces
40 20%
Scheme 9. Cyclization of the enynes 18 and 20. a) 1. [CpCo(CO)2], xylenes,
hn, D; 2. CuCl2 ´ 2 H2O, MeCN.
All these compounds are derived from the cobaltacyclo-
pentene 42 which is the reactive intermediate of the cycliza-
tion (Scheme 10). No trace of the diene 43 was observed
meaning that even the p-allyl hydride complex had been
formed, it did not cyclize. Indeed, the metallo-ene reaction of
an intermediate p-allyl cobalt complex would have led to a
1,4-diene bearing a tetrasubstituted diallylic position. There-
fore, the latter could not undergo a b-elimination as the
observation of 43 would have been a proof of a mechanism via
a p-allyl cobalt complex. This result is in contrast to that
obtained for the cyclization of 4. The 1,7-enyne 4 is a poor
ligand and its isomerization to the 1,6-enyne is faster than its
cyclization. Furthermore, when the allylic position is mono-
substituted, the behavior is inverted.
We anticipated that the formation of the p-allyl complex
was prevented for steric reasons. The enyne 18 or 20 adopts a
stable chairlike conformation, in which the methyl group is in
a pseudo-equatorial position. The formation of the p-allyl
complex would shift the methyl group to the axial position,
which would in turn lead to 1,3-diaxial interactions with one of
the ester groups. Therefore, the oxidative addition leads
preferentially to the cobaltacyclopentene 42, for which the
Scheme 8. Cyclization of the enynes 12 and 9.
The cyclohexadienes 32 and 33 arose from the intermediate
cobaltacyclopentene 34. b-Elimination followed by a reduc-
tive elimination allowed the formation of 32. For geometrical
reasons, b-elimination slows down and, then, the reductive
elimination is competitive affording the cyclobutene 35, which
in turn leads to 33 through an electrocyclic ring-opening
reaction; nevertheless, this remains a minor process.
To probe the viability of such a pathway in presence of a
cobalt(i) complex, we tried to cyclize the enyne 9; this yielded
only the cyclobutene 36, as a very stable cycloadduct, in 60%
yield. In this case, b-elimination is not possible and the
reductive elimination becomes exclusive. Attempts to execute
the reaction without cobalt mediator met with failure. No
consumption of the starting material was observed even after
R
E
E
E
R
R
E
E
H
CoHCp
E
E
E
18 or 20
43
R
H
CoCp
42
Scheme 10. Favored formation of a metallacycle versus a p-allyl complex
for 18 or 20.
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Chem. Eur. J. 2001, 7, No. 16

Cycloisomerization of 1,n-Enynes
3517±3525
(CH2), 0.05 (3C; TMS); IR (neat): nÄ ˆ 2950, 2170, 1750, 1735, 1430, 1250,
formation is more favored since the methyl stays in equatorial
position.
1
840 cm
.
Methyl 2-allyl-2-(3-trimethylsilylprop-2-ynyl)propanedioate (3): Yield:
86%; 1H NMR (400 MHz, CDCl3): d ˆ 5.60 (tdd, J ˆ 18.7, 10.1, 9.1 Hz,
Thus, in all cases, the cyclization proceeds via a cobaltacy-
clopentene, and we were unable to determine if an h3-allyl
hydride cobalt complex can undergo a metallo-ene reaction.
However, for steric reasons its formation is not favored in
intramolecular cyclization reactions.
ˆ
ˆ
1H; HC CH2), 5.15 (d, J ˆ 18.7 Hz, 1H; CH2 cis), 5.10 (d, J ˆ 10.1 Hz,
ˆ
ꢀ
1H; CH2 trans), 3.71 (s, 6H; OCH3), 2.79 (s, 2H; CH2C C), 2.77 (d, J ˆ
9.1 Hz, 2H; CH2CH CH2), 0.11 (s, 9H; TMS); 13C NMR (100 MHz,
ˆ
ˆ
ˆ
CDCl3): d ˆ 170.2 (2C; CO2Me), 131.9 (CH CH2), 119.8 ( CH2), 101.3
ꢀ
ꢀ
(C C), 88.3 (C C), 57.2 (C(CO2Me)2), 52.7 (2C; OMe), 36.6
ˆ
ꢀ
(CH2CH CH2), 24.1 (CH2C C), 0.0 (3C; TMS); IR (neat): nÄ ˆ 2170,
1740, 1640, 1430, 840 cm 1; elemental analysis calcd (%) for C14H22O4Si: C
59.54, H 7.85; found C 59.65, H 7.88.
Conclusion
Methyl
2-(but-3-enyl)-2-(3-trimethylsilylprop-2-ynyl)propanedioate
(4):[18b] Yield: 98%; 1H NMR (200 MHz, CDCl3): d ˆ 5.83 ± 5.73 (m, 1H;
In summary, we have shown that cobalt(i)-mediated cyclo-
isomerization of 1,n-enynes is very efficient for the selective
preparation of five- and six-membered ring systems in high
yields. We have disclosed that this cyclization associates two
different, but complementary, reactivities of the cobalt(i)
complexes. One is the formation of the p-allyl cobalt hydrides
which allow the isomerization of one double bond or more.
Thus, several 1,n-enynes are in equilibrium with the 1,6-
isomer which appears as the best ligand for the cobalt and
which can react irreversively with the metal to give a
cobaltacyclopentene. All the compounds that arise from this
intermediate have been isolated. As the resulting dienes are
very good ligands for cobalt(i) complexes, the reaction is
stoichiometric with respect to the mediator.
ˆ
ˆ
HC CH2), 5.12 ± 4.96 (m, 2H; CH2), 3.72 (s, 6H; CO2CH3), 2.85 (s, 2H;
ꢀ
ˆ
CH2C C), 2.16 ± 2.12 (m, 2H; CH2CH CH2), 1.97 ± 1.95 (m, 2H; CH2CH2),
0.12 (s, 9H; TMS); 13C NMR (50 MHz, CDCl3): d ˆ 170.6 (2C; CO2Me),
ˆ
ˆ
ꢀ
ꢀ
137.4 (HC CH2), 115.3 (C CH2), 110.2 (C CSi), 88.3 (C CSi), 56.9
ꢀ
(C(CO2Me)2), 52.7 (2C; 2 OCH3), 31.4 (CH2), 28.4 (CH2), 24.3 (CH2C C),
1
0.01 (3C; TMS); IR (neat): nÄ ˆ 2180, 1760, 1640 cm
.
Methyl 2-(Pent-4-enyl)-2-(3-trimethylsilylprop-2-ynyl)propanedioate (5):
Yield: 90%; 1H NMR (200 MHz, CDCl3): d ˆ 5.83 ± 5.59 (m, 1H;
ˆ
ˆ
HC CH2), 5.04 ± 4.91 (m, 2H; HC CH2), 3.70 (s, 6H; OMe), 2.80 (s, 2H;
ꢀ
ˆ
CH2C C), 2.10 ± 2.04 (m, 4H; CH2CH2), 1.71 ± 1.20 (m, 2H; CH2CH CH2),
0.12 (s, 9H; TMS); 13C NMR (50 MHz, CDCl3): d ˆ 170.8 (2C; CO2Me),
ˆ
ˆ
ꢀ
ꢀ
138.0 (HC CH2), 115.1 (HC CH2), 110.3 (C CSi), 89.0 (C CSi), 57.1
(C(CO2Me)2), 52.7 (2C; OMe), 33.7 (CH2), 31.6 (CH2), 24.2
ˆ
ꢀ
(CH2CH CH2), 23.2 (CH2C C), 0.02 (3C; TMS); IR (neat): nÄ ˆ 2180,
1760, 1640 cm 1; elemental analysis calcd (%) for C16H26O4Si: C 61.90, H
‡
8.44; found C 61.73, H 8.35; MS (70 eV, EI): m/z (%): 311 (55) [M‡H] , 295
‡
(60), 251 (97) [M C2H3O2] , 176 (80), 147 (80), 119 (100).
Besides the reactivity of these two intermediate cobalt
species, this study showed the crucial role of the complexation
of the starting material. The course of the reaction is driven by
the substitution of the triple bond and the degree of
substitution at the allylic position. Finally, this new catalysis
of the ene reaction is a further addition to the arsenal of
transition metal cycloisomerization reactions.
Methyl 2-[(E)-but-2-enyl]-2-(3-trimethylsilylprop-2-ynyl)-propanedioate
(6): Yield: 93%; 1H NMR (400 MHz, CDCl3): d ˆ 5.57 ± 5.39 (m, 1H;
ˆ
ˆ
HC CHMe), 5.19 ± 5.03 (m, 1H; HC CHMe), 3.61 (s, 6H; OMe), 2.66 (s,
ꢀ
ˆ
2H; CH2C C), 2.61 (d, J ˆ 4.0 Hz, 2H; CH2CH CHMe), 1.54 (d, J ˆ
6.5 Hz, 3H, CHMe), 0.04 (s, 9H; TMS); 13C NMR (100 MHz, CDCl3):
ˆ
ˆ
ˆ
d ˆ 170.4 (2C; CO2Me), 130.5 (CH2CH CHMe), 124.1 (CH2CH CHMe),
ꢀ
ꢀ
101.5 (C CSi), 88.1 (C CSi), 57.3 (C(CO2Me)2), 52.6 (2C; OMe), 35.4
ˆ
ꢀ
(CH2CH CH), 23.9 (CH2C C), 18.1 (CH3), 0.0 (3C; TMS); IR (CH2Cl2):
nÄ ˆ 3040, 2170, 1730, 1430, 1240, 960, 840 cm 1; elemental analysis calcd
(%) for C15H24O4Si: C 60.78, H 8.16; found: C 60.84, H 8.17; MS (70 eV, EI):
‡
‡
m/z (%): 296 (5) [M] , 237 (40) [M C2H3O2] , 161 (25), 133 (100), 105
Experimental Section
(70), 89 (35), 73 (45), 50 (50).
1H NMR and 13C NMR spectra were taken on 200 MHz Bruker AC200,
400 MHz Bruker ARX400 spectrometers. Chemical shifts are reported in
ppm referenced to the residual proton resonances of the solvants. Infrared
(IR) spectra were recorded by using a Perkin ± Elmer 1420 spectrometer.
Mass spectra (MS) were obtained on GC-MS Hewlett-Packard HP5971
apparatus. Thin-layer chromatography (TLC) was performed on Merck
silica gel 60F254. Silica gel Merck Geduran SI (40 ± 63 mm) was used for
flash column chromatography by using the Still method.[29]
Methyl 2-(3-phenylprop-2-ynyl)-2-[(E)-but-2-enyl]propanedioate (7):
Yield: 66%; 1H NMR (400 MHz, CDCl3): d ˆ 7.40 ± 7.37 (m, 2H; Ph),
ˆ
7.31 ± 7.29 (m, 3H; Ph), 5.65 (dq, J ˆ 15.3, 6.4 Hz, 1H; CHMe), 5.31 (dtq,
ˆ
J ˆ 15.3, 7.6, 1.5 Hz, 1H; CH2CH CHMe), 3.77 (s, 6H; OMe), 3.02 (s, 2H;
ꢀ
ˆ
CH2C C), 2.81 (d, J ˆ 7.6 Hz, 2H; CH2CH CHMe), 1.69 (dd, J ˆ 6.4,
1.5 Hz, 3H; CH3); 13C NMR (100 MHz, CDCl3): d ˆ 170.6 (2C; CO2Me),
ˆ
131.7 (2C; Ph), 130.7 (Ph), 128.3 (2C; Ph), 128.0 (HC CH), 124.1
ˆ
ꢀ
ꢀ
(HC CH), 123.3 (Ph), 84.5 (C CPh), 83.6 (C CPh), 57.6 (C(CO2Me)2),
ˆ
ꢀ
52.8 (2C; OMe), 35.6 (CH2CH CH), 23.6 (CH2C C), 18.2 (CH3); IR
(neat): nÄ ˆ 2240, 1730, 1595, 1570, 1480, 755, 690 cm 1; elemental analysis
calcd (%) for C18H20O4: C 71.98, H 6.71; found C 71.65, H 6.37; MS (70 eV,
General procedure for the preparation of the enynes 1 ± 8: a)A solution of
dimethylmalonate (15.6 g, 118 mmol) in THF (150 mL) was added to a
suspension of sodium hydride (60% in oil, 3.14 g, 78 mmol) in THF
(50 mL) at 08C. After being stirred at room temperature for 1 h,
silylpropargyl bromide (15 g, 78 mmol) or trans-crotyl bromide (10.53 g,
78 mmol) was added. After the solution was stirred for 1 h or overnight, the
reaction mixture was quenched by a saturated solution of NH4Cl and
extracted with diethyl ether (300 mL). The organic layer was washed with
brine, dried over MgSO4, and concentrated. Purification by distillation or
by flash chromatography (petroleum ether/ditehyl ether 80:20) led to 1 or 2
respectively.
‡
‡
EI): m/z (%): 301 (5) [M‡H] , 241 (35) [M C2H3O2] , 225 (20), 213 (25),
181 (100), 165 (25), 145 (35), 115 (50), 77 (10).
Methyl 2-(4,4-dimethylpent-2-ynyl)-2-[(E)-but-2-enyl]propanedioate (8):
1
ˆ
Yield: 70%; H NMR (400 MHz, CDCl3): d ˆ 5.5 ± 5.6 (m, 1H; CHMe),
ˆ
5.2 ± 5.3 (m, 1H; CH2CH CHMe), 3.70 (s, 6H; OMe), 2.70 (d, J ˆ 2.0 Hz,
ꢀ
ˆ
2H; CH2C C), 2.69 (s, 2H; CH2CH CHMe), 1.65 (d, J ˆ 5.1 Hz, 3H; Me),
1.16 (s, 9H; tBu); 13C NMR (100 MHz, CDCl3): d ˆ 170.7 (2C), 130.3
ˆ
ˆ
ꢀ
ꢀ
(CH2CH CHMe), 124.4 (CH2CH CHMe), 92.3 (C CtBu), 73.1 (C CtBu),
57.7 (C(CO2Me)2), 52.6 (2C; OMe), 35.4 (CH2), 31.2 (3C; CMe3), 27.4
b) The second alkylation followed the procedure given above for 1 and 2
but with the following quantities NaH (1.1 equiv); 1 or 2 (1 equiv); bromide
or mesylate (1 equiv).
ˆ
(CMe3), 22.7 (CH2), 18.4 ( CHMe); IR (neat): nÄ ˆ 2220, 1730, 1430, 1350,
1200, 970, 910 cm 1; elemental analysis calcd (%) for C16H24O4: C 68.54, H
‡
8.63; found C 68.65, H 8.36; MS (70 eV, EI): m/z (%): 281 (12) [M‡H] , 220
Methyl 2-(3-trimethylsilylprop-2-ynyl)propanedioate (1): Yield: 13.3 g,
70%; 1H NMR (400 MHz, CDCl3): d ˆ 3.72 (s, 6H; OCH3), 3.57 (t, J ˆ
(60), 205 (90), 161 (80), 145 (100), 133 (40), 119 (50), 105 (60), 91 (40).
ꢀ
7.8 Hz, 1H; HC(CO2Me)), 2.77 (d, J ˆ 7.8 Hz, 2H; CH2C CTMS), 0.09 (s,
Methyl 2-(2-methallyl)-2-(3-phenylprop-2-ynyl)propanedioate (9): Yield:
81%; 1H NMR (400 MHz, CDCl3): d ˆ 7.40 ± 7.28 (m, 5H; Ph), 4.96 (d, J ˆ
9H; Si(CH3)3); 13C NMR (100 MHz, CDCl3): d ˆ 168.4 (2C; CO2Me), 102.0
ˆ
ꢀ
ˆ ˆ
1.5 Hz, 1H; CH2), 4.91 (d, J ˆ 1.5 Hz, 1H; CH2), 3.78 (s, 6H; OMe), 3.08
(C CTMS), 87.2 (C CTMS), 52.7 (2C; OMe), 51.2 (CHCO2Me), 19.2
Chem. Eur. J. 2001, 7, No. 16
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0716-3521 $ 17.50+.50/0
3521

M. Malacria, C. Aubert, and O. Buisine
FULL PAPER
(s, 2H; CH2C C), 2.93 (s, 2H; CH2CMe ), 1.71 (s, 3H; Me); 13C NMR
(100 MHz, CDCl3): d ˆ 170.8 (2C; CO2Me), 140.0 (Ph), 131.7 (2C; Ph),
prepared 2-(2-iodo-1-methylethyl)[1,3]dioxolane[22] (1.94 g, 8 mmol), and
furnished 13 (1.27 g, 51%). 1H NMR (400 MHz, CDCl3): d ˆ 4.7 (d, J ˆ
4.1 Hz, 1H; OCHO), 4.0 ± 3.9 (m, 2H; CH2O), 3.9 ± 3.8 (m, 2H; CH2O),
3.74 (s, 6H; OMe), 3.64 (q, J ˆ 6.6 Hz, 1H; (MeO2C)2CH), 2.2 ± 2.1 (m, 1H;
CHMe), 1.86 ± 1.7 (m, 2H;CH2), 0.97 (d, J ˆ 6.6 Hz, 3H, Me); 13C NMR
(100 MHz, CDCl3): d ˆ 170.0 (CO2Me), 169.8 (CO2Me), 107.0 (OCO), 65.0
ꢀ
ˆ
ˆ
ˆ
ꢀ
128.3 (2C; Ph), 128.1 (Ph), 116.5 ( CH2), 110.7 (CMe CH2), 84.7 (C CPh),
ꢀ
83.9 (C CPh), 56.9 (C(CO2Me)2), 52.9 (2C; OMe), 39.9 (CH2), 23.7 (CH2),
23.3 (Me); IR (neat): nÄ ˆ 2230, 1730, 1640, 1570, 900, 750 cm 1; elemental
analysis calcd (%) for C18H20O4: C 71.98, H 6.71; found C 71.85, H 6.74; MS
‡
(70 eV, EI): m/z (%): 300 (2) [M] , 240 (17), 209 (15), 181 (100), 165 (25),
115 (35), 91 (17), 77 (5).
(CH2O), 64.9 (CH2O), 52.4 (2C; OMe), 49.6 (CH(CO2Me)2), 34.7 (CH2),
1
30.5, 14.3 (Me); IR (CDCl3): nÄ ˆ 1730, 1430, 1160, 1110 cm
Preparation of aldehydes 16 and 17:
.
Preparation of the enyne 12:
a) Alkylation of 13: Dialkylated compounds 14 and 15 were prepared by
using the procedure described above for compounds 3 ± 6.
6,6-Dimethyloct-1-yn-7-en-4-ol (10): 3,3-Dimethylpent-4-enal (2.24 g,
20 mmol) was added dropwise to a cooled solution (08C) of propargyl-
magnesium bromide (25 mmol) in diethyl ether (10 mL). After stirring for
45 min, the reaction mixture was hydrolyzed with a saturated solution of
NH4Cl and extracted with diethyl ether (20 mL). The organic layer was
washed with brine, dried (MgSO4), and concentrated. The crude residue
was purified by flash chromatography (petroleum ether/AcOEt 8:2) to
afford the alcohol 10 (3.21 g, quantitaive). 1H NMR (400 MHz, CDCl3):
Methyl 2-(2-[1,3]dioxolan-2-ylpropyl)-2-(3-trimethylsilylprop-2-ynyl)pro-
panedioate (14): Yield: 1.32 g, 75%; 1H NMR (400 MHz, CDCl3): d ˆ
4.55 (d, J ˆ 3.5 Hz, 1H; OCHO), 3.90 ± 3.75 (m, 2H; CH2O), 3.75 ± 3.65
ꢀ
(m, 2H; CH2O), 3.59 (s, 6H; OMe), 2.82 ± 2.68 (AB, 2H; CH2C C), 2.25
(dd, J ˆ 14.7, 3.0 Hz, 1H; CH2CHMe), 1.82 (dd, J ˆ 14.7, 7.1 Hz, 1H;
CH2CHMe), 1.65 (m, 1H; CHMe), 0.82 (d, J ˆ 7.1 Hz, 3H, Me), 0.0 (s, 9H;
TMS); 13C NMR (100 MHz, CDCl3): d ˆ 171.1 (CO2Me), 170.8 (CO2Me),
ˆ
d ˆ 5.85 (dd, J ˆ 17.4, 10.5 Hz, 1H; HC CH2), 4.96 (d, J ˆ 17.5 Hz, 1H;
ꢀ
ꢀ
ˆ
ˆ
107.3 (OCO), 101.5 (C CSi), 88.3 (C CSi), 65.2 (CH2O), 65.1 (CH2O), 56.7
HC CH2 trans), 4.93 (d, J ˆ 10.5 Hz, 1H; HC CH2 cis), 3.80 (quint, J ˆ
ꢀ
ꢀ
(C(CO2Me)2), 52.7 (2C; OMe), 33.2 (CH2), 32.5 (CHMe), 24.5 (CH2C C),
5.6 Hz, 1H; CH(OH)), 2.28 (dd, J ˆ 5.6, 2.6 Hz, 2H; CH2C ), 2.00 (t, J ˆ
1
ꢀ
15.5 (Me), 0.0 (3C; TMS); IR (CDCl3): nÄ ˆ 2170, 1730, 1260, 840 cm
.
2.6 Hz, 1H; CH), 1.53 (d, J ˆ 5.6 Hz, 2H; CH(OH)CH2), 1.03 (s, 6H; Me);
13
ˆ
ˆ
C NMR (100 MHz, CDCl3): d ˆ 148.5 (CH CH2), 111.2 ( CH2), 81.2
Methyl 2-(2-[1,3]dioxolan-2-ylpropyl)-2-(prop-2-ynyl)propanedioate (15):
Yield: 2.54 g, 80%; 1H NMR (400 MHz, CDCl3): d ˆ 4.63 (m, 1H; OCHO),
3.91 ± 3.89 (m, 2H; CH2O), 3.88 ± 3.79 (m, 2H; CH2O), 3.68 (s, 6H; OMe),
ꢀ
ꢀ
ꢀ
(C CH), 70.6 (C CH), 67.7 (CH(OH)), 48.7 (CH2C C), 36.1 (CMe2), 28.5
(Me), 27.9 (Me), 26.6 (CH2CMe2); IR (neat): nÄ ˆ 3400, 3300, 3070, 2110,
1
1630, 1610, 1190, 900 cm
.
ꢀ
2.79 (d, J ˆ 2.6 Hz, 2H; CH2C C), 2.30 (dt, J ˆ 14.7, 3.2 Hz, 1H;
ꢀ
CH2CHMe), 1.98 (t, J ˆ 2.6 Hz, 1H; C CH), 1.88 (ddd, J ˆ 14.7, 7.3,
5-Benzyloxy-3,3-dimethyloct-7-yn-1-ene (11): A solution of 10 (1.46 g,
10 mmol) in THF (10 mL) followed by benzyl bromide (1.31 mL, 11 mmol)
was added dropwise at room temperature to a suspension of NaH (60% in
oil, 0.48 g, 12 mmol) and ammonium tetrabutyl iodide (0.37 g, 1 mmol) in
THF (10 mL). After stirring for 10 h, the reaction mixture was hydrolyzed
with saturated solution of NH4Cl and extracted with diethyl ether (30 mL).
The organic layer was washed with brine until pH 7 was reached, dried
(MgSO4), and concentrated. Purification by flash chromatography (petro-
leum ether/diethyl ether 9:1) gave the ether 11 (2.46 g, quantitative).
1H NMR (400 MHz, CDCl3): d ˆ 7.55 ± 7.32 (m, 5H; Ph), 5.91 (dd, J ˆ 17.1,
3.2 Hz, 1H; CH2CHMe), 1.76 ± 1.70 (m, 1H; CHMe), 0.89 (d, J ˆ 7.3 Hz,
3H; Me); 13C NMR (100 MHz, CDCl3): d ˆ 171.0 (CO2Me), 170.7
ꢀ
ꢀ
(CO2Me), 107.2 (OCO), 79.0 (C CH), 71.6 (C CH), 65.2 (CH2O), 65.1
(CH2O), 56.4 (C(CO2Me)2), 52.7 (OMe), 52.5 (OMe), 33.2 (CH2), 32.5
ꢀ
(CHMe), 23.2 (CH2C C), 15.4 (Me); IR (CDCl3): nÄ ˆ 3280, 2120, 1730,
1
1200, 1110 cm
.
b) Hydrolysis of 14 and 15: A solution of 14 (0.85 g, 2.3 mmol) or 15 (3.44 g,
12 mmol) and formic acid (2.5 or 6 mL, 92 or 600 mmol, 40 equiv) in
petroleum ether (10 or 60 mL) was stirred at room temperature for 2 h or
overnight. The reaction mixture was diluted with diethyl ether and
neutralized by the addition of anhydrous K2CO3. The organic layer was
washed with brine, dried over MgSO4, and concentrated. Purification by
flash chromatography (petroleum ether/AcOEt 90:10) afforded 16
(0.765 g, quantitative) or 17 (1.7 g, 60%).
ˆ
ˆ
10.7 Hz, 1H; HC CH2), 5.05 (d, J ˆ 17.1 Hz, 1H; HC CH2 trans) 4.94 (d,
ˆ
J ˆ 10.7 Hz, 1H; HC CH2 cis), 4.6 ± 4.4 (AB, 2H; CH2Ph), 3.60 (quint, J ˆ
ꢀ
3.3 Hz, 1H; CH(OBn)), 2.51 ± 2.43 (m, 2H; CH2C ), 2.06 (t, J ˆ 2.5 Hz,
ꢀ
1H; CH), 1.8 ± 1.7 (m, 2H; CH(OBn)CH2), 1.12 (s, 3H; Me), 1.10 (s, 3H;
Me); 13C NMR (100 MHz, CDCl3): d ˆ 148.8 (CH CH2), 129.2 (Ph), 128.8
ˆ
ˆ
ꢀ
(2C; Ph), 128.3 (2C; Ph), 128.0 (Ph), 110.7 ( CH2), 81.8 (C CH), 75.8
Methyl 2-(2-methyl-3-oxo-propanyl)-2-(3-trimethylsilylprop-2-ynyl)propa-
ꢀ
ꢀ
(CH(OBn)), 71.5 (PhCH2O), 70.4 (C CH), 47.5 (CH2C C), 36.6 (CMe2),
nedioate (16): 1H NMR (400 MHz, CDCl3): d ˆ 9.46 (d, J ˆ 1.8 Hz, 1H;
28.3 (Me), 27.3 (Me), 25.1 (CH2CMe2); IR (neat): nÄ ˆ 3300, 2100, 1940,
ꢀ
CHO), 3.66 (s, 6H; OMe), 2.93 (s, 2H; CH2C C), 2.80 ± 2.40 (m, 2H;
1
1730, 1630, 1200, 910, 730 cm
.
CH2CHMe ‡ CHMe), 1.95 (dd, J ˆ 14.0, 3.2 Hz, 1H; CH2CHMe), 1.06 (d,
J ˆ 7.5 Hz, 3H; Me), 0.07 (s, 9H; TMS); 13C NMR (100 MHz, CDCl3): d ˆ
5-Benzyloxy-3,3-dimethyl-7-phenyloct-7-yn-1-ene (12): At room temper-
ature, under argon, copper(i) iodide (0.016 g, 0.08 mmol) and tetrakis(tri-
phenylphosphine)palladium(0) (0.063 g, 0.05 mmol) were added in one go
to a solution of 11 (0.133 g, 0.55 mmol) in benzene (3 mL) in the presence
of n-butylamine (0.27 mL, 2.7 mmol) and iodobenzene (0.23 g, 1.1 mmol).
After stirring overnight, the reaction mixture was diluted with diethyl ether
(10 mL) and hydrolyzed with saturated solution of NH4Cl (8 mL). The
organic layer was washed with a saturated solution of CuSO4 (10 mL) and
brine (2 Â 10 mL), dried (MgSO4), and concentrated. Purification of the
residue by flash chromatography (petroleum ether/CH2Cl2 70:30) afforded
12 (0.87 g, 50%). 1H NMR (400 MHz, CDCl3): d ˆ 7.6 ± 7.25 (m, 10H; Ph),
ꢀ
ꢀ
203.2 (CHO), 170.2 (2C; CO2Me), 101.5 (C CSi), 89.5 (C CSi), 52.9 (2C;
ꢀ
OMe), 42.4 (C(CO2Me)2), 42.1 (CHMe) 33.1 (CH2), 25.2 (CH2C C), 15.5
(Me), 0.0 (3C; TMS); IR (CDCl3): nÄ ˆ 2830, 2225, 1730, 1430, 1250,
1
840 cm
.
Methyl 2-(2-methyl-3-oxopropanyl)-2-(prop-2-ynyl)propanedioate (17):
1H NMR (400 MHz, CDCl3): d ˆ 9.49 (d, J ˆ 1.5 Hz, 1H; CHO), 3.70 (s,
3H; OMe), 3.69 (s, 3H; OMe), 2.79 ± 2.85 (ABX, J ˆ 1.5 Hz, 2H;
ꢀ
CH2C C), 2.55 ± 2.65 (ABX, 2H; CH2CHMe), 2.45 ± 2.55 (m, 1H; CHMe),
1.95 ± 2.05 (m, 1H; C CH), 1.10 (d, J ˆ 7.12 Hz, 3H; Me); 13C NMR
ꢀ
(100 MHz, CDCl3): d ˆ 202.8 (CHO), 170.1 (CO2Me), 170.0 (CO2Me), 78.1
ˆ
6.00 (dd, J ˆ 17.4, 10.7 Hz, 1H; HC CH2), 5.05 (d, J ˆ 17.1 Hz, 1H;
ꢀ
ꢀ
(C CH), 71.9 (C CH), 55.6 (C(CO2Me)2), 52.6 (2C, OMe), 42.1 (CHMe),
ˆ
ˆ
HC CH2 trans) 4.94 (d, J ˆ 10.7 Hz, 1H; HC CH2 cis), 4.86 ± 4.51 (AB,
ꢀ
32.6 (CH2), 20.7 (CH2C C), 15.1 (Me); IR (neat): nÄ ˆ 3280, 2250, 1730,
2H; CH2Ph), 3.75 (tdd, J ˆ 7.3, 5.1, 4.7 Hz, 1H; CH(OBn)), 2.84 (dd, J ˆ
1
1430, 1280, 1200, 910, 730 cm
.
ꢀ
ꢀ
16.7, 5.1 Hz, 1H; CH2C ), 2.66 (dd, J ˆ 16.7, 7.3 Hz, 1H; CH2C ), 1.88 (d,
J ˆ 5.1 Hz, 2H; CH(OBn)CH2), 1.21 (s, 3H; Me), 1.99 (s, 3H; Me);
13C NMR (100 MHz, CDCl3): d ˆ 148.6, 138.6, 131.7, 128.5, 128.4 (2C), 128.2
(2C), 128.1 (2C), 127.7 (2C), 124.0 (2C), 110.5, 87.4, 82.3, 76.2, 71.4, 36.5,
28.1, 27.1, 26.0; IR (neat): nÄ ˆ 2220, 1940, 1740, 1630, 1590, 1090, 900,
750 cm 1; elemental analysis calcd (%) for C23H26O: C 86.75, H 8.23; found
Methyl
2-(2-methylbut-3-enyl)-2-(3-trimethylsilylprop-2-ynyl)propane-
dioate (18): A solution of n-BuLi (2.1m, 1.2 mL, 2.5 mmol) in hexanes
was added dropwise to a cooled ( 788C) solution of methylphosphonium
bromide (0.893 g, 2.5 mmol) in THF (10 mL) and the mixture was allowed
to warm to room temperature. After being cooled again to 788C, a
solution of aldehyde 16 (0.72 g, 2.3 mmol) in THF (20 mL) was added. The
reaction mixture was stirred for 30 min at 788C and at room temperature
overnight. The reaction mixture was partitioned between CH2Cl2 and
saturated solution of NH4Cl. The organic layer was washed with brine,
dried over MgSO4, and concentrated. The crude residue was filtered on
Celite, washed with diethyl ether, and then purified by flash chromatog-
raphy (petroleum ether/diethyl ether 70:30) to afford 18 (0.534 g, 75%).
‡
C 85.40, H 8.06; MS (70 eV, EI): m/z (%): 318 (2) [M] , 235 (5), 206 (10),
159 (25), 115 (30), 91 (100), 65 (10).
Preparation of the enynes 18 and 20:
Methyl 2-(2-[1,3]dioxolan-2-ylpropyl)propanedioate (13): The preparation
followed the procedure described above for 1 with dimethylmalonate (2 g,
15 mmol), sodium hydride (60% in oil, 0.4 g, 10 mmol), and freshly
3522
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0716-3522 $ 17.50+.50/0
Chem. Eur. J. 2001, 7, No. 16

Cycloisomerization of 1,n-Enynes
3517±3525
1
ˆ
H NMR (200 MHz, CDCl3): d ˆ 4.84 (dd, J ˆ 16.5, 1.2 Hz, 1H; CH2 cis),
Compound 25: Yield: 22%; 1H NMR (400 MHz, C6D6): d ˆ 4.55 (s, 5H;
ˆ
ˆ
4.76 (dd, J ˆ 9.9, 1.2 Hz, 1H; CH2 trans), 4.48 (ddd, J ˆ 16.5, 9.9, 1.9 Hz,
Cp), 3.55 (s, 3H; OMe), 3.20 (s, 3H; OMe), 2.90 ± 2.42 (m, 6H; CHSi,
ˆ
ˆ
1H; HC CH2), 3.62 (s, 3H; OMe), 3.56 (s, 3H; OMe), 3.00 ± 2.62 (AB, 2H;
CH, CH2, CH2), 1.43 (AB, 2H; CH2), 0.98 (t, J ˆ 7.2 Hz, 3H; Me), 0.19 (s,
ꢀ
CH2C C), 2.11 ± 1.90 (m, 3H; CH2CH), 0.92 (d, J ˆ 6.2 Hz, 3H; Me), 0.04
9H; TMS).
(s, 9H; TMS); 13C NMR (50 MHz, CDCl3): d ˆ 170.8 (CO2Me), 170.5
Compound 26: Yield: 40%; 1H NMR (400 MHz, C6D6): d ˆ 4.55 (s, 5H;
ˆ
ˆ
ꢀ
ꢀ
(CO2Me), 143.4 (CH CH2), 113.5 ( CH2), 101.6 (C CSi), 88.3 (C CSi),
ˆ
ˆ
Cp), 3.57 (s, 3H; OMe), 3.13 (s, 3H; OMe), 3.01 (AB, 2H; HC CC CH),
56.4 (C(CO2Me)2), 52.7 (OMe), 52.4 (OMe), 38.0 (CH2), 34.4 (CHMe), 24.2
ˆ
2.64 ± 2.28 (m, 2H; CCH2CH2), 2.20 (d, J ˆ 14.1 Hz, 1H; CH2Si), 1.52 ±
ꢀ
(CH2C C), 22.6 (Me), 0.0 (3C; TMS); IR (CDCl3): nÄ ˆ 2230, 1730, 1640,
ˆ
1.35 (m, 2H; CCH2CH2), 1.28 (d, J ˆ 14.1 Hz, 1H; CH2Si), 0.95 (t, J ˆ
1235, 840 cm 1; elemental analysis calcd (%) for C16H26O4Si: C 61.90, H
7.3 Hz, 3H; Me), 0.12 (s, 9H; TMS); 13C NMR (50 MHz, C6D6): d ˆ 168.7
‡
8.44; found C 62.15, H 8.39; MS (70 eV, EI): m/z (%): 311 (2) [M‡H] , 251
ˆ
ˆ
(CO2Me), 166.8 (CO2Me), 95.5 (HC C), 94.3 (HC C), 80.7 (5C; Cp), 67.7
‡
(20)[M C2H3O2] , 227 (40), 147 (100), 119 (60), 89 (42), 73 (150), 60 (30).
ˆ
ˆ
(C(CO2Me)2), 51.4 (OMe), 50.9 (OMe), 40.5 (HC ), 38.3 (HC ), 22.9
Methyl
2-(2-methylbut-3-enyl)-2-(3-phenylprop-2-ynyl)propanedioate
(CH2), 19.3 (CH2), 14.4 (Me), 1.6 (3C; TMS).
(20): NEt3 (5 mL, 38 mmol), copper(i) iodide (38 mg, 0.2 mmol), and
iodobenzene were successively added to a solution of the alkyne 19
(0.915 g, 3.8 mmol) [prepared following the procedure described for 18 and
engaged directly in the next step] in DMF (15 mL). Then, Pd(OAc)2
(42 mg, 0.2 mmol) and PPh3 (0.105 g, 0.4 mmol) were simultenously added.
The resulting red solution was stirred for 5 h at room temperature. The
mixture was diluted with diethyl ether, washed with saturated solution of
NH4Cl and brine, dried, and concentrated. Purification by flash chroma-
tography (petroleum ether/diethyl ether 90:10) furnished 20 (0.445 g,
37%). 1H NMR (200 MHz, CDCl3): d ˆ 7.2 ± 7.4 (m, 5H; Ph), 5.58 (m, 1H;
Methyl 3-ethylidene-4-trimethylsilylmethylenecyclopentan-1,1-dicarbox-
ylate (27): The spectral data were in agreement with those described in
the literature.[2e]
Methyl 3-methyl-4-trimethylsilylmethylcyclopenta-2,4-dien-1,1-dicarbox-
ylate (28): Yield: 52%. 1H NMR (400 MHz, CDCl3): d ˆ 6.07 (s, 1H;
ˆ
CH), 5.86 (s, 1H), 3.72 (s, 6H; OMe), 1.90 (s, 3H; Me), 1.76 (s, 2H;
CH2Si), 0.04 (s, 9H; TMS); 13C NMR (50 MHz, CDCl3): d ˆ 168.8 (2C;
ˆ
ˆ
ˆ
ˆ
CO2Me), 148.4 (HC C), 146.9 (HC C), 127.4 ( CH), 124.0 ( CH), 52.7
(2C; OMe), 70.1 (C(CO2Me)2), 17.7 (CH2Si), 14.1 (Me), 1.7 (3C; TMS);
IR (CDCl3): nÄ ˆ 1720, 1620, 1560, 1430, 840 cm
1
.
ˆ
ˆ
HC CH2), 4.94 (d, J ˆ 17.1 Hz, 1H; CH2 cis), 4.85 (dd, J ˆ 10.8, 2.8 Hz,
ˆ
1H; CH2 trans), 3.72 (s, 3H; OMe), 3.67 (s, 3H; OMe), 2.9 ± 3.2 (AB, 2H;
Methyl
3-ethyl-4-trimethylsilylmethylcyclopenta-2,4-dien-1,1-dicarbox-
ꢀ
CH2C C), 2.1 ± 2.4 (m, 1H; CHMe), 2.20 (s, 2H; CH2CH), 1.02 (d, J ˆ
ylate (29): Yield: 40%; 1H NMR (400 MHz, CDCl3): d ˆ 6.01 (d, J ˆ
6.2 Hz, 3H; Me); 13C NMR (50 MHz, CDCl3): d ˆ 170.9 (CO2Me), 170.7
ˆ
ˆ
2.0 Hz, 1H; HC CCH2Me), 5.85 (s, 1H; HC ), 3.69 (s, 6H; OMe), 2.17
(dq, J ˆ 7.6 Hz, 2.0 Hz, 2H; CH2Me), 1.72 (s, 2H; CH2Si), 1.15 (t, J ˆ 7.6 Hz,
3H; Me), 0.00 (s, 9H; TMS); 13C NMR (100 MHz, CDCl3): d ˆ 170.6 (2C;
ˆ
(CO2Me), 143.4 (CH CH2), 131.7 (Ph), 128.2 (2C; Ph), 128.0 (2C; Ph),
ˆ
ꢀ
ꢀ
123.3 (Ph), 113.6 ( CH2), 84.5 (C CPh), 83.6 (C CPh), 56.6 (C(CO2Me)2),
ꢀ
52.8 (OMe), 52.2 (OMe), 38.2 (CH2), 34.5 (CHMe), 23.8 (CH2C C), 22.7
ˆ
ˆ
ˆ
ˆ
CO2Me), 154.6 (HC C), 149.8 (HC C), 126.9 ( CH), 125.7 ( CH), 71.8
(C(CO2Me)2), 54.3 (2C; OMe), 22.9 (CH2Me), 19.1 (CH2Si), 13.4 (Me), 0.0
(3C; TMS); IR (neat): nÄ ˆ 1725, 1245, 1430, 850 cm 1; elemental analysis
calcd (%) for C15H24O4Si: C 60.77, H 8.16; found C 60.71, H 7.95.
(Me); IR (neat): nÄ ˆ 2220, 1740, 1640, 1690, 1480, 1430, 1280, 1200, 910,
740 cm 1; elemental analysis calcd (%) for C19H22O4: C 72.59, H 7.05; found
C 72.88, H 6.74.
General procedure for the cyclization of the enynes: [CpCo(CO)2] (125 mL,
1 mmol) was added to a solution of the enyne (1 mmol) heated under reflux
in xylenes (20 mL), which were first degassed by three freeze-pump-thaw
cycles, and was irradiated (light from a projector lamp; ELW 300 W, 80%
of its power). The reaction was monitored by TLC, and after completion
the solvent was removed by vacuum transfer. The residue was purified by
flash chromatography to afford the cycloadducts. In the majority cases, the
exocycloadducts were too unstable to run a 13C NMR spectrum.
Methyl 4-ethylidene-3-phenylmethylidenecyclopentan-1,1-dicarboxylate
(30): Yield: 231 mg, 77%; 1H NMR (400 MHz, CDCl3): d ˆ 7.5 ± 7.2 (m,
ˆ
5H; Ph), 6.67 (d, J ˆ 2.0 Hz, 1H; CHPh), 5.97 (dq, J ˆ 7.1, 2.0 Hz, 1H;
ˆ
CHMe), 3.26 (s, 2H; CH2), 3.63 (s, 6H; OMe), 2.95 (s, 2H; CH2), 1.71 (d,
J ˆ 7.1 Hz, 3H; Me); 13C NMR (100 MHz, CDCl3): d ˆ 172.3 (2C; CO2Me),
139.2 (1C), 138.6 (1C), 138.0 (1C), 129.1 (2C; Ph), 128.9 (2C; Ph), 126.8
ˆ
ˆ
(Ph), 119.3 ( CH), 116.3 ( CH), 58.6 (C(CO2Me)2), 53.3 (2C; OMe), 40.1
(CH2), 37.3 (CH2), 15.4 (Me); IR (neat): nÄ ˆ 1740, 1590, 1490, 1060, 790,
730 cm 1; elemental analysis calcd (%) for C18H20O4: C 71.98, H 6.71; found
C 71.74, H 6.45.
General procedure for the cyclization of the enynes followed by oxidative
treatment: The cyclization was carried out following the preceeding
description. The residue was diluted with acetonitrile (10 mL) and CuCl2 ´
2H2O (1 equiv) was added. After being vigorously stirred for 30 min at
room temperature, the mixture was purified by flash chromatography
without concentration to afford the cycloadducts.
Methyl 4-ethyl-3-(2,2-dimethylpropanyl)cyclopenta-2,4-dien-1,1-dicarbox-
ylate (31): Yield: 194 mg, 66%; 1H NMR (200 MHz, CDCl3): d ˆ 6.67 (s,
ˆ
6H; OMe), 6.04 (d, J ˆ 2.2 Hz, 1H; CH), 5.96 (dt, J ˆ 2.2, 2.0 Hz, 1H;
ˆ
HC CCH2Me), 2.18 (dq, J ˆ 7.3, 2.0 Hz, 2H; CH2Me), 2.09 (s, 2H;
CH2tBu), 1.08 (t, J ˆ 7.3 Hz, 3H; Me), 0.86 (s, 9H; tBu); 13C NMR
Methyl 3-ethylidene-4-trimethylsilylmethylenecyclopentan-1,1-dicarbox-
ylate (21): Yield: 51 mg, 17% from 6; 1H NMR (400 MHz, C6D6): d ˆ
ˆ
ˆ
(50 MHz, CDCl3): d ˆ 168.7 (2C; CO2Me), 153.7 (HC C), 148.2 (HC C),
ˆ
ˆ
129.8 ( CH), 124.9 ( CH), 70.4 (C(CO2Me)2), 52.9 (2C; OMe), 40.1
(CH2tBu), 29.6 (3C;CMe3), 31.9; (CMe3), 21.5 (CH2Me), 12.0 (Me); IR
(CH2Cl2): nÄ ˆ 3050, 1730, 1670, 1220, 830 cm 1; elemental analysis calcd
(%) for C16H24O4: C 68.54, H 8.63; found C 68.49, H 8.59; MS (70 eV, EI):
ˆ
ˆ
5.98 (s, 1H; CHSi), 5.34 (q, J ˆ 6.9Hz, 1H; CHMe), 3.44 (s, 6H; OMe),
1.99 (s, 2H; CH2), 1.64 (s, 2H; CH2), 1.63 (d, J ˆ 6.9 Hz, 3H; Me), 0.12 (s,
9H; TMS).
h4-(Methyl 3-ethylidene-4-trimethylsilylethylenecyclopentan-1,1-dicarbox-
ylate)-h5-cyclopentadienyl cobalt(i) (22): Yield: 36 mg, 9% from 6;
1H NMR (400 MHz, C6D6): d ˆ 4.63 (s, 5H; Cp), 3.64 (s, 3H; OMe), 3.32
‡
m/z (%): 280 (10) [M] , 265 (20), 220 (40), 205 (100), 161 (55), 145 (75, 119
(25), 105 (25).
Compounds 32 and 33: Obtained as a mixture 224 mg, (32/33 75:25); Data
for 32: Yield: 52%; 1H NMR (400 MHz, CDCl3): d ˆ 7.3 ± 7.1 (m, 10H; Ph),
ˆ
ˆ
(s, 3H; OMe), 2.93 ± 2.30 (m, 4H; CH2 ‡ HC CC CH ), 1.60 (AB, 2H;
CH2), 0.55 (s, 3H; Me), 0.29 (s, 9H; TMS).
ˆ
ˆ
ˆ
6.21 (s, 1H; CHPh), 4.80 (d, J ˆ 1.0 Hz, 1H; CH2), 4.73 (s, 1H; CH2),
h4-(Methyl 3-ethyl-4-trimethylsilylmethylcyclopenta-2,4-dien-1,1-dicarb-
oxylate)-h5-cyclopentadienyl cobalt(i) (23): Yield: 168 mg, 40% from 6;
1H NMR (400 MHz, C6D6): d ˆ 4.52 (s, 5H; Cp), 3.56 (s, 3H; OMe), 3.10 (s,
4.5 ± 4.4 (AB, 2H; OCH2Ph), 3.75 ± 3.65 (m, 1H; HCOBn), 2.74 (ddd, J ˆ
ˆ
12.2, 4.1, 2.0 Hz, 1H; CH2C CHPh eq), 2.18 (dd, J ˆ 12.2, 10.1 Hz, 1H;
ˆ
CH2C CHPh ax), 1.89 (ddd, J ˆ 12.7, 4.1, 2.0 Hz, 1H; CH2CMe2 eq), 1.49
ˆ
ˆ
3H; OMe), 2.95 (d, J ˆ 2 Hz, 1H; CH), 2.92 (d, J ˆ 2 Hz, 1H; CH), 2.44
(m, 2H; CH2Me), 2.14 (d, J ˆ 14.2 Hz, 1H; CH2Si), 1.22 (d, J ˆ 14.2 Hz,
1H; CH2Si), 0.93 (t, J ˆ 7.6 Hz, 3H; Me), 0.08 (s, 9H; TMS); 13C NMR
(dd, J ˆ 12.7, 11.1 Hz, 1H; CH2CMe2 ax), 1.17 (s, 3H; Me), 1.11 (s, 3H; Me);
13
ˆ
C NMR (100 MHz, CDCl3): d ˆ 151.5 (C CH2), 138.5, 137.8, 136.3, 131.4
(2C; Ph), 127.5 (2C; Ph), 127.3 (2C; Ph), 126.8 (2C; Ph), 126.5, 125.4, 125.2,
ˆ
(100 MHz, C6D6): d ˆ 168.9 (CO2Me), 166.9 (CO2Me), 97.2 (HC C), 94.2
ˆ
109.1 ( CH2), 73.7 (CHOBn), 69.3 (OCH2Ph), 46.2, 44.4, 36.5 (CMe2), 27.4
ˆ
(HC C), 80.6 (5C; Cp), 67.7 (C(CO2Me)2), 51.4 (OMe), 51.0 (OMe), 40.7
(Me), 26.4 (Me); Data for 33: Yield: 18%; 1H NMR (400 MHz, CDCl3):
ˆ
ˆ
(HC ), 37.3 (HC ), 21.3 (CH2), 19.5 (CH2), 13.3 (Me), 1.6 (3C; TMS); IR
ˆ
ˆ
d ˆ 7.1 ± 7.3 (m, 10H; Ph), 6.49 (s, 1H; CH), 4.95 (s, 1H; CH2), 4.73 (s,
1
(neat): nÄ ˆ 3040, 1725, 1430, 1240, 850 cm
.
ˆ
1H; CH2), 4.3 ± 4.4 (AB, 2H; CH2Ph), 3.55 ± 3.65 (m, 1H; CHOBn), 3.27
Compound 24: Yield: 22%; 1H NMR (400 MHz, C6D6): d ˆ 5.87 (s, 1H;
(ddd, J ˆ 10.2, 6.6, 2.0 Hz, 1H; CH2C ˆ eq.), 2.06 (dd, J ˆ 10.7, 10.2 Hz, 1H;
ˆ
ˆ
ˆ
CHSi), 5.23 (m, 1H; CH), 3.34 (s, 6H; OMe), 2.90 ± 2.42 (m, 6H; 3 CH2),
1.23 (t, J ˆ 7.2 Hz, 3H; Me), 0.00 (s, 9H; TMS).
CH2C ax), 1.86 (ddd, J ˆ 12.7, 4.1, 2.0 Hz, 1H; CH2CMe2eq), 1.40 (dd, J ˆ
12.7, 11.1 Hz, 1H; CH2CMe2 ax), 1.18 (s, 3H; Me), 1.16 (s, 3H; Me); IR
Chem. Eur. J. 2001, 7, No. 16
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0716-3523 $ 17.50+.50/0
3523

M. Malacria, C. Aubert, and O. Buisine
FULL PAPER
(32 ‡ 33, CDCl3): nÄ ˆ 1950, 1880, 1800, 1700, 1620, 1590, 1250, 1200, 860,
Chem. 1996, 108, 686 ± 687; Angew. Chem. Int. Ed. Engl. 1996, 35,
662 ± 663; i) B. M. Trost, Y. Li, J. Am. Chem. Soc. 1996, 118, 6625 ±
6633; j) C. H. Oh, C. Y. Rhim, S. K. Hwang, Chem. Lett. 1997, 777 ±
778; k) H. Yamada, S. Aoyagi, C. Kibayashi, Tetrahedron Lett. 1997,
38, 3027 ± 3030; l) R. A. Widenhoefer, C. N. Stengone, J. Org. Chem.
1999, 64, 8681 ± 8692.
1
800 cm
.
Methyl
5-methyl-7-phenylbicyclo[3.2.0]hept-1(7)-ene-3,3-dicarboxylate
1
(36): Yield: 181 mg, 60%; H NMR (400 MHz, CDCl3): d ˆ 7.50 ± 7.31 (m,
ˆ
5H; Ph), 3.83 ± 3.28 (AB, 2H; CCH2C), 3.83 (s, 3H; OMe), 3.66 (s, 3H;
OMe), 2.65 (s, 2H; CH2), 2.66 ± 2.28 (AB, 2H; CH2), 1.22 (s, 3H; Me);
13
[3] For Ti-catalyzed cyclizations of 1,n-enynes: a) S. C. Berk, R. B.
Grossman, S. L. Buchwald, J. Am. Chem. Soc. 1993, 115, 4912 ±
4913; b) H. Urabe, T. Hata, F. Sato, Tetrahedron Lett. 1995, 36,
4261 ± 4264; c) K. Suzuki, H. Urabe, F. Sato, J. Am. Chem. Soc. 1996,
118, 8729 ± 8730; d) H. Urabe, K. Suzuki, F. Sato, J. Am. Chem. Soc.
1997, 119, 10014 ± 10027.
ˆ
C NMR (100 MHz, CDCl3): d ˆ 182.0 (C CPh), 172.4 (CO2Me), 171.8
ˆ
(CO2Me), 134.3 (C CPh), 130.8 (Ph), 128.8 (2C; Ph), 128.5 (2C; Ph), 128.4
ˆ
(Ph), 60.7 (CMe), 53.5 (OMe), 53.4 (OMe), 52.5 ( CCH2CMe), 48.0
(C(CO2Me)2), 44.6 (CH2), 34.8 (CH2), 26.9 (Me); IR (CH2Cl2): nÄ ˆ 1730,
1650, 1480, 1430, 1240, 1020, 860 cm 1; elemental analysis calcd (%) for
C18H20O4: C 71.98, H 6.71; found C 72.14, H 6.92.
[4] For Zr-mediated cyclizations of 1,n-enynes: a) J. M. Davis, R. J.
Whitby, A. Jaxa-Chamiec, Synlett 1994, 110 ± 112; b) K. Miura, M.
Funatsu, H. Saito, H. Ito, A. Hosomi, Tetrahedron Lett. 1996, 37,
9059 ± 9062; c) E.-i. Negishi, S. Ma, T. Sugihara, Y. Noda, J. Org.
Chem. 1997, 62, 1922 ± 1923.
[5] For Ni/Cr-, Ni/Zn-, and Ni-mediated cyclizations of 1,n-enynes:
a) B. M. Trost, J. M. Tour, J. Am. Chem. Soc. 1987, 109, 5268 ± 5270;
b) K. Tamao, K. Kobayashi, Y. Ito, J. Am. Chem. Soc. 1988, 110, 1286 ±
1288; c) A. V. Svachenko, J. Montgomery, J. Org. Chem. 1996, 61,
1562 ± 1563.
1
Compound 37: Yield: 67%; H NMR (400 MHz, CDCl3): d ˆ 5.62 (d, J ˆ
2.0 Hz, 1H), 5.05 (s, 1H), 4.68 (s, 1H), 3.75 (s, 3H; OMe), 3.74 (s, 3H;
OMe), 3.22 (dd, J ˆ 14.0, 2.0 Hz, 1H), 2.60 (dd, J ˆ 14.0, 2.0 Hz, 1H), 2.5 ±
2.3 (m, 2H;), 1.59 (m, 1H;), 1.11 (d, J ˆ 6.0 Hz, 3H; Me), 0.15 (s, 9H;
TMS); 13C NMR (100 MHz, CDCl3): d ˆ 172.0 (CO2Me), 171.1 (CO2Me),
155.1, 153.0, 126.1, 107.4, 55.6, 52.8
(OMe), 52.5 (OMe), 39.4, 37.7, 33.0,
18.4, 0.0 (3C; TMS); IR (CH2Cl2): nÄ ˆ
1730, 1650, 1480, 1430, 1240, 1020,
Heq
SiMe3
E
1
860 cm
; NOE experiments were
[6] For Rh-mediated cyclizations of 1,n-enynes: a) R. Grigg, P. Stevenson,
T. Worakun, J. Am. Chem. Soc. 1988, 110, 4967 ± 4972; b) P. A.
Wender, D. Sperandio, J. Org. Chem. 1998, 63, 4164 ± 4165, and
references therein; c) S. R. Gilbertson, G. S. Hoge, D. G. Genov, J.
Org. Chem. 1998, 63, 10077 ± 10080; for Pt version: d) N. Chatani, N.
Furukawa, H. Sakurai, S. Murai, Organometallics 1996, 15, 901 ± 903;
for Ru version: e) A. Kinoshita, M. Mori, J. Org. Chem. 1996, 61,
8356 ± 8357; f) M. Nishi, N. Adachi, K. Onozuka, H. Matsumura, M.
Mori, J. Org. Chem. 1998, 63, 9158 ± 9159.
[7] a) B. M. Trost, Acc. Chem. Res. 1990, 23, 34 ± 42; b) B. M. Trost,
Janssen Chimica Acta 1991, 9, 3 ± 9; c) B. M. Trost, Angew Chem. 1995,
107, 285 ± 307; Angew. Chem. Int. Ed. Engl. 1995, 34, 259 ± 281; d) I.
Ojima, M. Tzamarioudaki, Z. Li, R. J. Donovan, Chem. Rev. 1996, 96,
635 ± 662; e) B. M. Trost, M. J. Krische, Synlett 1998, 1 ± 16; f) A. J.
Fletcher, S. D. R. Christie, J. Chem. Soc. Perkin Trans. 1 2000, 1657 ±
1668.
H
H
used for the assignment of the 1,3-
diene moiety and the configuration of
the double bond (Figure 1).
Compound 38: Yield: 1H NMR
(400 MHz, CDCl3): d ˆ 5.57 (s, 1H),
5.07 (s, 1H), 5.00 (s, 1H), 3.73 (s, 6H),
2.54 ± 2.37 (m, 2H), 1.72 (t, J ˆ
14.0 Hz, 1H), 1.9 ± 1.67 (AB, 2H),
E
NOE
H
Figure 1. NOE contacts ob-
served for 37.
1.16 (d, J ˆ 6.0 Hz, 3H), 0.00 (s, 9H); 13C NMR (100 MHz, CDCl3): d ˆ
172.3 (2C), 138.9, 135.2, 119.5, 109.8, 55.4, 52.8, 52.7, 37.7, 31.6, 23.8,18.9,
1.0 (3C).
Compounds 39 and 40: Obtained as an inseparable mixture (39/40 74:26);
Data for 39: 1H NMR (400 MHz, CDCl3): d ˆ 6.27 (d, J ˆ 1.0 Hz, 1H;
ˆ
ˆ
ˆ
CHPh), 4.83 (s, 1H; CH2), 4.79 (d, J ˆ 1.3 Hz, 1H; CH2), 3.76 (s, 3H;
OMe), 3.74 (s, 3H; OMe), 2.90 (ABX, J ˆ 13.1, 2.3 Hz, 2H), 2.20 (dd, J ˆ
18.7, 2.2 Hz, 1H), 1.09 (d, J ˆ 6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3):
[8] a) K. P. C. Vollhardt, Angew. Chem. 1984, 96, 525 ± 541; Angew. Chem.
Int. Ed. Engl. 1984, 23, 539 ± 556; b) D. Grothjahn in Comprehensive
Organometallic Chemistry II, Vol. 12 (Ed.: L. Hegedus), Pergamon,
Oxford, 1995, pp. 741 ± 770.
ˆ
ˆ
ˆ
d ˆ 171.9 (CO2Me), 171.0 (CO2Me), 149.4 (C ), 139.0 (C ), 137.5 (C ),
ˆ
ˆ
ˆ
129.1 (2C; Ph), 128.9 (2C; Ph), 126.5 ( CH), 126.0 ( CH), 109.7 ( CH2),
57.0 (C(CO2Me)2), 52.7 (OMe), 52.4 (OMe), 43.5 (CH2), 39.6 (CH2), 35.0
(CHMe), 18.1 (Me). Data for 40: H NMR (400 MHz, CDCl3): character-
1
[9] a) K. M. Brummond, J. L. Kent, Tetrahedron 2000, 56, 3263 ± 3283;
b) Y. K. Cheung, Coord. Chem. Rev. 1999, 188, 297 ± 341; c) S. T.
Ingate, J. Marco-Contelles, Org. Prep. Proced. Int. 1998, 30, 121 ± 143;
d) N. E. Schore in Comprehensive Organometallic Chemistry II,
Vol. 12 (Ed.: L. Hegedus), Pergamon, Oxford, 1995, pp. 703 ± 739;
e) N. E. Schore, Org. React. 1991, 40, 1 ± 90; f) N. E. Shore in
Comprehensive Organic Synthesis, Vol. 5 (Eds.: B. M. Trost, I. Flem-
ing, L. A. Paquette), Pergamon, Oxford, 1991, pp. 1037 ± 1064.
[10] a) O. Pardigon, A. Tenaglia, G. Buono, J. Org. Chem. 1995, 60, 1868 ±
1871; b) M. Lautens, W. Tam, J. C. Lautens, L. G. Edwards, C. M.
Crudden, A. C. Smith, J. Am. Chem. Soc. 1995, 117, 6863 ± 6879; c) R.
Liattansakul, J. K. Snyder, Tetrahedron Lett. 1999, 40, 1049 ± 1082.
[11] a) P. Cruciani, R. Stammler, C. Aubert, M. Malacria, J. Org. Chem.
1996, 61, 2699 ± 2708; b) J. L. Renaud, M. Petit, C. Aubert, M.
Malacria, Synlett 1997, 931 ± 932.
istic chemical shifts d ˆ 6.64 (d, J ˆ 1.7 Hz, 1H), 5.12 (s, 1H), 4.79 (d, J ˆ
1.3 Hz, 1H), 3.74 (s, 3H; OMe), 3.56 (s, 3H; OMe), 1.13 (d, J ˆ 6.3 Hz, 3H;
Me); IR (39 ‡ 40, CDCl3): nÄ ˆ 1730, 1690, 1640, 1490, 1440, 1430, 1250,
1
1030 cm
.
Acknowledgements
Financial support was provided by CNRS and MRES. O.B. thanks the
company GlaxoWellcome for a fellowship during his Ph.D.
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Cycloisomerization of 1,n-Enynes
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Received: October 5, 2000
Revised: March 23, 2001 [F2782]
Chem. Eur. J. 2001, 7, No. 16
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