Reaction of enol ethers with alkynes catalyzed by transition metals: 5-exo-dig versus 6-endo-dig cyclizations via cyclopropyl platinum or gold carbene complexes

Article abstract of DOI:10.1002/chem.200204646

The intramolecular reaction of enol ethers with alkynes in methanol is catalyzed by electrophilic Pt^II, Pd^II, and Au^III chlorides and by a Cu¹ complex to give five- or six-membered rings bearing dimethyl acetals

Full text of DOI:10.1002/chem.200204646

FULL PAPER
Reaction of Enol Ethers with Alkynes Catalyzed by Transition Metals:
5
-exo-dig versus 6-endo-dig Cyclizations via Cyclopropyl Platinum or Gold
Carbene Complexes
Cristina Nevado, Diego J. C a¬ rdenas, and Antonio M. Echavarren*[a]
Abstract: The intramolecular reaction of enol ethers with alkynes in methanol is
II
II
III
I
catalyzed by electrophilic Pt , Pd , and Au chlorides and by a Cu complex to give
five- or six-membered rings bearing dimethyl acetals.The reaction takes place by an
anti addition of the enol ether and the metal to the alkyne.The possible involvement
of vinylidene complexes in this reaction is excluded.In addition to the usual 5- exo-dig
Keywords: alkynes ¥ cyclization Á
density functional calculations ¥ gold
(
or 6-exo-dig) pathways, a 6-endo-dig pathway has also been found to take place with
¥
platinum
certain enynes.One case of 5- endo-dig cyclization has also been found.A general
scheme for the alkoxycyclization of enynes catalyzed by transition metals based on
DFT calculation of PtCl2 and AuCl3 complexes that includes exo and endo
cyclizations is presented.
Introduction
We have recently shown that enynes I react with PtCl to form
2
complexes II, which evolve by an intramolecular reaction of
2
the (h -alkyne)PtCl with the alkene to form a cyclopropyl
2
[1]
Pt ± carbene intermediate III (Scheme 1). Subsequent attack
of the nucleophile (alcohol or water) at the cyclopropyl
carbons a and b of intermediate III gives carbo- or hetero-
cycles IV or V.[ Similar intermediates might be also involved
in the transition metal catalyzed intramolecular attack of
1]
[2]
allylsilanes and allylstannanes to alkynes, as well as in the
skeletal rearrangement of enynes that yield conjugated
dienes.[
3, 4]
DFT calculations also support the formation of
intermediates similar to III in the first step of the intra-
molecular reaction of furans with alkynes catalyzed by Pt .
II [5]
Scheme 1.PtCl
or water.
2
-catalyzed cyclization of enynes in the presence of alcohols
We found that the reaction proceeds via an attack at carbon
a with enynes bearing 1,2-disubstiuted or 1,1,2-trisubstituted
alkenes.However, by reducing the electronegativity of the
substituents at the tether Z, preferential attack at carbon b
was observed, yielding six-membered ring compounds V.[
Although some of these cyclizations are also catalyzed by
III
II [1]
II [6]
Au , Ru , and Pd , the cyclization with these catalysts is
more limited in scope.
1]
The related cyclization of silyl enol ethers with alkynes
catalyzed by [W(CO) L] (L ˆ THF, amine) has been found to
5
proceed with exo-dig or endo-dig selectivity depending on the
reaction conditions.[ Tungsten vinylidenes have been pro-
posed to be key intermediates in the formation of endo-dig
products.
7]
[
a] Prof.Dr.A.M.Echavarren, C.Nevado, Dr.D.J.Ca
Departamento de QuÌmica Org a¬ nica
Universidad Aut o¬ noma de Madrid
Cantoblanco, 28049, Madrid (Spain)
Fax : (‡34)913973966
¬rdenas
We reasoned that the selectivity of the opening of III could
be controlled by attaching a strong electron-donating sub-
stituent at either a or b (Scheme 2).[ Thus, attaching an -OR
substituent at a (VI, Scheme 2) would selectively give rise to
five-membered ring intermediate VII, whereas the alternative
E-mail: anton.echavarren@uam.es
8]
Supporting Information (atomic coordinates for structures of Figures 2,
5, and for this article is available on the WWW under
http://www.chemeurj.org/ or from the author.
4
,
7
Chem. Eur. J. 2003, 9, 2627 ± 2635
DOI: 10.1002/chem.200204646
¹ 2003 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
2627

A.M.Echavarren et al.
FULL PAPER
PtCl2
PtCl2
OR
[M]
TsN
OMe
TsN
MeOH
OMe
Z
Z
Z
OR
OMe
1
5
VI
VII
MeO2C
[
M]
MeO2C
MeO2C
OMe
OMe
MeO2C
OMe MeOH
PtCl2
PtCl2
2
6
Z
RO
RO
[
M]
OR
OR
IX
RO
RO
OMe
OMe
7: R = Ac
9: R = TIPS
OMe MeOH
VIII
Scheme 2.Hypothetical openings of alkoxycyclopropyl carbene inter-
mediates.
3: R = Ac
: R = TIPS
4
HO
substitution at b would favor cleavage to form six-membered
ring VIII.In the presence of an alcohol or water, these
intermediates might evolve to form acetals or carbonyl
compounds, respectively.
It is important to note that Dankwardt has recently found
that the cyclization of tert-butyldimethylsilyl enol ethers of
O
OMe
H
8
[
M]
MeO2C
MeO2C
MeO2C
MeO2C
R
OMe
OMe
MeOH
OMe
R
1
1
0: R = H
1: R = Me
12: R = H
13: R = Me
2
-ethynylacetophenones proceeds in a 6-endo-dig mode to
[9]
afford 1-naphthol derivatives. Remarkably, this cyclization
can be catalyzed by Rh , Pt , Pd , Au , Ru , and Ag ,
I
II
II
III
II
I
MeO C
Me
2
CHO
MeO2C
although more general transformations were found with
I
[
Rh(CO) Cl] , PdCl , and PtCl .With [Rh(CO) Cl] , Rh ±
14
2
2
2
2
2
2
vinylidene complexes were found to be intermediates in the
cyclization.We have found that the reaction of enol ethers,
and some trialkylsilyl enol ethers, with alkynes takes place in
TIPSO
O
Me
PtCl2
MeOH
CO2Me
MeO2C CO2Me
15
MeO2C
16
the presence of a variety of late transition metals to give cyclic
compounds by exo-dig or endo-dig pathways.[
10]
From these
Scheme 3.Transition-metal catalyzed cyclization of enol ethers and silyl
enol ether 15 in the presence of MeOH.
experimental results, as well as from DFT calculations on
cyclizations promoted by PtCl and AuCl , a more complete
2
3
picture of the reaction of alkynes with alkenes emerges.
configuration according to semiempirical calculations (PM3
À1
Hamiltonian), which show that 8 is about 2 kcalmol more
Results and Discussion
stable than the a anomer.TBS protecting groups were also
cleaved by PtCl or AuCl in methanol.However, TIPS groups
2
3
[
11]
Cyclization of enol ethers with alkynes: Reaction of (E)-1
were tolerated.Thus, 4 (1:0.8 E/Z) gave carbocycle 9 in
moderate to good yield with the four catalysts examined
(entries 13 ± 16).
in methanol under reflux[ proceeded satisfactorily with
12]
PtCl2 (5 mol%), PdCl2 (10 mol%), [Cu(MeCN) ]PF
4
6
(
10 mol%), or AuCl3 (5 mol%) as the catalysts to give
Formation of six-membered rings is also possible with the
electrophilic transition metal catalysts.However, the cycliza-
tion of 10 (1:1.3 E/Z) could only be performed with the more
exclusively 5 (Table 1, entries 1 ± 4).The clean formation of 5
by an exo-dig cyclization is noteworthy, because substrates
similar to 1 react anomalously to give cyclopropane deriva-
tives with electrophilic transition metal as the catalysts.[1b, 4f, g]
Substrate (E)-2 reacted in methanol similarly to give 6
reactive AuCl as the catalyst, giving rise to carbocycle 12 in
3
94% yield (entry 17).Substrate 11 (1:1 E/Z), bearing an
additional methyl group at the enol ether, was more reactive
than 10 and gave 13 in good or moderate yield by using PtCl2
or [Cu(MeCN) ]PF as the catalysts (entries 18, 19).In this
(
entries 5 ± 8).The best results with 1 ± 2 were obtained with
PtCl , PdCl , or AuCl as the catalysts (entries 1, 2, 4 ± 6,
2
2
3
4
6
and 8).
case, cleavage of the acetal took place in the presence of
Diacetate 3 (1:0.7 E/Z mixture) reacted with PtCl , PdCl ,
AuCl leading to aldehyde 14, which was isolated in 43% yield
2
2
3
(entry 20).The reaction of TIPS enol ether 15[ with PtCl in
7b]
or [Cu(MeCN) ]PF to give carbocycle 7 in 86 ± 88% yield
4
6
2
(
entries 9 ± 11).However, the reaction of 3 with AuCl gave
methanol gave a,b-unsaturated bicyclic ketone 16 in 70%
yield (entry 21).Cleavage of the intermediate labile acetal
and conjugation of the alkene occur under the reaction
conditions.
3
bicyclic acetal 8 (58%) as a single isomer, as a result of the
cleavage of the acetates by AuCl in methanol (entry 12).
[13]
3
The configuration at the acetal center (C-4) could not be
assigned on the basis of the observed vicinal coupling constant
of 2.4 Hz, which do not allow to distinguish between a b- or a-
configuration (dihedral angle of 56 or 658, respectively).
However, the most stable isomer corresponds to the b-
The cyclization of 17 (6.2:1 E/Z) with PtCl gave a 13:1
2
mixture of acetals 18 and 19 in 70% combined yield
(Scheme 4).The cis configuration of these heterocycles at
the ring fusion was assigned on the basis of NOESY experi-
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Chem. Eur. J. 2003, 9, 2627 ± 2635

Cyclizations of Enol Ethers
2627±2635
Table 1.Cyclization of substrates of Scheme 3. [a]
D
D
D
Catalyst[b]
CD3O
CD3O
CD3O
CD3O
MeO2C
MeO2C
Entry
Enol ether
Product
Yield [%]
N
N
H
OCD3
Ts
Ts
1
2
3
4
5
6
7
8
9
1
1
1
1
2
2
2
2
3
3
3
3
4
4
4
4
PtCl
PdCl
[Cu(MeCN)
AuCl
PtCl
PdCl
[Cu(MeCN)
AuCl
PtCl
PdCl
[Cu(MeCN)
AuCl
PtCl
PdCl
[Cu(MeCN)
2
5
5
5
5
6
6
6
6
7
7
7
8
9
9
9
9
84
81
77
97
97
97
70
95
86
88
88
58
84
81
57[
90
94
90
68[
43
70
H
OCD3
[D7]-6
2
4
4
4
4
4
]PF
]PF
]PF
]PF
]PF
6
6
6
6
6
[
D7]-18
[D7]-19
3
4
Figure 1.Products of cyclizations on [D ]methanol.
2
2
of the dimethyl acetal with the solvent is a facile process under
the reaction conditions.However, no transesterification of the
ester of 6 was observed.In addition, it is significant that in all
cases the cyclizations are faster than the addition of methanol
to the enol ether or the alkyne functions of the starting
enyne.[
3
2
10
11
12
13
14
15
16
17
18
19
20
21
2
3
2
16]
2
c]
The stereoselective deuteration of [D ]-18 and [D ]-6
7
7
AuCl
AuCl
3
demonstrates that the CÀC and the CÀM are formed anti on
the alkyne, which suggests that alkenyl ± metal complexes
similar to III (Scheme 1) are involved as intermediates in the
cyclization of the w-acetylenic enol ethers.[ On the other
hand, formation of 19 and 21 suggests that an endo-dig attack
10
11
11
11
15
3
12
13
13
14
16
PtCl
[Cu(MeCN)
AuCl
PtCl
2
d]
17]
3
2
2
[
a] The reactions were carried out under reflux for 17 h.[b] 5 mol% of
of the enol ether to the (h -alkyne)platinum complex X to give
PtCl or AuCl and 10 mol% of PdCl or [Cu(MeCN) ]PF .[c] 81% yield
2
3
2
4
6
cyclopropyl platinum carbene XI is possible (Scheme 5).
Opening of the cyclopropane of XI, would then give
zwitterionic intermediate XII, which would finally give XIII.
Cyclization of a platinum(ii) vinylidene complex XIV, similar
based on unrecovered starting material.[d] 99% yield based on unrecov-
ered starting material.
to that proposed for the reactions with [W(CO)6][ or Rh is
7]
I[9]
ruled out since it would have resulted in deuteration at C-4 of
1
9 via complex XV.
PtCl2
R
PtCl2
PtCl2
R
R
OMe
Z
OMe
OMe
Z
Z
X
XI
XII
R = H
Scheme 4. exo- vs endo Cyclization of substrates 17 and 20.
H
H
PtCl2
R
PtCl2
OMe
Z
OMe
OMe
XIII
Z
ments.Interestingly, substrate 20, with a methyl substituent on
OMe
Z
the alkyne, led selectively to endo-dig cyclization with PtCl in
2
XIV
XV
methanol giving 21.In this case, more reproducible results
Scheme 5.Mechanism for the 6- endo-dig cyclization.
were realized with AuCl as the catalyst, which gave 21 as the
3
only product, isolated in 40% yield.
Octahydroquinolines 19 and 21 result from endo cycliza-
Importantly, the mechanism proposed in Scheme 5 suggests
that the endo-dig cyclization would be also favored if the
alkyne and the alkene were tethered by just two atoms,
instead of three.In that case, cyclization of XVI (Scheme 6)
would proceed through bicyclic system XVII, which would
open to form XVIII.The alternative pathway, leading finally
to five-membered rings, would be less favorable since it would
proceed through highly strained XIX.
tion,[ a type of reaction that has been found in the
14]
[7]
cyclization of w-acetylenic silyl enol ethers with [W(CO) ],
6
from which tungsten vinylidene complexes were proposed as
intermediates.[ A rhodium ± vinylidene complex was also
proposed for the formation of naphthalenes by endo cycliza-
tion of tert-butyldimethylsilyl enol ethers with alkynes.[
However, the formation of 21 from methyl substituted 20
clearly excludes the involvement of a similar platinum or gold
vinylidene complex in the cyclization.To further secure that
15]
9]
In the event, reaction of tert-butyldimethylsilyl enol ether
22[7b] with PtCl as the catalyst (5 mol%) in toluene under
2
conclusion, the reaction of 17 was carried out in [D ]methanol
reflux gave 1-silyloxydiene 23, which was hydrolyzed to
known 24[ (50% overall yield).Formation of 23 can be
explained by proton abstraction from an intermediate of type
XVIII, to form a conjugated diene, followed by cleavage of
4
7b]
with PtCl as the catalyst.Under these conditions, in addition
2
to >95% deuterium incorporation at the alkene, exchange of
the acetal with [D ]methanol occurs yielding [D ]-18 and
4
7
‡
[
D ]-19 (Figure 1).The cyclization of
7
2 with PtCl2 in
the CÀPt bond by H .This cyclization corresponds formally to
[
D ]methanol gave [D ]-6, which indicates that exchange
a 6-endo-dig/endo-trig process.
4
7
Chem. Eur. J. 2003, 9, 2627 ± 2635
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A.M.Echavarren et al.
FULL PAPER
PtCl2
PtCl2
Z
Z
H
H
R
R
H
H
OR'
OR'
RO
XVII
OR
IV
XXI
XVI
a
R'OH
PtCl2
a
R'OH
PtCl2
PtCl2
PtCl2
PtCl2
a R
5-exo-dig
6-endo-dig
H
Z
Z
b
b
Z
R
H
a
R
OR
H
H
III
H
XX
OR
II
XIX
XVIII
b
R'OH
b
R'OH
PtCl2
EtO2C
toluene
THF
EtO2C
EtO2C
Z
H
R
OTBS
OTBS
O
Z
Z
R
22
23
24 (50%)
R
OR'
H
H
OR'
XXII
Scheme 6.6- endo-dig/endo-trig cyclization.
V
XXIII
Scheme 7.General mechanism for the PtCl
enynes.
2
-catalyzed cyclization of
A more general mechanistic scheme for the transition metal-
catalyzed alkoxycyclization of enynes: The possible pathways
XXVa faster than the endo process (E ˆ 10.3 and
À1
are summarized in Scheme 7 for PtCl as the catalyst starting
11.2 kcalmol , respectively).Both reactions are exothermic
2
a
from a complex II.In addition to the
[1]
5-exo-dig cyclization via complex III,
a
6-endo-dig process would give complexes
such as XX.Attack at center a would give
compounds of general structure XXI.
This pathway is that followed by 20 and,
in part, 17.Reaction at center b would
give seven-membered ring derivatives
XXII.Such a process has not yet been
reduced to practice.Cyclopropanes of
structure XXIII, which have been ob-
[
1b, 4b, f±g, 18]
served when Z ˆ O or NTs,
are
probably derived from intermediates XX
by a hydrogen-shift.
We decided to analyze the exo- and
endo cyclizations of model enynes with
PtCl2 and AuCl3 to obtain a clearer
picture of the reactions of enynes pro-
moted by electrophilic metal halides.
Three different types of substrates were
considered, in order to understand the
effect of the presence of a heteroatom in
the chain and the dependence of the
cyclization mode on the type of alkyne
(
terminal or internal).The model Pt
complexes present water as an additional
ligand.[
1b]
The results of the cyclization of 6-oct-
en-1-yne are summarized in Figure 2.An
important feature of the starting complex
XXIVa is the polarization induced by
PtCl on the bonded alkyne.The internal
2
carbon of the asymmetrically bonded
alkyne becomes more electrophilic than
the terminal one (natural charges being
‡
0.05 and À0.25, respectively), which
À1
makes the exo-cyclization reaction to give
Figure 2.Energy profile for the cyclization of PtCl
2
-complex XXIVa (values in kcalmol ).
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Chem. Eur. J. 2003, 9, 2627 ± 2635

Cyclizations of Enol Ethers
2627±2635
À1
(
À19.5 and À27.6 kcalmol ),
the six-membered-ring product
XXVIa being more stable.
These findings perfectly paral-
lel the experimental results.
To obtain information about
the effect of an heteroatom in
the tether between the alkyne
and the alkene, cyclizations of
model complex XXIVb were
studied (Figure 3).Interesting-
ly, the heteroatom does not
further polarize the alkyne.
The electron deficiency that
the electronegative heteroatom
could induce on the internal
alkyne carbon is compensated
by donation from the metal
fragment, as shown from the
natural charges of carbons
(
À0.01 and À0.24, for the in-
ternal an terminal ones, respec-
tively).In this case, the exo-
cyclization mode leading to
XXVb is less favorable both
kinetical and thermodynami-
cally than the endo cyclization
to form six-membered-ring
complex XXVIb, in spite of
the higher electrophilic charac-
ter of C-2, which contrasts with
the results shown in Figure 1.
The reason for this preference
is that geometrical restrictions
are stronger for the formation
of TS compared with the formation of TS , due to the shorter
À1
Figure 3.Energy profile for the cyclization of PtCl
2
complex XXIVb (values in kcalmol ).
Internal alkynes containing an electronegative heteroatom
within the chain suffer endo cyclization to six-membered rings
preferentially.In this case, the theoretical model also accounts
for the observed results (Figure 5).Starting from XXIVc, the
preferred cyclization for both kinetic and thermodynamic
reasons leads to XXVIc.These reactions show higher
activation barriers (12.5 and 14.2 kcalmol for the endo
and exo cyclizations, respectively) and are less exothermic
(À21.8 and À17.0 kcalmol , respectively) than those of
3
1
CÀO distances.As a consequence, the less strained six-
membered ring derivative is formed through a lower energy
À1
transition state TS , which is 1.5 kcalmol more stable than
4
TS3.
This hypothesis was confirmed by studying the intermolec-
ular reaction between propargyl alcohol coordinated to
Pt(H O)Cl and trans-2-butene, which showed that, in fact,
À1
2
2
À1
the preferred pathway leads to formation of the CÀC bond
with C-2 of the alkyne (exo-type cyclization) through a
XXIVa and XXIVb (Figures 2 and 3) probably due to steric
hindrance imposed by the methyl group.In the cases of XXVc
and XXVIc, the dihedral angles between the coordination and
the carbene planes are 20 ± 258 higher than those of XXVb
and XXVIb.The alkyne of XXIVc is only slightly polarized
and in the opposite sense (natural charges are À0.04 and
‡0.02 for C-3 and C-2, respectively), in spite of the presence
of the electronegative O atom.
À1
transition state which is 2.3 kcalmol more stable than the
alternative endo-type transition state (Figure 4).
Me
Me
Cl
Cl
Pt OH2
Me
HO
HO
2.3
Cl
Pt OH2
Cl
Cl
Bader analysis of the starting alkyne ± PtCl complexes of
Me
2
6.2
terminal alkynes (XXIVa and XXIVb) show a single bond
critical point located between the terminal carbon and the
metal, the internal alkyne carbon being not coordinated.Thus,
it can be said that a hypothetical resonance structure
containing a vinyl cation has a considerable contribution in
these complexes (Figure 6).Therefore, terminal alkynes
Me
+
Pt OH2
Me
Cl
HO
À1
Figure 4.Activation energies [kcalmol ] for the model intermolecular
reaction of propargyl alcohol with trans-2-butene.
Chem. Eur. J. 2003, 9, 2627 ± 2635
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A.M.Echavarren et al.
FULL PAPER
carbenes present longer AuÀC
bonds (2.0 ± 2.1 vs 1.8 ± 1.9 ä for
platinum carbenes).
Conclusion
Unlike other cyclizations of enynes
that give 1,3- or 1,4-dienes as a
result of cycloisomerization, the
cyclization of w-acetylenic enol
ethers provides carbo- and hetero-
cycles bearing two different func-
tionalities that could be later trans-
formed selectively.Since enol
ethers are readily synthesized by
a variety of methods,[ this exper-
imentally simple catalytic cycliza-
tion could be applied for the ready
access to complex organic mole-
cules.
19]
These results support the pro-
posal that the cyclization of enynes
II
II [6, 20]
with electrophilic Pt , Pd ,
III
I
Au , Cu , take place by a common
mechanism.This conclusion is also
supported by the similar profile of
the reaction of enynes with PtCl2
or AuCl as the electrophiles (Fig-
3
ures 2, 4, 5, and 7) and by the
results of Dankwardt in the cycli-
zation of tert-butyldimethylsilyl
enol ethers of 2-ethynylacetophe-
nones.[ The observed regioselec-
tivity is a result of both the elec-
tronic effect of the coordination of
the alkyne to the metal and the
geometrical constraints of an intra-
molecular process.In the absence
9]
À1
2
Figure 5.Energy profile for the cyclization of PtCl -complex XXIVc (values in kcalmol ).
of ring strain, coordinated terminal alkynes are attacked by
the alkene at the internal carbon.
A more complete picture of the cyclization of enynes
2
initiated by the h -coordination to electrophilic metal frag-
Figure 6.Bonding of terminal alkynes to Pt II in Pt(alkyne)(H
complexes.
O)Cl
2
2
ments such as PtCl or AuCl includes both exo-dig and endo-
2
3
dig cyclization modes.The corresponding transition states
differ little in energy, which suggests that substituents
positioned at strategic positions could highly influence the
cyclization pathways.
1
complexes of PtCl are better described as h species.On the
2
other hand, a single bond critical point involving both carbons
is found for complex XXIVc, which corresponds to a h -
2
alkyne complex.
We also studied the reaction of the oxygen-containing
Experimental Section
internal alkyne promoted by AuCl (Figure 7).In this case, the
3
II
cyclizations are not as exothermic as in the case of the Pt -
General procedure for the synthesis of enol ethers by Wittig reaction:
nBuLi (1.2 equiv) was slowly added at À408C to suspension of (methox-
ymethyl)triphenylphosphonium chloride (1.2 equiv) in THF and the
resulting mixture was stirred at À408C for 40 min.Then a solution of the
corresponding aldehyde (1.0 equiv) was added and the mixture was stirred
catalyzed reactions, but have considerable lower activation
À1
energies, still favoring the endo process (4.4 vs 6.9 kcalmol ).
The structures of the resulting cyclopropyl gold carbenes
XXVIII and XXIX are very similar to those of the platinum
analogues XXVc and XXVIc, respectively, although the gold
at 238C for 30 min.Treatment with NH
4
Cl (pH 8), extractive workup
(Et O), and chromatography on deactivated silica gel (packed with 5%
2
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Cyclizations of Enol Ethers
2627±2635
J ˆ 2.8 Hz, 1H, E and Z), 1.11 ± 0.98 (m,
1
3
4
2H, E and Z); C NMR (75 MHz,
CDCl
3
): d ˆ 149.62, 148.34, 102.63, 98.50,
8
5
2
3.08, 82.83, 70.72, 70.44, 65.70, 65.20,
9.99, 56.64, 44.73, 29.95, 26.41, 22.34,
2.09, 18.74, 18.41, 12.66; elemental anal-
56 3 2
ysis calcd (%) for C28H O Si : C 67.68, H
1
1.36; found: C 67.83, H 11.42.
Compound 10: colorless oil, 1:1.3 E/Z;
1
H NMR (300 MHz, CDCl
3
): d ˆ 6.28 (dt,
J ˆ 12.5, 1.2 Hz, 1H, E), 5.84 (dt, J ˆ 6.1,
1
.6 Hz, 1H, Z), 4.64 (dt, J ˆ 12.5, 7.2 Hz,
1
3
3
H, E), 4.26 (dt, J ˆ 6.1, 6.7 Hz, 1H, Z),
.71 (s, 12H, E and Z), 3.54 (s, 3H, E),
.46 (s, 3H, Z), 2.83 (d, J ˆ 2.4 Hz, 2H,
E), 2.81 (d, J ˆ 2.8 Hz, 2H, Z), 2.13 ± 1.79
1
3
(
m, 8H, E and Z); C NMR (75 MHz,
CDCl
; DEPT): d ˆ 170.66 (C), 170.64
C), 147.70 (CH), 146.78 (CH), 104.96
CH), 101.40 (CH), 78.97 (C), 78.74 (C),
1.35 (C), 71.17 (C), 59.50 (CH ), 56.75
3
(
(
7
2
(
(
(
2
1
CH or CH
CH or CH
CH or CH
3
3
3
), 56.60 (CH or CH
), 53.44 (CH or CH
3
), 55.82
), 53.37
3
), 33.17 (CH
2
), 31.86 (CH
), 22.57 (CH
2
),
),
2.91 (CH
8.64 (CH
2
), 22.67 (CH
2
2
2
); elemental analysis calcd (%)
: C 61.40, H 7.14; found: C
1.69, H 7.48.
for C13
6
18 5
H O
Compound 11: yellow oil, 1:1 E/Z;
1
H NMR (300 MHz, CDCl
m, 1H), 5.70 (m, 1H), 3.73 (s, 6H), 3.72
s, 6H), 3.53 (s, 3H), 3.49 (s, 3H), 2.86 (d,
3
): d ˆ 5.77
(
(
J ˆ 3.8 Hz, 2H), 2.82 (d, J ˆ 3.8 Hz, 2H),
.15 ± 2.08 (m, 4H), 2.03 ± 1.90 (m, 4H),
1.80 ± 1.72 (m, 4H), 1.57 (d, J ˆ 1.6 Hz,
2
À1
Figure 7.Energy profile for the cyclization of the AuCl
3
complex XXVII (values in kcalmol ).
1
3
3
H), 1.51 (d, J ˆ 1.6 Hz, 3H); C NMR
(
75 MHz, CDCl
3
; DEPT): d ˆ 171.30 (C),
Et
3
N in hexane) provided substrates 1 ± 4, 10, 11, and 17 in 16 ± 48% (non
171.29 (C), 143.09 (CH), 142.87 (CH), 113.28 (C), 113.00 (C), 79.65 (CH),
79.37 (CH), 72.03 (C), 71.78 (C), 59.90 (CH ), 59.82 (CH ), 53.38 (CH ),
[
7b]
optimized) yields.Substrate 22 has been described before.
3
3
3
1
53.27 (CH
3
), 31.29 (CH
2
), 30.23 (CH
2
), 29.09 (CH
2
), 24.04 (CH
2
), 23.43
Compound 1: yellow oil, E isomer; H NMR (300 MHz, CDCl
3
): d ˆ 7 .7 2
(
CH ), 23.15 (CH
2
2
), 17.54 (CH
3
3
), 13.33 (CH ); FAB-HMRS: calcd for
(
(
3
d, J ˆ 8.3 Hz, 2H), 7.28 (d, J ˆ 8.3 Hz, 2H), 6.48 (d, J ˆ 12.5 Hz, 1H), 4.63
C
14
H
20
O
5
: 268.1311; found: 268.1319.
Compound 17: white vitreous solid, 6.2:1 E/Z; m.p. 65 ± 678C; 1H NMR
(300 MHz, CDCl
dt, J ˆ 12.5, 7.7 Hz, 1H), 4.10 (d, J ˆ 2.4 Hz, 2H), 3.75 (d, J ˆ 7.7 Hz, 2H),
1
3
.52 (s, 3H), 2.42 (s, 3H), 1.99 (t, J ˆ 2.4 Hz, 1H); C NMR (75 MHz,
; DEPT): d ˆ 152.66 (CH), 144.10 (C), 136.82 (C), 130.10 (CH),
28.40 (CH), 96.41 (CH), 78.10 (C), 74.24 (C), 56.70 (CH ), 45.49 (CH ),
S: 279.0929;
CDCl
3
3
): d ˆ 7.80 (d, J ˆ 8.5 Hz, 2H, E and Z), 7.25 (d, J ˆ 8.5 Hz,
1
3
3
2
2H, E and Z), 5.74 (m, 1H, E), 5.72 (m, 1H, Z), 4.40 (m, 1H, E and Z), 4.27
(dd, J ˆ 18.2, 2.4 Hz, 1H, Z), 4.25 (dd, J ˆ 18.6, 2.4 Hz, 1H, E), 3.87 (dd, J ˆ
18.2, 2.4 Hz, 1H, Z), 3.85 (dd, J ˆ 18.6, 2.4 Hz, 1H, E), 3.49 (s, 3H, Z), 3.33
5.61 (CH
2
), 22.21 (CH
3
); EI-HRMS: calcd for C14H17NO
3
found: 279.0919.
(
s, 3H, E), 2.43 (m, 2H, E and Z), 2.15 (t, J ˆ 2.4 Hz, 1H, Z and E), 2.19 ±
1
Compound 2: colorless oil, E isomer; H NMR (300 MHz, CDCl
3
): d ˆ 6.33
13
1
1
7
5
2
6
.36 (m, 6H, E and Z); C NMR (75 MHz, CDCl
70.74 (C), 150.15 (CH), 149.18 (CH), 99.84 (CH), 95.85 (CH), 79.71 (CH),
9.61 (CH), 71.27 (C), 70.96 (C), 66.26 (CH ), 65.99 (CH ), 60.24 (CH),
9.57 (CH), 40.39 (C), 40.13 (C), 30.40 (CH ), 26.64 (CH ), 22.87 (CH ),
2.53 (CH ), 20.80 (CH ); elemental analysis calcd (%) for C19 S: C
3
; DEPT): d ˆ 170.83 (C),
(
3
d, J ˆ 12.5 Hz, 1H), 4.41 (dt, J ˆ 12.5, 8.1 Hz, 1H), 4.37 (s, 6H), 3.44 (s,
H), 2.73 (d, J ˆ 2.8 Hz, 2H), 2.62 (dd, J ˆ 8.1, 1.2 Hz, 2H), 1.98 (t, J ˆ
.8 Hz, 1H); 13C NMR (75 MHz, CDCl
; DEPT): d ˆ 170.90 (C), 151.10
), 53.41
17 5
); FAB-HMRS: calcd for C12H O :
2
2
2
3
2
2
2
(
CH), 95.59 (CH), 79.48 (CH), 72.12 (C), 58.09 (C), 56.56 (CH
CH ), 31.40 (CH ), 23.03 (CH
41.1076; found: 241.1079.
3
2
3
H27NO
4
(
3
2
2
4.84, H 6.95, N 4.20; found: C 64.93, H 6.73, N 4.12.
2
1
Compound 20: yellow oil, 1: 1.8 Z:E; H NMR (300 MHz, CDCl
3
): d ˆ 7 .8 2
1
Compound 3: pale yellow oil, 1:0.7 E/Z; H NMR (300 MHz, CDCl
.33 (dt, J ˆ 11.9, 0.8 Hz, 1H, E), 6.00 (dt, J ˆ 6.7, 1.2 Hz, 1H, Z), 4.60 (dt,
J ˆ 11.9, 8.1 Hz, 1H, E), 4.27 (dt, J ˆ 8.1, 6.7 Hz, 1H, Z), 4.01 (s, 3H, E),
3
): d ˆ
(
d, J ˆ 8.5 Hz, 2H, Z isomer), 7.81 (d, J ˆ 8.5 Hz, 2H, E isomer), 7.27 (d, J ˆ
.5 Hz, 2H, Z isomer), 7.24 (d, J ˆ 8.5 Hz, 2H, E isomer), 5.76 (m, 1H, Z
isomer), 5.74 (m, 1H, E isomer), 4.41 (dd, J ˆ 7.1, 4.2 Hz, 1H, E isomer),
.29 (m, 1H, Z isomer), 4.22 (dc, J ˆ 18.20, 2.2 Hz, 1H, Z isomer), 4.18 (dc,
J ˆ 18.6, 2.2 Hz, 1H, E isomer), 3.86 (dc, J ˆ 18.20, 2.2 Hz, 1H, Z isomer),
6
8
2
.27 (d, J ˆ 2.8 Hz, 2H, Z), 2.24 (d, J ˆ 2.8 Hz, 2H, E), 2.22 (dd, J ˆ 8.1,
4
1
2
.2 Hz, 2H, Z), 2.08 (dd, J ˆ 8.1, 0.8 Hz, 2H, E), 2.06 (s, 6H), 2.05 (s, 6H),
1
3
.01 (t, J ˆ 2.8 Hz, 1H), 1.99 (t, J ˆ 2.8 Hz, 1H); C NMR (75 MHz,
; DEPT): d ˆ 170.83 (C), 170.74 (C), 150.15 (CH), 149.18 (CH), 99.84
CH), 95.85 (CH), 79.71 (CH), 79.61 (CH), 71.27 (C), 70.96 (C), 66.26
3
.82 (dc, J ˆ 18.6, 2.2 Hz, E isomer), 3.50 (s, 3H, Z isomer), 3.35 (s, 3H, E
CDCl
3
isomer), 2.42 (s, 3H, Z isomer), 2.40 (s, 3H, E isomer), 2.04 ± 1.8 (m, 2H, Z
(
(
(
and E isomers), 1.68 (t, J ˆ 2.2 Hz, 3H, E isomer), 1.65 (t, J ˆ 2.2 Hz, 3H, Z
CH
CH
2
), 65.99 (CH
), 26.64 (CH
2
), 60.24 (CH
3
), 59.57(CH
), 22.53 (CH
20 5
H O : C 62.67, H 7.51; found: C 62.48, H 7.74.
3
), 40.39 (C), 40.13 (C), 30.40
13
isomer), 1.57 ± 0.82 (m, 6H, Z and E isomer); C NMR (75 MHz, CDCl
3
,
2
2
), 22.87 (CH
2
2
), 20.80 (2 Â CH ); elemental
3
DEPT): d ˆ 143.54 (C), 143.07 (C), 143.02 (CH, E isomer), 142.15 (CH, Z
isomer), 138.81 (C), 138.52 (C), 129.73 (2 Â CH, Z isomer), 129.48 (2 Â CH,
E isomer), 128.52 (2 Â CH, E isomer), 128.24 (2 Â CH, Z isomer), 114.68
(C), 114.60 (C), 80.78 (C), 80.28 (C), 76.41 (C), 75.93 (C), 60.32, 60.09,
analysis calcd (%) for C14
1
Compound 4: colorless oil, 1:0.8 E/Z; H NMR (300 MHz, CDCl
3
): d ˆ 6.32
(
8
d, J ˆ 12.5 Hz, 1H, E), 6.28 (dt, J ˆ 6.3, 1.2 Hz, 1H, Z), 4.71 (dt, J ˆ 12.5,
.1 Hz, 1H, E), 4.37 (dt, J ˆ 7.8, 6.3 Hz, 1H, Z), 3.60 (s, 4H, Z), 3.57 (s, 4H,
59.13, 55.40, 36.81 (CH
(CH ), 27.68 (CH ), 26.22 (CH
22.14 (CH ), 22.10 (CH
), 4.15 (2 Â CH
2
), 34.74 (CH
2
), 33.09 (CH
2 2
), 32.55 (CH ), 29.67
E), 3.53 (s, 3H, Z), 3.49 (s, 3H, E), 2.25 (d, J ˆ 2.8 Hz, 2H), 2.21 (dd, J ˆ 7 .8 ,
2
2
2
), 25.98 (CH
2
), 25.34 (CH
2
), 23.76 (CH
2
),
‡
1
.2 Hz, 2H, Z), 2.03 (dd, J ˆ 8.1, 1.0 Hz, 2H, E), 1.91 ± 1.88 (t,
3
3
3
); EI-MS: m/z: 347 (1) [M] , 316
Chem. Eur. J. 2003, 9, 2627 ± 2635
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
2633

A.M.Echavarren et al.
FULL PAPER
(
C
23), 302 (21), 242 (18), 192 (100); elemental analysis calcd (%) for
S: C 65.68, H 7.25, N 4.03; found: C 65.63, H 7.14, N 4.25; EI-
HRMS: calcd for C19 S: 347.1555; found: 347.1569.
Compound 15: TIPS enol ether 15 was prepared in 80% yield following the
53.14 (CH
(CH ); elemental analysis calcd (%) for C14
59.15, H 7.86.
3
), 52.61 (2 Â CH
3
), 43.99 (CH), 39.07 (CH
2 2
), 28.88 (CH ), 25.21
19
H
25NO
3
2
22 6
H O
: C 58.73, H 7.74; found: C
H
25NO
3
Dimethyl 4-dimethoxymethyl-4-methyl-3-methylenecyclohexane-1,1-di-
procedure described for the corresponding diethyl ester.[
(
1
1
1
7b]
1
H NMR
): d ˆ 4.82 (brs, 1H), 3.71 (s, 3H), 3.68 (s, 3H), 3.15 (m,
H), 2.79 (d, J ˆ 2.8 Hz, 2H), 1.97 (t, J ˆ 2.8 Hz, 1H), 2.10 ± 1.29 (m, 6H),
; DEPT): d ˆ 170.25 (C),
70.17 (C), 152.85 (C), 103.21 (CH), 79.73 (CH), 70.09 (C), 60.60 (C), 52.43
), 38.99 (CH), 29.45 (CH ), 24.12 (CH ), 22.39 (CH ), 22.34 (CH ),
7.93 (CH ), 12.43 (CH).
1
carboxylate (13): pale yellow oil; H NMR (300 MHz, CDCl ): d ˆ 4.94
3
300 MHz, CDCl
3
(brs, 1H), 4.86 (brs, 1H), 4.31 (s, 1H), 3.72 (s, 3H), 3.70 (s, 3H), 3.51 (s,
3H), 3.45 (s, 3H), 2.81 (m, 2H), 1.99 (m, 1H), 1.86 (m, 1H), 1.42 ± 1.31 (m,
.14 ± 1.04 (m, 21H); 13C NMR (75 MHz, CDCl
13
3
2H), 1.02 (s, 3H); C NMR (75 MHz, CDCl ; DEPT): d ˆ 172.93 (C), 171.
3
76 (C), 147.30 (C), 113.53 (CH ), 110.16 (CH), 59.31 (CH ), 58.95 (CH ),
2
3
3
(
1
2 Â CH
3
2
2
2
2
3 3 2 2
57.33 (C), 53.35 (CH ), 53.10 (CH ), 45.06 (C), 38.68 (CH ), 32.18 (CH ),
3
28.05 (CH ), 20.05 (CH ); EI-HRMS: calcd for C H O : 269.1389; found:
2
3
14 21
5
‡
2
69.1391 [M À OCH
3
] .
General procedure for the cyclization of w-acetylenic enol ethers: A
mixture of the w-acetylenic enol ethers (0.15 mmol) and the catalyst (0.05 ±
0
After being cooled to room temperature, the solvent was evaporated and
the residue was purified by chromatography on silica gel deactivated with
5
Dimethyl 4-formyl-4-methyl-3-methylenecyclohexane-1,1-dicarboxylate
1
.1 equiv) was heated in methanol (4 mL) under reflux under Ar for 17 h.
(14): yellow oil; H NMR (300 MHz, CDCl ): d ˆ 9.32 (d, J ˆ 1.22 Hz,
3
1H), 5.15 (brs, 1H), 4.95 (brs, 1H), 3.72 (s, 3H), 3.71 (s, 3H), 2.93 (dd, J ˆ
4.1, 2.0 Hz, 1H), 2.50 (dt, J ˆ 4.1, 1.7 Hz, 1H), 2.27 (dd, J ˆ 13.2, 2.0 Hz,
1H), 2.13 (dt, J ˆ 13.2, 4.1 Hz, 1H), 2.02 ± 1.90 (m, 1H), 1.57 ± 1.46 (m, 1H),
3
% Et N in hexane.Although the reactions were faster at higher
1
3
concentrations, substantial amounts of the corresponding aldehydes were
observed.
1.15 (s, 3H); C NMR (75 MHz, CDCl ; DEPT): d ˆ 202.77 (C), 171.48
3
(2 Â C), 143.09 (C), 114.48 (CH ), 56.14 (C), 52.76 (CH ), 52.54 (CH ), 51.81
2
3
3
(
C), 38.50 (CH
2
), 30.22 (CH
2
2 3
), 27.85 (CH ), 19.84 (CH ); elemental analysis
N-(p-Toluenesulfonyl)-3-dimethoxymethyl-4-methylenepyrrolidine
pale yellow oil; H NMR (300 MHz, CDCl
(5):
1
13 18 5
calcd (%) for C H O : C 61.40, H 7.14; found: C 61.28, H 7.16.
3
): d ˆ 7.70 (d, J ˆ 8.1 Hz, 2H),
7
1
.33 (d, J ˆ 8.1, 0.8 Hz, 2H), 5.12 (q, J ˆ 2.3 Hz, 1H), 5.01 (q, J ˆ 2.3 Hz,
Dimethyl 3-methyl-4-oxo-2,4,5,6,7,7a-hexahydroindene-1,1-dicarboxylate
(16): white vitreous solid; m.p. 106 ± 1088C; H NMR (300 MHz, CDCl ):
H), 4.13 (d, J ˆ 7.3 Hz, 1H), 3.79 (m, 2H), 3.42 (dd, J ˆ 10.1, 2.3 Hz, 1H),
.31 (s, 3H), 3.27 (s, 3H), 3.18 (dd, J ˆ 10.1, 6.5 Hz, 1H), 2.90 (m, 1H), 2.43
1
3
3
(
d ˆ 3.75 (s, 3H), 3.72 (s, 3H), 3.09 (brd, J ˆ 18 Hz, 1H), 2.77 (brd, J ˆ
s, 3H); 13C NMR (75 MHz, CDCl
; DEPT): d ˆ 143.66 (C), 143.10 (C),
3
18 Hz, 1H), 2.45 (m, 1H), 2.23 ± 2.10 (m, 2H), 2.09 (s, 3H), 2.07 ± 1.98 (m,
1
(
32.44 (C), 129.62 (CH), 127.90 (CH), 109.71 (CH
), 53.74 (CH ), 52.62 (CH ), 49.61 (CH ), 45.26 (CH), 21.50 (CH
HRMS: calcd for C15 S: 311.1191; found: 311.1181.
Dimethyl 3-dimethoxymethyl-4-methylenecyclopentane-1,1-dicarboxylate
2
), 104.72 (CH), 59.19
2H), 1.84 ± 1.68 (m, 1H), 1.15 (qd, J ˆ 12.7, 2.8 Hz, 1H); 13C NMR (75 MHz,
CH
3
3
2
2
3
); EI-
CDCl ; DEPT): d ˆ 199.23 (C), 171.67 (C), 170.70 (C), 149.51 (C), 131.88
3
H
21NO
4
(C), 61.91 (C), 52.73 (CH ), 52.29 (CH ), 51.90 (CH ), 46.04 (CH ), 40.57
2
3
2
3
(CH
3
2 18 5
), 27.49, 23.39, 15.66 (CH ); elemental analysis calcd (%) for C14H O :
6): yellow oil; 1H NMR (300 MHz, CDCl
C 63.15, H 6.81; found: C 63.53, H 7.12.
(
1
2
3
): d ˆ 5.05 (m, 1H), 5.01 (m,
H), 4.24 (d, J ˆ 6.5 Hz, 1H), 3.71 (s, 6H), 3.35 (s, 3H), 3.33 (s, 3H), 2.85 ±
cis-3a-Dimethoxymethyl-3-methylene-N-(p-toluenesulfonyl)octahydroin-
dole (18): white vitreous solid; m.p. 84 ± 878C; H NMR (300 MHz,
1
3
1
.93 (m, 3H), 2.52 (m, 1H); 2.10 (m, 1H); C NMR (75 MHz, CDCl
), 109.30 (CH ), 106.62
), 52.71 (CH ), 52.65 (CH ), 44.54
); EI-HRMS: calcd for C12 : 241.1076;
)] ; elemental analysis calcd (%) for C13
3
;
DEPT): d ˆ 172.02 (C), 171.82 (C), 147.11 (CH
2
2
CDCl ): d ˆ 7.74 (d, J ˆ 8.1 Hz, 2H), 7.30 (d, J ˆ 8.1 Hz, 2H), 5.16 (t, J ˆ
3
(
(
CH), 58.40 (C), 53.96 (CH
CH), 41.75 (CH
3
), 53.91 (CH
3
3
3
2.0 Hz, 1H), 5.04 (m, 1H), 4.11 (dt, J ˆ 13.9, 2.6 Hz, 1H), 4.01 (m, 1H), 3.93
2
), 35.19 (CH
2
‡
H
17
O
5
(dt, J ˆ 13.9, 2.0 Hz, 1H), 3.76 (s, 1H), 2.42 (s, 3H), 1.90 ± 1.81 (m, 2H),
found: 241.1086 [M À OCH
3
H
20
O
6
:
1.69 ± 1.59 (m, 1H), 1.52 ± 1.42 (m, 2H), 1.17 ± 1.05 (m, 3H); C NMR
13
C 57.34, H 7.40; found: C 57.73, H 7.74.
(75 MHz, CDCl ; DEPT): d ˆ 144.46 (C), 142.96 (C), 137.24 (C), 129.48
3
1
,1-Bis(acetoxymethyl)-3-dimethoxymethyl-4-methylenecyclopentane (7):
2 3
(CH), 127.17 (CH), 109.74 (CH ), 108.15 (CH), 61.21 (CH), 59.68 (CH ),
1
57.95 (CH ), 54.71 (C), 50.02 (CH ), 28.97 (CH ), 22.61 (CH ), 22.53 (CH ),
yellow oil; H NMR (300 MHz, CDCl
4
2
3
): d ˆ 5.05 (brs, 1H), 5.04 (brs, 1H),
.23 (d, J ˆ 6.1 Hz, 1H), 4.08 ± 3.73 (m, 4H), 3.37 (s, 3H), 3.34 (s, 3H),
.90 ± 2.80 (m, 1H), 2.26 (brs, 2H), 2.04 (s, 6H), 1.84 ± 1.75 (m, 1H), 1.65 ±
.55 (m, 1H); 13C NMR (75 MHz, CDCl
C), 149.20 (C), 110.18 (CH ), 107.82 (CH), 68.23 (CH
CH ), 54.78 (CH ), 44.79 (CH), 44.65 (C), 41.08 (CH
2 Â CH ); elemental analysis calcd (%) for C15
3
2
2
2
2
21.47 (CH
3
), 20.14 (CH
2
); elemental analysis calcd (%) for C19
H
27NO
4
S: C
62.44, H 7.45, N 3.83; found: C 62.44, H 7.26, N 3.75.
1
3
; DEPT): d ˆ 171.79 (C), 171.71
cis-4a-Dimethoxymethyl-N-(p-toluenesulfonyl)-1,2,4a,5,6,7,8,8a-octahy-
droquinoline (19): white vitreous solid; m.p. 137 ± 1408C; H NMR
(
(
(
2
2
), 66.23 (CH
), 33.41 (CH
2
), 54.89
), 21.53
1
3
3
2
2
(
5
3
300 MHz, CDCl
3
): d ˆ 7.72 (d, J ˆ 8.1 Hz, 2H), 7.30 (d, J ˆ 8.1 Hz, 2H),
.75 (ddd, J ˆ 10.2, 3.8, 2.1 Hz, 1H), 5.50 (m, 1H), 4.33 (s, 1H), 4.10 (m,
H), 3.62 (s, 3H), 3.48 (s, 3H), 3.30 (dt, J ˆ 16.9, 2.1 Hz, 2H), 2.43 (s, 3H),
3
24 6
H O : C 59.98, H 8.05;
found: C 60.30, H 8.16.
1
3
1
-Hydroxymethyl-4-methoxy-6-methylene-3-oxabicyclo[3.2.1]octane (8):
1.80 ± 1.08 (m, 8H); C NMR (75 MHz, CDCl
3
; DEPT): d ˆ 143.06 (C),
1
colorless oil; H NMR (300 MHz, CDCl
3
): d ˆ 4.96 (brs, 1H), 4.92 (brs,
137.29 (C), 131.34 (CH), 129.59 (CH), 127.13 (CH), 123.18 (CH), 110.71
1
3
1
H), 4.43 (d, J ˆ 2.4 Hz, 1H), 3.80 (dd, J ˆ 10.1, 1.2 Hz, 1H), 3.53 ± 3.48 (m,
(CH), 59.38 (CH
3
), 58.44 (CH
3
), 53.29 (CH), 45.90 (C), 40.94 (CH ), 27.75
2
H), 3.39 (s, 3H), 2.65 (m, 1H), 2.47 (m, 1H), 2.19 (m, 1H), 2.03 (dd, J ˆ
0.9, 2.8 Hz, 1H), 1.39 (ddd, J ˆ 10.9, 4.8, 2.8 Hz, 1H), 1.39 (overlapping
(CH ), 24.37 (CH
2
2
), 23.25 (CH
2
), 21.44 (CH ), 20.87 (CH ); elemental
3
2
analysis calcd (%) for C19
H
27NO S: C 62.44, H 7.45, N 3.83; found: C 62.24,
4
1
3
signal, OH); C NMR (75 MHz, CDCl
(
(
1
3
; DEPT): d ˆ 149.95 (C), 106.45
H 7.19, N 3.72.
CH
2
), 101.99 (C), 77.26 (C), 69.69 (CH
2
), 67.29 (CH
2 3
), 54.60 (CH ), 47.97
cis-4a-Dimethoxymethyl-4-methyl-N-(p-toluenesulfonyl)-1,2,4a,5,6,7,8,8a-
CH), 37.20 (CH
2
), 32.30 (CH
2
); GC/EI-HRMS: calcd for C
9
H
13
O
2
:
1
octahydroquinoline (21): colorless oil; H NMR (300 MHz, CDCl
3
): d ˆ
‡
53.0916 [M À OMe] ; found: 153.0910.
,1-Bis(triisopropylsilyloxymethyl)-3-dimethoxymethyl-4-methylenecyclo-
7
.69 (d, J ˆ 8.5 Hz, 2H), 7.27 (d, J ˆ 8.5 Hz, 2H), 5.47 (m, 1H), 4.29 (s, 1H),
1
4.10 ± 4.01 (m, 2H), 3.57 (s, 3H), 3.45 (s, 3H), 3.32 (m, 1H), 2.40 (s, 3H),
1
13
pentane (9): colorless oil; H NMR (300 MHz, CDCl
4
(
1
3
): d ˆ 4.99 (m, 1H),
1.98 ± 1.93 (m, 1H), 1.76 (m, 3H), 1.63 ± 0.82 (m, 7H); C NMR (75 MHz,
.91 (m, 1H), 4.19 (d, J ˆ 6.9 Hz, 1H), 3.63 ± 3.37 (m, 4H), 3.36 (s, 3H), 3.30
CDCl
127.89 (2 Â CH), 120.87 (CH), 112.08 (CH), 60.24 (CH
(CH), 48.77 (C), 42.44 (CH ), 37.29 (CH ), 25.35 (CH
(CH ), 22.17 (CH ), 20.80 (CH
3
, DEPT): d ˆ 136.09 (C), 130.26 (2  CH), 129.85 (C), 128.70 (C),
), 58.76 (CH ), 55.16
), 22.59
s, 3H), 2.78 (m, 1H), 2.32 ± 2.16 (m, 2H), 1.74 (dd, J ˆ 13.5, 8.5 Hz, 1H),
3
3
1
3
.50 (dd, J ˆ 13.5, 9.9 Hz, 1H), 1.05 ± 1.01 (m, 42H); C NMR (75 MHz,
2
2
2
), 24.46 (CH
2
‡
CDCl
3
; DEPT): d ˆ 151.68 (C), 108.79 (CH
), 54.74 (CH ), 53.60 (CH ), 49.17 (C), 45.09 (CH), 39.88 (CH
), 18.74 (CH
Si : C 65.85, H 11.43; found: C 66.00, H 11.44.
Dimethyl 4-dimethoxymethyl-3-methylenecyclohexane-1,1-dicarboxylate
2
), 107.87 (CH), 67.40 (CH
2
),
2
3
3
); EI-MS: m/z: 379 (12) [M] , 348 (42), 304
6
3
5.84 (CH
2.57 (CH
2
3
3
2
),
(17), 260 (32), 192 (100); EI-HRMS: calcd for C20
found: 347.1818.
4
H29NO S: 379.1817;
2
3
), 12.63 (CH);eacp;elemental analysis calcd (%)
for C29
H
60
O
4
2
2
-(tert-Butyldimethylsilyloxy)-1-methylcyclohexa-2,4-dienecarboxylic eth-
1
yl ester (23): yellow oil; H NMR (300 MHz, CDCl
3
): d ˆ 5.84 ± 5.77 (m,
(
(
2
(
12): colorless oil; 1H NMR (300 MHz, CDCl
3
): d ˆ 4.90 (brs, 1H), 4.85
1H), 5.42 ± 5.35 (m, 1H), 5.07 (d, J ˆ 5.9 Hz, 1H), 4.19 ± 4.04 (m, 2H), 2.93
brs, 1H), 4.47 (d, J ˆ 8.1 Hz, 1H), 3.71 (s, 6H), 3.35 (s, 3H), 3.33 (s, 3H),
(ddd, J ˆ 17.2, 3.8, 2.2 Hz, 1H), 2.16 (ddd, J ˆ 17.2, 4.8, 1.4 Hz, 1H), 1.28 (s,
.72 (dt, J ˆ 14.5, 8.1 Hz, 2H), 2.40 (m, 1H), 2.13 (m, 1H), 2.0 (m, 1H), 1.83
6H), 1.24 (t, J ˆ 7.2 Hz, 3H), 0.91 (s, 9H), 0.20 (s, 3H), 0.19 (s, 3H);
m, 1H), 1.65(m, 1H); 1 C NMR (75 MHz, CDCl
3
; DEPT): d ˆ 171.53 (C),
13
C NMR (75 MHz, CDCl
, DEPT): d ˆ 175.81 (C), 154.75 (C), 123.48
3
3
1
71.41 (C), 142.62 (C), 112.43 (CH
2
), 103.91 (CH), 56.81 (C), 53.31 (CH
3
),
(CH), 116.52 (CH), 100.24 (CH), 60.68 (CH
2
), 36.03 (CH
2
), 25.41 (3 Â
2634
¹ 2003 WILEY-VCH Verlag GmbH & Co.KGaA, Weinheim
www.chemeurj.org Chem. Eur. J. 2003, 9, 2627 ± 2635

Cyclizations of Enol Ethers
2627±2635
CH
was confirmed by COSY and HMBC experiments.
Computational methods: The calculations were performed with the
3
), 20.04 (CH
3
), 17.96 (C), 14.13 (CH
3
), À0.5 (2 Â CH
3
).The structure
3873; c) H.Kusama, H.Yamabe, N.Iwasawa, Org. Lett. 2002, 4, 2569 ±
2571; d) N.Iwasawa, T.Miura, K.Kiyota, H.Kusama, K.Lee,
Org.
Lett. 2002, 4, 4463 ± 4466.
[
21]
[8] Relative nucleophilicities of enol ethers: a) J.Burfeinds, M.Patz, M.
M¸ller, H.Mayr, J. Am. Chem. Soc. 1998, 120, 3629 ± 3634; b) H.
Shimmel, G.Remennikov, A.R.Ofial, R.Loss, B.Kempf, B.Janker,
GAUSSIAN 98 series of programs.
The geometries of all complexes
were optimized at the DFT level using the B3LYP hybrid functional.[ The
22]
standard 6-31G(d) basis set was used for C, H, O, and Cl and the
LANL2DZ relativistic pseudo potential was used for Pt and Au.Harmonic
frequencies were calculated at the same level of theory to characterize the
stationary points and to determine the zero-point energies (ZPE).Intrinsic
reaction coordinate calculations (IRC) were performed to ensure that the
transition states actually connect the proposed reagents and products.The
bonding characteristics of the different local minima were analyzed by
means of two different partition techniques, namely, the atoms in molecules
B.Irrgang, N.Hering, M .F .Gotta, T.Bug, H.Mayr,
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[
10] HgCl -promoted cyclization of trimethylsilyl enol ethers with alkynes:
2
a) M.A.Boaventura, J.Drouin, Bull. Soc. Chim. Fr. 1987, 1015 ± 1026;
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[
23]
with EtAlCl : K.Imamura, E.Yoshikawa, V.Gevorgyan, Y.Yama-
(
AIM) theory of Bader and a Natural Bond Orbital (NBO) analysis of
2
[
24]
moto, Tetrahedron Lett. 1999, 40, 4081 ± 4084.
Weinhold et al. The first approach is based in a topological analysis of the
electron charge density, 1(r) and its Laplacian ! 1(r).More specifically, we
2
[11] The starting enol ethers were readily prepared by Wittig alkenylation
of the corresponding aldehydes and ketones.
12] Almost quantitative cyclizations were also realized at room temper-
ature in some cases.
13] At shorter reaction times, 7 and the acetate of 8 were also obtained.
14] endo Cyclizations have been observed in the reaction of allyl silanes
have located the so called bond critical points (bcp), i.e., points where 1(r)
is minimum along the bond path and maximum in the other two directions.
These points are associated with the positions of the chemical bonds.The
NBO technique permits to describe the different bonds of the system in
terms of the natural hybrid orbitals centered on each atom and provides
also useful information on the charge distribution of the system.
[
[
[
4
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Acknowledgement
We are grateful to the MCyT (Project BQU2001-0193-C02-01) for support
of this research and to the CAM for a predoctoral fellowship to C.N. We
also acknowledge Johnson Matthey PLC for a generous loan of PtCl
PdCl
[
[
[
2
and
2
.
[
[
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2
was found with a substrate derived from
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Received: December 6, 2002 [F4646]
Chem. Eur. J. 2003, 9, 2627 ± 2635
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
2635