Gold(I)-catalyzed intramolecular cyclopropanation of dienynes

Article abstract of DOI:10.1002/chem.200501089

Gold(I) complexes are the most active catalysts for the biscyclopropanation of dienynes to form tetracyclic compounds. Pt^II and Zn^II are also able to promote the biscyclopropanation, although less efficiently. The configurations obta

Full text of DOI:10.1002/chem.200501089

DOI: 10.1002/chem.200501089
Gold(i)-Catalyzed Intramolecular Cyclopropanation of Dienynes
Cristina Nieto-Oberhuber,[a, b] SalomØ López,[a] M. Paz MuÇoz,[b]
Eloísa JimØnez-NfflÇez,[a, b] Elena BuÇuel,[b] Diego J. Cµrdenas,[b] and
Antonio M. Echavarren*[a, b]
Abstract: Gold(i) complexes are the
most active catalysts for the biscyclo-
propanation of dienynes to form tetra-
cyclic compounds. PtII and ZnII are also
able to promote the biscyclopropana-
tion, although less efficiently. The con-
figurations obtained in all cases with
the use of gold(i) catalysts can be ex-
plained by the pathway proceeding
through anti cyclopropyl gold carbenes.
Similar intermediates are most proba-
bly involved in reactions catalyzed by
RuII and PtII. Two different cyclopropa-
nation pathways have been found; they
depend on the structures of the cyclo-
propyl gold carbenes (anti or syn) and
the relative arrangements of the metal
carbenes and the alkenes.
Keywords: alkynes · cyclization ·
density functional calculations
·
gold · platinum · zinc
Introduction
Transition-metal-catalyzed reactions of 1,6-enynes[1,2] that
proceed through the selective coordination of the metal to
the alkyne (I) take place through exo-cyclopropyl metal car-
benes II or the related endo intermediates (Scheme 1).[2,3]
Reactions between II and alcohols or water gives products
of alkoxy- or hydroxycyclization III. In the absence of nucle-
ophiles, enynes undergo skeletal rearrangements to form
dienes IV (single cleavage) and/or V (double cleavage).[4,5]
We proposed the involvement of intermediates II in PtII-
catalyzed cyclization of enynes on the basis of DFT calcula-
tions[2a,b] and the isolation of cyclopropanecarbaldehyde in
PtII-[2b] or PdII-mediated hydroxycyclization[6] of certain
enynes. Recently, we have also proposed similar intermedi-
ates in AuI-catalyzed hydroxy- and alkoxycyclization[3,7] and
Scheme 1. exo-Cyclization of enynes through cyclopropyl metal carbenes
II.
the skeletal rearrangements of 1,6-enynes.[8] Cyclopropyl de-
rivatives were also obtained by Trost et al. in intermolecular
reactions between dienynes and alkenes.[9] Other theoretical
work has also supported the involvement of intermediates II
in these reactions.[2,3,10]
Strong evidence for the existence of intermediates such as
II was also obtained in the reactions of dienynes such as 1
catalyzed by electrophilic metal complexes described by
Muraiꢀs group (Scheme 2).[11] The ruthenium carbene inter-
mediate is trapped intramolecularly by the terminal alkene
yielding tetracycle 2 containing two cyclopropanes.
[a] C. Nieto-Oberhuber, Dr. S. López, E. JimØnez-NfflÇez,
Prof. Dr. A. M. Echavarren
Institute of Chemical Research of Catalonia (ICIQ)
Av. Països Catalans 16, 43007 Tarragona (Spain)
Fax : (+34)977-920-225
E-mail: aechavarren@iciq.es
[b] C. Nieto-Oberhuber, M. P. MuÇoz, E. JimØnez-NfflÇez, Dr. E. BuÇuel,
Dr. D. J. Cµrdenas, Prof. Dr. A. M. Echavarren
Departamento de Química Orgµnica
Universidad Autónoma de Madrid
Cantoblanco, 28049 Madrid (Spain)
Malacriaꢀs group has described related examples in the
PtCl2-catalyzed reactions of substrates 3, containing prop-
argyl alcohol or ether units in their structures, to form tetra-
Supporting information (atomic coordinates for structures) for this ar-
ticle is available on the WWW under http://www.chemeurj.org/ or
from the author.
1694
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 1694 – 1702

FULL PAPER
Here we report details of this work, including a theoretical
study of the AuI-catalyzed intramolecular cyclopropanation.
Results and Discussion
Scope of the intramolecular cyclopropanation: In addition
to readily available [Au(PPh3)Cl],[15] we also assayed as cat-
alysts the new AuI complexes 6a-e,[16] with bulky, biphenyl-
Scheme 2. RuII-catalyzed biscyclopropanation of dienyne 1.[11]
cycles 4 (Scheme 3).[12] In this reaction, the cyclopropyl plati-
num carbene VII is probably formed as an intermediate.[10]
based phosphanes.[17] Cationic complex 7 was prepared by
chloride abstraction of [Au(PPh3)Cl] with AgSbF6 in aceto-
nitrile. Complexes with N-heterocyclic donor ligands 8a–c[18]
were also tested as catalysts. Complex 8a and several relat-
ed complexes have been independently prepared by Nolan
et al.[19]
Scheme 3. PtII-catalyzed biscyclopropanation of dienynes 3.[12]
In a cyclization of this kind, the relative configuration of
the second cyclopropane is determined by the conformation
We had found that dienynes 9–11 react with a catalyst
formed from [Au(PPh3)Me] and protic acid in MeOH to
give methoxycyclization products 12–14 exclusively
(Scheme 5).[3,7]
À
of the cyclopropyl metal carbene around the single C C
bond. The observed stereochemistry of the last cyclopropa-
nation can be interpreted by assuming a more favored anti-
periplanar arrangement of the cyclopropane and the metal
carbene (anti-VIIIa) (Scheme 4), which is in full agreement
Scheme 4. syn- and anti-Cyclopropyl metal carbenes.
with the results of the calculations.[2b,c,3] Such an arrange-
ment is also consistent with the results of Brookhart
et al.,[13] which show preferred antiperiplanar conformations
for iron (5a) and ruthenium (5b) cyclopropyl carbene com-
plexes.
Scheme 5. Methoxycyclization of dienynes 9–11.
In the absence of MeOH, dienyne 9 reacts with a variety
of AuI complexes to give tetracycle 15 as the major or exclu-
sive product under very mild conditions (Table 1). An active
catalyst could also be generated by treatment of [Au-
(PPh3)Me] with trifluoroacetic acid (TFA). No reaction was
observed in DMF or in the presence of additional PPh3
Using cationic gold(i) complexes [Au(PPh3)]+ XÀ (X =
BF4, Sb F), we have recently reported examples of biscyclo-
6
propanation reactions occurring at temperatures much
lower that those required with RuII and PtII catalysts.[3,14]
Chem. Eur. J. 2006, 12, 1694 – 1702
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1695

A. M. Echavarren et al.
Table 1. Intramolecular cyclopropanation of dienyne 15 with [AuI]
(2 mol%).
Table 2. Intramolecular cyclopropanation of dienyne 9 in the presence of
PtII (5 mol%) or ZnII.
Entry Catalyst[a]
AuCl
T [8C] t [h] Product(s) (yield [%])
23
À40
À40
À40
À40
À40
À40
À40
À30
1
3
3
3
3
3
3
3
15 (60) + 16 (2%)
15 (13)
15 (22)
15 (47)
15 (55)
15 (24)
15 (64)
15 (50)
1
AuCl/AgSbF6
2
[Au(SMe2)Cl]/AgSbF6
Entry MXn [mol%]
L[a]
t
Product(s) (yield,
[%]; ratio)[b]
3
[Au(PPh3)Cl]/AgSbF6
[h]
4
[Au(PCy3)Cl]/AgSbF6
1
2
PtCl2 (5)
PtCl2 (5)
–
17
17
15 (30)
15 + 16 + 17 (70;
3:1.6:1)
5
[Au{P(C6F5)3}Cl]/AgSbF6
PCy3
6
[Au{P(o-Tol)3}Cl]/AgSbF6
7
[Au(AsPh3)Cl]/AgSbF6
3
PtCl2 (5)
P(oTol)3
17
15 + 16 + 17 (89;
6:8:1)
8
9
[Au(PPh3)Cl]/AgBF4
0.3 15 (78) + 16 (7)
[Au(PPh3)Me]/TFA[b]
23 240
15 (63)
10
11
12
13
14
15
6a
6c
7
8a
8b
8c
À40
À40
23
À40
À40
À40
3
3
15 (78)
15 (49) + 16 (30)
15 + 16 + 17 (74;
4
PtCl2 (5)
17
2:2.6:1)
0.1 15 (98)
3
3
3
15 (71)
15 (71)
15 (79)
15 + 16 + 17 (77;
5
6
PtCl2 (5)
17
1.7:2.6:1)
[a] 2 mol% AuI complex and (for reactions in entries 1–8, 10, 11, 13–15)
2 mol% AgI salt. [b] 3 mol% gold(i) and 6 mol% TFA.
[ZnCl2(PPh3)]/
AgSbF6 (50)
[ZnCl2(PPh3)]
Zn(OTf)2 (50)
Zn(OTf)2 (50)
-
0.5
15 (9) + 16 (21)[c]
7
8
9
-
-
7[d]
16 (11)[e]
16 (10)[f]
16 (7)[g]
(1 equiv). The tetracyclization was usually complete with
quantitative conversion in less than 3 h at À408C with most
AuI catalysts, the exceptions being catalysts generated from
AuCl, [Au(SMe2)Cl], and [Au{P(C6F5)3}Cl]/(Table 1, en-
tries 1, 2, and 5), which gave lower yields. For preparative
purposes, the best conversion was achieved by use of cation-
ic catalyst 7, which resulted in almost quantitative formation
of tetracycle 15 in just 5 min at room temperature (Table 1,
entry 12). Whilst skeletal rearrangement derivative 16 could
also be detected as a minor product in some of the reactions,
a substantial amount of 16 was formed with complex 6c
(Table 1, entry 11), which bears a rather bulky phosphane as
ligand.
15[d]
24[d]
PPh3
[a] An equimolar amount of L was used. [b] Yield of isolated product;
product ratios determined by GC and/or 1H NMR spectroscopy. [c] 88%
conversion; yield of 16 determined by 1H NMR spectroscopy. [d] Re-
action performed at 708C. [e] 71% conversion; yield of 16 determined by
1H NMR spectroscopy. [f] 65% conversion; yield of 16 determined by
1H NMR spectroscopy. [g] 74% conversion; yield of 16 determined by
1H NMR spectroscopy.
Tetracycles were also obtained in the reactions of other
dienynes (Scheme 6). The disulfone 10 and the diacetate 19
cyclized in excellent yields in the presence of catalyst 7 in
5 min at room temperature to give the tetracycles 18 and 20,
respectively. In the case of the N-toluene-4-sulfonyl deriva-
tive 21, use of the cationic AuI complex 7 gave a 50% yield,
whereas a better yield was obtained with [Au(PPh3)Cl] and
AgSbF6 in CH2Cl2 at 08C. The propargyl ester 23 afforded
24 as a single isomer in the presence of the neutral AuI com-
plex 8c. The cyclization of 25, an analogue of substrate 1
(Scheme 2) with three additional methyl groups on the al-
kenes, provided the tetracycle 26 in good yield under very
mild conditions. On the other hand, the reaction of 27 in the
presence of catalyst 7 was relatively slower and provided a
mixture of the tetracycle 28 and the skeletal rearrangement
product 29.
The use of PtII and ZnII as catalysts in the tetracyclization
of 9 was also examined (Table 2). In all cases, reactions cata-
lyzed by PtII were slower than those catalyzed by AuI
(Table 1). The reaction proceeded more satisfactorily with
complexes prepared in situ from PtCl2 and 1 equivalent of
PCy3 as ligand, which gave the best selectivity and yield of
15 (ca. 37%) (Table 2, entry 2). With other bulky phos-
phanes, in addition to tetracycle 15, the skeletal rearrange-
ment product 16 was obtained as the major compound,
along with Alder-ene cycloisomerization derivative 17[2a,b]
(Table 2, entries 3–5). Interestingly, although ZnII has
seldom been used in enyne cyclizations,[20] we found that 9
reacted in the presence of [ZnCl2(PPh3)][21] and AgSbF6
(50 mol% each) in 1,2-dichloroethane at room temperature
to afford a mixture of tetracycle 15 and skeletal rearrange-
ment product 16, although the yield of isolated product was
low (Table 2, entry 6). With [ZnCl2(PPh3)] or Zn(OTf)2 in
the absence of AgI, 16 was obtained along with other un-
characterized compounds (Table 2, entries 7–9).
In all cases single diastereomers were obtained. The con-
figurations of the tetracyclic compounds were determined
by NOESY experiments. In the case of the bissulfone 18,
the configuration was confirmed by an X-ray structure de-
termination (Figure 1).
1696
www.chemeurj.org
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 1694 – 1702

Gold(i)-Catalyzed Intramolecular Cyclopropanation
FULL PAPER
It is interesting to note that tetracycles 15, 18, 20, 22, and
24 possess the same carbon skeleton as myliol (30), an un-
usual sesquiterpene that was isolated as the major compo-
nent of pentane extracts of the liverwort (Hepaticae) Mylia
taylorii.[22,23] Other members of this family of sesquiterpene
are anastreptene (31),[24] dihydromylione A (32),[25] and
myli-4(15)-en-9-one (33).[26]
Stereoselectivity and the mechanism of the double cyclopro-
panation: The relative configuration between the two cyclo-
propane rings common to the natural products 30–33 is the
opposite of that obtained in the cyclization of the dienynes.
An explanation of the formation of products 35 and 36, with
opposite configurations at the dimethylcyclopropane, is pre-
sented in Scheme 7. Thus, a simplified dienyne such as 34
Scheme 6. Cyclization of dienynes 10, 19, 21, 23, 25, and 27.
Scheme 7. Mechanistic proposal for the stereoselective formation of tet-
racycles 32 via anti-IX.
could form either anti-IX or syn-IX cyclopropyl gold(i) car-
benes, which would undergo intramolecular cyclopropana-
tion to give 35 (unnatural configuration) or 36 (ent-myliol-
type configuration).
The stereoselectivity of the last cyclopropanation appears
to be a result of the kinetically controlled trapping of anti-
IX. To gain insight into the mechanism of this process we
carried out DFT calculations starting from model complex
34, which shows the metal coordinated in an h1 fashion to
the alkyne (Figure 2). As also observed with a simpler 1,6-
Figure 1. Structure of the tetracycle 18 (ORTEP diagram with thermal el-
lipsoids at 50% probability).
Chem. Eur. J. 2006, 12, 1694 – 1702
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1697

A. M. Echavarren et al.
Figure 2. Reaction pathway for the biscyclopropanation from complex 34 calculated at the B3LYP/6–31G(d) (C,H,P), LANL2DZ (Au) level (ZPE-cor-
rected energies are given in kcalmolÀ1). Color code: Au: yellow; C: gray; P: purple; H: turquoise.
enyne,[3] complex 34 evolves exothermically through anti
attack of the alkene to the (h1-alkyne)gold moiety to form
anti-IX through an early transition state TS1. Remarkably,
the second cyclopropanation takes place via transition state
TS2 in a single step to form a corner-metalated cyclopropane
X in a slightly endothermic process. However, this reaction
is kinetically reasonable and much more favorable than the
possible isomerization of anti-IX to syn-IX (see Figure 3), a
process for which an activation energy as high as 24.7 kcal-
molÀ1 has been estimated in a model system.[8] Corner met-
alation of the cyclopropane would be expected to be more
favorable for a poor back-donor such as AuI.[27,28] A concert-
ed cyclopropanation by a platinum carbene has also been
identified as the most favorable pathway for the cyclopropa-
nation of a model system in which a propargylic hydroxyl
group could act as an additional coordination site for the
metal.[10]
Complex syn-IX can be formed directly by syn attack of
the alkene on the (h1-alkyne)gold moiety in complex 34’, a
slightly more stable conformer of 34 (Figure 3). However,
the activation energy required to reach TS3 in this syn pro-
cess is much higher than that required in the anti attack of
the alkene to form anti-IX (10.3 vs. 2.9 kcalmolÀ1). Complex
syn-IX shows a weak stabilizing interaction between the
electrophilic gold(i) carbene and the alkene that might ex-
plain why 34’ does not evolve to form a cyclobutene inter-
mediate. Intermediate syn-IX evolves by a complex two-
It is interesting to note that, whereas in the cyclopropana-
tion of anti-IX the gold carbene behaves as a two-electron
electrophile (such as in the formation of bromonium ions
from alkenes), the gold carbene of syn-IX behaves as a
proton or a carbenium ion, producing an open carbocation-
type species XI. In either case, both processes appear to be
electrophilic cyclopropanations of alkenes.[29]
Conclusion
Highly alkynophilic gold(i) complexes are the most active
catalysts for the biscyclopropanation of dienynes to form
complex tetracyclic compounds. These reactions are remark-
ably clean in most cases and take place at room temperature
in a few minutes. PtII and ZnII are also able to promote the
biscyclopropanation, although less efficiently. The common
configuration obtained in all cases can be explained by the
pathway shown in Figure 2, proceeding through intermedi-
ates such as anti-IX. Similar intermediates are most proba-
bly involved in reactions catalyzed by RuII and PtII. Interest-
ingly, two different cyclopropanation pathways have been
uncovered, depending on the structures of cyclopropyl gold
carbenes (anti or syn) and the relative arrangements of the
carbenes and the alkenes. Similar mechanisms might be op-
erative in the recently developed intermolecular AuI-cata-
lyzed cyclopropanation of alkenes with diazo com-
pounds.[30,31]
À
step process to form firstly a C C bond in intermediate XI
and finally an edge-metalated cyclopropane XII. A subse-
quent demetalation would furnish 36 (Scheme 7), with the
relative configuration fond in myliol (30) and related sesqui-
terpenes. Overall, however, this alternative biscyclopropana-
tion proceeding via syn-IX is kinetically and thermodynami-
cally much less favorable than that proceeding via anti-IX.
Experimental Section
Computational methods: Calculations were performed with Gaussi-
an 98.[32] The geometries of all complexes were optimized by application
1698
www.chemeurj.org
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 1694 – 1702

Gold(i)-Catalyzed Intramolecular Cyclopropanation
FULL PAPER
Figure 3. Reaction pathway for the biscyclopropanation from complex 34’ calculated at the B3LYP/6–31G(d) (C,H,P), LANL2DZ (Au) level (ZPE-cor-
rected energies are given in kcalmolÀ1). The biscyclopropanation pathway from complex 34 (blue) is included for comparison. Color code: Au: yellow;
C: gray; P: purple; H: turquoise.
of density functional theory (DFT) at the generalized gradient approxi-
mation through the use of the B3LYP hybrid functional.[33] The standard
6–31G(d) basis set was used for C, H, and P. The LANL2DZ basis set,
which includes the relativistic effective core potential (ECP) of Hay and
Wadt[34] and employs a split-valence (double-x) basis set, was used for
Au. Energies include zero-point energy (ZPE) correction. Harmonic fre-
quencies were calculated at the same level to characterize the stationary
points and to determine the zero-point energies. The starting approxi-
mate geometries for the transition states (TSs) were located graphically.
Intrinsic reaction coordinate calculations were used to confirm the actual
reagent and products for all transition states.
25.68, 20.36, 17.74, 16.59 (one carbon signal overlaps) ppm; HMRS-CI
m/z calcd for C26H30O4S2: 471.1664; found 471.1675 [M+1]+.
2-((E)-3,7-Dimethylocta-2,6-dienyl)-2-(prop-2-ynyl)propane-1,3-diol:
A
solution of dimethyl geranylpropargylmalonate (9) (2.000 g, 6.53 mmol)
in THF (8 mL) was added dropwise at 08C to a suspension of LiAlH4
(496 mg, 13.06 mmol) in THF (8 mL). The reaction mixture was stirred at
238C for 3 h, and was then cooled to 08C and quenched with a saturated
solution of tartaric acid. After extractive workup (Et2O) and chromatog-
raphy the diol was obtained as a colorless oil. Yield 70% (1055.4 mg).
1H NMR (300 MHz, CDCl3): d = 5.14 (m, 1H), 5.04 (m, 1H), 3.64 (m,
4H), 2.31 (brs, 2H), 2.25 (d, J = 2.0 Hz, 2H), 2.08–2.00 (m, 7H), 1.67 (s,
3H), 1.63 (s, 3H), 1.59 8 s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d =
138.72, 131.64, 124.12, 118.60, 81.35, 70.65, 67.72, 42.86, 40.04, 30.05,
26.47, 25.71, 21.43, 17.69, 16.09 ppm; HMRS-ESI m/z calcd for C16H27O2
251.2011; found 251.2014 [M+1]+.
Chemical: All reactions were carried out under Ar or N2 in dry solvents.
Chromatography purifications were carried out with flash grade silica gel
(SDS Chromatogel 60 ACC, 40–60 mm).
Compounds 9 and 17 have been described.[2a,b] The synthesis of the AuI
complexes 6a–e, 7, and 8a–c is described in the accompanying paper.[7]
Tetramethyl (E)-7,12-dimethyltrideca-6,11-dien-1-yne-4,4,9,9-tetracarbox-
1
ylate (25): Pale yellow oil. H NMR (400 MHz, CDCl3): d = 5.20 (t, J =
Synthesis of dienynes
7.5 Hz, 1H), 4.91 (t, J = 7.5 Hz, 1H), 3.72 (s, 6H), 3.69 (s, 6H), 2.80 (s,
2H), 2.75 (d, J = 2.6 Hz, 2H), 2.60 (s, 2H), 2.58 (s, 2H), 2.02 (t, J =
2.7 Hz, 1H), 1.68 (s, 3H), 1.59 (s, 3H), 1.50 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3): d = 171.70, 170.60, 135.82, 133.00, 124.67, 117.69,
76.69, 71.76, 57.56, 52.72, 52.34, 41.67, 31.07, 31.00, 26.04, 22.43, 17.91,
16.82 ppm; HRMS-ESI m/z calcd for C23H32O8Na: 459.1995; found
459.1999 [M+Na]+.
(E)-7,11-Dimethyl-4,4-bis(phenylsulfonyl)dodeca-6,10-dien-1-yne
(E)-4,8-Dimethyl-1,1-bis(phenylsulfonyl)nona-3,7-diene[7]
(10):
(500 mg,
1.15 mmol) was added at 08C to a suspension of NaH (55 mg, 1.38 mmol,
60% mineral oil) in DMF (15 mL). After 20 min, propargyl bromide
(138 mg, 1.15 mmol) was added, and the resulting mixture was stirred at
238C for 12 h. After extractive workup (Et2O/10% HCl) and chromatog-
raphy (hexane/EtOAc 4:1), 10 (245 mg, 45%) was obtained as a pale
yellow solid: mp 78–79.58; 1H NMR (300 MHz, CDCl3): d = 8.16–8.14
(m, 2H), 8.13–8.11 (m, 2H), 7.73–7.68 (m, 2H), 7.59–7.55 (m, 4H), 5.42
(t, J = 6.5 Hz, 1H), 5.12–5.10 (m, 1H), 3.18 (d, J = 2.8 Hz, 2H), 3.04 (d,
J = 6.5 Hz, 2H), 2.16–2.02 (m, 5H), 1.69 (s, 3H), 1.62 (s, 3H), 1.58 (s,
2-((E)-3,7-Dimethylocta-2,6-dienyl)-2-(prop-2-ynyl)propane-1,3-diyl diac-
etate (19): A solution of the above diol (1.000 g, 4.0 mmol) in CH2Cl2
(4 mL) was added to a solution of DMAP (48.8 mg, 0.4 mmol) and pyri-
dine (650 ml, 8.0 mmol). Ac2O (1.5 mL, 16 mmol) was then added drop-
wise. The mixture was stirred at 238C overnight, and after extractive
workup (CH2Cl2) and chromatography, 19 was obtained as a colorless oil.
3H) ppm; 13C NMR (75 MHz, CDCl3):
131.52, 128.45, 123.91, 114.87, 89.27, 76.11, 73.99, 39.88, 27.69, 26.18,
d = 140.44, 136.48, 134.64,
Chem. Eur. J. 2006, 12, 1694 – 1702
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1699

A. M. Echavarren et al.
Yield 92% (1230 mg). 1H NMR (400 MHz, CDCl3): d = 5.06 (m, 2H),
4.05 (m, 4H), 2.25 (d, J = 2.4 Hz, 2H), 2.18 (d, J = 8.0 Hz, 2H), 2.13–
2.02 (m, 4H), 2.06 (s, 6H), 2.00 (t, J = 2.7 Hz, 1H), 1.68 (s, 3H), 1.61 (s,
3H), 1.60 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3; DEPT): d = 170.71
(2 C), 139.57 (C) 131.64 (C) 124.07 (CH), 117.47 (CH), 71.90 (CH), 71.10
(C) 65.49 (2”CH2), 40.67 (C), 40.03 (CH2), 29.70 (CH2), 26.47 (CH2),
25.67 (2”CH3), 22.02 (CH2), 20.82 (CH3), 17.67 (CH3), 16.04 (CH3) ppm;
HMRS-ESI m/z calcd for C20H29O4: 333.2071; found 333.2072 [MÀ1]+.
i: Butadiene monoxide (0.946 mL, 11.75 mmol) and dimethyl propargyl-
malonate (1.78 mL, 11.75 mmol) were added to
a mixture of [Pd2-
(dba)3·dba] (338.7 mg, 0.589 mmol) and dppe (245.5 mg, 0.616 mmol) in
dry THF (10 mL). The mixture was stirred for 3 h at 238C, the volatiles
were evaporated, and the residue was dissolved in Et2O and filtered
through a plug of Celite. After chromatography (hexane/EtOAc 4:1 to
2:1), dimethyl 2-(4-hydroxybut-2-enyl)-2-(prop-2-ynyl)malonate was ob-
tained as a colorless oil (1.64 g, 58%): 1H NMR (400 MHz, CDCl3): d =
5.80 (dtt, J = 15.5, 5.6, 1.2 Hz, 1H), 5.51 (dtt, J = 15.1, 7.5, 1.5 Hz, 1H),
4.09 (d, J = 5.6 Hz, 2H), 3.74 (s, 6H), 2.82–2.80 (m, 2H), 2.79 (d, J =
2.9 Hz, 2H), 2.02 (t, J = 2.6 Hz, 1H), 1.5 (brs, 1H).
N-((E)-3,7-Dimethylocta-2,6-dien-1-yl)-N-(prop-2-ynyl)-N-(toluene-4-sul-
fonyl)amine (21)
i: A solution of toluene-4-sulfonamide (863 mg, 5.04 mmol) in DMF
(10 mL) was added at 08C to a suspension of NaH (60% in mineral oil,
202 mg, 5.04 mmol) in DMF (5 mL), followed by geranyl bromide
(1.00 mL, 5.04 mmol). The mixture was stirred for 4 h at 238C and was
then quenched with H2O. After extractive workup (EtOAc/HCl (10%))
and chromatography (hexane/EtOAc 20:1 to 10:1), N-((2E)-3,7-dimethy-
locta-2,6-dienyl)toluene-4-sulfonamide[35] was obtained as a vitreous solid
(203 mg, 13%): 1H NMR (300 MHz, CDCl3): d = 7.74 (d, J = 8.1 Hz,
2H), 7.30 (d, J = 8.3 Hz, 2H), 5.04 (m, 2H), 4.27 (t, J = 5.3 Hz, 1H),
3.55 (t, J = 6.5 Hz, 2H), 2.42 (s, 3H), 1.98–1.91 (m, 4H), 1.66 (s, 3H),
1.56 (s, 3H), 1.53 (s, 3H) ppm.
ii: A solution of the dimethyl 2-(4-hydroxybut-2-enyl)-2-(prop-2-ynyl)-
malonate (554 mg, 2.3 mmol) in DMF (2 mL) was added at 08C to a sus-
pension of NaH (101 mg, 2.5 mmol, 60% mineral oil) in DMF (3 mL).
After 30 min, neryl bromide was added and the mixture was stirred over-
night. After extractive workup (water/Et2O) and chromatography
(hexane/EtOAc 95:5), 27 (373 mg, 55%) was obtained: 1H NMR
(400 MHz, CDCl3): d = 5.70 (dt, J = 15.2, 5.9 Hz, 1H), 5.48 (dt, J =
15.2, 7.6 Hz, 1H), 4.92 (s, 1H), 4.86 (s, 1H), 3.87 (d, J = 6.5 Hz, 2H),
3.82 (s, 2H), 3.72, (s, 6H), 2.79 (d, J = 7.3 Hz, 2H), 2.77 (d, J = 2.6 Hz,
2H), 2.00 (t, J = 2.6 Hz, 1H), 1.70 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3): d = 170.10, 142.18, 132.05, 126.25, 112.02, 73.72, 71.51, 69.85,
56.87, 52.69, 35.04, 22.69, 19.40 ppm; HMRS-CI m/z calcd for C16H22O5:
295.1545; found 295.1551 [M+1]+.
ii: N-((2E)-3,7-Dimethyl-octa-2,6-dienyl)toluene-4-sulfonamide (170 mg,
0.55 mmol) was added at 08C to a suspension of NaH (60% mineral oil,
22 mg, 0.55 mmol) in DMF (10 mL). After 10 min, propargyl bromide
(80% in toluene, 82 mg, 0.55 mmol,) was added, and the resulting mix-
ture was stirred at 238C overnight. After the usual workup (EtOAc/HCl
(10%)) and chromatography (hexane/EtOAc 30:1), 21 was obtained as a
colorless oil (133 mg, 70%): 1H NMR (300 MHz, CDCl3): d = 7.42 (d, J
= 8.5 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H), 5.05 (m, 2H), 4.05 (d, J =
2.4 Hz, 2H), 3.82 (d, J = 7.3 Hz, 2H), 2.42 (s, 3H), 2.05–1.96 (m, 4H),
1.67 (s, 3H), 1.65 (s, 3H), 1.58 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3;
DEPT): d = 143.35 (C), 142.48 (C), 136.17 (C), 131.88 (C), 129.38 (CH),
127.80 (CH), 123.71 (CH), 117.77 (CH), 77.08 (CH), 73.29 (C), 43.84
(CH2), 39.60 (CH2), 35.22 (CH2), 26.14 (CH2), 25.67 (CH3), 21.51 (CH3),
17.65 (CH3), 16.11 (CH3) ppm; EI-MS m/z (%): 69.00 (71), 91.00 (100),
155.00 (11), 190.15 (9), 222.00 (21), 276.10 (1).
Cyclization reactions: The enyne (0.10–0.50 mmol) in CH2Cl2 (1 mL) was
added to a mixture of gold(i) complex (2 mol%) in CH2Cl2 (2 mL) and
the mixture was stirred for the time and at the temperature indicated in
Scheme 6. The resulting mixture was filtered through SiO2 and the sol-
vent was evaporated to give the corresponding product, which was puri-
fied by column chromatography (EtOAc/hexane mixtures).
Tetracycle 15: Colorless oil: 1H NMR (500 MHz, CDCl3): d = 3.43 (s,
3H), 3.34 (s, 3H), 2.87 (qd, J = 7.3, 1.8 Hz, 1H), 2.80 (dd, J = 14.5,
1.8 Hz, 1H), 2.49 (d, J = 14.5 Hz, 1H), 2.28 (dd, J = 14.5, 2.8 Hz, 1H),
1.57 (m, 2H), 1.13 (dd, J = 7.3, 2.9 Hz, 1H), 1.09 (d, J = 8.9 Hz, 1H),
1.06 (s, 3H), 1.03–0.96 (m, 4H), 0.92 (s, 3H), 0.78 (td, J = 13.0, 4.4 Hz,
1H), 0.64 (td, J = 8.6, 6.0 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3): d
=
173.77, 171.67, 68.18, 52.74, 52.41, 40.14, 38.21, 34.92, 34.30, 33.07,
28.96, 28.23, 23,96, 20.24, 17.56, 16.59, 14.40 (one carbon signal over-
laps) ppm; HMRS-FAB m/z calcd for C18H26O4: 306.1813; found
306.1818. The structure of 15 was confirmed by COSY and NOESY ex-
periments.
(E)-7,11-Dimethyldodeca-6,10-dien-1-yn-3-yl 4-methoxybenzoate (23)
i: A solution of (4E)-5,9-dimethyl-4,8-deca-4,8-dienal[36] (353 mg,
1.96 mmol) in THF (5 mL) was added at 08C to a solution of propargyl-
magnesium bromide (0.5m in THF, 5.88 mL, 2.94 mmol) and the mixture
was stirred at 238C for 2 h. After extractive workup (Et2O) and chroma-
tography (hexane/EtOAc 30:1), (E)-7,11-dimethyldodeca-6,10-dien-1-yn-
3-ol was obtained as a yellow oil (218 mg, 54%): 1H NMR (300 MHz,
CDCl3): d = 5.16–5.04 (m, 2H), 4.35 (m, 1H), 2.47 (t, J = 2.0 Hz, 1H),
2.13–2.08 (m, 2H), 1.98–1.91 (m, 5H), 1.72–1.65 (m, 1H), 1.61 (s, 3H),
1.55 (s, 3H), 1.52 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3; DEPT): d =
136.33 (C), 131.38 (C), 124.17 (CH), 122.97 (CH), 84.99 (C), 72.84 (CH),
61.78 (CH), 39.63 (CH2), 37.51 (CH2), 31.83 (CH2), 26.53 (CH2), 17.59
(CH3), 15.92 (CH3) ppm; HRMS-EI m/z calcd for C14H22O: 205.1592;
found 205.1589 [MÀ1]+.
Dimethyl 3-((E)-2,6-Dimethylhepta-1,5-dienyl)cyclopent-3-ene-1,1-dicar-
boxylate (16): Yellow oil: 1H NMR (300 MHz, CDCl3): d = 5.73 (brs,
1H), 5.41 (brs, 1H), 5.09 (m, 1H), 3.74 (s, 6H), 3.20 (d, J = 1.8 Hz, 2H),
3.06 (s, 2H), 2.2–2.0 (m, 4H), 1.82 (s, 3H), 1.68 (s, 3H), 1.60 (s,
3H) ppm; 13C NMR (75 MHz, CDCl3):
d = 172.66, 139.26, 138.74,
131.74, 124.62, 123.92, 120.29, 59.29, 52.81, 43.45, 41.15, 40.39, 26.76,
25.66, 18.28, 17.67 ppm; HMRS-CI m/z calcd for C18H26O4: 306.1831;
found 306.1833.
Tetracycle 18: White solid: mp 72.5–748C; 1H NMR (500 MHz, CDCl3):
d = 8.17 (d, J = 7.3 Hz, 2H), 8.05 (d, J = 7.4 Hz, 2H), 7.73–7.68 (m,
2H), 7.63–7.57 (m, 4H), 2.85 (d, J = 16.2 Hz, 1H), 2.76 (ddd, J = 15.8,
7.3, 2.2 Hz, 1H), 2.45 (dd, J = 15.8, 2.8 Hz, 1H), 2.38 (dd, J = 16.4,
2.2 Hz, 1H), 1.73 (dt, J = 13.1, 3.2 Hz, 1H), 1.67–1.61 (m, 1H), 1.26 (dd,
J = 7.1, 2.8 Hz, 1H), 1.18 (s, 3H), 1.11 (s, 3H), 0.97 (d, J = 8.8 Hz, 1H),
0.93–0.85 (m, 1H), 0.83 (s, 3H), 0.77–0.69 (m, 2H) ppm; 13C NMR
(125 MHz, CDCl3; DEPT): d = 173.95 (C), 135.91 (C), 134.46 (CH),
134.33 (CH), 132.14 (CH), 130.84 (CH), 128.56 (CH), 128.51 (CH),
100.68 (C), 39.96 (CH), 36.78 (CH2), 36.27 (CH2), 33.24 (C), 32.74 (CH2),
31.54 (C), 27.91 (CH3), 24.69 (CH), 23.97 (CH), 20.58 (C), 17.67 (CH3),
16.16 (CH2), 13.66 (CH3) ppm; HMRS-EI m/z calcd for C26H30O4S2:
470.1586; found 470.1577. The structure of 18 was confirmed by COSY,
NOESY, HMBC, and HMQC experiments and by X-ray diffraction.
ii: A solution of (E)-7,11-dimethyldodeca-6,10-dien-1-yn-3-ol (50 mg,
0.24 mmol) in CH2Cl2 (1.5 mL) was added to a mixture of pyridine
(0.078 mL, 0.97 mmol) and p-anisoyl chloride (83 mg, 0.48 mmol) in
CH2Cl2 (2.5 mL). The mixture was stirred for 24 h at 238C and was then
heated at reflux in CH2Cl2 for 1 h. The solvent was evaporated and the
resulting oil was purified by chromatography (hexane/EtOAc 9:1) to give
1
23 as a colorless oil (75 mg, 86%): H NMR (400 MHz, CDCl3): d = 8.02
(d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 5.41 (td, J = 6.6, 2.1 Hz,
1H), 5.18–5.05 (m, 2H), 3.86 (s, 3H), 2.48 (d, J = 2.3 Hz, 1H), 2.23 (q, J
= 7.3 Hz, 2H), 2.11–1.91 (m, 6H), 1.68 (s, 3H), 1.60 (m, 3H), 1.56 (s,
3H) ppm; 13C NMR (100 MHz, CDCl3): d
= 165.19, 163.55, 136.69,
131.81, 131.47, 124.19, 122.42, 113.6, 81.64, 73.48, 63.60, 55.43, 53.20,
39.66, 34.86, 26.62, 25.66, 23.52, 17.67, 16.00ppm; HMRS-ESI m/z calcd
for C23H33O8: 437.2175; found 437.2168 [M+H]+.
1
Tetracycle 20: H NMR (400 MHz, CDCl3): d = 4.07 (s, 2H), 3.90 (dd, J
= 15.2, 11.1 Hz, 2H), 2.09 (s, 3H), 2.04 (s, 3H), 1.75 (ddd, J = 14.4, 7.4,
1.7 Hz, 1H), 1.73–1.57 (m, 2H), 1.55 (q, J = 14.4 Hz, 2H), 1.27 (dd, J =
14.4, 2.4, Hz, 1H), 1.05–0.94 (m with a s at 1.01, 5H), 0.94 (s, 3H), 0.89–
Dimethyl 2-[(E)-4-(2-methylallyloxy)but-2-enyl]-2-(prop-2-ynyl)malonate
(27)
0.76 (m with a s at 0.87, 5H), 0.66 (td, J = 8.5, 6.2 Hz, 1H) ppm;
1700
www.chemeurj.org
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 1694 – 1702

Gold(i)-Catalyzed Intramolecular Cyclopropanation
FULL PAPER
13C NMR (100 MHz, CDCl3): d
= 171.35, 66.92, 66.21, 54.92, 38.02,
[1] Reviews: a) G. C. Lloyd-Jones, Org. Biomol. Chem. 2003, 1, 215–
236; b) C. Aubert, O. Buisine, M. Malacria, Chem. Rev. 2002, 102,
813–834; c) S. T. Diver, A. J. Giessert, Chem. Rev. 2004, 104, 1317–
1382; d) A. M. Echavarren, M. MØndez, M. P. MuÇoz, C. Nevado, B.
Martín-Matute, C. Nieto-Oberhuber, D. J. Cµrdenas, Pure Appl.
Chem. 2004, 76, 453–463; e) A. M. Echavarren, C. Nevado, Chem.
Soc. Rev. 2004, 33, 431–436; f) L. AÇorbe, G. Domínguez, PØrez-
Castells, Chem. Eur. J. 2004, 10, 4938–4943; g) C. Bruneau, Angew.
Chem. 2005, 117, 2380–2386; Angew. Chem. Int. Ed. 2005, 44, 2328–
2334.
[2] a) M. MØndez, M. P. MuÇoz, A. M. Echavarren, J. Am. Chem. Soc.
2000, 122, 11549–11550; b) M. MØndez, M. P. MuÇoz, C. Nevado,
D. J. Cµrdenas, A. M. Echavarren, J. Am. Chem. Soc. 2001, 123,
10511–10520; c) C. Nevado, D. J. Cµrdenas, A. M. Echavarren,
Chem. Eur. J. 2003, 9, 2627–2635; d) M. P. MuÇoz, M. MØndez, C.
Nevado, D. J. Cµrdenas, A. M. Echavarren, Synthesis 2003, 2898–
2902; e) C. Nevado, C. Ferrer, A. M. Echavarren, Org. Lett. 2004, 6,
3191–3194; f) M. P. MuÇoz, J. Adrio, J. C. Carretero, A. M. Echavar-
ren, Organometallics 2005, 24, 1293–1300.
[3] C. Nieto-Oberhuber, M. P. MuÇoz, E. BuÇuel, C. Nevado, D. J.
Cµrdenas, A. M. Echavarren, Angew. Chem. 2004, 116, 2456–2460;
Angew. Chem. Int. Ed. 2004, 43, 2402–2406.
[4] S. Oi, I. Tsukamoto, S. Miyano, Y. Inoue, Organometallics 2001, 20,
3704–3709.
[5] a) B. M. Trost, G. J. Tanoury, J. Am. Chem. Soc. 1988, 110, 1636–
1638; b) B. M. Trost, M. K. Trost, Tetrahedron Lett. 1991, 32, 3647–
3650; c) B. M. Trost, M. Yanai, K. Hoogsteed, J. Am. Chem. Soc.
1993, 115, 5294–5295; d) N. Chatani, T. Morimoto, T. Muto, S.
Murai, J. Am. Chem. Soc. 1994, 116, 6049–6050; e) N. Chatani, N.
Furukawa, H. Sakurai, S. Murai, Organometallics 1996, 15, 901–903;
f) A. Fürstner, F. Stelzer, H. Szillat, J. Am. Chem. Soc. 2001, 123,
11863–11869; g) N. Chatani, H. Inoue, T. Kotsuma, S. Murai, J.
Am. Chem. Soc. 2002, 124, 10294–10295; h) F. Marion, J. Coulomb,
C. Courillon, L. Fensterbank, M. Malacria, Org. Lett. 2004, 6, 1509–
1511; i) G. B. Bajracharya, I. Nakamura, Y. Yamamoto, J. Org.
Chem. 2005, 70, 892–897.
37.18, 35.14, 31.75, 31.21, 28.34, 28.20, 25.95, 24.06, 20.90, 20.83, 20.20,
17.47, 16.55, 14.38ppm; HMRS-ESI m/z calcd for C20H30O4Na [M+Na]+:
357.2042; found 357.2033. This structure was confirmed by COSY,
NOESY, HMBC, and HMQC experiments.
Tetracycle 22: Vitreous solid: 1H NMR (500 MHz, CDCl3): d = 7.71 (d,
J = 8.4 Hz, 2H), 7.32 (d, J = 7.9 Hz, 2H), 3.37–3.34 (m, 3H), 3.31 (d, J
= 9.6 Hz, 1H), 2.42 (s, 3H), 1.66–1.64 (m, 1H), 1.63–1.60 (m, 1H), 1.03
(d, J = 4.7 Hz, 1H), 1.02–0.96 (m, 1H), 0.98 (s, 3H), 0.90 (s, 3H), 0.88 (s,
3H), 0.85 (m, 1H), 0.67 (m, 1H), 0.69 (d, J
= 8.8 Hz, 1H) ppm;
13C NMR (125 MHz, CDCl3; DEPT): d = 143.18 (C), 134.42 (C), 129.61
(CH), 127.41 (CH), 51.78 (CH2), 48.03 (CH2), 35.10 (CH), 34.63 (CH2),
29.80 (C), 28.07 (CH3), 24.48 (C), 23.83 (CH), 22.28 (CH), 21.56 (CH3),
20.46 (C), 17.57 (CH3), 16.46 (CH2), 12.49 (CH3) ppm; HMRS-CI m/z
calcd for C20H27NO2S: 345.1762; found 345.1766. The structure of 22 was
confirmed by COSY, NOESY, HMBC, and HMQC experiments.
Tetracycle 24: 1H NMR (400 MHz, CDCl3): d = 7.90 (d, J = 7.9 Hz,
2H), 6.84 (d, J = 9.7 Hz, 2H), 5.70 (dd, J = 10.5, 6.7 Hz, 1H), 3.78 (s,
3H), 2.56–2.44 (m, 1H), 2.06–1.97 (m, 1H), 1.79–1.69 (m, 1H), 1.62–1.48
(m, 1H), 1.46–1.34 (m, 2H), 1.46–1.34 (m, 2H), 1.21 (s, 3H), 1.15 (d, J =
6.3 Hz, 1H), 0.97 (s, 3H), 0.87 (s, 3H), 0.81 (d, J = 9.2 Hz, 1H), 0.53
(ddd, J = 9.4, 5.0, 3.7 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): d =
166.47, 131.54, 123.57, 113.50, 84.66, 55.42, 35.13, 34.05, 33.53, 31.93,
29.45, 25.78, 25.59, 23.66, 22.16, 18.35, 17.93, 17.88 ppm; HRMS-EI m/z
calcd for C22H28O3Na: 363.1936; found 363.1944 [M+Na]+. The structure
of 24 was confirmed by COSY, NOESY, HMBC, and HMQC experi-
ments.
Tetracycle 26: 1H NMR (400 MHz, CDCl3): d = 3.70 (s, 3H), 3.69 (s,
3H), 3.68 (s, 3H), 3.67 (s, 3H), 2.68 (d, J = 13.6 Hz, 1H), 2.64 (d, J =
13.6 Hz, 1H), 2.41 (d, J = 13.6 Hz, 1H), 2.29 (d, J = 13.6 Hz, 1H), 2.29–
2.20 (m, 1H), 2.14 (d, J = 14.6, 4.1 Hz, 1H), 1.80–1.55 (m, 2H), 1.21 (s,
3H), 1.13 (s, 3H), 1.04 (s, 3H), 0.57–0.52 (m, 2H), 0.34 (dd, J = 11.8,
3.8 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): d
= 173.10, 172.82,
172.70, 172.36, 58.73, 55.81, 52.94, 52.35, 43.90, 42.95, 31.41, 30.03, 29.55,
28.59, 28.27, 24.02, 23.60, 22.06, 19.60, 17.75, 13.96 ppm; HRMS-EI m/z
calcd for C23H33O8: 437.2175; found 437.2168 [M+H]+. The structure of
26 was confirmed by COSY, NOESY, HMBC, and HMQC experiments.
[6] C. Nevado, L. Charruault, V. Michelet, C. Nieto-Oberhuber, M. P.
MuÇoz, M. MØndez, M.-N. Rager, J. P. GenÞt, A. M. Echavarren,
Eur. J. Org. Chem. 2003, 706–713.
[7] C. Nieto-Oberhuber, M. P. MuÇoz, S. López, E. JimØnez-NfflÇez, C.
Nevado, E. Herrero-Gómez, M. Raducan, A. M. Echavarren, Chem.
Eur. J. 2006, 12, 1677–1693.
[8] C. Nieto-Oberhuber, S. López, M. P. MuÇoz, D. J. Cµrdenas, E.
BuÇuel, C. Nevado, A. M. Echavarren, Angew. Chem. 2005, 117,
6302–6304; Angew. Chem. Int. Ed. 2005, 44, 6146–6148.
[9] a) B. M. Trost, A. S. K. Hashmi, Angew. Chem. 1993, 105, 1130–
1132; Angew. Chem. Int. Ed. Engl. 1993, 32, 1085–1087; b) B. M.
Trost, A. S. K. Hashmi, J. Am. Chem. Soc. 1994, 116, 2183–2184;
c) B. M. Trost, A. S. K. Hashmi, R. G. Ball, Adv. Synth. Catal. 2001,
343, 490–494.
Tetracycle 28: 1H NMR (CDCl3, 400 MHz): d
= 4.07 (dd, J = 12.0,
4.7 Hz, 1H), 3.84 (dd, J = 11.8, 1.1 Hz, 1H), 3.70 (s, 3H), 3.69 (s, 3H),
3.31 (d, J = 12 Hz, 1H), 3.13 (t, J = 11.5 Hz, 1H), 2.60 (d, J = 2.9 Hz,
2H), 2.50 (d, J = 14.2 Hz, 1H), 2.46 (d, J = 14.1 Hz, 1H), 1.10 (td, J =
5.9, 2.9 Hz, 1H), 1.08–1.03 (m with a s at 1.06, 4H), 0.60–0.55 (m, 1H),
0.53 (dd, J = 8.7, 5.0 Hz, 1H), 0.39 (t, J = 5.1 Hz, 1H) ppm; 13C NMR
(100 MHz, CDCl3): d = 172.89, 172.32, 71.8, 71.81, 67.35, 59.58, 53.03,
41.59, 36.55, 32.16, 31.08, 25.47, 24.53, 20.94, 17.91, 17.48 ppm; HRMS-EI
m/z calcd for C16H22O5Na: 317.1365; found 317.1365 [M+Na]+. The
structure of 28 was confirmed by COSY, NOESY, HMBC, and HMQC
experiments.
Dimethyl 3-[(E)-3-(2-methylallyloxy)prop-1-enyl]cyclopent-3-ene-1,1-di-
1
carboxylate (29): H NMR (400 MHz, CDCl3): d = 6.38 (d, J = 16.2 Hz,
1H), 5.64 (dt, J = 15.8, 6.1 Hz, 1H), 5.56 (s, 1H), 4.96 (s, 1H), 4.90 (s,
1H), 4.02 (s, 1H), 4.00 (s, 1H), 3.89 (s, 3H), 3.74 (s, 3H), 3.13 (s, 1H),
3.10 (1H), 1.74 (3H) ppm; 13C NMR (400 MHz, CDCl3): d = 166.18,
127.90, 127.58, 126.69, 119.88, 112.19, 74.17, 70.23, 52.90, 40.94, 39.77,
19.54 (two carbons signals overlap) ppm; HRMS-EI m/z calcd. for
C16H22O5Na: 317.1365; found 317.1362 [M+Na]+.
[10] E. Soriano, P. Ballesteros, J. Marco-Contelles, Organometallics 2005,
24, 3182–3191.
[11] N. Chatani, K. Kataoka, S. Murai, N. Furuakwa, Y. Seki, J. Am.
Chem. Soc. 1998, 120, 9104–9105.
[12] a) E. Mainetti, V. Mouriꢂs, L. Fensterbank, M. Malacria, J. Marco-
Contelles, Angew. Chem. 2002, 114, 2236–2239; Angew. Chem. Int.
Ed. 2002, 41, 2132–2135; b) Y. Harrak, C. Blaszykowski, M. Ber-
nard, K. Cariou, E. Mainetti, V. Mouriꢂs, A.-L. Dhimane, L. Fen-
sterbank, M. Malacria, J. Am. Chem. Soc. 2004, 126, 8656–8657.
[13] M. Brookhart, W. B. Studabaker, G. R. Husk, Organometallics 1987,
6, 1141–1145.
Acknowledgements
[14] Cyclization of 1,5-enynes with AuI catalysts: a) V. Mamane, T.
Gress, H. Krause, A. Fürstner, J. Am. Chem. Soc. 2004, 126, 8654–
8655; b) M. R. Luzung, J. P. Markham, F. D. Toste, J. Am. Chem.
Soc. 2004, 126, 10858–10859; c) L. Zhang, S. A. Kozmin, J. Am.
Chem. Soc. 2004, 126, 11806–11807; d) X. Shi, D. J. Gorin, F. D.
Toste, J. Am. Chem. Soc. 2005, 127, 5802–5803; e) L. Zhang, S. A.
Kozmin, J. Am. Chem. Soc. 2005, 127, 6962–6963.
This work was supported by the MEC (project CTQ2004–02869, predoc-
toral fellowships to C.N.-O., M.P.M., E. J.-N., and a Torres Quevedo con-
tract to S.L.) and the ICIQ Foundation. We thank Dr. J. Bennet-Buch-
holz (ICIQ) for the X-ray diffraction of 18, the Centro de Computación
Científica (UAM) for computation time, and Johnson Matthey PLC for a
loan of metal salts.
Chem. Eur. J. 2006, 12, 1694 – 1702
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1701

A. M. Echavarren et al.
[15] A. K. Al-Sa’ady, C. A. McAuliffe, R. V. Parish, J. A. Sandeank,
Inorg. Synth. 1985, 23, 191–194.
[16] C. Nieto-Oberhuber, S. López, A. M. Echavarren, J. Am. Chem.
Soc. 2005, 127, 6178–6179.
[28] Corner- vs. edge-bromination of cyclopropanes: J. M. Coxon, W. B.
Smith, J. Org. Chem. 2000, 65, 2192–2194, and references therein.
[29] Lead references on the mechanism of cyclopropanation mediated by
late transition metal carbenes: a) C. Rodríguez-García, A. Oliva,
R. M. OrtuÇo, V. Branchadell, J. Am. Chem. Soc. 2001, 123, 6157–
6163; b) J. M. Fraile, J. I. García, V. Martínez-Merino, J. A. Mayoral,
L. Salvatella, J. Am. Chem. Soc. 2001, 123, 7616–7625; c) F. Bernar-
di, A. Bottoni, G. P. Miscione, Organometallics 2001, 20, 2751–2758;
d) B. F. Straub, J. Am. Chem. Soc. 2002, 124, 14195–14201; e) I.
Iwakura, T. Ikeno, T. Yamada, Org. Lett. 2004, 6, 949–952.
[17] a) S. Kaye, J. M. Fox, F. A. Hicks, S. L. Buchwald, Adv. Synth. Catal.
2001, 343, 789–794; b) E. R. Strieter, D. G. Blackmond, S. L. Buch-
wald, J. Am. Chem. Soc. 2003, 125, 13978–13980; c) S. D. Walker,
T. E. Barder, J. R. Martinelli, S. L. Buchwald, Angew. Chem. 2004,
116, 1907–1912; Angew. Chem. Int. Ed. 2004, 43, 1871–1876.
[18] a) B. Bovio, A. Burini, B. R. Pietroni, J. Organomet. Chem. 1993,
452, 287–291; b) X. Hu, I. Castro-Rodriguez, K. Olsen, K. Meyer,
Organometallics 2004, 23, 755–764, and references therein; c) S.
Singh, S. S. Kumar, V. Jancik, H. W. Roesky, H.-G. Schmidt, M. Nol-
temeyer, Eur. J. Inorg. Chem. 2005, 3057–3062.
[30] M. R. Fructos, T. R. Belderrain, P. de FrØmont, N. M. Scott, S. P.
Nolan, M. M. Díaz-Requejo, P. J. PØrez, Angew. Chem. 2005, 117,
5418–5422; Angew. Chem. Int. Ed. 2005, 44, 5284–5288.
[31] Evidence for the formation of gold(i) carbenes on treatment of
diazo compounds with gold(i) complexes: R. Bertani, R. A. Michel-
in, M. Mozzon, P. Traldi, R. Seraglia, L. Busetto M. C. Cassani, P.
Tagliatesta, G. D’Arcangelo, Organometallics 1997, 16, 3229–3233.
[32] Gaussian 98 (Revision A.11): M. J. Frisch, G. W. Trucks, H. B. Schle-
gel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V. G. Zakrzawe-
ski, J. A. Montgomery, R. E. Stratmann, J. C. Burant, S. Dapprich,
J. M. Millam, A. D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J.
Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli,
C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q.
Cui, K. Morokuma, D. K. Malick, A. D. Rabuck, K. Raghavachari,
J. B. Foresman, J. Ciolowski, J. V. Ortiz, B. B. Stefanov, G. Liu, A.
Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L. Martin,
D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
C. Gonzalez, M. Challacombe, P. M. W. Gill, B. G. Johnson, W.
Chen, M. W. Wong, J. L. Andres, M. Head-Gordon, E. S. Replogle,
J. Pople, Gaussian, Inc., Pittsburgh, PA, 1998.
[19] P. de Fremont, N. M. Scott, E. D. Stevens, S. P. Nolan, Organometal-
lics 2005, 24, 2411–2418.
[20] a) H. Strickler, J. B. Davis, G. Ohloff, Helv. Chim. Acta 1976, 59,
1328–1332; b) For an isolated example of a low-yield skeletal rear-
rangement of a 1,6-enyne promoted by ZnCl2: W. D. Schmitz, N. B.
Messerschmidt, D. Romo, J. Org. Chem. 1998, 63, 2058–2059.
[21] A. K. S. Chauhan, N. Singh, R. C. Srivastava, Appl. Organomet.
Chem. 2003, 17, 856–859.
[22] a) V. Benesova, P. Sedmera, V. Herout, F. Sorm, Collect. Czech.
Chem. Commun. 1973, 38, 1084–1090; b) V. Benesova, H. M. Chau,
V. Herout, Phytochemistry 1973, 12, 211–212; c) V. Benesova, P.
Sedmera, V. Herout, F. Sorm, Tetrahedron Lett. 1971, 12, 2679–
2682.
[23] a) H. Nozaki, J. Chem. Soc. Perkin Trans. 2 1979, 514–518; b) A.
Matsuo, H. Nozaki, M. Nakayama, Y. Kushi, S. Hayashi, N. Kamijo,
V. Benesova, V. Herout, J. Chem. Soc. Chem. Commun. 1976, 1006–
1007.
[24] a) N. H. Andersen, Y. Ohta, A. Moore, C.-L. W. Tseng, Tetrahedron
1978, 34, 41–46; b) N. H. Andersen, P. Bissonette, C. B. Liu, B.
Shunk, Y. Ohta, C.-L. W. Tseng, A. Moore, S. Huneck, Phytochemis-
try 1977, 16, 1731–1751.
[33] a) P. J. Stephens, F. J. Devlin, C. F. Chabalowski, M. J. Frisch, J.
Phys. Chem. 1994, 98, 11623–11627; b) W. Kohn, A. D. Becke,
R. G. Parr, J. Phys. Chem. 1996, 100, 12974–12980.
[34] a) P. J. Hay, W. R. Wadt, J. Chem. Phys. 1985, 82, 270–283; b) W. R.
Wadt, P. J. Hay, J. Chem. Phys. 1985, 82, 284–298; c) P. J. Hay, W. R.
Wadt, J. Chem. Phys. 1985, 82, 299–310.
[25] A. Matsuo, H. Nozaki, M. Shigemori, M. Nakayama, S. Hayashi, Ex-
perimentia 1977, 33, 991–992.
[35] D. Xu, C. Y. Park, K. B. Sharpless, Tetrahedron Lett. 1994, 35, 2495–
2498.
[26] K.-I. Hayashi, K.-I. Asano, M. Tanaka, D. Takaoka, H. Nozaki, Phy-
tochemistry 1998, 48, 461–466.
[36] a) G. Saucy, R. Marbet, Helv. Chim. Acta 1967, 50, 2091–2095; b) G.
Saucy, R. Marbet, Helv. Chim. Acta 1967, 50, 2095–2100.
[27] a) C. Meyer, N. Blanchard, M. Defosseux, J. Cossy, Acc. Chem. Res.
2003, 36, 766–772; b) M. R. A. Blomberg, P. E. M. Siegbahn, J.-E.
Bꢃckvall, J. Am. Chem. Soc. 1987, 109, 4450–4456.
Received: September 4, 2005
Published online: December 16, 2005
1702
www.chemeurj.org
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 1694 – 1702