Intramolecular hydroarylation of alkynes catalyzed by platinum or gold: Mechanism and endo selectivity

Article abstract of DOI:10.1002/chem.200401069

The cyclization of differently substituted aryl alkynes with Pt ^II or Au^I catalysts proceeds by endo-dig pathways. When Ag^I was used to generate reactive cationic Au^I catalysts, 2H-chromenes dimerize to form cyclobutane derivatives by a Ag ^I-catalyzed process. A DFT study on the cycliza-tion mechanism shows a kinetic and thermodynamic preference for 6-endodig versus 5-exo-dig cyclizations in Pt^II-catalyzed processes. Calculations indicate that although Friedel-Crafts and the cyclopropanation processes via metal cyclopropyl carbenes show very similar activation energies, platinum cyclopropyl carbenes are the stationary points with the lowest energy.

Full text of DOI:10.1002/chem.200401069

FULL PAPER
Intramolecular Hydroarylation of Alkynes Catalyzed by Platinum or Gold:
Mechanism and endo Selectivity
Cristina Nevado[b] and Antonio M. Echavarren*[a, b]
Abstract: The cyclization of differently
substituted aryl alkynes with PtII or AuI
catalysts proceeds by endo-dig path-
ways. When AgI was used to generate
reactive cationic AuI catalysts, 2H-
chromenes dimerize to form cyclobu-
tion mechanism shows a kinetic and
thermodynamic preference for 6-endo-
dig versus 5-exo-dig cyclizations in PtII-
catalyzed processes. Calculations indi-
cate that although Friedel–Crafts and
the cyclopropanation processes via
metal cyclopropyl carbenes show very
similar activation energies, platinum
cyclopropyl carbenes are the stationary
points with the lowest energy.
Keywords: alkynes · cyclization ·
density functional calculations
·
tane derivatives by
process. A DFT study on the cycliza-
a
AgI-catalyzed
gold · platinum
Introduction
to give 1,1-diarylalkenes, probably via alkenyl cation inter-
mediates.[6]
The hydroarylation of alkynes (also known as alkenylation
of arenes) catalyzed by electrophilic transition-metal com-
plexes has received much attention as a valuable synthetic
alternative to the Heck and cross-coupling processes for the
synthesis of alkenyl arenes.[1] Fujiwara et al. have reported
the hydroarylation of a wide range of alkynes catalyzed by
cationic complexes of PdII and PtII.[2] Heteroaromatic com-
pounds, such as pyrroles, indoles, and furans, also react with
alkynoates in the presence of Pd(OAc)2.[3] s-Aryl or s-heter-
oaryl-Pd species were proposed as intermediates in this re-
action.[2,3] Reetz and Sommer have found that AuIII and AuI
complexes also catalyze the hydroarylation of alkynes.[4] Re-
lated results were reported by He with AuIII.[5] In addition,
metal trifluoromethanesulfonates (M(OTf)n; M = Sc, Zr,
In) catalyze the alkenylation of arenes with internal alkynes
Similarly, aryl-alkynoates and alkynanilides cyclize in the
presence of Pd(OAc)2 in trifluoroacetic acid to give coumar-
ins and quinolin-2(1H)-ones, respectively.[7] Trost and Toste
developed an apparently similar palladium-catalyzed alkeny-
lation of phenols with alkynoates that affords coumarins.[8]
However, this reaction is mechanistically different because
0
À
it is assumed to be catalyzed by Pd and proceeds via Pd H
intermediates.[9]
Murai, Chatani and co-workers reported the cyclization of
electron-rich aromatic rings with alkynes and RuII and PtII
as catalysts.[10] The scope of this reaction was later extended
to substrates in which the arene moiety does not possess
strong electron-donating groups by the use of GaCl3 as a
catalyst.[11] exo-dig Cyclization is preferred when three or
four carbon atoms separate the alkyne and the arene. How-
ever, the endo-dig cyclization mode was observed in sub-
strates with two carbon atoms in the tether. Fꢀrstner et al.
reported a similar reaction for the synthesis of phenan-
threnes that is catalyzed by PtCl2 or other metal halides,
such as AuCl3, GaCl3, and InCl3.[12] Sames et al. developed a
PtCl4-catalyzed intramolecular hydroarylation under mild
conditions for the synthesis of chromenes, 1,2-dihydroquino-
lines, and coumarins.[13] Cycloisomerization of w-aryl-1-al-
kynes has been performed by Nishizawa et al. at room tem-
perature with HgII as the catalyst.[14,15]
[a] Prof. Dr. A. M. Echavarren
Institute of Chemical Research of Catalonia (ICIQ)
43007 Tarragona (Spain)
Fax : (+34)977-920-225
E-mail: aechavarren@iciq.es
[b] C. Nevado, Prof. Dr. A. M. Echavarren
Departamento de Quꢁmica Orgꢂnica, Universidad Autꢃnoma de
Madrid
Cantoblanco, 28049 Madrid (Spain)
Substrates of type 1 usually give 2 by a 6-endo-dig path-
way, instead of 3, the product of a 5-exo-dig cyclization.[16]
The simplified mechanism of Scheme 1 shows intermediates
representative of those usually proposed[10–14] based on a
Supporting information for this article is available on the WWW
under http://www.chemeurj.org or from the author. This information
includes atomic coordinates for structures of stationary points in
Figure 1, Figure 3, Figure 5.
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DOI: 10.1002/chem.200401069
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this behavior is followed when different catalysts are used.
Herein we present different AuI catalysts[26] for the cycliza-
tion of aryl alkynes. The use of AgI to generate the reactive
cationic AuI catalyst led to an unexpected dimerization of
2H-chromenes promoted by AgI. We also report computa-
tional work on the mechanism of the cyclization of two
model systems with PtCl2 that shows a kinetic and thermo-
dynamic preference for 6-endo-dig versus 5-exo-dig cycliza-
tions. Significantly, our results suggest that metal cycloprop-
yl carbenes are probable intermediates in this electrophilic
aromatic substitution reaction.
Scheme 1. Proposed Friedel–Crafts mechanism for the metal-catalyzed 6-
endo-dig cyclization of 4-aryl-1-alkynes.
Results and Discussion
Cyclization of arylalkynes with PtII or AuI catalysts: The
cyclization of N-propargyl-N-tosyl anilines 7a–c to form N-
tosyl-1,2-dihydroquinolines 8a–c with PtCl2 as catalyst pro-
ceeded in toluene under reflux with low-to-moderate
yields.[21] The use of a cationic AuI catalyst formed in situ
from [Au(PPh3)Me] and HBF4, which presumably forms
[Au(PPh3)]BF4, gave 8a–c in good yields at 23–508C
(Table 1, entries 1, 4, and 6).[26] The yields of these reactions
were higher in toluene, and an excess of protic acid was re-
Friedel–Crafts alkenylation reaction.[17] Thus, h2-coordina-
tion of MXn to 1 affords 4, which undergoes an electrophilic
aromatic substitution to give the Wheland-type intermediate
5. Intermediate 5 would then give 2 by a formal 1,3-H shift
or alternative pathways.[10] In accordance with this mecha-
nism, electron-donating substituents X facilitate the hydro-
arylation process. However, the fact that 6 is not formed
from 4 remains unsolved when
the exo cyclization of enynes is
Table 1. Cyclization of N-propargyl-N-tosyl anilines 7a–c catalyzed by cationic AuI complexes.
the most common pathway fol-
lowed by substrates bearing ter-
minal alkynes.[18] In fact, it has
been pointed out that the slip-
page of MXn towards C2 of the
alkyne in the transformation of
4 to 5 is unlikely because this
would result in a rather unsta-
ble primary alkenyl cation Entry
Substrate
Catalyst(mol%)
Solvent
T[8C]
t[h]
Product
Yield[%]
(anti-Markovnikov process).[14]
1
7a
7a
7a
7b
7b
7c
7c
7c
1
[Au(PPh3)Me] (3), HBF4 (6)
[Au(PPh3)Cl] (3), AgSbF6 (3)
[Au(PPh3)Cl] (3), AgBF4 (3)
[Au(PPh3)Me] (3), HBF4 (6)
[Au(PPh3)Cl] (3), AgSbF6 (3)
[Au(PPh3)Me] (3), HBF4 (6)
[Au(PPh3)Cl] (3), AgSbF6 (3)
[Au(PPh3)Cl] (3), AgBF4 (3)
toluene
CH2Cl2
CH2Cl2
toluene
CH2Cl2
toluene
CH2Cl2
CH2Cl2
23
40
40
23
23
23
23
23
4
2
17
4
2
4
2
2
8a
8a
8a
8b
8b
8c
8c
8c
71
2
3
4
5
6
7
8
72
Importantly, metal vinylidene
intermediates[19,20] are not in-
volved in these cyclizations, as
shown by deuteration experi-
ments[21] and by the fact that in-
ternal alkynes are also cyclized
45[a]
71
80
92
76
82 (96)[b]
with electrophilic metal com- [a] Determined by H NMR spectroscopy. [b] Based on 85% conversion.
plexes.[12]
Although the mechanistic hy-
pothesis shown in Scheme 1 is plausible and is inspired by a
fundamental mechanism in organic chemistry, an alternative
explanation based on the formation of metal cyclopropyl
carbenes could also account for the experimental results.
Indeed, we have shown that the PtII-catalyzed reaction of
furans with alkynes proceeds via metal cyclopropyl car-
benes,[21,22,23] similar to those involved in the alkoxycycliza-
tion and skeletal rearrangement of enynes.[18,24,25]
quired to efficiently generate the cationic AuI species. We
have also found that catalysts formed from [Au(PPh3)Cl]
(3 mol%) and a silver salt (3 mol%) allowed these cycliza-
tions to be performed under protic acid-free conditions in
CH2Cl2 as the solvent. Generally, the best conversions were
obtained with AgSbF6 (Table 1, entries 2, 5, and 7), although
in the case of the most reactive substrate, 7c, AgBF4 also
gave satisfactory results (Table 1, entry 8).
We have reported that PtCl2 catalyzes the cyclization of
arenes with alkynes for the synthesis of 1,2-dihydroquino-
lines and chromenes.[21] In all cases, substrates of type 1 re-
acted by the 6-endo-dig pathway. We set out to test whether
The reaction of phenol 9 with the [Au(PPh3)Cl]/AgSbF6
catalytic system led only to depropargylated derivative 11.[27]
However, PtCl2 as the catalyst gave 2,3-dihydro-1H-benzo-
[c]azepine (10) in 60% yield (73% based on 82% conver-
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Intramolecular Hydroarylation of Alkynes
FULL PAPER
sion) (Scheme 2) by an unusual 7-endo-dig cyclization of 9.
The 6-exo-dig cyclization product 12 was not observed, de-
spite its higher stability (stability: Z-12>E-12>10; PM3
calculations). Interestingly, the monopropargyl ether of
2,3,5,6-tetramethylhydroquinone (13) reacts in the presence
of PtCl2 to give spiro derivative 14 in a moderate yield as
well as duroquinone (15) (Scheme 2). In this case, 14 is
formed by attack of the more electron-rich ipso-carbon
atom by a 5-endo-dig process. Quinone 15 arises by depro-
pargylation of 13 to form 2,3,5,6-tetramethylhydroquinone,
followed by air oxidation.
zation was suppressed when the reaction was carried out in
wet toluene (Table 2, entry 2). 2H-Chromene 18 was isolated
as the exclusive cyclization product with [Au(PPh3)Me] and
HBF4 (Table 2, entry 3), which allowed us to perform the re-
action at room temperature. On the other hand, a 2:1 mix-
ture of 18 and 19 was obtained with [Au(PPh3)Cl] and
AgSbF6 (Table 2, entry 4). The reversed regioselectivity was
observed in the PtCl2-catalyzed reaction of 17 (Table 2,
entry 5).
Sesamol propargyl ether (23) reacts with a PtII catalyst to
afford 6H-[1,3]dioxolo[4,5-g]chromene (24) in excellent
yield.[21] Surprisingly, when cationic AuI catalysts generated
in the presence of AgI were used, in addition to 2H-chro-
mene 24, symmetrical dimer 25 was obtained (Scheme 3).
The structure of 25 was confirmed by X-ray diffraction. Sub-
strate 26 reacted with PtCl2 as catalyst to give a 1:1 mixture
6,7-dimethoxy-2H-chromene (27) and 6,7-dimethoxy-4H-
chromene (28) in moderate yields (Scheme 3). In contrast,
[Au(PPh3)Me] and HBF4 gave 27 selectively. With [Au-
(PPh3)Cl] and AgSbF6, 26 gave a mixture of 27 and dimer
29.
The [2+2] cycloaddition of cinnamic acids to form truxillic
or truxinic acids is not promoted by Ag2O.[28,29] However,
the dimerization of 2H-chromenes is catalyzed by AgI. Thus,
heating 2H-chromene 27 with AgSbF6 in CH2Cl2 led to 29 in
40% yield (Scheme 4). This reaction takes place in the dark,
which excludes a photocycloaddition similar to that cata-
lyzed by CuI.[30] A greater yield (58%) was obtained from
[Au(PPh3)Cl] and AgSbF6 (3 mol% each) in CH2Cl2 at
358C for 4 h. However, 27 was recovered unchanged after
being heated with [Au(PPh3)Cl] in CH2Cl2 at 23–408C, in
the presence or absence of sunlight.
Scheme 2.
The regioselectivity in the cyclization of resorcinol prop-
argyl derivatives 16 and 17 was studied with different cata-
lysts and under different conditions (Table 2). Reaction of
16 with PtCl2 led to a mixture of 18 and 19, in addition to
isomerized 4H-chromene 20 (Table 2, entry 1). This isomeri-
Mechanism for the electrophilic aromatic substitution with
(h2-alkyne)metal complexes: We decided to carry out a
computational study of the arene cyclizations with alkynes
by means of density functional calculations (DFT) on the 5-
exo-dig and 6-endo-dig cyclizations of 4-(butyn-3-yl)phenol
and 3-(butyn-3-yl)phenol as
model compounds with PtCl2.
We have previously reported
Table 2. Cyclization of resorcinol derivatives 16 and 17 catalyzed by PtII or cationic AuI complexes.
that qualitatively similar results
are obtained with PtII, AuI, or
AuIII in the calculations per-
formed for the cyclization of
enynes.[26,31]
The first step involves coordi-
nation of the alkyne to the
metal to form 30 and 31, re-
spectively (Scheme 5). A 5-exo-
dig cyclization from 30 would
give platinum cyclopropyl car-
bene 32. Alternatively, 33 could
be involved as an intermediate
in this reaction by a simple
electrophilic aromatic substitu-
tion. Similarly, in the 6-endo-dig
Entry Substrate Catalyst(mol%)
Solvent
toluene
T[8C] t[h] Yield[%] Product ratio
1
16
16
16
16
17
PtCl2 (5)
100
100
23
17 63
18 + 19 + 20
(3:3:2)
18 + 19 (2:1)
2
PtCl2 (5)
10:1 toluene-
H2O
toluene
15 72
3
[Au(PPh3)Me] (3), HBF4
(6)
[Au(PPh3)Cl] (3), AgSbF6 CH2Cl2
(3)
5
2
56
40
18
4
23
18 + 19 (2:1)
21 + 22 (1:2)
5[a]
PtCl2 (5)
toluene
100
15 76
[a] Yields after hydrogenation (H2, Pd/C) of the crude reaction mixture.
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A. M. Echavarren and C. Nevado
cyclization pathway, platinum cyclopropyl carbenes 34 and
35 or Friedel–Crafts intermediates 36 and 37 were consid-
ered.
A minimum structure for 32 could not be obtained. The
only minimum located in the 5-exo-dig cyclization of 30 was
the zwitterionic intermediate 33. However, formation of 33
from 30 is a highly endothermic process (+21.7 kcalmolÀ1).
The transition state (TS1) lies 22.3 kcalmolÀ1 above 30.
These calculations are in agreement with the experimental
results, which show that 5-exo-dig cyclization products are
not formed in the cyclization of 4-aryl-1-ynes. (Figure 1).
Figure 1. Reaction coordinate for the 5-exo-dig cyclization of 4-(butyn-3-
yl)phenol. Calculations at the B3LYP/6-31G(d) level (ZPE-corrected en-
ergies are given in kcalmolÀ1).
Scheme 3.
The structure of transition state TS1 is shown in Figure 2a,
in which the closest interaction between the electrophilic
À
part of the molecule and the arene ring occurs with C6 (C2
À
C6 distance of 1.956 ꢅ). The C2 C5 distance is considerably
longer (2.139 ꢅ). Intermediate 33 (Figure 2b) shows a highly
distorted structure, in which the angles around C6 are very
far from the tetrahedral bond angles of sp3-hybridized
carbon atoms. This strain may explain the high energy of
this intermediate and, in consequence, the improbability of
the 5-exo-dig pathway.
Scheme 4.
Figure 2. a) Structure of transition state TS1 showing the closest interac-
À
tion between the electrophile and the arene ring. The C2 C5 distance is
2.139 ꢅ. b) A view of intermediate 33 showing the highly distorted struc-
ture around C6, with very different C2-C6-C5 angles (82.68) and C2-C6-
C7 (118.58).
Scheme 5. Starting complexes 30 and 31 and hypothetical intermediates
for the 5-exo-dig and 6-endo-dig cyclization.
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Intramolecular Hydroarylation of Alkynes
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In the 6-endo-dig cyclization pathway, the formation of
the platinum cyclopropyl carbene 34 is an almost thermo-
neutral process: 14.7 kcalmolÀ1 are required to reach the
corresponding transition state (TS2) (Figure 3). Interestingly,
Figure 4. Structures of transitions states TS2 and TS3 that highlight the
À
closest interaction between the electrophile and the arene ring. The C1
À
C6 distance in TS2 is 2.565 ꢅ and for TS3 the C1 C5 distance is 2.478 ꢅ.
slightly more facile: transition state TS5 lies 13.2 kcalmolÀ1
above 31. However, formation of zwitterionic intermediates
37 is more endothermic (4.9 versus 0.4 kcalmolÀ1). In con-
Figure 3. Reaction coordinates for the 6-endo-dig cyclization of 4-(butyn-
3-yl)phenol with PtCl2. Calculations at the B3LYP/6-31G(d) level (ZPE-
corrected energies are given in kcalmolÀ1). Values in parentheses take
solvent effects into consideration.
À
trast to TS2, the closest C C bond lengths in TS4 between
the electrophile and the arene occurs with C6 (2.214 ꢅ), the
position para to the donor hydroxyl group (Figure 6). In
À
TS5, the C1 C6 distance is even shorter (2.179 ꢅ).
a Friedel–Crafts mechanism is also possible. Another transi-
tion state (TS3), which lies 16.2 kcalmolÀ1 above the corre-
sponding metal-coordinated aryl-alkyne, was found. Surpris-
ingly, analysis of the energy gradient profile showed a re-
markable and rapid decrease from TS3 that finally led to 34
as the unique minimum structure. Zwitterionic intermediate
36 could only be found when solvent effects were consid-
ered.[32]
Intermediates 36 and 37 show structures resembling the
Wheland cations that have been characterized structurally
in typical electrophilic aromatic substitution reactions
(Figure 7).[33] In contrast to 33 (Figure 2), which shows very
different C2-C6-C5 angles (82.68) and C2-C6-C7 (118.58),
the angles around C6 in 36 and 37 are closer to sp3 hybridi-
zation. In 36, the C2-C6-C5 angle is 100.38, while the C2-C6-
C7 angle is 106.48. In intermediate 37 these angles are
À
Formation of platinum cyclopropyl carbene 34 from 30 is
an asynchronous process. Although TS2 and TS3 are very
similar in energy, they show remarkable structural differen-
103.68 and 106.38, respectively. The Pt C bond lengths of
1.960–1.965 ꢅ are longer that those found for the carbene
complexes (see Figure 7).[34]
À
ces (Figure 4). In TS2, formation of the C1 C5 bond pre-
À
cedes that of the C1 C6 bond
owing to the donor effect of the
À
hydroxy group. The C C dis-
tances to the forming cyclopro-
À
pane ring are 2.188 ꢅ (C1 C5)
À
and 2.565 ꢅ (C1 C6), respec-
tively. On the other hand, the
À
closest distance in TS3 is C1 C6
À
(2.050 ꢅ), whereas the C1 C5
distance is 2.478 ꢅ.
In the case of PtII complex of
3-(butyn-3-yl)phenol (31), for-
mation of 35 is almost thermo-
neutral with an activation
energy of 14.7 kcalmolÀ1 via
TS4 (Figure 5).
A
Friedel–
Crafts mechanism is also possi-
ble in the cyclization of 31. This
Figure 5. Reaction coordinates for the 6-endo-dig cyclization of 3-(butyn-3-yl)phenol with PtCl2. Calculations
transformation is kinetically at the B3LYP/6-31G(d) level (ZPE-corrected energies are given in kcalmolÀ1).
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A. M. Echavarren and C. Nevado
Platinum cyclopropyl carbenes 34 and 35 show structures
similar to that of endo-carbene 39, derived by 6-endo-dig
cyclization of (E)-2-octen-1-yne (Figure 9). Remarkably, the
Figure 6. Structures of transition states TS4 and TS5 that highlight the
À
closest interactions between the electrophile and the arene ring. The C1
C5 distance in TS5 is 2.638 ꢅ.
Figure 9. Structure of the cyclopropyl platinum carbenes 34 and 35 com-
pared to 39, intermediate in the 6-endo-dig cyclization of (E)-2-octen-1-
yne (computed at the B3LYP/6-31G(d) level).[31]
Pt=C bond length is identical in the three complexes. The
lengths of the cyclopropane bonds conjugated with the plati-
À
À
num carbene (C1 C5 and C1 C6) in 34 and 35 are distinct,
being shorter than the cyclopropane bonds para to the hy-
Figure 7. Structures of Friedel–Crafts intermediates 36 and 37 that show
the angles between the ipso-carbon atom, the plane of the cyclohexadien-
yl ring, and the electrophile (a) or H6 (b).
À
À
droxyl (C1 C5 in 34 and C1 C6 in 35). A very similar struc-
ture was found for 34 when solvents effects were considered.
Interestingly, platinum carbenes 34 and 35 resemble the
products of intramolecular Buchner additions of diazoke-
tones to aryl rings.[35]
Although DFT calculations support the involvement of
cyclopropyl metal carbenes as intermediates in, at least,
some intramolecular reactions of arenes with alkynes, a
more definitive answer to this issue would be provided by
the trapping of these intermediates. This has already been
demonstrated in the reaction of furans with alkynes.[21,22] In
this case, DFT calculations indicated that 40 cyclizes exo-
thermically to form platinum cyclopropyl carbene 41, which
evolves to form 42, and finally phenols of type 43
(Scheme 6). Isolation of a,b-unsaturated carbonyl com-
pounds, such as 4, strongly supports the involvement of in-
termediates 42, and, consequently, a cyclopropanation path-
way for that process.
Figure 8. Opening of the cyclopropane in intermediate 35 to form 37 via
TS6 (computed at the B3LYP/6-31G(d) level).
À
The opening of the C1 C5 cyclopropane bond in inter-
mediate 35 to form Wheland intermediate 37, proceeds via
TS6 (Figure 5 and Figure 8). This late transition state resem-
Conclusion
À
bles intermediate 37 and shows an almost fully cleaved C1
C5 bond. In the transformation of 35 to 37, the C1 C2 bond
The cyclization of differently substituted substrates with PtII
or AuI catalysts proceeds by endo-dig pathways. When AgI
was used to generate reactive cationic AuI catalysts, 2H-
À
À
shortens and the carbene C2 Pt bond lengthens to become
an alkenyl–Pt bond.
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Intramolecular Hydroarylation of Alkynes
FULL PAPER
gies, although platinum cyclopropyl carbene 35 is the sta-
tionary point with the lowest energy.
Experimental Section
Unless otherwise stated, all reactions were carried out under Ar in dry,
freshly distilled solvents under anhydrous conditions. THF was dried by
means of 4 ꢅ molecular sieves. Toluene and DMF were distilled from
sodium/benzophenone and CaH2, respectively, and were stored over 4 ꢅ
molecular sieves. Chromatography purifications were carried out on flash
grade silica gel (SDS Chromatogel 60ACC, 40–60 mm) with distilled sol-
vents. NMR spectra were recorded at 238C on
a Bruker AC-300
(300 MHz for 1H, and 75 MHz for 13C) and Bruker AMX-500 (500 MHz
1
for H, and 125 MHz for 13C). EI-MS were obtained with a probe temper-
Scheme 6.
ature of 3008C, ion source at 3008C, and 70 eV electron energy. The
FAB-MS spectra were obtained with m-nitrobenzyl alcohol as the matrix.
Both MS (FAB, EI) were recorded on a HP1100mSD spectrometer. Ele-
mental analyses were performed on a LECO CHNS932 micro-analyzer.
Melting points were determined with a Gallenkamp melting point appa-
ratus.
chromenes were shown to dimerize. This is a AgI-catalyzed
process.
A computational study of the cyclization mechanism of
two model systems with PtCl2 shows a kinetic and thermo-
dynamic preference for 6-endo-dig versus 5-exo-dig cycliza-
tions. For the 5-exo-dig pathway, the two atoms tethering
the arene and the alkyne are not sufficient to allow the for-
mation of a low-energy Wheland intermediate.
Our results suggest that metal cyclopropyl carbenes are
probable intermediates in the 6-endo-dig cyclization. Thus,
in the cyclization of 30, with an electron-releasing substitu-
Compounds 7a–c,[21] 8a–c,[21] 16,[37] 17,[38] 18,[39] 23,[21] and 24[21] have been
previously described.
General procedure for the alkylation of amines and phenols: A solution
containing NaH (1.2 equiv, 60% in mineral oil) in dried DMF (volume of
DMF necessary to make the concentration of NaH 1.0m) was cooled to
08C. A solution of the corresponding amine or phenol (1.0 equiv) in
DMF (volume of DMF necessary to make the concentration 1.0m) was
added dropwise. The mixture was warmed to room temperature, stirred
for 20 min, and the alkylating agent (1.0 equiv) was added. The reaction
mixture was stirred at room temperature for 4 h, quenched with 10%
aqueous HCl, and diluted with Et2O. The organic layer was washed sever-
al times with water and then dried over MgSO4. The solvent was evapo-
rated and the residue was purified by chromatography (hexane/EtOAc
mixtures) to give the corresponding alkylated products.
À
ent at the meta position with respect to the new C C bond,
both transition states TS2 and TS3 converge to give platinum
cyclopropyl carbene 34 as the first intermediate in the proc-
ess. This pathway corresponds to an electrophilic aromatic
substitution reaction proceeding by initial formation of two
bonds between the electrophile and the arene. This mecha-
nistic picture differs from the generally accepted two-step
electrophilic aromatic substitution reaction,[36] in that, in-
stead of the loosely bonded p-complex intermediate, the
metal cyclopropyl carbene appears as a well-defined energy
minimum in the reaction coordinate very similar to those
found in the cyclizations of 1,6-enynes.[25] In the case of sub-
strate 31, with the electron-releasing substituent at the para
Five-step synthesis of 9 (see Scheme 7):
3-[(2-(Trimethylsilyl)ethoxy)methoxy]benzonitrile: To
a suspension of
NaH (60% in mineral oil, 880 mg, 22.00 mmol) in THF (10 mL) at 08C,
was added a solution of 3-hydroxybenzonitrile (2.50 g, 21.0 mmol) in
THF (5 mL), followed by trimethylsilylethoxymethyl chloride (SEMCl,
3.9 mL, 22.0 mmol). The mixture was stirred for 2 h at 238C and then
quenched with H2O. After extractive workup (Et2O) and chromatogra-
phy (hexane/EtOAc 9:1), the title compound was obtained (3.70 g, 70%)
1
as a pale yellow oil. H NMR (300 MHz, CDCl3): d = 7.44–7.28 (m, 4H),
5.27 (d, J = 0.8 Hz, 2H), 3.81–3.75 (m, 2H), 0.99 (ddd, J = 8.1, 8.1,
0.8 Hz, 2H), 0.04 ppm (s, 9H); 13C NMR (75 MHz, CDCl3, DEPT): d =
158.23 (C), 130.94 (CH), 125.99 (CH), 121.79 (CH), 120.16 (CH), 119.27
(CH2), 113.87 (CH2), 93.56 (CH2), 67.28 (CH2), 18.65 (CH2), À0.82 ppm
(CH3); FAB-HRMS: [M+1]+: calcd for C13H20NO2Si: 250.1263; found:
250.1269.
À
position with respect the formed C C bond, a less clear-cut
mechanistic picture arises. The Friedel–Crafts and the cyclo-
propanation processes showed very similar activation ener-
Scheme 7. Synthesis of 9.
Chem. Eur. J. 2005, 11, 3155 – 3164
www.chemeurj.org
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3161

A. M. Echavarren and C. Nevado
[3-((2-(Trimethylsilyl)ethoxy)methoxy)phenyl]methanamine:
of 3-[(2-(trimethylsilyl)ethoxy)methoxy]benzonitrile (3.70 g, 14.80 mmol)
in THF (10 mL) was added to suspension of LiAlH4 (850 mg,
A
solution
107–1088C; 1H NMR (300 MHz, CDCl3): d = 4.50 (s, 1H), 4.41 (d, J =
2.4 Hz, 2H), 2.54 (t, J = 2.4 Hz, 1H), 2.28 (s, 6H), 2.19 ppm (s, 6H);
a
13C NMR (75 MHz, CDCl3): d
= 149.45, 149.00, 128.19 (2C), 120.75
22.40 mmol) in THF (10 mL). The mixture was stirred at 358C for 4 h,
cooled to 08C, and quenched with H2O (1.6 mL, 88.89 mmol). The mix-
ture was diluted with EtOAc and Na2SO4 was added. After stirring for
1 h, the reaction mixture was filtered through Celite and dried over
MgSO4. The solvent was evaporated to give the crude amine (3.37 g,
90%) as a pale yellow oil. The amine was used without further purifica-
tion in the following tosylation step. 1H NMR (300 MHz, CDCl3): d =
7.23 (t, J = 7.8 Hz, 1H), 7.01–6.89 (m, 3H), 5.20 (s, 2H), 3.80 (s, 2H),
3.76–3.56 (m, 2H), 2.37 (s, 2H), 0.98–0.89 (m, 2H), À0.02 ppm (s, 9H).
(2C), 80.20, 75.26, 61.09, 13.82 (2C), 12.80 ppm (2C); elemental analysis
calcd (%) for C13H16O2: C 76.44, H 7.90; found: C 76.11, H 7.72.
1,2-Dimethoxy-4-(prop-2-ynyloxy)benzene (26): This compound was ob-
tained following the general procedure for the propargylation from 3,4-
dimethoxyphenol and propargyl bromide after chromatography (hexane/
EtOAc 5:1) as
a
colorless oil. (2.22 g, 60%). 1H NMR (300 MHz,
CDCl3): d = 6.79 (d, J = 8.7 Hz, 1H), 6.60 (d, J = 2.8 Hz, 1H), 6.49
(dd, J = 8.7, 2.8 Hz, 1H), 4.65 (d, J = 2.4 Hz, 2H), 3.86 (s, 3H), 3.84 (s,
3H), 2.52 ppm (t, J = 2.4H, 1H); 13C NMR (75 MHz, CDCl3, DEPT): d
= 152.07 (C), 149.81 (C), 144.11 (C), 111.56 (CH), 104.39 (CH), 101.36
(CH), 78.75 (C), 75.29 (CH), 56.40 (CH2), 56.31 (CH3), 55.78 ppm (CH3);
EI-HRMS: calcd for C11H12O3: 192.0786; found: 192.0787.
[3-((2-(Trimethylsilyl)ethoxy)methoxy)phenyl]-N-tosylmethanamine: To a
solution of the corresponding amine (3.40 g, 13.50 mmol) in CH2Cl2, was
added NEt3 (2.1 mL, 14.00 mmol) at 08C. Then a solution of TsCl (2.50 g,
13.50 mmol) in CH2Cl2 was added and the reaction mixture was stirred at
238C. The crude mixture was washed with a solution of HCl (10%) and
brine. After drying with Na2SO4, and evaporation of the solvent, the resi-
due was chromatographed (hexane/EtOAc 10:1) to give the title com-
pound (1.75 g, 32%) as a colorless oil. 1H NMR (300 MHz, CDCl3): d =
7.75 (d, J = 8.5 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H), 7.17 (t, J = 8.0 Hz,
1H), 6.91 (ddd, J = 8.0, 2.4, 1.0 Hz, 1H), 6.85–6.81 (m, 2H), 5.15 (brs,
2H), 4.08 (d, J = 6.3 Hz, 2H), 3.75–3.69 (m, 2H), 2.43 (s, 3H), 0.96–0.91
(m, 2H), À0.02 ppm (s, 9H) (the NH signal was not observed); 13C NMR
General procedure for the cyclization of arylalkynes with PtCl2: A so-
lution of the 4-aryl-1-alkyne (0.1 mmol) and PtCl2 (0.005 mmol) in tolu-
ene (1.5 mL) was stirred at 1008C for the stated times. The resulting mix-
ture was filtered through a short path of Celite, and the solvent was
evaporated. Column chromatography (hexane/EtOAc mixtures) gave the
corresponding cyclic compounds.
General procedure for the cyclization of 4-aryl-1-alkynes with [Au-
(PPh3)Me] and HBF4: A mixture of 4-aryl-1-alkyne (0.1 mmol) and [Au-
(PPh3)Me] (0.003 mmol) was dissolved in toluene (1.5 mL). HBF4 (1 mL,
0.006 mmol) was added and the reaction mixture was stirred at 238C for
the stated times. The mixture was diluted with Et2O, washed with 5%
aqueous NaHCO3, and the organic phases were dried over MgSO4. The
solvent was evaporated and the residue was purified by column chroma-
tography (hexane/EtOAc mixtures) to give the corresponding cyclic com-
pounds.
(75 MHz, CDCl3): d
= 158.30, 144.12, 138.46, 137.55, 130.37, 127.88,
127.86, 121.70, 116.34, 116.24, 93.41, 66.94, 47.80, 22.17, 18.67,
À0.78 ppm; FAB-HRMS: calcd for C20H30NO4SiS: 408.1665; found:
408.1679.
N-[3-((2-(Trimethylsilyl)ethoxy)methoxy)benzyl]-N-tosylbut-2-yn-1-
amine: This compound was obtained following the general procedure for
the propargylation after chromatography (hexane/EtOAc 10:1) as a col-
orless oil (721 mg, 64%). 1H NMR (300 MHz, CDCl3): d = 7.79 (d, J =
8.3 Hz, 2H), 7.32 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 8.1 Hz, 1H), 7.00–
6.94 (m, 3H), 5.20 (s, 2H), 4.28 (s, 2H), 3.92–3.87 (m, 2H), 3.79–3.70 (m,
General procedure for the cyclization of 4-aryl-1-alkynes with [Au-
(PPh3)Cl] and AgX (X
= SbF6, BF4): A mixture of [Au(PPh3)Cl]
(0.003 mmol) and AgX (0.003 mmol) was dissolved in toluene (1.5 mL).
4-Aryl-1-alkyne (0.1 mmol) was added and the reaction mixture was stir-
red at room temperature for the stated times. The mixture was filtered
through a short path of Celite, and solvent was evaporated. The residue
was purified by column chromatography (hexane/EtOAc mixtures) to
yield the corresponding cyclic compounds.
2H), 2.44 (s, 3H), 1.53 (t,
J = 2.4 Hz, 3H), 0.99–0.91 (m, 2H),
À0.01 ppm (s, 9H); 13C NMR (75 MHz, CDCl3): d
= 158.37, 144.26,
137.12, 136.67, 130.37, 130.16, 128.51, 122.62, 117.30, 116.44, 93.50, 82.52,
76.92, 74.77, 66.92, 50.34, 36.24, 22.20, 18.68, À0.77 ppm; FAB-HRMS:
[M+1]+: calcd for C24H34NO4SiS: 460.1978; found: 460.1985.
(Z)-2,3-Dihydro-5-methyl-2-tosyl-1H-benzo[c]azepin-8-ol (10): Colorless
oil; 1H NMR (300 MHz, CDCl3): d = 7.74 (d, J = 8.3 Hz, 2H), 7.32 (d,
J = 8.3 Hz, 2H), 7.18 (d, J = 8.4 Hz, 1H), 6.83 (dd, J = 8.4, 2.7 Hz,
1H), 6.71 (d, J = 2.7 Hz, 1H), 5.67 (td, J = 7.0, 1.5 Hz, 1H), 4.96 (s, 1H,
-OH), 4.14 (s, 2H), 3.60 (d, J = 7.0 Hz, 2H), 2.46 (s, 3H), 2.06 ppm (s,
3H); 13C NMR (75 MHz, CDCl3, DEPT): d = 154.99 (C), 143.32 (C),
141.56 (C), 136.12 (C), 135.08 (C), 133.48 (C), 129.62 (CH), 127.67 (CH),
127.52 (CH), 119.30 (CH), 116.62 (CH), 115.12 (CH), 49.75 (CH2), 44.18
(CH2), 22.29 (CH3), 21.54 ppm (CH3); FAB-HRMS: [M+1]+: calcd for
C18H20NO3S: 330.1164; found: 330.1165.
N-[(3-Hydroxy)benzyl]-N-tosylbut-2-yn-1-amine (9): TBAF (3.1 mL,
3.12 mmol; 1.0m in THF) was added to N-[3-((2-(trimethylsilyl)ethoxy)-
methoxy)benzyl]-N-tosylbut-2-yn-1-amine (721 mg, 1.56 mmol) in HMPA
(5 mL) and the mixture was stirred at 908C for 17 h. The reaction was di-
luted with EtOAc, washed with brine and water, and the organic phase
was dried over Na2SO4. The solvent was evaporated and the residue
chromatographed (hexane/EtOAc 3.5:1). The product was further puri-
fied by trituration with CH2Cl2/hexane to give 9 (298 mg, 58%) as a
white solid. M.p. 113–1148C; 1H NMR (300 MHz, CDCl3): d = 7.79 (d, J
= 8.1 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 7.19 (t, J = 7.8 Hz, 1H), 6.90–
6.86 (m, 2H), 6.77 (ddd, J = 7.8, 2.4, 0.8 Hz, 1H), 4.26 (s, 2H), 3.90 (d, J
= 2.4 Hz, 2H), 2.44 (s, 3H), 1.54 ppm (t, J = 2.4 Hz, 3H) (the OH signal
not observed); 13C NMR (75 MHz, CDCl3): d = 156.57, 143.98, 137.87,
136.84, 130.48, 129.94, 128.60, 121.67, 116.02, 115.68, 82.54, 72.09, 50.25,
36.89, 22.15, 3.86 ppm; EI-HRMS: calcd for C18H19NO3S: 329.1086;
found: 329.1073.
14: Yellow oil; 1H NMR (300 MHz, CDCl3): d
= 6.25 (dt, J = 3.2,
1.6 Hz, 1H), 5.30 (dt, J = 6.1, 2.4 Hz, 1H), 4.96 (dd, J = 2.4, 1.6 Hz,
2H), 1.92 (dd, J = 2.0, 1.2 Hz, 6H), 1.88 ppm (dd, J = 2.0, 1.2 Hz, 6H);
13C NMR (75 MHz, CDCl3, DEPT): d = 185.63 (C), 152.68 (2C), 132.02
(CH), 131.17 (2C), 129.87 (CH), 91.50 (C), 78.96 (CH2), 15.14 (2CH3),
12.17 ppm (2CH3); EI-HRMS: calcd for C13H16O2: 204.1150; found:
204.1156.
2,3,5,6-Tetramethylhydroquinone: To a suspension of duroquinone (1.0 g,
6.10 mmol) in THF (4 mL) and MeOH (2 mL), was slowly added NaBH4
(300 mg, 8.0 mmol). The reaction mixture was stirred at 238C for 30 min
and then cooled to 08C. Additional MeOH was slowly added until no
more gas evolution was observed. A small amount of water was added
and a solid precipitated. The solid was filtered off and washed with Et2O
to yield the title compound (1.02 g, quantitative) as a white solid, which
was used without further purification in the following propargylation
1
2H-Chromen-7-ol (19): Pale yellow oil; H NMR (300 MHz, CDCl3): d =
6.82 (d, J = 8.1 Hz, 1H), 6.38–6.27 (m, 3H), 5.62 (dt, J = 9.7, 3.4 Hz,
1H), 5.62 (dt, J = 9.7, 3.4 Hz, 1H), 4.79 ppm (dd, J = 3.4, 1.6 Hz, 2H);
13C NMR (75 MHz, CDCl3): d = 155.24, 151.35, 127.50, 124.23, 118.84,
111.26, 108.17, 103.28, 65.63 ppm; EI: m/z: 147.1 [MÀ1]+.
1
4H-Chromen-5-ol (20): Pale yellow oil; H NMR (300 MHz, CDCl3): d =
6.82 (d, J = 8.1 Hz, 1H), 6.38–6.27 (m, 3H), 5.62 (dt, J = 9.7, 3.4 Hz,
1H), 5.62 (dt, J = 9.7, 3.4 Hz, 1H), 4.79 ppm (dd, J = 3.4, 1.6 Hz, 2H);
13C NMR (75 MHz, CDCl3): d = 155.24, 151.35, 127.50, 124.23, 118.84,
111.26, 108.17, 103.28, 65.63 ppm.
1
step. H NMR (300 MHz, CDCl3): d = 2.18 (s, 6H), 1.58 ppm (brs, 2H).
2,3,5,6-Tetramethyl-4-(prop-2-ynyloxy)phenol (13): This compound was
obtained following the general procedure for the propargylation from
2,3,5,6-tetramethylhydroquinone and propargyl bromide after chromatog-
raphy (hexane/EtOAc 20:1 to 8:1) as a pale yellow solid (31%). M.p.
5-Methoxy-2H-chromene (21) and 7-methoxy-2H-chromene (22): These
compounds were hydrogenated in situ (toluene solution) with Pd/C
3162
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 3155 – 3164

Intramolecular Hydroarylation of Alkynes
FULL PAPER
(10%) at room temperature for 2 h to give a 1:2 mixture of 3,4-dihydro-
5-methoxy-2H-chromene (21’) and 3,4-dihydro-7-methoxy-2H-chromene
(22’): 1H NMR (300 MHz, CDCl3): d = 7.09 (t, J = 8.5 Hz, 1H, 21’),
6.97 (ddd, J = 8.5, 1.2, 0.8 Hz, 1H, 22’), 6.53–6.44 (m, 2H 21’, 1H 22’),
6.40 (d, J = 2.8 Hz, 1H, 22’), 4.23–4.17 (m, 2H 21’, 2H 22’), 3.86 (s, 3H,
21’), 3.80 (s, 3H, 22’), 2.76 (t, J = 6.5 Hz, 2H, 22’), 2.70 (t, J = 6.5 Hz,
2H, 21’), 2.07–1.98 ppm (m, 4H, 2H 22’, 2H 21’); 13C NMR (75 MHz,
CDCl3): d = 159.63, 158.65, 156.38, 156.20, 130.86, 127.41, 115.00, 112.00,
110.18, 107.65, 102.35, 102.17, 67.16, 66.71, 56.07, 55.93, 24.82, 23.16,
22.50, 19.85 ppm; EI-HRMS: calcd for C10H12O2: 164.0837; found:
164.0830.
25: White solid; 1H NMR (300 MHz, CDCl3): d = 6.56 (s, 1H), 6.51 (s,
1H), 5.91 (m, 2H), 4.09 (d, J = 11.6 Hz, 1H), 3.73 (d, J = 11.6 Hz, 1H),
3.01–2.91 ppm (m, 2H); 13C NMR (75 MHz, CDCl3; DEPT): d = 149.61
(C), 146.50 (C), 142.51 (C), 118.73 (C), 107.76 (CH), 100.91 (CH2), 99.58
(CH), 66.29 (CH2), 41.06 (CH), 33.38 ppm (CH). The structure was con-
firmed by NOESY, COSY, HMBC, HMQC experiments and X-ray dif-
fraction.
mura, K. Matsuda, M. Irie, Y. Fujiwara, J. Am. Chem. Soc. 2000,
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[8] B. M. Trost, F. D. Toste, J. Am. Chem. Soc. 1996, 118, 6305–6306.
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[10] N. Chatani, H. Inoue, T. Ikeda, S. Murai, J. Org. Chem. 2000, 65,
4913–4918.
[11] H. Inoue, N. Chatani, S. Murai, J. Org. Chem. 2002, 67, 1414–1417.
[12] a) A. Fꢀrstner, V. Mamame, J. Org. Chem. 2002, 67, 6264–6267;
b) A. Fꢀrstner, V. Mamame, Chem. Commun. 2003, 2112–2113;
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4556–4575.
[13] a) S. J. Pastine, S. W. Youn, D. Sames, Org. Lett. 2003, 5, 1055–1058;
b) S. J. Pastine, S. W. Youn, D. Sames, Tetrahedron 2003, 59, 8859–
8868.
6,7-Dimethoxy-2H-chromene (27): Yellow oil; 1H NMR (300 MHz,
CDCl3): d = 6.52 (s, 1H), 6.41 (s, 1H), 6.35 (dt, J = 9.4, 1.0 Hz, 1H),
5.65 (dt, J = 9.4, 3.7 Hz, 1H), 4.74 (dd, J = 3.7, 1.0 Hz, 2H), 3.84 (s,
3H), 3.83 ppm (s, 3H); 13C NMR (75 MHz, CDCl3, DEPT): d = 149.52
(C), 148.49 (C), 143.48 (C), 124.38 (CH), 119.19 (CH), 114.34 (C), 109.95
(CH), 100.54 (CH), 65.36 (CH2), 55.48 (CH3), 55.92 ppm (CH3); EI-
HRMS: calcd for C11H12O3: 192.0786; found: 192.0787.
[14] M. Nishizawa, H. Takao, V. K. Yadav, H. Imagawa, T. Sugihara,
Org. Lett. 2003, 5, 4563–4565.
6,7-Dimethoxy-4H-chromene (28): Yellow oil; 1H NMR (300 MHz,
CDCl3): d = 6.47 (s, 1H), 6.45 (dt, J = 6.4, 2.0 Hz, 1H), 4.90 (dt, J =
6.4, 3.5 Hz, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 3.32 ppm (m, 2H); 13C NMR
(75 MHz, CDCl3, DEPT): d = 149.08 (C), 147.54 (C), 143.67 (C), 140.50
(C), 111.42 (CH), 100.64 (CH), 99.82 (CH), 56.24 (CH3), 55.90 (CH3),
22.79 ppm (CH2) (one C signal is missing owing to overlapping); EI-
HRMS: calcd for C11H12O3: 192.0786; found: 192.0789.
29: White solid; 1H NMR (300 MHz, CDCl3): d = 6.69 (s, 1H), 6.68 (s,
1H), 3.80 (d, J = 11.4 Hz, 1H), 3.55 (s, 3H), 3.50 (d, J = 11.4 Hz, 1H),
3.38 (s, 3H), 3.00 (d, J = 8.0 Hz, 1H), 2.73 ppm (d, J = 8.0 Hz, 1H);
13C NMR (75 MHz, CDCl3, DEPT): d = 149.87 (C), 149.62 (C), 145.37
(C), 117.89 (C), 114.02 (CH), 102.75 (CH), 65.72 (CH2), 56.66 (CH3),
55.19 (CH3), 40.75 (CH), 33.69 ppm (CH); EI-HRMS: calcd for
C22H24O6: 384.1573; found: 384.1578. The structure was confirmed by
NOESY, COSY, HMBC, HMQC experiments.
[15] Cyclization of silyloxyalkynes with Tf2NH: L. Zhang, S. A. Kozmin,
J. Am. Chem. Soc. 2004, 126, 10204—10205.
[16] An exception is the cyclization of alkynes bearing electron-with-
drawing groups that cyclized by a 5-exo-dig pathway. See refs. [12a]
and [12c]
[17] Similar mechanisms have been proposed for cyclization of heterocy-
cles with alkynes: J. W. Dankwardt, Tetrahedron Lett. 2001, 42,
5809–5812.
[18] 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) M. Mꢆndez, V. Mamem, A. Fꢀrstner, Chemtracts: Org.
Chem. 2003, 16, 397–425; d) S. T. Diver, A. J. Giessert, Chem. Rev.
2004, 104, 1317–1382.
[19] For cyclizations that proceed via metal vinylidene intermediates:
a) C. A. Merlic, M. E. Pauly, J. Am. Chem. Soc. 1996, 118, 11319–
11320; b) K. Sangu, K. Fuchibe, T. Akiyama, Org. Lett. 2004, 6,
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1344–1346; e) T. Miura, N. Iwasawa, J. Am. Chem. Soc. 2002, 124,
518–519; f) T. Miura, H. Murata, K. Kiyota, H. Kusama, N. Iwasa-
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Computational methods: Calculations were performed with the GAUS-
SIAN98 series of programs.[40] The geometries of all complexes were op-
timized at the DFT level with the B3LYP hybrid functional.[41] The stan-
dard 6-31G(d) basis set was used for C, H, O, and Cl and the LANL2DZ
relativistic pseudopotential was used for Pt. 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 transi-
tion states actually connect the proposed reagents and products.
[20] Alkenylation of phenols via allenylidene intermediates: Y. Nishi-
bayashi, Y. Inada, M. Hidai, S. Uemura, J. Am. Chem. Soc. 2002,
124, 7900–7901.
[21] B. Martꢁn-Matute, C. Nevado, D. J. Cꢂrdenas, A. M. Echavarren, J.
Am. Chem. Soc. 2003, 125, 5757–5766.
[22] B. Martꢁn-Matute, D. J. Cꢂrdenas, A. M. Echavarren, Angew. Chem.
2001, 113, 4890–4893; Angew. Chem. Int. Ed. 2001, 40, 4754–4757.
[23] AuIII-catalyzed reaction of furans with alkynes: a) A. S. K. Hashmi,
T. M. Frost, J. W. Bats, J. Am. Chem. Soc. 2000, 122, 11553–11554;
b) A. S. K. Hashmi, T. M. Frost, J. W. Bats, Org. Lett. 2001, 3, 3769–
3771; c) A. S. K. Hashmi, J. P. Weyrauch, M. Rudolph, E. Kurpejov-
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Acknowledgements
This work was supported by the DGICYT (Project BQU2001–0193-C02–
01) and the ICIQ Foundation. We thank the CAM for a predoctoral fel-
lowship to C.N. and the Centro de Computaciꢃn Cientꢁfica (UAM) for
computation time. We also thank Drs. Diego J. Cꢂrdenas (UAM) and
Carles Bo (ICIQ) for helpful discussions and assistance with the compu-
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Received: October 20, 2004
Published online: March 18, 2005
3164
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www.chemeurj.org
Chem. Eur. J. 2005, 11, 3155 – 3164