Gold(I)-catalyzed cyclizations of 1,6-enynes: Alkoxycyclizations and exol endo skeletal rearrangements

Article abstract of DOI:10.1002/chem.200501088

Gold(1) complexes are the most active catalysts for alkoxy- or hydroxycyclization and for skeletal rearrangement reactions of 1,6-enynes. Intramolecular alkoxycyclizations also proceed efficiently in the presence of gold(I) catalysts. The first examples o

Full text of DOI:10.1002/chem.200501088

FULL PAPER
DOI: 10.1002/chem.200501088
Gold(i)-Catalyzed Cyclizations of 1,6-Enynes: Alkoxycyclizations and exo/
endo Skeletal Rearrangements
Cristina Nieto-Oberhuber,[a,b] M. Paz MuÇoz,[b] SalomØ López,[a]
Eloísa JimØnez-NfflÇez,[a,b] Cristina Nevado,[b] Elena Herrero-Gómez,[a]
Mihai Raducan,[a] and Antonio M. Echavarren*[a,b]
Abstract: Gold(i) complexes are the
most active catalysts for alkoxy- or hy-
droxycyclization and for skeletal rear-
rangement reactions of 1,6-enynes. In-
tramolecular alkoxycyclizations also
proceed efficiently in the presence of
gold(i) catalysts. The first examples of
the skeletal rearrangement of enynes
by the endocyclic cyclization pathway
are also documented. Iron(iii) is also
able to catalyze exo and endo skeletal
rearrangements of 1,6-enynes, although
the scope of this transformation is
more limited. The gold(i)-catalyzed en-
docyclic cyclization proceeds by
a
mechanism different from those fol-
lowed in the presence of PdII, HgII, or
RhI catalysts.
Keywords: alkynes · cyclization ·
gold · iron · rearrangement
Introduction
Reactions of 1,6-enynes catalyzed by electrophilic transi-
tion-metal complexes or salts proceed through two general
pathways, depending on whether the metal coordinates se-
lectively to the alkyne (as in I) or to both the alkyne and
the alkene (as in II) (Scheme 1).[1–3] In the second case, an
oxidative cyclometalation could then form III, which should
usually evolve by b-hydrogen elimination to give Alder-ene
type products.[2,4–6] Cyclopropyl metal carbenes IV or V are
formed from I by exo-dig or endo-dig processes, respective-
ly.[2,7] Reactions of IV with alcohols or water give products
of alkoxy- or hydroxycyclization VI and/or VII.[2,8] Inter-
mediates V can undergo a-CH insertion and elimination to
form VIII,[3b,9,10] whereas reactions with alcohols afford
IX.[3a]
In the absence of nucleophiles, enynes undergo skeletal
rearrangement to form dienes X (single cleavage) and/or XI
Scheme 1. Mechanisms for the endo- and exo-alkoxycyclization of
enynes.
[a] C. Nieto-Oberhuber, Dr. S. López, E. JimØnez-NfflÇez,
E. Herrero-Gómez, M. Raducan, Prof. Dr. A. M. Echavarren
Institute of Chemical Research of Catalonia (ICIQ)
Av. Països Catalans 16, 43007 Tarragona (Spain)
Fax : (+34)977-920-225
(double cleavage) (Scheme 2).[1,5,11,12] Cyclobutenes XII have
been proposed as intermediates for the formation of dienes
X.[12,13] Interestingly, cyclobutenes of type XIII have also
been isolated in certain reactions catalyzed by PdII,[13] AuI,[14]
and PtII.[15]
E-mail: aechavarren@iciq.es
[b] C. Nieto-Oberhuber, M. P. MuÇoz, E. JimØnez-NfflÇez, C. Nevado,
Prof. Dr. A. M. Echavarren
Departamento de Química Orgµnica
Universidad Autónoma de Madrid
Cantoblanco, 28049 Madrid (Spain)
By using cationic gold(i) complexes [Au(L)(S)]+ XÀ as
catalysts we uncovered the first examples of the 6-endo-dig
Chem. Eur. J. 2006, 12, 1677 – 1693
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the accompanying paper in this issue we analyze the mecha-
nism and stereoselectivity observed in the double cyclopro-
panation reaction catalyzed by gold(i).[18]
Results and Discussion
[AuI(PPh3)(S)]+-catalyzed intermolecular alkoxy- and hy-
droxycyclization: Alkoxycyclization was observed when
enynes were allowed to react in alcohols ROH as solvent in
the presence of a catalyst formed in situ from [Au(PPh3)Me]
and a protic acid such as HBF4, phosphotungstic acid trihy-
drate, or trifluoroacetic acid (TFA) (Table 1). Under these
conditions the complex [Au(PPh3)(ROH)]+ is presumably
generated. No cyclizations were observed with the protic
acids in the absence of AuI. Addition of PPh3 or diphos-
phanes (dppe, dppe, dppf) (3 mol%) resulted in unreactive
gold(i) complexes, but the reaction could be carried out in
the presence of bulky and electron-rich PCy3 (Table 1,
entry 6). Hydroxycyclization of 1 in aqueous acetone gave a
1:1 mixture of alcohol 2c and bicyclic lactone 3 (Table 1,
entry 5). The cyclization of enol ether 6 could be carried out
in the presence of only 1 mol% of catalyst (Table 1, en-
tries 7 and 8). The reactions in the presence of gold(i) usual-
ly proceeded at room temperature, although the cyclization
Scheme 2. exo-Skeletal rearrangement and formal [2+2] cycloaddition
products.
skeletal rearrangement of 1,6-enynes,[16] a type of reaction of
enynes that, somewhat surprisingly, had not been reported
before with other transition-metal catalysts. Gold(i) com-
plexes are also excellent catalysts for the cyclization of a va-
riety of enynes.[14,17] Here we report the results of an in-
depth study of the cyclization of 1,6-enynes with different
gold(i) complexes, resulting variously in alkoxy- or hydroxy-
cyclization or in skeletal rearrangement. We have also found
that FeIII catalyzes the skeletal rearrangement, and in one
case gives 6-endo-dig skeletal rearrangement products, al-
though the scope of this transformation is more limited. In
Table 1. Alkoxy- or hydroxycyclization of enynes on treatment with [Au(PPh3)Me] (3 mol%) and protic acid (6 mol%).
Entry
1
Enyne
ROH
HA
t [h]
Product (yield [%])
1, Z = C(CO2Me)2
MeOH
HBF4
4
2a (97)
2
3
1
1
MeOH
MeOH
TFA
H3PW12O40
3
4
2a (82)
2a (96)
[a]
4
1
EtOH
TFA
TFA
HBF4
24
24
12
2b (75)
(100, 1:1)
5 (85)
5
1
H2O/acetone
MeOH
6[b]
4, Z = C(SO2Ph)2
7
6, Z = C(CO2Me)2
MeOH
MeOH
MeOH
TFA
0.5
2
7 (95)
7 (96)
9(85)
[a]
[b]
8[c]
9[d]
6
H3PW12O40
H3PW12O40
8, Z = NTs
17
[b]
10[d]
10, Z = C(SO2Ph)2
MeOH
H3PW12O40
17
11 (96)
[a] The trihydrate was used. [b] PCy3 (3 mol%) was also added. [c] 1 mol% [Au(PPh3)Me] and 2 mol% protic acid. [d] Reaction was carried out under
reflux.
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Gold(i)-Catalyzed Cyclizations of 1,6-Enynes
FULL PAPER
of the less reactive substrates 8 and 10 had to be performed
at reflux in methanol (Table 1, entries 9 and 10). In all cases
the alkoxycyclizations proceeded more readily in the pres-
ence of gold(i) than in the presence of platinum(ii) cata-
lysts.[2]
As previously observed for PtII-catalyzed alkoxy- and hy-
droxycyclizations,[2] the AuI-catalyzed process is stereospecif-
ic. Treatment of 12 in MeOH, EtOH, or aqueous acetone
thus gave 13a–c as single diastereomers (Table 2). These re-
Table 2. Alkoxy- or hydroxycyclization of enynes 12 in the presence of
[Au(PPh3)Me] and protic acid.
Scheme 3. Regioselective and/or stereospecific methoxycyclizations of 14,
16, and 18.
Entry [Au(PPh3)Me] HA
ROH
T
t
Product
[mol%]
([mol%])
[8C] [h] (yield
[%])
1
2
3
4
5
6
7
5
5
3
3
3
3
3
HBF4 (25)
TFA (25)
TFA (6)
HBF4 (6)
H3PW12O40
TFA (6)
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
65
23
23
23
23
23
23
0.5 13a (78)
4
4
4
7
4
4
13a (96)
13a (82)
13a (82)
13a (67)
13b (79)
13c (63)[b]
Table 3. AuI-catalyzed intramolecular reactions between allylsilane and
alkyne functional units.
[a]
TFA (6)
H2O/ace-
tone
[a] The trihydrate was used. [b] The skeletal rearrangement product and
a tetracyclic derivative were also obtained in 22% and 15% yields, re-
spectively.[18]
Entry Allylsilane [Au]
([mol%])
HA (mol%) Product
([mol%])
(yield
[%])
1
2
3
20
20
20
[Au(PPh3)Me] (3)
[Au(PPh3)Me] (3)
[Au(PPh3)Cl] (5)/AgSbF6
(5)
[Au(PPh3)Me] (3)
[Au(PPh3)Cl] (5)
TFA (6)
H3PW12O40
-
21 (93)
21 (82)
21 (94)
[a]
actions were carried out at room temperature over 4–7 h in
the presence of 3 mol% catalyst and provided adducts 13a–
c in satisfactory yields. However, the hydroxycyclization of
12 also afforded products of skeletal rearrangement and bis-
cyclopropanation.[18]
4
22
22
HBF4 (6)
-
23 (97)
23 (97)
5[b]
[a] The trihydrate was used. [b] The reaction was carried out at 658C.
The corresponding treatment of bissulfone 14 proceeded
more slowly to give 15 (Scheme 3), which can be attributed
to the strongly electron-withdrawing effect of the sulfone
groups. Enyne 16, the Z diastereomer of 12, reacted in
MeOH to give ether 17, the diastereomer of 13a, exclusive-
room temperature (Table 3, entry 3). Desilylation assisted
by attack of MeOH presumably takes place on an inter-
mediate of type IV (Scheme 1).[19b]
À
ly. On the other hand, the regioselectivity in the C C bond
Although, in general, the cationic catalysts generated in
situ from [Au(PPh3)Me] and protic acid (6 mol%) proved to
be satisfactory for the cyclization of enynes, we sought to
develop alternative conditions that could allow the reactions
to be performed under neutral conditions. We reasoned that
highly active AuI catalysts should be formed by chloride ab-
straction from [Au(L)Cl] complexes bearing bulky phos-
phanes as ligands.[14] In particular, we focused on the bulky,
biphenyl-based phosphanes developed by Buchwald in the
formation (the formation of products of type VI or VII;
Scheme 1) is dictated by the substituents at the alkene, the
AuI-catalyzed reaction of enyne 18 in methanol thus giving
the six-membered derivative 19. In this case, the best results
were achieved with a catalyst formed in situ from [Au-
(PPh3)Cl] and AgSbF6.
The allylsilane 20 reacted in the presence of cationic
gold(i) complexes to give the diene 21[19] (Table 3, entries 1
and 2). In the case of the more reactive substrate 22, the
cyclization could also be carried out in the presence of the
neutral complex [Au(PPh3)Cl], although the reaction had to
be performed in MeOH at reflux (Table 3, entry 5). With a
catalyst formed from [Au(PPh3)Cl] by chloride abstraction
with AgSbF6, the cyclization of 20 could be carried out at
À
À
context of palladium-catalyzed C C and C X bond-forma-
tion reactions.[20,21] The gold(i) complexes 24a–d were thus
readily prepared by the known procedure for the synthesis
of [Au(PPh3)Cl] (Figure 1),[22] whilst the cationic complexes
24e and 25 were prepared by chloride abstraction from the
corresponding neutral complexes with AgSbF6 in acetoni-
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A. M. Echavarren et al.
Table 4. AuI-catalyzed methoxycyclization of enyne 1.
Entry
Complex
Time
[h]
Conversion
[%][a]
Yield of
2a [%]
1
2
3
4
5
6
7
8
AuCl
[Au(SMe2)Cl]
[Au(PPh3)Cl]
[Au(PCy3)Cl]
[Au{P(C6F5)3}Cl]
[Au(AsPh3)Cl]
[Au{P(o-Tol)3}Cl]
[Au{P(1-Naph)3}Cl]
24a
24b
24c
24d
24e
26a
26b
26c
24
24
3
3.5
5
4
24
12
0.5
0.25
0.25
0.25
0.25
1.5
5
32
<2
10
<2
84
77
77
78
90
76
97
90
92
89
91
71
87
34
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
>98
Figure 1. AuI complexes with bulky phosphane or N-heterocyclic ligands.
9
10
11
12
13
14
15
16
trile.[12] The AuI complexes 26a–c, with N-heterocyclic donor
ligands,[23] were also tested as catalysts for the methoxycycli-
zation of enyne 1 (Table 2). Complex 26a and other related
complexes have been independently prepared by Nolan
et al.[24]
24
The reaction of 1 in MeOH proceeded inefficiently in the
presence of catalysts generated from AuCl or [Au(Me2S)Cl]
and AgSbF6 (Table 4, entries 1–2).[25,26] However, complexes
[Au(L)Cl]—where L = PPh3, PCy3, P(C6F5)3, or AsPh3—
gave 2a in similar yields in 3–5 h (Table 4, entries 3–6).
Treatment of 1 with [Au(L)Cl] complexes containing the
bulkier phosphanes P(o-Tol)3 or P(1-Napth)3 resulted in
slower reactions (Table 4, entries 7 and 8). Remarkably, use
of the complexes 24a–e provided 2a in 15–30 min at room
temperature (Table 4, entries 9–13), whilst cyclization with
AuI complexes 26a–c, containing N-heterocyclic donor li-
gands, was not as efficient (Table 4, entries 14–16).
Cyclization of enyne 27 to give 28 proceeded more satis-
factorily in the presence of catalyst 24c (Table 5, entry 9),
although reaction times were in all cases longer than those
require to cyclize enyne 1 (Table 4), which bears a more re-
active trisubstituted alkene. Similarly, enyne 29 reacted with
MeOH in the presence of catalysts 24e or 25 to give 30 in
excellent yield (Scheme 4). In contrast, the nitro derivative
31 failed to provide any methoxycyclized derivative under
the same conditions. After long reaction times (72 h, 238C),
ketone 32 was obtained in moderate yield (15–22%) as a
result of the AuI-catalyzed hydration of the alkyne by the
traces of water contained in the methanol.[27] Interestingly,
the double bond migration
[a] Conversions were determined by GC.
Table 5. AuI-catalyzed methoxycyclization of enyne 27.
Entry
Complex
t
Conversion
[%][a]
Yield
[%]
[h]
1
2
3
4
5
6
7
8
AuCl
48
48
18
18
48
48
30
18
18
20
24
48
50
21
93
>98
66
68
>98
>98
>98
>98
73
35
5
[Au(Me2S)Cl]
[Au(Ph3P)Cl]
[Au(Cy3P)Cl]
[Au{(C6F5)3P}Cl]
[Au(Ph3 As)Cl]
[Au{(o-Tol)3P}Cl]
24a
24c
26a
26b
26c
70
83
44
48
79
68
94
76
51
48
9
10
11
12
84
[a] Levels of conversion were determined by GC.
hydroxy group on the cyclopropyl gold carbene intermediate
to afford ether 34 quantitatively (Scheme 5). Similarly, sub-
products 31’ and 32’ were also
detected in the crude reaction
mixtures. Addition of 4 Š mo-
lecular sieves inhibited the hy-
dration of the alkyne.
[AuIPPh3)(S)]+-catalyzed in-
tramolecular alkoxycyclization:
The corresponding treatment
of substrate 33, containing a
propargylic alcohol, resulted in
intramolecular attack of the
Scheme 4. Methoxycyclization of cinnamyl derivatives 29 and 31.
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Gold(i)-Catalyzed Cyclizations of 1,6-Enynes
FULL PAPER
readily at room temperature in CH2Cl2 and were completed
in less than 1 h, giving the corresponding 1,3-dienes
(Table 7). The reaction did not take place in solvents such as
MeCN or toluene, and no reaction was observed with [Au-
(PPh3)Cl] alone. In addition, the reaction was not catalyzed
by AgI salts. The reaction could also be performed in the
presence of AuCl3 or AuCl (Table 7, Entries 5 and 6), al-
though it was very slow in the latter case. The rearrange-
ment was stereospecific, as shown in the reactions of enynes
50 and 16, each with a Z configuration at the alkene, which
gave Z-dienes 55 and 57, respectively (Table 7, entries 8 and
10). In the case of substrate 50, the allylic alcohol did not in-
terfere in the rearrangement.
Surprisingly, in contrast with 1 (entry 1, Table 7), enyne 58
gave 59 as the major 1,3-diene, along with the exo-skeletal
rearrangement product 60 (Scheme 6). Diene 59 is the prod-
uct of an endocyclic skeletal rearrangement (see below).
Trost had reported the reaction of 58 to give 59 catalyzed by
[Pd(OAc)2]/bis(2-methoxyphenylphosphane)propane.[28]
However, the involvement of a palladium hydride in this re-
action was proposed and the cyclization takes place through
an intramolecular insertion of an alkenylpalladium com-
plex.[28–30] It is interesting to note that products with this
structure have also been obtained by the ring-closing meta-
thesis of enynes catalyzed by a second-generation ruthenium
Grubbs catalyst[31] and, more
Scheme 5. Intramolecular alkoxycyclization of enyne 33.
strates 35–40, containing hydroxy groups in their alkene
chains, underwent intramolecular cyclizations to give 41–46
(Table 6). These cyclizations took place within 5–30 min at
room temperature in the presence of a catalyst formed from
[Au(PPh3)Cl] and AgSbF6. In contrast, when PtCl2 was used
as catalyst, the reaction had to be performed at 808C for 3 h
(Table 6, entry 6). Cyclization of enynes 36–40 gave 1:1 mix-
tures of diastereomers, epimeric at C-5 of the tetrahydrofur-
an ring. In the case of substrate 40, containing two hydroxy
groups, exclusive formation of tetrahydrofurans 46a/46b
was observed as the result of the opening of the cyclopropyl
gold carbene intermediate by the less hindered secondary
hydroxy moiety (Table 6, entry 7).
Skeletal rearrangement: On application of catalysts formed
in situ from [Au(PPh3)Cl]/AgX (X = BF4 or SbF6), the
enynes underwent skeletal rearrangement (Scheme 2). The
rearrangements of enynes 1, 16, 18, and 47–50 proceeded
recently, in the cycloisomeriza-
Table 6. Intramolecular alkoxycyclization of enynes 35–40.
tion of enynes with RhI, which
proceeds via vinylidene inter-
mediates.[32,33] Enyne 27 gave a
mixture of endo (61) and exo
(62) skeletal rearrangement
products (Scheme 6). The reac-
tion behavior of substrates 29
and 31 was studied to deter-
mine the effect of substituents
at the alkene. As expected, 29
reacted more rapidly than 31,
containing an electron-with-
drawing para-nitrophenyl sub-
stituent. Monitoring of the re-
Entry
1
Enyne
t [min]
Product(s) (yield [%])
35, R = H
45
41 (76)
2
3
4
36, R = Me
15
30
30
42a/42b (1:1, 60)
43a/43b (1:1, 85)
44a/44b (1:1, 82)
1
actions by H NMR in CD2Cl2
at 58C showed pseudo-first
order behavior, with k(29)/
37, R = tBu
k(31)
= 2.6. The exo/endo
38, R = CH=CH2
ratio depended on the elec-
tronic effects of substituents at
the alkene: cinnamyl (27) and
p-nitrocinnamyl (31) deriva-
tives thus afforded 1:1.1–1.9
ratios of endo/exo products,
whereas the exo pathway was
more clearly favored in the re-
action of p-methoxycinnamyl
derivative 29 (1:5.5–7 ratios).
Enynes with NTs as tethers
were particularly prone to un-
5
39, R = Ph
5
45a/45b (1:1, 80)
45a/45b (1:1, 82)
6[a]
39
180
7
40, R = C(OH)Me2
10
46a/46b (1:1, 77)
[a] Reaction carried out with PtCl2 (3 mol%) in toluene at 808C.
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A. M. Echavarren et al.
Table 7. exo-Skeletal rearrangement of enynes in the presence of [Au(PPh3)Cl] (2 mol%) and AgX (2 mol%).
(Scheme 8), whilst in MeOH
the reaction proceeded exo-
cyclically (Table 1, entry 9).
The opposite was the case with
enyne 18, which rearranged
exocyclically (Table 7, entry 9)
but reacted by the endo path-
way with respect to the alkene
in MeOH (Scheme 3).
Entry Enyne
AgX
t
Product (yield [%])
[min]
51
1
1, Z = C(CO2Me)2, R1 = R2 = Me, R3 = H
AgSbF6 25
(91)[a]
2[b]
1
–
5
51
We also decided to compare
these results with those of re-
actions catalyzed by harder
Lewis acids. Thus, after investi-
gation of a variety of Lewis
acids, we found that FeCl3
itself was also able to catalyze
skeletal rearrangements of
enynes (Table 8). This is in
contrast with the cyclization of
certain enynes promoted by
stoichiometric amounts of
FeCl3, which resulted in cycli-
zation with concomitant addi-
tion of chloride to the triple
bond.[34] On the other hand,
treatment of enyne 1 with the
(98)
52
(100)
3
47, Z = C(SO2Ph)2, R1 = R2 = R3 = H
AgSbF6
5
53[c]
(96)
53[c]
(70)
53[c]
(81)
4
48,[c] Z = C(CO2Me)2, R1 = Me, R2 = R3 = H
AgBF4 10
5[d]
48
–
–
5
6[e]
48
840
54[b]
(100)
7
8
9
49,[b] Z = C(SO2Ph)2, R1 = Me, R2 = R3 = H
AgBF4 15
50, Z = C(CO2Me)2, R1 = Me, R2 = CH2OH, R3
H
=
55
(67)
AgSbF6
AgBF4
5
5
56
(76)
18, Z = C(CO2Me)2, R1 = R2 = H, R3 = Me
16, Z = C(CO2Me)2, R1 = Me, R2 = (CH2)2CH=
CMe2, R3 = H
57
(47)
10[f]
AgSbF6 60
Fe0
complex
[Fe(CO)4-
(acetone)] had been reported
to give Alder–ene cycloisome-
rization.[35] The reactions had
to be carried out with 5 mol%
catalyst in toluene at 80–908C
and were more limited in
scope than those catalyzed by
[a] Isomerization product 87 was also obtained as a minor product (see Table 8, entry 1). [b] The reaction was
carried out in the presence of catalyst 24e (2 mol%). [c] E/Z 4:1. [d] The reaction was carried out in the pres-
ence of AuCl3 (5 mol%). [e] The reaction was carried out in the presence of AuCl (10 mol%). [f] The reaction
was performed at À48C.
dergo the endo-skeletal rearrangement (Scheme 7). The N-
propargyl-N-allyl toluene-4-sulfonylamine 67 thus gave a
>10:1 mixture of endo (68) and exo (69) rearranged prod-
ucts, whereas the more highly substituted 8 exclusively af-
forded 70. Diene 70 was also formed as a minor product
(12–19% yield) in the skeletal rearrangement of enyne 8 in
the presence of 5 mol% PtCl2 (toluene, reflux) or 5 mol%
PtCl4 (toluene, 238C). In platinum-catalyzed reactions of 8,
Alder–ene cycloisomerization was the major pathway.[2a,b]
Enynes 71a,b also underwent endo rearrangement to yield
72a,b as the major products. In these cases the bicyclo-
[4.1.0]heptenes 74a,b were also obtained as byproducts,
whilst similar bicyclic derivatives were also obtained in the
cyclizations of 75 and 84. On the other hand, 79 and 82 rear-
ranged quite cleanly to give the endo products 80 and 83, re-
spectively. The formation of bicyclo[4.1.0]heptenes and endo
skeletal rearrangement products in some of these cycliza-
tions strongly suggests that a common intermediate V
(Scheme 1) is involved for both processes.
AuI. The exo-skeletal rearrangement was the most favored
process for enynes with Z = C(CO2Me)2 or C(SO2Ph)2
(Table 8, entries 1–6). However, enyne 8 gave 70, the endo
rearrangement derivative, as the major product (Table 8,
entry 7), although the exo rearrangement diene 89 was also
formed in the FeIII-catalyzed process. In the cyclization of 1,
in addition to 51, a second diene 87 was also formed as the
result of the isomerization of the endocyclic double bond of
51 (Table 8, entry 1). Diene 87 has also been observed as a
minor product in reactions of 1 catalyzed by AuI complexes.
Mechanistic insights into the skeletal rearrangement of
enynes catalyzed by AuI complexes: Since metal carbenes
have been proposed as intermediates in enyne cyclization
reactions,[1d,2,16] and as, on the other hand, products of endo
cyclization had been observed in cyclization of enynes cata-
lyzed by Grubbs carbenes,[31] we wished to examine the pos-
sible involvement of alkene metathesis in the skeletal rear-
rangement of enynes. For that purpose, experiments involv-
ing mixtures of two different enynes were carried out to de-
termine whether any cross-over was occurring in the pres-
ence of AuI catalysts.
Interestingly, the exo/endo selectivity may be different in
the methoxycyclization and the skeletal rearrangement of
enynes. Thus, substrate 8 underwent skeletal rearrangement
by an endo pathway in the presence of [Au(PPh3)]+
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Gold(i)-Catalyzed Cyclizations of 1,6-Enynes
FULL PAPER
In the event, treatment of a
1:1 mixture of 58 and 8 with
AuI gave a mixture of 59 and
60 (arising from 58), together
with 70, which is derived from
8 (Scheme 8a). Similar treat-
ment of
a 1:1 mixture of
enynes 1 and 47 afforded only
those products expected from
fully intramolecular processes
(Scheme 8b).
With regards to the forma-
tion of endo rearrangement
products, we found that treat-
ment of enyne 18 with Hg-
(OTf)2 (2 mol%)[7] as catalyst
surprisingly afforded diene 90
(Scheme 9), in contrast with
findings from the AuI-cata-
lyzed reaction of 18 described
above (Table 7, entry 9). Treat-
ment of [D1]-18 with Hg(OTf)2
gave [D1]-90, which demon-
strates that there is no skeletal
rearrangement in this transfor-
mation. On the other hand,
[D1]-18 reacted in the presence
of a AuI catalyst to give [D1]-
56, the product of a single exo
rearrangement, whilst enyne
[D1]-75 gave a mixture of endo
products [D1]-76 and [D1]-78.
Scheme 6. endo-Skeletal rearrangements of enynes with malonate as the tether.
Table 8. Skeletal rearrangement of enynes in the presence of FeCl3 in toluene at 908C.
Entry
1
Enyne
t [h]
Product(s) (yield [%], ratio])
1, Z = C(CO2Me)2, R1 = R2 = Me
12
(88, 0.8:1)
(84)
2
3
4
5
47, Z = C(SO2Ph)2, R1 = R2 = H
12
12
15
17
48,[b] Z = C(CO2Me)2, R1 = Me, R2 = R3 = H
49,[b] Z = C(SO2Ph)2, R1 = Me, R2 = H
58, Z = C(CO2Me)2, R1 = R2 = H
(79)
(85)
(98)[a]
6
4, Z = C(SO2Ph)2, R1 = R2 = Me
8, Z = NTs, R1 = R2 = Me
12
17
(36)
7[c]
(63, 0.4:1)
[a] Based on 84% conversion. [b] E/Z 4:1. [c] The reaction was performed at 808C.
Chem. Eur. J. 2006, 12, 1677 – 1693
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1683

A. M. Echavarren et al.
Scheme 8. Experiments aimed at determining cross-metathesis between
different enynes.
Scheme 9. HgII- and AuI-catalyzed cyclization and experiments with deu-
terated substrates in the exo- and endo-skeletal rearrangement.
The formation of the same type of skeleton, but with dif-
ferent deuteration patterns, in the reactions of 18 and 75 in-
dicates that two different mechanisms are operating. For the
endo rearrangement, the formation of D1-76 from D1-75 can
be explained by evolution of intermediate V (Scheme 10).
Scheme 7. endo-Skeletal rearrangement of enynes with TsN- as the
tether.
1684
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Chem. Eur. J. 2006, 12, 1677 – 1693

Gold(i)-Catalyzed Cyclizations of 1,6-Enynes
FULL PAPER
multaneously and, in consequence, the Alder-ene cycloiso-
merization does not compete and the cyclizations proceed
exclusively through complexes of type I (Scheme 1). Howev-
er, when the reaction of enyne 1 was attempted in DMSO
as the solvent at 508C in the presence of the highly reactive
AuI complex 24e, a mixture of dienes 23 and 91 was ob-
tained (Scheme 12).
Scheme 10. Proposed mechanism for the endo-skeletal rearrangement
with AuI.
Opening of cyclopropane V to form XIV, followed by
À
proton loss and final cleavage of the M C bond, could also
be conceived as a possible mechanism for the formation of
products XV. However, this mechanism can be excluded be-
cause an intermediate like XVI would be formed from 75,
which would not explain the formation of 76. In addition, in-
volvement of a metal vinylidene as an intermediate[32] is ex-
cluded by the observed deuteration pattern and by the fact
that the cyclization also proceeded with enynes containing a
methyl substituent at C-2 of the alkene, which would not be
able to undergo the required b-hydride elimination.
Scheme 12. Formation of dienes 23 and 91 from 1 with 24e as catalyst in
DMSO.
To interpret the different reactivity of 18 with HgII, we
propose the involvement of intermediate XVII, which
would undergo proton loss to give XVIII, followed by
proto-demercuration (Scheme 11). A similar mechanism has
recently been proposed independently by Mikami et al.[36]
and by Yamamoto et al. for the Pd0-catalyzed endo-cycliza-
tion of enynes.[37]
Diene 23 is the product of formal Alder–ene type cyclo-
isomerization of 1. However, treatment of [D1]-1 with 24e
(3 mol%) in DMSO at 508C afforded dienes [D1]-23 and
[D1]-91 with a deuteration pattern that excluded the partici-
pation of Alder-ene type cycloisomerization in this transfor-
mation, as this would have resulted in the formation of [D1]-
23’.[2b] This result, and the formation of 91, can be satisfacto-
rily explained by ring-opening of intermediate XIX to car-
bocation XX, followed by proton loss.
Importantly, cation [Au(PPh3)]+, which is isolobal to
H+,[38] cannot coordinate to the alkene and the alkyne si-
Conclusion
Gold(i) complexes are the most active catalysts for the
alkoxy-/hydroxycyclization and skeletal rearrangement of
enynes. In particular, gold(i) catalysts generated by chloride
abstraction with a silver salt or cationic complexes such as
24e and 25 are, by far, more active as catalysts than the PtII
salts or complexes used for alkoxycyclization, hydroxycycli-
zation, and skeletal rearrangement reactions.[2] Gold(i) com-
plexes are selective alkynophilic catalysts, promoting reac-
tions through the exclusive coordination of the metal com-
plex to the alkyne of the enyne. With these catalysts, the
first examples of skeletal rearrangement of enynes by the
Scheme 11. Proposed mechanism for the HgII-catalyzed cycloisomeriza-
tion.
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1685

A. M. Echavarren et al.
eral oil) in DMF (5 mL). After 20 min, a solution of p-nitrocinnamyl bro-
mide (798 mg, 3.13 mmol) in DMF (15 mL) was added and the resulting
mixture was stirred at 238C for 16 h. After extractive workup (Et2O/10%
HCl), chromatography (hexane/EtOAc 10:1), and recrystallization from
hexane, 31 was obtained (704 mg, 81%) as yellow crystals, m.p. 73–758C:
1H NMR (400 MHz, CDCl3): d = 8.16 (d, J = 8.87 Hz, 2H), 7.46 (d, J =
8.8 Hz, 2H), 6.59 (d, J = 15.7 Hz, 1H), 6.24 (q, J = 7.7, 15.6 Hz, 1H),
3.77 (s, 6H), 3.01 (d, J = 6. 7 Hz, 2H), 2.85 (d, J = 2.7 Hz, 2H), 2.08 (t,
J = 2. 7 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3; DEPT, HMQC, and
HMBC): d = 168.89, 146.90, 143.23, 132.57, 128.67, 126.78, 123.94, 71.93,
71.92, 57.00, 52.94, 36.08, 23.18 ppm; IR (KBr): n˜ = 1731 cmÀ1; HRMS-
ESI: m/z calcd for C17H17NO6Na: 354.0954; found 354.0965 [M+Na]+.
endocyclic cyclization pathway have been documented. This
endocyclic cyclization proceeds by a mechanism different
from those followed in the presence of PdII, HgII, or RhI cat-
alysts.
Experimental Section
Unless otherwise stated, all reactions were carried out under Ar under
anhydrous conditions. Chromatography purifications were carried out
with flash grade silica gel (SDS Chromatogel 60 ACC, 40–60 mm).
The following compounds have been described: a) Starting enynes: 1,[39]
4,[2a,b] 6,[2c] 7,[40] 8,[41] 10,[2a,b] 12,[2a,b] 16,[42] 18,[13a] 20,[19] 22,[19] 27,[52] 47,[43]
48,[44] 49,[4a] 58,[44] 67,[45] 72a,[46] 71b,[47] 75,[2a,b] 79,[8] and 84;[48] b) carbo-
and heterocycles: 2a,[2a,b] 5,[2a,b] 9,[8] 11,[2a,b] 13a,[2a,b] 17,[2a,b] 19,[2a,b] 21,[49]
23,[50] 51,[51] 52,[10a] 53,[52] 54,[2a,b] 56,[44] 59,[29] 60,[52] 62,[52] 68,[10b] 69,[10b]
73a,[53] 76,[54] 77,[55] 78,[10] 79,[8] 81,[53] 89,[53] 90,[53] and 91.[56]
1-(1-Cinnamylcyclohexyl)prop-2-yn-1-ol (33): Propargylmagnesium bro-
mide (0.5m in THF, 11.39 mL, 5.69 mmol) was added at À408C to a solu-
tion of 1-trans-cinnamylcyclohexanecarbaldehyde[57] (1.00 g, 4.38 mmol)
in THF (10 mL), and the mixture was stirred for 2 h at this temperature
and for 1 h at 238C. After extractive workup (Et2O) and chromatography
(hexane/EtOAc 10:1), 33 was obtained as a colorless oil (643 mg, 58%):
1H NMR (300 MHz, CDCl3): d = 7.32 (m, 5H), 6.53 (d, J = 16.0 Hz,
1H), 6.35 (q, J = 7.3 Hz, 1H), 4.35 (dd, J = 6.7, 2.0 Hz, 1H), 2.57 (d, J
= 2.2 Hz, 1H), 2.52 (dq, J = 8.1, 2.2 Hz, 2H), 2.00 (d, J = 6.7 Hz, 1H),
Synthesis of new enynes
(E)-1,1-Bis(phenylsulfonyl)-4,8-dimethylnona-3,7-diene: Bis(phenylsulfo-
nyl)methane (500 mg, 1.68 mmol) was added at 08C to a suspension of
NaH (68 mg, 1.68 mmol, 60% in mineral oil) in DMF (15 mL). After
20 min, geranyl bromide (365 mg, 1.68 mmol) was added, and the result-
ing mixture was stirred at 238C for 12 h. After extractive workup (Et2O/
10% HCl) and chromatography (2:1 hexane/EtOAc), the title compound
1.65–1.51 (m, 10H) ppm; 13C NMR (75 MHz, CDCl3; DEPT):
d =
137.52 (C), 132.69 (CH), 128.46 (CH), 127.55 (CH), 127.51 (CH), 127.01
(CH), 126.81 (CH), 126.02 (CH), 83.34 (CH), 74.82 (C), 68.55 (CH),
41.48 (C), 35.97 (CH2), 31.18 (CH2), 30.10 (CH2) 26.00 (CH2), 21.37
(CH2), 21.27 (CH2) ppm; HRMS-CI: m/z calcd for C18H23O: 253.1592;
found 253.1583 [M+1]+.
was obtained (552 mg, 76%) as
a
white solid: 1H NMR (300 MHz,
CDCl3): d = 7.98–7.97 (m, 2H), 7.96–7.94 (m, 2H), 7.72–7.67 (m, 2H),
7.61–7.55 (m, 4H), 5.08–5.01 (m, 2H), 4.42 (t, J = 6.1 Hz, 1H), 3.10 (m,
2H), 2.01–1.86 (m, 4H), 1.68 (d, J = 1.2 Hz, 3H), 1.59 (s, 3H), 1.47 (d, J
= 1.2 Hz, 3H) ppm; 13C NMR (75 MHz, CDCl3): d = 139.69, 138.19,
134.49, 131.75, 129.64, 129.03, 123.78, 118.03, 84.35, 39.44, 26.27, 25.67,
24.62, 17.71, 16.13 ppm; HMRS-FAB: m/z calcd for C23H29O4S2:
433.1507; found 433.1499 [M+1]+; elemental analysis (%) calcd for
C23H28O4S2: C 63.86, H 6.52; found: C 63.79, H 6.18.
Dimethyl 2-(3-methyl-2-buten-4-ol)-2-(prop-2-ynyl)malonate (50): 2-
Methyl-2-vinyloxirane (0.57 mL, 5.87 mmol) and dimethyl propargylmal-
onate (0.89 mL, 5.87 mmol) were added at 238C to a suspension of [Pd2-
(dba)3·dba] (337 mg, 0.59 mmol) and Ph3P (154 mg, 0.59 mmol) in
CH3CN. The mixture was stirred at this temperature for 16 h. Then
CH3CN was evaporated (without heating) and the mixture was diluted
with CH2Cl2 and filtered through Celite. After chromatography (hexane/
EtOAc 10:1 to 3:1), 50 was obtained as a yellow oil and as a E/Z isomer
mixture (1.20 g, 81%): 1H NMR (300 MHz, CDCl3): d = 5.22 (tdd, J =
7.7, 2.8, 1.2 Hz, 1H; E isomer), 5.07 (td, J = 8.1, 1.2 Hz, 1H; Z isomer),
4.1 (brs, 2H; Z isomer), 3.99 (s, 2H; E isomer), 3.75 (s, 6H; Z isomer),
3.74 (s, 6H; E isomer), 2.89 (dm, J = 7.7 Hz, 2H; E isomer), 2.83 (d, J=
(E)-4,4-Bis(phenylsulfonyl)-7,11-dimethyldodeca-6,10-dien-1-yne
(E)-1,1-Bis(phenylsulfonyl)-4,8-dimethylnona-3,7-diene
(14):
(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), 14 (245 mg, 45%) was obtained as a pale
yellow solid: 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, 3H) ppm;
13C NMR (75 MHz, CDCl3): d = 140.44, 136.48, 134.64, 131.52, 128.45,
123.91, 114.87, 89.27, 76.11, 73.99, 39.88, 27.69, 26.18, 25.68, 20.36, 17.74,
16.59 (one carbon signal overlaps) ppm; HMRS-CI: m/z calcd for
C26H31O4S2: 471.1664; found 471.1675 [M+1]+.
2.8 Hz, 2H; E isomer, 2H; Z isomer), 2.78 (d, J
= 2.8 Hz, 2H; Z
isomer), 2.06 (t, J = 2.8 Hz, 2H), 2.05 (s, 1H; E isomer), 1.81 (m, 3H; Z
isomer), 1.70 (s, 3H; E isomer) ppm; 13C NMR (75 MHz, CDCl3; DEPT):
d = 170.3 (2 C; E isomer, Z isomer), 140.0 (C; Z isomer), 139.9 (C; E
isomer), 120.4 (CH; Z isomer), 117.9 (CH; E isomer), 88.0 (CH; E
isomer), 81.9 (CH; Z isomer), 78.9 (2 C; E isomer, Z isomer), 72.0 (C; Z
isomer), 71.4 (C; E isomer), 68.4 (CH2; E isomer), 61.2 (CH2; Z isomer),
56.9 (2 C; E isomer, Z isomer), 52.9 (CH3; Z isomer), 52.8 (CH3; E
isomer), 30.3 (CH2; Z isomer), 30.2 (CH2; E isomer), 22.6 (CH3; E
isomer), 21.7 (CH3; Z isomer) ppm; HRMS-EI: m/z calcd for C13H18O5:
254.1154; found 254.1158.
Dimethyl 2-(p-methoxycinnamyl)-2-propargylmalonate (29): A solution
of dimethyl 2-propargylmalonate (0.22 mL, 1.44 mmol) in DMF (5 mL)
was added at 08C to a suspension of NaH (63.0 mg, 1.57 mmol, 60% in
mineral oil) in DMF (3 mL). After 20 min, a solution of p-methoxycin-
namyl bromide (597 mg, 2.60 mmol) in DMF (10 mL) was added and the
resulting mixture was stirred at 238C for 18 h. After extractive workup
(Et2O/10% HCl) and chromatography (hexane/EtOAc 10:1), 29 (398 mg,
87%) was obtained as a white, waxy solid: 1H NMR (400 MHz, CDCl3):
d = 7.26 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.8 Hz, 2H), 6.46 (d, J =
15.7 Hz, 1H), 5.85 (q, J = 15.5, 7.7 Hz, 1H), 3.80 (s, 3H), 3.76 (s, 6H),
2.94 (d, J = 7.7 Hz, 2H), 2.84 (d, J = 2.7 Hz, 2H), 2.05 (t, J = 2.7 Hz,
N-((2Z)-3,7-Dimethyl-octa-2,6-dienyl)-N-(prop-2-ynyl)toluene-4-sulfona-
mide (82): A solution of N-(prop-2-ynyl)toluene-4-sulfonamide (1.00 g,
4.79 mmol) in DMF (10 mL) was added at 08C to a suspension of NaH
(60% in mineral oil, 192 mg, 4.79 mmol) in DMF (5 mL), followed by
neryl bromide (1.04 g, 4.79 mmol). The mixture was stirred for 17 h at
238C and was then quenched with H2O. After extractive workup (Et2O/
HCl 10%) and chromatography (hexane/EtOAc 30:1), 82 (1.03 g, 62%)
was obtained as a yellow oil: 1H NMR (300 MHz, CDCl3): d = 7.72 (d,
J=8.3 Hz, 2H), 7.28 (d, J = 7.9 Hz, 2H), 5.12–5.02 (m, 2H), 4.05 (d, J=
2.4 Hz, 2H), 3.79 (d, J = 7.3 Hz, 2H), 2.42 (s, 3H), 2.06 (m, 4H), 1.97 (t,
1H) ppm; 13C NMR (100 MHz, CDCl3): d
= 170.20, 159.14, 134.05,
J
= 2.6 Hz, 1H), 1.72 (d, J = 1.2 Hz, 3H), 1.66 (s, 3H), 1.57 (s,
3H) ppm; 13C NMR (75 MHz, CDCl3; DEPT): d = 143.32 (C), 142.30
(C), 136.21 (C), 132.07 (C), 129.35 (CH), 127.77 (CH), 123.62 (CH),
118.76 (CH), 77.07 (CH), 73.37 (C), 43.63 (CH2), 35.39 (CH2), 31.75
(CH2), 26.47 (CH2), 25.65 (CH3), 23.42 (CH3), 21.49 (CH3), 17.62
(CH3) ppm; HRMS-EI: m/z calcd for C20H27NO2S: 345.1762; found
345.1751.
129.78, 127.42, 120.68, 113.89, 71.52, 71.51, 57.26, 55.26, 52.78, 35.85,
22.80 ppm; HRMS-ESI: m/z calcd for C18H20O5Na: 339.1208; found
339.1199 [M+Na]+.
Dimethyl 2-(p-nitrocinnamyl)-2-propargylmalonate (31): A solution of
dimethyl 2-propargylmalonate (561 mg, 2.64 mmol) in DMF (10 mL) was
added at 08C to a suspension of NaH (133.2 mg, 3.33 mmol, 60% in min-
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Chem. Eur. J. 2006, 12, 1677 – 1693

Gold(i)-Catalyzed Cyclizations of 1,6-Enynes
FULL PAPER
Synthesis of alcohols 35–40
0.156 mL, 0.467 mmol) was added at
À458C to a solution of aldehyde 93
(131 mg, 0.467 mmol) in THF (5 mL).
The solution was warmed up to 238C
and after 2 h was quenched with a sa-
turated aqueous solution of NH4Cl,
washed with saturated aqueous NaCl
solution, and dried over MgSO4. The
solvent was evaporated and the resi-
due was chromatographed (hexane/
EtOAc 3:2) to yield 36 (115 mg,
83%) as
a
colorless oil. 1H NMR
(300 MHz, CDCl3): d = 4.97 (tq, J =
7.7, 1.2 Hz, 1H), 3.71 (overlapping s
and m, 7H), 2.80–2.73 (m, 4H), 2.15–
2.00 (m, 2H), 2.00 (t, J = 2.7 Hz, 1H), 1.64 (s, 3H), 1.55–1.45 (m, 2H),
1.18 (d, J = 6.3 Hz, 3H) ppm; 13C NMR, DEPT (75 MHz, CDCl3): d =
171.09 (2 C), 141.04 (C), 117.87 (CH), 79.79 (C), 71.92 (CH), 68.34 (CH),
57.76 (C), 53.34 (2”CH3), 37.91 (CH2), 36.90 (CH2), 31.26 (CH2), 24.11
(CH3), 23.22 (CH2), 16.77 (CH3) ppm; HRMS-ESI: m/z calcd for
C16H25O5: 297.1702; found 297.1703; elemental analysis (%) calcd for
C16H24O5: C 64.84, H 8.16; found: C 64.78, H 8.07.
Dimethyl 2-((E)-6,7-dihydroxy-3,7-dimethyloct-2-enyl)-2-(prop-2-ynyl)-
malonate (40): A solution of OsO4 (4% wt. in water, 3.3 mL, 0.55 mmol)
was added to
a solution of N-methylmorpholine N-oxide (1.623 g,
12 mmol) in tert-butyl alcohol (10 mL) and water (10 mL). Dienyne 12
(3.342 g, 10.92 mmol), dissolved in tert-butyl alcohol (20 mL) and water
(10 mL), was added at 238C to the former solution. After stirring for 6 h,
the mixture was extracted with CH2Cl2, washed with a saturated aqueous
solution of NaHSO3 and with saturated aqueous NaCl solution, and dried
over MgSO4. The solvent was evaporated and the residue mixture was
chromatographed (hexane/EtOAc 1:1) to give 40 (2.397 g, 65%) as a
pale brown oil: 1H NMR (300 MHz, CDCl3): d = 5.05–4.97 (m, 1H),
3.74 (s, 6H), 3.30 (dd, J = 10.4, 2.0 Hz, 1H), 2.83–2.76 (m, 4H), 2.30–
2.03 (m, 2H), 2.01 (t, 2.6 Hz, 1H), 1.66 (s, 3H), 1.65–1.52 (m, 2H), 1.47–
1.33 (m, 2H), 1.20 (s, 3H), 1.16 (s, 3H) ppm; 13C NMR, DEPT (75 MHz,
CDCl3): d = 170.46 (C), 170.45 (C), 140.14 (C), 117.75 (CH), 79.08 (C),
77.72 (CH), 72.94 (C), 71.31 (CH), 57.10 (C), 52.74 (2”CH3), 36.92
(CH2), 30.63 (CH2), 29.36 (CH2), 26.29 (CH3), 23.33 (CH3), 22.61 (CH2),
16.03 (CH3) ppm; HRMS-ESI: m/z calcd for C18H28O6Na: 363.1784;
found 363.1785 [M+Na]+.
Dimethyl 2-((E)-6-hydroxy-3,7,7-trimethyloct-2-enyl)-2-(prop-2-ynyl)mal-
onate (37): A solution of tert-butylmagnesium chloride in hexanes (1.0m,
0.350 mL, 0.35 mmol) was added at 08C to a solution of aldehyde 93
(98 mg, 0.35 mmol) in THF (4 mL). The solution was stirred for 30 min
at 08C and the cooling bath was then removed so that the solution could
reach 238C. The reaction was quenched with a saturated aqueous solu-
tion of NH4Cl, washed with saturated aqueous NaCl solution, and dried
over MgSO4. The solvent was evaporated and the residue was chromato-
graphed (hexane/EtOAc 5:1) to give 37 (50 mg, 42%) as a colorless oil.
1H NMR (400 MHz, CDCl3): d = 4.98 (tq, J = 7.7, 1.26 Hz, 1H), 3.73 (s,
6H), 3.15 (brd, J = 10.4 Hz, 1H), 2.82–2.76 [overlapping dd (J = 7.8,
3.2 Hz, 2H) and dd (J = 2.7, 1.3 Hz, 2H)], 2.26–2.17 (m, 1H), 2.11–2.02
(m, 1H), 2.00 (t, J = 2.7 Hz, 1H), 1.65 (s, 3H), 1.67–1.60 (overlapping s
and m, 4H), 1.45 (brs, 1H), 1.37–1.26 (m, 1H), 0.89 (s, 9H) ppm;
13C NMR, DEPT (100 MHz, CDCl3): d = 170.49 (C), 170.45 (C), 140.54
(C), 117.48 (CH), 79.21 (CH), 79.08 (C), 71.25 (CH), 57.19 (C), 52.72
(CH3), 52.70 (CH3), 37.32 (CH2), 34.91 (C), 30.68 (CH2), 29.29 (CH2),
25.70 (3”CH3), 22.62 (CH2), 16.08 (CH3) ppm; HRMS-ESI: m/z calcd
for C19H31O5: 339.2171; found 339.2170.
Dimethyl
2-((E)-3-methyl-6-oxohex-2-enyl)-2-(prop-2-ynyl)malonate
(93): A solution of NaIO4 (330 mg, 1.54 mmol) in water (2.5 mL) was
added to a solution of 40 (240 mg, 0.706 mmol) in acetone (10 mL). The
mixture was stirred for 2 h and then filtered through Celite. It was then
partitioned between CH2Cl2 and water and, after extractive workup and
chromatography (hexane/EtOAc 5:1), aldehyde 93 (101 mg, 51%) was
1
obtained as a colorless oil. H NMR (300 MHz, CDCl3): d = 9.73 (t, J =
1.8 Hz, 1H), 5.01–4.93 (m, J = 7.7, 2.3 Hz, 1H), 3.72 (s, 6H), 2.81–2.73
(two overlapping d, J = 7.6, 2.7 Hz, 4H), 2.54–2.46 (m, 2H), 2.32 (t, J =
7.4 Hz, 2H), 2.00 (t, J
DEPT (75 MHz, CDCl3): d = 201.96 (CH), 170.27 (2 C), 138.48 (C),
118.19 (CH), 79.04 (C), 71.33 (CH), 57.00 (C), 52.73 (2”CH3), 42.08
(CH2), 32.02 (CH2), 30.58 (CH2), 22.59 (CH2), 16.29 (CH3) ppm; HRMS-
ESI: calcd for C15H20O5Na: 303.1208; found 303.1198 [M+Na]+.
Dimethyl 2-((E)-6-hydroxy-3-methylocta-2,7-dienyl)-2-(prop-2-ynyl)mal-
onate (38):
A solution of vinylmagnesium bromide in THF (1.0m,
=
2.7 Hz, 1H), 1.66 (s, 3H) ppm; 13C NMR,
0.156 mL, 0.467 mmol) was added at À08C to a solution of aldehyde 93
(146 mg, 0.521 mmol) in THF (5 mL). The solution was warmed up to
238C and after 1 h was quenched with a aqueous solution of NH4Cl
(pH 8), washed with saturated aqueous NaCl solution, and dried over
MgSO4. The solvent was evaporated and the residue was chromatograph-
ed (hexane/EtOAc 4:1) to yield 38 (89 mg, 55%) as a colorless oil.
1H NMR (400 MHz, CDCl3): d = 5.86 (ddd, J = 17.2, 10.4, 6.2 Hz, 1H),
5.22 (dt, J = 17.2, 1.4 Hz, 1H), 5.11 (dt, J = 10.4, 1.3 Hz, 1H), 4.97 (dt,
J = 7.7, 1.2 Hz, 1H), 4.06 (q, J = 6.4 Hz, 1H), 3.73 (s, 6H), 2.82–2.76
(two overlapping d, J = 7.8, 2.7 Hz, 4H), 2.15–2.01 (m, J = 7.0 Hz, 2H),
2.00 (t, J = 2.6 Hz, 1H), 1.66 (s, 3H), 1.65–1.57 (m, 3H) ppm; 13C NMR,
DEPT (100 MHz, CDCl3): d = 170.43 (2 C), 141.06 (CH), 140.11 (C),
117.45 (CH), 114.73 (CH2), 79.17 (C), 72.69 (CH), 71.26 (CH), 57.14 (C),
52.70 (2”CH3), 35.72 (CH2), 35.08 (CH2), 30.66 (CH2), 22.61 (CH2),
16.18 (CH3) ppm; HRMS-ESI: m/z calcd for C17H24O5Na: 331.1521;
found 331.1530 [M+Na]+.
Dimethyl 2-((E)-6-hydroxy-3-methylhex-2-enyl)-2-(prop-2-ynyl)malonate
(35): Dimethyl 2-((E)-3-methyl-6-oxohex-2-enyl)-2-(prop-2-ynyl)malo-
nate (93, 99 mg, 0.353 mmol) was dissolved in THF (4 mL) at 08C.
DIBAL-H solution in CH2Cl2 was added (0.350 mL, 0.350 mmol) and the
mixture was stirred for 45 min at 08C. After that time, the reaction was
quenched with a saturated aqueous sodium/potassium tartrate solution
(2 mL) and EtOAc (2 mL). This was stirred for 1 h, and the reaction mix-
ture was then extracted with CH2Cl2, washed with saturated aqueous
NaCl solution, and dried over MgSO4. Flash chromatography (hexane/
EtOAc 2:1) yielded 35 (64 mg, 65% yield) as a colorless oil. 1H NMR
(400 MHz, CDCl3): d = 4.97 (t, J = 7.7 Hz, 1H), 3.73 (s, 6H), 3.60 (t, J
= 6.4 Hz, 2H), 2.81–2.76 (two overlapping d, J = 7.8, 2.8 Hz, 4H), 2.07
(t, J = 7.5 Hz, 2H), 2.00 (t, J = 2.5 Hz, 1H), 1.72–1.60 (overlapping s
and m, 5H) ppm; 13C NMR, DEPT (100 MHz, CDCl3): d = 170.44 (2 C),
140.09 (C), 117.45 (CH), 79.15 (C), 71.28 (CH), 62.44 (CH2), 57.14 (C),
52.71 (2”CH3), 36.20 (CH2), 30.66 (2”CH2), 22.62 (CH2), 16.07
(CH3) ppm; HRMS-ESI: m/z calcd for C15H23O5: 283.1545; found
283.1549.
Dimethyl
2-((E)-6-hydroxy-3-methyl-6-phenylhex-2-enyl)-2-(prop-2-
ynyl)malonate (39): A solution of phenylmagnesium bromide in hexane
(1.0m, 0.156 mL, 0.467 mmol) was added at 08C to a solution of aldehyde
93 (98 mg, 0.350 mmol) in THF (5 mL). This mixture was stirred for
30 min, the cooling bath was removed, and the mixture was stirred for an
additional 30 min, quenched with saturated aqueous NH4Cl, washed with
saturated aqueous NaCl solution, and dried over MgSO4. The solvent
was evaporated and the residue was chromatographed (hexane/EtOAc
3:1) to yield 39 (72 mg, 57% yield) as a colorless oil. 1H NMR (400 MHz,
Dimethyl
2-((E)-6-hydroxy-3-methylhept-2-enyl)-2-(prop-2-ynyl)malo-
nate (36): A solution of methylmagnesium bromide in hexane (3.0m,
Chem. Eur. J. 2006, 12, 1677 – 1693
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1687

A. M. Echavarren et al.
CDCl3): d = 7.31–7.17 (m, 5H), 4.90 (dt, J = 7.7, 1.1 Hz, 1H), 4.56 (dd,
J = 7.7, 5.3 Hz, 1H), 3.66 (s, 6H), 2.75–2.69 (two overlapping d, J = 7.9,
2.6 Hz, 4H), 2.12–1.95 (m, 2H), 1.93 (t, J = 2.6 Hz, 1H), 1.86–1.65 (m,
3H), 1.59 (s, 3H) ppm; 13C NMR, DEPT (100 MHz, CDCl3): d = 170.44
(C), 170.43 (C), 144.71 (C), 140.01 (C), 128.47 (2”CH), 127.54 (CH),
125.87 (2”CH), 117.53 (CH), 79.17 (C), 74.02 (CH), 71.28 (CH), 57.14
(C), 52.72 (CH3), 52.71 (CH3), 37.09 (CH2), 36.21 (CH2), 30.67 (CH2),
22.62 (CH2), 16.19 (CH3) ppm; HRMS-ESI: m/z calcd for C21H26O5Na:
381.1678; found 381.1672 [M+Na]+.
CDCl3): d = 63.11 ppm; HRMS-ESI (from MeCN solution) m/z calcd
for C22H30AuNP: 536.1781; found 536.1779 [M+MeCNÀCl]+.
Complex 24c: Yield 61%. 1H NMR (400 MHz, CDCl3): d = 7.57–7.55
(m, 1H), 7.47–7.45 (m, 2H), 7.23 (m, 1H), 7.05 (s, 2H), 2.95 (hept, J =
7.0 Hz, 1H), 2.21 (hept, J = 6.7 Hz, 2H), 2.05–2.01 (m, 4H), 1.83–1.71
(m, 6H), 1.67–1.61 (m, 2H), 1.53–1.42 (m, 3H), 1.35 (s, 3H), 1.34 (s, 3H),
1.28 (s, 3H), 1.26 (s, 3H), 1.23–1.13 (m, 7H), 0.92 (s, 3H), 0.91 (s,
3H) ppm; 13C NMR (100 MHz, CDCl3): d = 150.06, 145.48, 133.82 (d,
3J
=
8.1 Hz), 132.04 (d, 1J
=
3.2 Hz), 130.35 (d, 1J
=
P
13C,31
P
13C,31
P
13C,31
Synthesis of [Au(L)Cl] complexes: These complexes were prepared by
the literature procedure for the synthesis of [Au(PPh3)Cl]:[22] sodium
tetrachloroaurate(iii) dihydrate or tetrachloroauric acid (1 mmol) was dis-
solved in water, and the orange solution was cooled in ice. 2,2’-Thiodi-
ethanol (3 mmol) was slowly added (ca. 45 min) to this solution with stir-
ring. A solution of the phosphine ligand (1 mmol) in EtOH was added
dropwise to give a white solid. The solid was filtered off, washed with
MeOH, and dried in vacuo.
1.8 Hz), 127.08 (d, 1J
= 7.1 Hz), 121.70, 37.23 (d, 1J
= 33.5 Hz),
P
13C,31
P
13C,31
34.30, 30.93, 30.81, 27.01 (d, 1J
=
13.5 Hz), 26.69 (d, 1J
=
13C,31
P
13C,31
P
12.9 Hz), 24.36, 23.12 ppm; 31P NMR (161.98 MHz, CDCl3): d 38.48 ppm;
HRMS-ESI: m/z calcd for C33H49AuPNa: 731.2823; found 731.2789
[M+Na]+.
Complex 24d: Yield 51%. 1H NMR (400 MHz, CDCl3): d = 7.66–7.42
(m, 4H), 7.23–7.20 (m, 1H), 6.66 (d, J = 8.4 Hz, 2H), 3.70 (s, 6H), 2.18–
2.13 (m, 2H), 1.98–1.93 (m, 2H), 1.83–1.64 (m, 8H), 1.48–1.36 (m, 4H),
1.33–1.15 (m, 6H) ppm; 13C NMR (100 MHz, CDCl3): d = 176.44, 152.44
[Au(PCy3)Cl]: Yield 84%; 1H NMR (400 MHz, CDCl3): d = 2.03–1.93
(m, 9H), 1.89–1.85 (m, 6H), 1.75–1.72 (m, 3H), 1.52–1.41 (m, 6H), 1.35–
(d, 1J
= 7.9 Hz), 151.08 (d, 1J
= 3.9 Hz), 150.19 (d, 1J
=
P
13C,31
P
13C,31
P
13C,31
1.21 (m, 9H) ppm; 13C NMR (100 MHz, CDCl3): d = 33.28 (d, 1J
=
2.4 Hz), 149.25, 146.27 (d, 1J
= 3.3 Hz), 146.16 (d, 1J
= 2.9 Hz),
= 3.8 Hz),
13C,31
P
13C,31
P
13C,31P
31 Hz), 30.75, 26.96 (d, 2J
=
12.2 Hz), 25.80 (d, 3J
=
123.60, 74.54, 55.58 (d, 1J
= 34.20 Hz), 49.52 (d, 1J
13C,31
P
13C,31
P
13C,31
P
13C,31
P
1.5 Hz) ppm; 31P NMR (161.98 MHz, CDCl3): d = 57.12 ppm; HRMS-
ESI (from MeCN solution) m/z calcd for C20H36AuNP: 518.2251; found
518.2241 [M+MeCNÀCl]+.
48.45, 45.94 (d, J
= 12.8 Hz), 45.80 (d, J
= 14.3 Hz), 44.94 (d,
P
1
1
13C,31
P
13C,31
1J
= 1.6 Hz) ppm; 31P NMR (161.98 MHz, CDCl3): d = 41.79 ppm;
13C,31
P
HRMS-ESI (from MeCN solution) m/z calcd for C28H38AuPNO2:
648.2306; found 648.2286 [M+MeCNÀCl]+.
[Au{P(C6F5)3}Cl]: Yield 82% ppm; 31P NMR (161.98 MHz, CDCl3): d =
57.08 ppm; HRMS-FAB: m/z calcd for C18F15AuP: 728.9164; found
728.9169.
Synthesis of cationic gold complexes 24e and 25: A mixture of [Au(L)Cl]
complex (0.5 mmol) and AgSbF6 (0.5 mmol) was suspended in MeCN
(4 mL). The reaction mixture was stirred at 238C for 12 h, the solvent
was evaporated, and the crude product was dissolved in MeCN (1 mL).
The mixture was then filtered through a pad of Celite, and the solvent
was evaporated under reduced pressure to give the cationic complexes as
white solids.
Complex 24e: Yield 73%. 1H NMR (400 MHz, CDCl3): d = 7.85 (m,
1H), 7.65–7.50 (m, 5H), 7.35–7.30 (m, 1H), 7.20 (m, 2H), 2.42 (s, 3H),
1.42 (d, J1H,31P) = 16.3 Hz, 18H) ppm; 13C NMR (100 MHz, CDCl3): d =
1
[Au{P(o-Tol)3}Cl]: Yield 49%. H NMR (400 MHz, CDCl3): d = 7.46 (tt,
J = 7.5, 1.5 Hz, 3H), 7.35 (m, 3H), 7.19 (t, J = 7.7 Hz, 3H), 6.92 (ddd, J
= 13.3, 7.8, 1.1 Hz, 3H), 2.67 (s, 9H) ppm; 13C NMR (100 MHz, CDCl3):
d = 143.0 (d, 2J
= 12 Hz), 133.49 (d, 3J
= 9.6 Hz), 132.42 (d,
P
13C,31
P
13C,31
3J
=
9.1 Hz), 131.97 (d, 4J
=
2.6 Hz), 126.69 (d, 2J
=
P
13C,31
P
13C,31
P
13C,31
1
3
10.5 Hz), 125.00 (d, J
= 61.3 Hz), 23.31 (d, J
= 11.3 Hz) ppm;
13C,31
P
13C,31
P
31P NMR (161.98 MHz, CDCl3):
d = 11.50 ppm; HRMS-ESI (from
MeCN solution) m/z calcd for C23H24AuNP: 542.1312; found 542.1318
[M+MeCNÀCl]+.
149.00 (d, J
=
11.7 Hz), 142.36 (d, J =
7.20 Hz), 133.22 (d,
= 3.8 Hz), 131.43 (d, J = 2.4 Hz),
13C,31
P
13C,31P
[Au(AsPh3)Cl]: Yield 88%. 1H NMR (400 MHz, CDCl3): d = 7.55–7.50
(m, 15H) ppm; 13C NMR (100 MHz, CDCl3): d = 133.23, 131.44, 131.05,
129.62 ppm; HRMS-ESI (from MeCN solution) m/z calcd for
C20H18AuNAs: 544.0321; found 544.0306 [M+MeCNÀCl]+.
J
= 7.6 Hz), 133.04 (d, J
13C,31
13C,31
P
P
13C,31P
129.44, 129.20, 127.99, 127.56 (d, J
= 7.8 Hz), 123.72 (d, J
=
P
13C,31
P
13C,31
53.2 Hz), 118.97, 38.00 (d, J
= 27.2 Hz), 30.77, 2.20 ppm; 31P NMR
13C,31
P
(162 MHz, CDCl3):
d
=
60.29 ppm; HRMS-ESI m/z calcd for
C22H30AuNP: 536.1781; found 536.1791 [MÀSbF6]+.
[Au{P(1-Naph)3}Cl]: This compound was prepared by the described pro-
cedure.[58] Yield 80%. 1H NMR (400 MHz, CDCl3): d = 8.82 (d, J =
8.5 Hz, 3H), 8.09 (d, J = 8.0 Hz, 3H), 8.00 (d, J = 8.2 Hz, 3H), 7.61 (dd,
J = 7.9, 7.1 Hz, 3H), 7.51 (dd, J = 8.1, 7.5 Hz, 3H), 7.33 (m, 6H) ppm;
1
Complex 25: Yield 95%. H NMR (400 MHz, CDCl3): d = 7.62–7.46 (m,
15H), 2.49 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): d = 134.11 (d,
J
=
13.2 Hz), 132.89 (d,
J
=
2.9 Hz), 129.78 (d,
= 66.55 Hz), 2.64 (one carbon signal was not
P
J
=
13C,31
P
13C,31
P
13C,31
P
13C NMR (100 MHz, CDCl3): d = 135.04 (d, 3J
= 8.1 Hz), 134.14 (d,
12.44 Hz), 126.38 (d, J
13C,31
13C,31
P
observed) ppm; 31P NMR (162 MHz, CDCl3): d = 32.36 ppm; HRMS-
2
3J
= 8.1 Hz), 133.94 (d, J
= 11.8 Hz), 133.51, 129.26 (d, 4J
1
3
3
1
13C,31
P
13C,31
P
C
,
P
ESI m/z calcd for C20H18AuNP: 500.0842; found 500.0829 [MÀSbF6]+.
2
2
= 1.3 Hz), 127.79, 126.97, 126.50 (d, J
= 14.4 Hz), 125.13 (d, J
13C,31
13C,31
P
P
= 12.0 Hz), 122.53 (d, 1J
= 62.7 Hz) ppm; 31P NMR (161.98 MHz,
N-Methyl-N’-(2,4,6-trimethylphenyl)imidazolium iodide:[59] MeI (1.91 g,
13.5 mmol) was added dropwise to a solution of 1-(2,4,6-trimethyl)imida-
zole[60] (500 mg, 2.7 mmol) in THF (2 mL). The mixture was heated at
reflux while the white product precipitated. After 48 h, the reaction mix-
ture was filtered to give a white solid (1.98 mmol, 73%). The solid was
used without any further purification. 1H NMR (300 MHz, CDCl3): d =
9.91 (s, 1H), 7.86 (t, J = 1.8 Hz, 1H), 7.18 (t, J = 1.8 Hz, 1H), 6.99 (s,
2H), 4.36 (s, 3H), 2.33 (s, 3H), 2.08 (s, 6H) ppm; 13C NMR (75 MHz,
CDCl3): d = 141.39, 137.66, 134.25, 130.46, 129.85, 124.69, 123.07, 37.96,
21.06, 17.91 ppm; HRMS-EI: m/z calcd for C13H15N2I: 327.0358; found
327.0359 [MÀ1]+.
13C,31
P
CDCl3): d = 9.59 ppm: HRMS-ESI (from MeCN solution) m/z calcd for
C32H24AuNP: 650.1312; found 650.1335 [M+MeCNÀCl]+.
Complex 24a: Yield 69%. 1H NMR (400 MHz, CDCl3): d = 7.76–7.71
(m, 1H), 7.57–7.44 (m, 5H), 7.33–7.28 (m, 1H), 7.18 (d, J = Hz, 3H),
2.08–1.94 (m, 4H) 1.83–1.74 (m, 4H), 1.68–1.43 (m, 6H) 1.33–1.18 (m,
8H) ppm; 13C NMR (100 MHz, CDCl3): d = 149.09, 134.29, 132.48 (d,
3J
=
7.4 Hz), 130.71, 129.24, 128.64, 128.35, 127.43 (d, 3J
=
P
13C,31
P
13C,31
8.4 Hz), 124.43, 36.58 (d, 1J
= 33.3 Hz), 31.16 (d, 3J
= 4.5 Hz),
P
= 14 Hz), 25.58 ppm;
13C,31
P
13C,31
29.42, 26.54 (d, 2J
= 10 Hz), 24.43 (d, 2J
13C,31
P
13C,31
P
31P NMR (161.98 MHz, CDCl3):
d = 47.15 ppm; HRMS-ESI(from
MeCN solution) m/z calcd for C26H34AuNP: 588.2094; found 588.2075
[M+MeCNÀCl]+.
General procedure for the synthesis of NHC AuI complexes 26a–c:[61]
Ag2O (0.5 mmol) was added to a solution of the imidazolium ligand
(1 mmol)[62] in CH2Cl2. The suspension became clear after stirring for 3 h
at 238C. A solution of [Au(Me2S)Cl] (1 mmol) in CH2Cl2 was added
dropwise, the reaction mixture was stirred for another 4 h, the solution
was filtered through Celite, and the solvent was partially evaporated. Ad-
dition of hexane resulted in the precipitation of the NHC AuI complex.
Complex 24b: Yield 43%. 1H NMR (400 MHz, CDCl3): d = 7.87 (td, J
= 7.7, 1.7 Hz, 1H), 7.51 (m, 5H), 7.31 (m, 1H), 7.13 (dd, J = 8.0. 1.0 Hz,
2H), 1.41 (d, J = 15.6, 18H) ppm; 13C NMR (100 MHz, CDCl3): d =
150.16 (d, 2J
= 13.5 Hz), 142.10 (d, 3J
= 6.3 Hz), 133.46 (d,
P
13C,31
P
13C,31
4J
= 3.0 Hz), 133.22 (d, 3J
= 7.5 Hz), 129.19, 128.67, 128.22,
P
13C,31
P
13C,31
3
1
1
126.67 (d, J
= 6.8), 126.06 (d, J
= 45.3 Hz), 37.75 (d, J =
13C,31P
Complex 26a: Yield 49%. 1H NMR (400 MHz, CDCl3): d
= 7.08 (s,
13C,31
P
13C,31
P
25.7 Hz), 30.84 (d, 2J
=
6.7 Hz) ppm; 31P NMR (161.98 MHz,
2H), 6.97 (brs, 4H), 2.33 (s, 6H), 2.09 (s, 12H) ppm; 13C NMR
13C,31
P
1688
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 1677 – 1693

Gold(i)-Catalyzed Cyclizations of 1,6-Enynes
FULL PAPER
(100 MHz, CDCl3): d = 139.79, 134.68, 129.49, 122.12, 21.13, 17.75 (one
signal is missing) ppm; HRMS-FAB: m/z calcd for C21H26AuN2Cl:
537.1372; found 537.1361 [M+H]+. This complex has been also described
by Nolan et al.[24]
171.91, 148.45, 134.23, 131.95, 129.29, 74.71, 58.65, 52.71, 51.51, 43.67,
38.68, 35.42, 25.69, 24.65, 22.45, 17.66 ppm; HMRS-CI: m/z calcd for
C18H27O5: 323.1858; found 323.1860 [MÀ1]+.
3-(1-Methoxy-1,5-dimethyl-4-hexenyl)-4-methylene-1,1-bis(phenylsulfo-
nyl)cyclopentane (15): White solid: 1H NMR (300 MHz, CDCl3): d
=
1
Complex 26b: Yield 60%. H NMR (500 MHz, CDCl3): d = 7.14 (d, J =
8.07–8.01 (m, 4H), 7.72–7.66 (m, 2H), 7.60–7.53 (m, 4H), 5.10 (m, 1H),
4.97 (s, 1H), 4.92 (s, 1H), 3.48 (dq, J = 17.0, 2.8 Hz, 1H), 3.08 (s, 3H),
2.72 (m, 4H), 1.95 (m, 2H), 1.69 (s, 3H), 1.61 (s, 3H), 1.56 (m, 2H), 1.04
(s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d = 137.21, 135.98, 134.57,
134.39, 131.61, 131.04, 124.11, 110.98, 91.89, 76.57, 48.89, 48.72, 40.84,
34.91, 32.80, 25.63, 21.69, 19.01, 17.61 ppm; HRMS-CI m/z calcd for
C27H34O4S2: 485.1820; found 485.1797 [MÀOH]+.
2.0 Hz, 1H), 6.95 (brs, 2H), 6.88 (d, J = 2.0 Hz, 1H), 3.95 (s, 3H), 2.32
(s, 3H), 2.00 (s 6H) ppm; 13C NMR (125 MHz, CDCl3): d
= 172.69,
139.71, 134.80, 134.69, 129.45, 122.18, 121.69, 38.37, 21.12, 17.85 ppm;
HRMS-ESI: m/z calcd for C13H18AuN2Cl: 433.0746; found 433.0739
[M+H]+.
Complex 26c: 1H NMR (400 MHz, CDCl3): d = 6.92 (brs, 2H), 3.82 (s,
6H) ppm; 13C NMR (100 MHz, CDCl3): d = 174.32, 121.72, 38.19 ppm;
HRMS-ESI (from MeCN solution) m/z calcd for C7H11AuN3: 334.0619;
found 334.0623 [M+MeCNÀCl]+.
Dimethyl
3-[methoxy(4-methoxyphenyl)methyl]-4-methylenecyclopen-
tane-1,1-dicarboxylate (30): Colorless oil: 1H NMR (CDCl3, 400 MHz): d
= 7.18 (d, J = 8.6 Hz, 2H), 6.87 (d, J = 8.5 Hz, 2H), 4.90 (brs, 1H),
4.46 (brs, 1H), 4.08 (d, J = 6.3 Hz, 1H), 3.80 (s, 3H), 3.73 (s, 3H), 3.67
(s, 3H), 3.16 (s, 3H), 2.99–2.93 (m, J = 16.0, 2.4 Hz, 1H), 2.90–2.84 (m,
2H), 2.48 (dd, J = 13.5, 8.0 Hz, 1H), 2.30 (dd, J = 13.5 Hz, 8.9 Hz,
General procedures for AuI-catalyzed intermolecular alkoxycyclization:
The protic acid (6 mol%) was added to a mixture of the enyne (0.2–
0.5 mmol) and gold(i) catalyst [Au(PPh3)Me] (3 mol%) in the stated sol-
vent (3–5 mL of MeOH, EtOH, or aqueous acetone) and the mixtures
were stirred under the conditions stated in Tables 1 and 2 and Scheme 3.
The resulting mixture was filtered through Celite, the solvent was evapo-
rated, and the residue was chromatographed (hexane/EtOAc) to give the
corresponding carbo- or heterocycle. Alternatively, complex [Au(L)Cl]
and a AgI salt or the corresponding cationic AuI complex were used as
the catalyst (Tables 4 and 5 and Scheme 4). Routinely, synthetic grade
MeOH or EtOH (>99.8% purity) were used as solvents, without further
drying.
1H) ppm; 13C NMR (CDCl3, 100 MHz; DEPT): d
= 172.11, 172.08,
159.11, 148.36, 132.62, 128.47, 113.60, 108.69, 85.36, 58.59, 56.88, 55.22,
52.65, 49.29, 42.06, 35.76 ppm; HRMS-ESI: m/z calcd for C19H24O6Na:
371.1471; found 371.1456 [M+Na]+.
Dimethyl 2-((E)-3-(4-nitrophenyl)allyl)-2-(2-oxopropyl)malonate (32):
1
Yellow solid: H NMR (CDCl3, 400 MHz): d = 8.14 (d, J = 8.5 Hz, 2H),
7.43 (d, J = 8.8 Hz, 2H), 6.45 (d, J = 15.8 Hz, 1H), 6.28 (q, J = 15.6,
7.7 Hz, 1H), 3.74 (s, 6H), 3.14 (s, 2H), 2.97 (d, J = 7.6 Hz, 2H), 2.12 (s,
3H) ppm; 13C NMR (CDCl3, 100 MHz; DEPT): d
= 204.89, 170.54,
General procedure for AuI-catalyzed intramolecular alkoxycyclization or
skeletal rearrangement of enynes: The enyne (0.10–0.50 mmol) in CH2Cl2
(1 mL) was added to a mixture of [Au(PPh3)Cl] (2 mol%) and silver(i)
salt (2 mol%) (or the corresponding cationic AuI complex) in CH2Cl2
(2 mL) and the mixture was stirred for the time and at the temperature
indicated in Schemes 5–7 and Tables 6 and 7. The resulting mixture was
filtered through SiO2 and the solvent was evaporated to give the corre-
sponding product.
147.10, 143.20, 132.06, 129.94, 126.75, 124.01, 55.27, 52.93, 46.13, 37.28,
30.27 ppm; IR (KBr): n˜ = 1740, 1709 cmÀ1; HRMS-ESI: m/z calcd for
C17H19NO7Na: 372.1059; found 372.1061 [M+Na]+. The structure of 32
was confirmed by COSY, NOESY, HMQC, and HMBC experiments.
Isomer 32’ was also obtained as a byproduct (ca. 5:1 32/32’ ratio) that
could not be separated from 32: 1H NMR (CDCl3, 400 MHz): d = 8.18
(d, J = 8.5 Hz, 2H), 7.38 (d, J = 8.8 Hz, 2H), 6.59 (d, J = 11.8 Hz, 1H),
5.71, (dt, J = 11.8, 7.4 Hz, 1H), 3.69 (s, 6H), 3.11 (s, 2H), 3.08 (d, J =
7.6 Hz, 2H), 2.03 (s, 3H) ppm; 13C NMR (CDCl3, 100 MHz): d = 204.89,
170.54, 147.10, 143.20, 132.06, 129.94, 126.75, 124.01, 55.27, 52.93, 46.13,
37.28, 30.27 ppm. Recovered enyne 31 was also contaminated with 31’
(ca. 5:1 31/31’ ratio): 1H NMR (CDCl3, 400 MHz): d = 8.19 (d, J =
8.7 Hz, 2H), 7.45 (d, J = 8.8 Hz, 2H), 6.63 (d, J = 11.9 Hz, 1H), 5.68
(dt, J = 11.8, 7.5 Hz, 1H), 3.70 (s, 6H), 3.09 (d, J = 7.5 Hz, 2H), 2.81 (d,
J = 2.6 Hz, 2H), 1.85 (t, J = 2.7 Hz, 1H).
Tricycle 34: Yellow oil: 1H NMR (300 MHz, CDCl3): d = 7.30 (m, 5H),
5.00 (s, 1H), 4.76 (s, 1H), 4.71 (s, 1H), 4.04 (s, 1H), 2.53 (d, J = 4.05 Hz,
1H), 1.69–1.31 (m, 12H) ppm; 13C NMR (75 MHz, CDCl3; DEPT): d =
149.36 (C), 142.74 (C), 127.81 (CH), 127.09 (CH), 125.94 (CH), 102.88
(CH2), 83.07 (CH), 82.74 (CH), 48.79 (CH), 43.11 (C), 41.71 (CH2), 35.78
(CH2), 33.02 (CH2), 26.02 (CH2), 23.23 (CH2), 22.25 (CH2) ppm; HRMS-
EI: m/z calcd for C18H22O: 254.1671; found 254.1663. The structure of 34
was confirmed by COSY, NOESY, HMBC, and HMQC experiments.
General procedure for FeIII-catalyzed skeletal rearrangement of enynes:
The same procedure was followed but with FeCl3 (5 mol%) as catalyst in
toluene at 80–908C (Table 8).
Dimethyl 3-(1-ethoxy-1-methylethyl)-4-methylenecyclopentane-1,1-dicar-
1
boxylate (2b): Colorless oil: H NMR (300 MHz, CDCl3): d = 4.97 (brd,
J = 8.9 Hz, 2H), 3.70 (s, 3H), 3.69 (s, 3H), 3.37 (m, 2H), 2.92–2.78 (m,
3H), 2.51 (ddd, J = 13.3, 8.1, 1.6 Hz, 1H), 2.00 (dd, J = 13.3, 9.3 Hz,
1H), 1.16 (s, 3H), 1.10 (m, 6H) ppm; 13C NMR (75 MHz, CDCl3): d =
172.01, 171.90, 148.34, 110.33, 76.41, 58.54, 56.19, 52.63, 49.47, 43.39,
36.01, 23.23, 22.59, 15.84 ppm; EI-HMRScalcd for C 15H23O4: 283.1545;
found 283.1544 [MÀ1]+.
Bicyclic lactone 3: Colorless oil: 1H NMR (500 MHz, CDCl3): d = 5.17
(dd, J = 2.0, 1.9 Hz, 1H), 5.14 (dd, J = 3.1, 2.6 Hz, 1H), 3.82 (s, 3H),
2.98 (dt, J = 17.9, 2.5 Hz, 1H), 2.77 (dd, J = 17.9, 1.5 Hz, 1H), 2.67 (d,
J = 5.0 Hz, 1H), 2.62 (dd, J = 12.3, 1.8 Hz, 1H), 2.04 (dd, J = 12.3,
5.1 Hz, 1H), 1.53 (s, 3H), 1.41 (s, 3H) ppm; 13C NMR (125 MHz,
CDCl3): d = 170.45, 170.40, 144.73, 112.20, 84.91, 56.41, 52.71, 50.81,
37.89, 33.39, 27.84, 27.51 ppm; EI-HMRScalcd for C 12H16O4: 224.1048;
found 224.1038. The structure was confirmed by COSY, NOESY, HMBC,
and HMQC experiments.
Dimethyl 4-methylene-3-(2-methyltetrahydrofuran-2-yl)cyclopentane-1,1-
dicarboxylate (41): Colorless oil. 1H NMR (300 MHz, CDCl3): d = 5.02
(q, J = 2.0 Hz, 2H), 3.84–3.74 (m, 2H), 3.71 (s, 3H), 3.70 (s, 3H), 2.93–
2.80 (m, 3H), 2.62 (dd, J = 13.2, 8.6 Hz, 1H), 2.01–1.52 (m, 4H), 1.13 (s,
3H) ppm; 13C NMR, DEPT (75 MHz, CDCl3): d = 171.92 (2 C), 148.29
(C), 110.34 (CH2), 84.99 (C), 67.23 (CH2), 58.48 (C), 52.67 (CH3), 52.63
(CH3), 50.53 (CH), 43.29 (CH2), 36.82 (CH2), 34.90 (CH2), 26.02 (CH2),
23.87 (CH3) ppm; HRMS-ESI: m/z calcd for C15H22O5Na: 305.1365;
found 305.1361 [M+Na]+. The structure of 41 was confirmed by COSY,
NOESY, HMQC, and HMBC experiments.
(3R*)-Dimethyl 3-[(1R*)-1-ethoxy-1,5-dimethyl-4-hexenyl]-4-methylene-
cyclopentane-1,1-dicarboxylate (13b): Colorless oil: 1H NMR (300 MHz,
CDCl3): d = 5.10 (m, 1H), 5.00 (s, 1H), 4.89 (s, 1H), 3.72 (s, 3H), 3.71
(s, 3H), 3.35 (m, 2H), 2.96–2.82 (m, 4H), 2.77–2.50 (m, 1H), 2.15 (ddd, J
= 14.5, 8.9, 7.9 Hz, 1H), 2.09–1.95 (m, 2H), 1.66 (s, 2H), 1.60 (s, 2H),
1.12 (t, J = 6.9 Hz, 3H), 1.02 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3):
d = 172.13, 171.96, 148.65, 131.28, 124.63, 110.40, 78.03, 58.58, 56.01,
52.62, 48.25, 43.76, 35.68, 35.25, 25.66, 22.32, 19.96, 17.58, 15.73 ppm; EI-
HRMScalcd for C 20H32O5: 352.2250; found 352.2251.
Carbocycle 13c: 1H NMR (300 MHz, CDCl3): d = 5.05 (brs, 2H), 4.92
(s, 1H), 3.68 (s, 3H), 3.67 (s, 3H), 2.84 (m, 2H), 2.66 (tq, J = 8.0, 2.0 Hz,
1H), 2.55 (m, 2H), 2.13–1.95 (m, 2H), 1.64 (s, 3H), 1.58 (s, 3H), 1.47 (td,
J = 8.9, 1.6 Hz, 2H), 1.16 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d =
Dimethyl 3-(2,5-dimethyltetrahydrofuran-2-yl)-4-methylenecyclopentane-
1,1-dicarboxylate (42a/42b): Colorless oil. 1H NMR (500 MHz, CDCl3):
5.06 (m, 1H (major)), 5.01 (m, 3H (2H minor, 1H major)), 4.09–4.00 (m,
2H (both)), 3.71 (s, 3H), 3.701 (s, 6H), 3.699 (s, 3H), 2.93–2.83 (m, 5H
(2H major, 3H minor)), 2.78 (ddq, J = 9.7, 8.2, 1.9 Hz, 1H (major)),
2.69–2.59 (m, 2H (1H major, 1H minor)), 2.04–1.83 (m, 6H (3H major,
3H minor), 1.74 (ddd, J = 12.0, 7.7, 2.4 Hz, 1H (minor)), 1.63 (dt, J =
12.4, 8.2 Hz, 1H (major)), 1.59–1.50 (m, J
=
10.5, 9.4, 7.8 Hz, 1H
Chem. Eur. J. 2006, 12, 1677 – 1693
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1689

A. M. Echavarren et al.
(minor)), 1.45 (ddt, J = 12.1, 9.6, 7.9 Hz, 1H (major)), overlapping 1.20
(d, J = 5.0 Hz, 3H minor) and 1.19 (d, J = 5.0 Hz, 3H major), 1.15 (s,
6H) ppm; 13C NMR, DEPT (125 MHz, CDCl3): d = 171.99 (2 C), 171.94
(2 C), 148.44 (C), 148.09 (C), 110.59 (CH2), 110.42 (CH2), 85.26 (C),
85.07 (C), 75.62 (CH), 73.67 (CH), 58.56 (C), 58.50 (C), 52.71 (2”CH3),
52.67 (2”CH3), 50.75 (2”CH), 43.50 (CH2), 43.47 (CH2), 36.90 (CH2),
36.84 (CH2), 35.96 (CH2), 34.99 (CH2), 33.82 (CH2), 33.75 (CH2), 25.62
(CH3), 24.35 (CH3), 22.08 (CH3), 21.03 (CH3) ppm; HRMS-ESI: m/z
calcd for C16H25O5Na: 319.1545; found 319.1536 [M+Na]+. The struc-
tures of 42a/42b were confirmed by COSY, NOESY, HMQC, and
HMBC experiments.
171.95 (2 C), 149.01 (C), 148.34 (C), 110.86 (CH2), 110.72 (CH2), 86.56
(CH), 85.47 (C), 84.86 (C), 83.94 (CH), 71.33 (C), 70.32 (C), 58.67 (C),
58.56 (C), 52.88 (2”CH3), 52.77 (2”CH3), 50.89 (CH), 50.87 (CH), 43.53
(CH2), 43.48 (CH2), 36.80 (CH2), 36.12 (CH2), 35.38 (CH2), 35.25 (CH2),
27.73 (CH3), 27.64 (CH3), 26.14 (CH2), 25.67 (CH2), 25.43 (CH3), 24.76
(CH3), 24.04 (CH3), 22.71 (CH3) ppm; HRMS-ESI: m/z calcd for
C18H28O6Na: 363.1784; found 363.1780 [M+Na]+. The structures of 46a/
46b were confirmed by COSY, NOESY, HMBC, and HMQC experi-
ments.
Dimethyl 3-((Z)-3-hydroxy-2-methylprop-1-enyl)cyclopent-3-ene-1,1-di-
1
carboxylate (55): Yellow oil: H NMR (300 MHz, CDCl3): d = 5.85 (brs,
Dimethyl 3-(5-tert-butyl-2-methyltetrahydrofuran-2-yl)-4-methylenecyclo-
pentane-1,1-dicarboxylate (43a/43b): Colorless oil. 1H NMR (400 MHz,
CDCl3): d = 5.02–5.04 (q, J = 2.02 Hz, 2H), 4.99–5.01 (m, J = 1.1 Hz,
1H), 4.93–4.95 (m, J = 1.1 Hz, 1H), 3.721 (s, 3H), 3.717 (s, 3H), 3.713 (s,
3H), 3.711 (s, 3H), 3.55–3.62 (m, 2H), 2.74–2.96 (m, 6H), 2.63–2.71 (ddd,
J = 1.9, 8.5, 13.4 Hz, 1H), 2.56–2.63 (m, 1H), 2.04–2.11 (dd, J = 9.1,
13.4 Hz, 1H), 1.88–1.95 (dd, J = 9.7, 13.4 Hz, 1H), 1.60–1.85 (overlap-
ping m, 8H), 1.127 (s, 3H), 1.101 (s, 3H), 0.86 (s, 9H), 0.85 (s, 9H) ppm;
13C NMR (100 MHz, CDCl3): d = 172.09, 172.00, 171.99, 171.97, 148.57,
148.52, 110.56, 110.01, 87.93, 85.27, 84.51, 83.97, 58.58, 58.55, 52.66, 52.64
(2 C), 52.59, 51.14, 50.73, 43.56, 43.37, 36.83, 36.14 (2 C), 35.20, 33.58,
33.07, 26.42(2 C), 25.94 (3 C), 25.83, 25.81 (3 C), 25.41 ppm; HRMS-EI:
m/z calcd for C19H31O5: 339.2171; found 339.2171.
1H), 5.44 (brs, 1H), 4.25 (s, 2H), 3.73 (s, 6H), 3.14 (brs, 2H), 3.05 (s,
2H), 1.88 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): d = 172.44, 140.02,
137.80, 126.79, 123.29, 62.38, 59.37, 52.90, 43.10, 40.39, 22.19 ppm;
HRMS-EI: m/z calcd for C13H17O5: 253.1076; found 253.1070 [MÀ1]+.
Dimethyl 3-((Z)-2,6-dimethylhepta-1,5-dienyl)cyclopent-3-ene-1,1-dicar-
boxylate (57): Pale yellow oil: 1H NMR (300 MHz, CDCl3): d = 5.73 (s,
1H), 5.38 (s, 1H), 5.12 (tsext, J = 8.7, 1.4 Hz, 1H), 3.73 (s, 6H), 3.16 (d,
J = 1.8 Hz, 2H), 3.03 (s, 2H), 2.20 (m, 2H), 2.13 (m, 2H), 1.77 (s, 3H),
1.68 (d, J = 1.0 Hz, 3H), 1.60 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3;
DEPT): d = 172.59 (C), 139.42 (C), 138.48 (C), 131.82 (C), 124.58 (CH),
123.92 (CH), 121.04 (CH), 59.37 (C), 52.79 (CH3), 43.13 (CH2), 40.23
(CH2), 33.37 (CH2), 27.05 (CH2), 25.67 (CH3), 24.66 (CH3), 17.63 (CH3).
HMRS-ESI: m/z calcd for C18H26O4: 306.1831; found 306.1824. The struc-
ture of 57 was confirmed by a NOESY experiment.
Dimethyl 3-(2-methyl-5-vinyltetrahydrofuran-2-yl)-4-methylenecyclopen-
tane-1,1-dicarboxylate (44a/44b): Colorless oil. 1H NMR (400 MHz,
CDCl3): d = 5.83 (dtd, J = 17.0, 10.2, 6.8 Hz, 2H), 5.22 (dddd, J = 17.1,
9.3, 1.6, 1.2 Hz, 2H), 5.10–5.00 (overlapping m, 6H), 4.36 (m, J = 6.8 Hz,
2H), 3.720 (s, 6H), 3.717 (s, 6H), 2.97–2.80 (overlapping m, 6H), 2.73–
2.60 (overlapping m, 2H), 2.15–1.85 (overlapping m, 6H), 1.82–1.60
(overlapping m, 4H), 1.19 (s, 3H), 1.18 (s, 3H) ppm; 13C NMR, DEPT
Dimethyl
(E)-5-benzylidenecyclohex-3-ene-1,1-dicarboxylate
(61):
1
Yellow oil: H NMR (300 MHz, CDCl3): d = 7.42–7.19 (m, 5H), 6.60 (d,
J = 10.1 Hz, 1H), 6.34 (brs, 1H), 5.87 (m, 1H), 3.73 (s, 6H), 2.95 (d, J =
1.4 Hz, 2H), 2.76 (dd, J = 4.2, 2.2 Hz, 2H) ppm; 13C NMR (75 MHz,
CDCl3): d = 171.35, 137.08, 131.15, 129.17, 128.11, 128.02, 127.59, 126.67,
125.08, 52.76, 52.71, 37.69, 31.90 ppm; HRMS-ESI: m/z calcd for
C17H18O4Na: 286.1205; found 309.1092 [M+Na]+.
(100 MHz, CDCl3): d
= 171.91 (4 C), 148.33 (C), 148.11 (C), 140.15
(CH), 139.10 (CH), 115.16 (2”CH2), 110.55 (CH2), 110.52 (CH2), 85.81
(C), 85.44 (C), 80.75 (CH), 78.92 (CH), 58.52 (2 C), 52.69 (2”CH3), 52.65
(2”CH3), 50.84 (CH), 50.74 (CH), 43.44 (CH2), 43.41 (CH2), 36.93
(CH2), 36.80 (CH2), 35.43 (CH2), 35.24 (CH2), 32.64 (CH2), 32.49 (CH2),
25.29 (CH3), 23.84 (CH3) ppm; HRMS-ESI: m/z calcd for C17H24O5Na:
331.1521; found 331.1508 [M+Na]+. The structures of 44a/44b were con-
firmed by COSY, NOESY, HMBC, and HMQC experiments.
Dimethyl 3-((E)-4-methoxystyryl)cyclopent-3-ene-1,1-dicarboxylate (64):
Colorless oil: H NMR (CDCl3, 400 MHz): d = 7.17 (d, J = 8.7 Hz, 2H),
1
6.83 (d, J
= 8.7 Hz, 2H), 6.43 (d, J = 12.0 Hz, 1H), 6.14 (d, J =
12.0 Hz, 1H), 5.63 (brs, 1H), 3.81 (s, 3H), 3.70 (s, 6H), 3.02 (brs, 2H),
2.86 (brs, 2H) ppm; 13C NMR (CDCl3, 100 MHz): d = 172.32, 158.77,
138.42, 130.19, 130.08, 128.41, 124.82, 133.35, 59.34, 55.41, 52.92, 42.13,
40.31 ppm; HRMS-ESI: m/z calcd for C18H20O5: 339.1208; found
339.1222. The structure of 64 was confirmed by HMQC, HMBC, COSY,
and NOESY experiments.
Dimethyl 3-(2-methyl-5-phenyltetrahydrofuran-2-yl)-4-methylenecyclo-
pentane-1,1-dicarboxylate (45a/45b): Colorless oil. 1H NMR (400 MHz,
CDCl3): d = 7.29–7.28 (m, 8H; both isomers), 7.26–7.21 (m, 2H; both
isomers), 5.12–5.07 (m, 2H; major isomer), 5.06–5.02 (m, 2H; minor
isomer), 4.98–4.91 (m, 2H; both isomers), 3.74 (s, 3H; minor isomer),
3.730 (s, 3H; major isomer), 3.727 (s, 3H; minor isomer), 3.71 (s, 3H;
Dimethyl 5-((Z)-4-methoxybenzylidene)cyclohex-3-ene-1,1-dicarboxylate
1
(63): Colorless oil: H NMR (CDCl3, 400 MHz): d = 7.17 (d, J = 8.7 Hz,
2H), 6.83 (d, J = 8.7 Hz, 2H), 6.6 (d, J = 10.1 Hz, 1H), 6.28 (brs, 1H),
5.86–5.81 (m, 1H), 3.76 (s, 3H), 3.72 (6H), 2.94 (brd, J = 1.4 Hz, 2H),
2.76–2.75 (brm, 2H) ppm; HRMS-ESI: m/z calcd for C18H20O5: 339.1208;
found 339.1222. The structure of 63 was confirmed by HMQC, HMBC,
COSY, and NOESY experiments.
major isomer), 3.04–2.87 (m, 6H; both isomers), 2.83–2.75 (ddd, J
=
13.4, 8.3, 2.1 Hz, 1H (minor isomer)), 2.70 (ddd„ J = 13.4, 8.3, 1.0 Hz,
1H; major isomer), 2.39–2.26 (m, 2H; both isomers), 2.18–1.78 (m, 8H;
both isomers), 1.32 (s, 3H; major isomer), 1.29 (s, 3H; minor iso-
mer) ppm; 13C NMR, DEPT (100 MHz, CDCl3): d
= 171.99 (2 C),
Dimethyl 3-((E)-4-nitrostyryl)cyclopent-3-ene-1,1-dicarboxylate (66):
1
Yellow solid; H NMR (CDCl3, 400 MHz): d = 8.16 (d, J = 8.9 Hz, 2H),
171.92 (2 C), 148.39 (C), 148.27 (C), 143.41 (C), 142.72 (C), 128.29 (2”
CH), 128.23 (2”CH), 127.16 (CH), 127.14 (CH), 125.91 (2”CH), 125.76
(2”CH), 110.76 (CH2), 110.49 (CH2), 86.05 (C), 85.32 (C), 81.57 (CH),
79.24 (CH), 58.58 (C), 58.56 (C), 52.73 (2”CH3), 52.67 (2”CH3), 51.12
(CH), 50.87 (CH), 43.53 (CH2), 43.47 (CH2), 37.00 (CH2), 36.60 (CH2),
36.20 (CH2), 35.95 (CH2), 35.32 (CH2), 35.03 (CH2), 25.36 (CH3), 23.15
(CH3) ppm; HRMS-EI: m/z calcd for C21H26O5: 358.1780; found
358.1773. The structures of 45a/45b were confirmed by COSY, NOESY,
HMQC, and HMBC experiments.
7.50 (d, J
16.1 Hz, 1H), 5.86 (brs, 1H), 3.77 (s, 6H), 3.27 (brs, 2H), 3.19 (brs,
2H) ppm; 13C NMR (CDCl3, 100 MHz): d
172.05, 146.81, 146.21,
= 8.8 Hz, 2H), 7.04 (d, J = 15.7 Hz, 1H), 6.47 (d, J =
=
143.63, 139.21, 131.09, 130.79, 127.71, 126.75, 58.4, 53.02, 41.19,
39,39 ppm; HRMS-ESI: m/z calcd for C17H17NO6Na: 354.0954; found
354.0955 [M+Na]+. The structure of 66 was confirmed by HMQC,
HMBC, COSY, and NOESY experiments.
Dimethyl
5-((Z)-4-nitrobenzylidene)cyclohex-3-ene-1,1-dicarboxylate
1
(65): Yellow solid; H NMR (CDCl3, 400 MHz): d = 8.15 (d, J = 8.8 Hz,
2H), 7.37 (d, J = 8.5 Hz, 2H), 6.54 (d, J = 10.1 Hz, 1H), 6.35 (brs, 1H),
6.03–5.98 (m, J = 10.1 Hz, 1H), 3.74 (s, 6H), 2.99 (d, J = 1.5 Hz, 2H),
Dimethyl 3-[5-(2-hydroxypropan-2-yl)-4-methylene-2-methyltetrahydro-
furan-2-yl]cyclopentane-1,1-dicarboxylate (46a/46b): Colorless oil.
1H NMR (500 MHz, CDCl3): d = 5.06 (m, 2H), 5.02 (m, 1H), 4.94 (m,
1H), 3.78–3.71 (overlapping m, 2H), 3.73 (s, 6H), 3.72 (s, 3H), 3.71 (s,
3H), 2.98–2.74 (m overlapping qt, J = 15.0, 2.4 Hz and qt, J = 8.3,
1.6 Hz, 6H), 2.70 (ddd, J = 13.1, 8.7, 1.5 Hz, 1H), 2.61 (dd, J = 13.0,
8.3 Hz, 1H), 2.10 (dd, J = 13.3, 8.3 Hz, 2H), 1.97–1.66 (m, 10H), 1.23 (s,
3H), 1.19 (s, 3H), 1.16 (s, 3H), 1.15 (s, 3H), 1.10 (s, 3H), 1.09 (s, 3H)
ppm; 13C NMR, DEPT (125 MHz, CDCl3): d = 172.35 (C), 171.99 (C),
2.81–2.80 (brm, 2H) ppm; 13C NMR (CDCl3, 100 MHz): d
= 170.94,
145.96, 134.95, 130.68, 129.68, 125.26, 124.21, 123.63, 53.91, 52.94, 37.73,
31.72 (one signal is missing due to overlapping) ppm; HRMS-ESI: m/z
calcd for C17H17NO6Na: 354.0954; found 354.0955 [M+Na]+. The struc-
ture of 65 was confirmed by HMQC, HMBC, COSY, and NOESY ex-
periments.
1690
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 1677 – 1693

Gold(i)-Catalyzed Cyclizations of 1,6-Enynes
FULL PAPER
3-(Prop-2-ylidene)-1-(toluene-4-sulfonyl)-1,2,3,6-tetrahydropyridine (70):
1H NMR (300 MHz, CDCl3): d = 7.68 (d, J = 8.3 Hz, 2H), 7.30 (d, J =
8.3 Hz, 2H), 6.37 (dt, J = 10.3, 2.1 Hz, 1H), 5.55 (dt, J = 10.3, 3.5 Hz,
1H), 3.93 (s, 2H), 3.80 (s, 2H), 2.45 (s, 3H), 1.80 (s, 3H), 1.71 (s,
3H) ppm; 13C NMR (75 MHz, CDCl3; DEPT): d = 143.26 (C), 134.19
(C), 129.84 (C), 129.69 (C), 129.26 (CH), 127.63 (CH), 124.43 (CH),
120.84 (CH), 44.98 (CH2), 44.96 (CH2), 21.43 (CH3), 20.23 (CH3), 19.55
(CH3) ppm; HMRS-EI: m/z calcd for C15H19NO2S: 277.1136; found
277.1145. The structure of 71 was confirmed by COSY, NOESY, HMBC,
and HMQC experiments.
(CH), 114.83 (CH), 46.21 (CH), 36.12 (CH), 22.22 (CH), 21.45 (CH3),
20.44 (CH3), 17.20 (CH3), 15.29 (CH) ppm; HRMS-EI: m/z calcd for
C15H19NO2S: 277.1136; found 277.1144. The structure of 75b was con-
firmed by COSY, HMBC, HMQC, and NOESY experiments and by se-
lective NOE experiments (irradiation on signals at 4.27 and 0.00 ppm).
3-((E)-Benzylidene)-1-(toluene-4-sulfonyl)-1,2,3,6-tetrahydropyridine
(80): White solid: mp 57–598C; 1H NMR (300 MHz, CDCl3): d = 7.73
(d, J = 8.3 Hz, 2H), 7.38–7.25 (m, 5H), 7.11 (d, J = 6.7 Hz, 2H), 6.54
(dt, J = 10.1, 2.4 Hz, 1H), 6.37 (s, 1H), 5.78 (dtd, J = 10.1, 3.4, 1.6 Hz,
1H), 4.01 (d, J
= 1.2 Hz, 2H), 3.95 (t, J = 3.2 Hz, 2H), 2.44 (s,
3H) ppm; 13C NMR (75 MHz, CDCl3; DEPT): d = 135.89 (C), 134.31
(C), 129.48 (C), 129.00 (CH), 128.87 (C), 128.10 (CH), 127.74 (CH),
127.09 (CH), 127.02 (CH), 126.00 (CH), 124.08 (CH), 49.78 (CH2), 45.85
(CH2), 21.43 (CH3) ppm; HRMS-EI calcd for C19H19NO2S: 325.1136;
found 325.1136. The structure of 80 was confirmed by COSY, HMBC,
HMQC, and NOESY experiments.
3-Ethylidene-1-(toluene-4-sulfonyl)-1,2,3,6-tetrahydropyridine (72a): Vis-
cous, yellow oil: Isomer mixture, E/Z 4:1; 1H NMR (500 MHz, CDCl3): d
= 7.72 (dd, J = 8.3, 3.0 Hz, 2H; minor isomer), 7.67 (d, J = 8.3 Hz, 2H;
major isomer), 7.32 (dd, J
= 8.5, 4.0 Hz, 2H; minor), 7.28 (d, J =
8.3 Hz, 2H; major), 6.30 (dt, J = 10.1, 3.4 Hz, 1H), 5.60 (m, 1H), 5.29
(q, J = 7.6 Hz, 1H), 3.70 (t, J = 2.4 Hz, 2H), 3.65 (t, J = 1.2 Hz, 2H),
2.32 (s, 3H; minor), 2.33 (s, 3H; major), 1.63 (d, J = 7.2 Hz, 3H; minor),
3-(1,5-Dimethylhex-4-enylidene)-1-(toluene-4-sulfonyl)-1,2,3,6-tetrahy-
1.59 (d, J
=
7.3 Hz, 3H; major) ppm; 13C NMR (125 MHz, CDCl3;
1
dropyridine (83): Viscous, colorless oil: H NMR (300 MHz, CDCl3): d =
DEPT; major isomer): d = 143.49 (C), 137.14 (C), 133.77 (C), 129.54
(CH), 127.86 (CH), 123.60 (CH), 122.87 (CH), 122.72 (CH), 49.67 (CH2),
45.72 (CH2), 21.53 (CH3), 12.45 (CH3) ppm; HRMS-EI: m/z calcd for
C14H17NO2S: 263.0980; found 263.0984. The structure of 73a was con-
firmed by COSY, HMBC, HMQC, and NOESY experiments (major E
isomer).
7.22 (d, J = 8.2 Hz, 2H), 7.27 (d, J = 8.6 Hz, 2H), 6.33 (dt, J = 10.3,
2.2 Hz, 1H), 5.54 (dt, J = 10.3, 3.7 Hz, 1H), 5.10 (tq, J = 5.7, 1.4 Hz,
1H), 3.87 (q, J = 1.2 Hz, 2H), 3.74 (td, J = 2.9, 0.5 Hz, 2H), 2.40 (s,
3H), 2.16–2.04 (m, 4H), 1.69 (d, J = 0.6 Hz, 3H), 1.67 (d, J = 1.0 Hz,
3H), 1.60 (dd, J = 1.40, 0.4 Hz, 3H) ppm; 13C NMR (75 MHz, CDCl3;
DEPT): d = 143.27 (C), 134.05 (C), 133.85 (C), 132.33 (C), 129.29 (CH),
127.66 (CH), 124.68 (CH), 123.46 (CH), 122.69 (C), 121.27 (CH), 45.07
(CH2), 44.78 (CH2), 34.44 (CH2), 26.52 (CH2), 25.68 (CH3), 21.44 (CH3),
17.75 (CH3), 17.56 (CH3) ppm; HRMS-EI: m/z calcd for C20H27NO2S:
345.1762; found 345.1769.
7-Methyl-3-(toluene-4-sulfonyl)-3-azabicyclo[4.1.0]hept-4-ene
Isomer mixture, 10:1; white solid: mp 96–988C (major isomer); colorless
oil (minor isomer); 1H NMR (500 MHz, CDCl3): d
7.74 (d, J
(74a):
=
=
8.2 Hz, 2H; minor isomer), 7.67 (d, J = 8.2 Hz, 2H; minor), 7.63 (d, J =
8.3 Hz, 2H; major isomer), 7.30 (d, J = 7.9 Hz, 2H; major), 6.63 (d, J =
8.5 Hz, 1H; minor), 6.28 (d, J = 8.1 Hz, 1H; major), 5.40 (dd, J = 8.1,
5.4 Hz, 1H; major), 5.03 (dd, J = 7.5, 4.2 Hz, 1H; minor), 4.08 (d, J =
2.5 Hz, 1H; minor), 3.88 (d, J = 11.5 Hz, 1H), 3.35 (dd, J 12.0, 5.6 Hz,
1H; minor), 2.94 (dd, J = 11.5, 3.0 Hz, 1H; major), 2.43 (s, 3H; minor),
2.42 (s, 3H; major), 1.23–1.20 (m, 1H; major), 0.96 (d, J = 6.1 Hz, 3H;
major), 0.85–0.82 (m, 1H), 0.74 (d, J = 5.6 Hz, 3H; minor), 0.72–0.68
(m, 1H; major) ppm; 13C NMR (125 MHz, CDCl3; DEPT; major
isomer): d = 143.59 (C), 134.88 (C), 129.70 (CH), 127.21 (CH), 120.74
(CH), 111.85 (CH), 40.73 (CH2), 26.39 (CH), 21.72 (CH), 21.55 (CH3),
17.44 (CH3), 15.46 (CH) ppm; HRMS-EI: m/z calcd for C14H17NO2S:
263.0980; found 263.0992.
(1aR*,4aS*,8R*)-4-(Toluene-4-sulfonyl)-1,1a,4,4a,5,6,7,8-octahydrocy-
1
clopropa[d]quinoline (85): White solid: H NMR (500 MHz, CDCl3): d =
7.62 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 6.11 (d, J = 7.7 Hz,
1H), 5.50 (dd, J = 7.6, 5.4 Hz, 1H), 3.91 (dd, J = 11.2, 4.1 Hz, 1H), 2.41
(s, 3H), 1.83 (m, 1H), 1.78 (qd, J = 13.7, 3.78 Hz, 2H), 1.55 (m, 1H),
1.44 (m, 1H), 1.42 (sext.t, J = 13.2, 3.2 Hz, 1H), 1.22 (qt, J = 12.9,
3.5 Hz, 1H), 0.90 (t, J = 3.9 Hz, 1H), 0.92–0.85 (m, 1H), 0.33 (dd, J =
8.2, 4.2 Hz, 1H), À0.18 (t, J = 4.1 Hz, 1H) ppm; 13C NMR (125 MHz,
CDCl3; DEPT): d = 143.14 (C), 136.30 (C), 129.61 (CH), 126.60 (CH),
117.35 (CH), 115.08 (CH), 52.73 (CH), 36.36 (CH2), 33.86 (C), 30.80
(CH2), 25.40 (CH2), 24.31 (CH2), 21.51 (CH2), 21.10 (CH), 15.32 (CH3);
EI-MS( m/z): 303.2 [M]+; HRMS-EI: m/z calcd for C17H21NO2S:
303.1293; found 303.1290; elemental analysis (%) calcd for C17H21NO2S:
C 67.29, H 6.98, N 4.62, S10.57; found: C 66.97, H 7.82, N 4.52, S10.77.
The structure of 85 was confirmed by COSY and NOESY experiments.
3-Ethylidene-6-methyl-1-(toluene-4-sulfonyl)-1,2,3,6-tetrahydropyridine
(72b) and 2-methyl-4-propenyl-1-(toluene-4-sulfonyl)-2,5-dihydro-1H-
pyrrole (73b): Compound 72b: Orange solid: mp 65–678C; 1H NMR
(500 MHz, CDCl3): d = 7.63 (d, J = 8.3 Hz, 2H), 7.20 (d, J = 8.0 Hz,
2H), 6.18 (dd, J = 10.2, 0.8 Hz, 1H), 5.56 (s, 1H), 5.30 (q, J = 7.0 Hz,
1H), 4.47 (quint, J = 6.5 Hz, 1H), 4.23 (d, J = 15.6 Hz, 1H), 3.88 (dt, J
= 15.8, 2.0 Hz, 1H), 2.41 (s, 3H), 1.56 (dd, J = 7.1, 2.0 Hz, 3H), 1.34 (d,
1-(Toluene-4-sulfonyl)-2-vinyl-2,4,5,6,7,7a-hexahydro-1H-indole
(86):
1
Colorless oil: H NMR (300 MHz, CDCl3): d = 7.73 (d, J = 8.1 Hz, 2H),
7.30 (d, J = 7.9 Hz, 2H), 6.43 (dd, J = 17.6, 10.9 Hz, 1H), 5.10 (d, J =
10.9 Hz, 1H) 4.95 (d, J = 17.4 Hz, 1H), 4.27 (dd, J = 12.5, 4.3 Hz, 1H),
4.12 (d, J = 14.9 Hz, 1H), 4.07 (m, 1H), 2.65 (d, J = 15.6 Hz, 1H), 2.52
(m, 1H), 2.42 (s, 3H), 1.80 (m, 3H), 1.39 (m, 2H), 1.22 (m, 1H) ppm;
13C NMR (75 MHz, CDCl3; DEPT): d = 143.32 (C), 138.61 (C), 129.73
(CH), 127.52 (CH), 125.21 (C), 115.08 (CH2), 68.05 (CH), 54.74 (CH2),
36.32 (CH2), 26.08 (CH2), 25.63 (CH2), 23.99 (CH2), 21.51 (CH3) (two
carbon signals overlap) ppm; EI-MS( m/z): 302.1 [MÀ1]+.
J
=
6.8 Hz, 3H) ppm. Compound 73b: vitreous solid; 1H NMR
(500 MHz, CDCl3): d = 7.75 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 7.9 Hz,
2H), 6.07 (d, J = 15.9 Hz, 1H), 5.56 (m, 1H), 5.35 (brs, 1H), 4.51 (quint,
J = 5.8 Hz, 1H), 4.30 (ddd, J = 13.6, 4.7, 1.7 Hz, 1H), 4.14 (m, 1H),
2.44 (s, 3H), 1.78 (d, J = 6.8 Hz, 3H), 1.44 (d, J = 6.5 Hz, 3H) ppm;
13C NMR (125 MHz, CDCl3; DEPT): d = 143.33 (C), 142.82 (C), 137.26
(C), 135.37 (C), 134.87 (C), 129.73 (CH; endo), 129.48 (CH; exo), 128.98
(CH; endo), 127.48 (CH; endo), 127.43 (CH; exo), 126.43 (CH; exo),
126.65 (CH; exo), 122.52 (CH; exo), 121.62 (CH; exo), 63.14 (CH; exo),
54.42 (CH2; exo), 50.63 (CH; endo), 44.91 (CH2; exo), 22.86 (CH3; exo),
21.52 (CH3), 21.48 (CH3), 19.96 (CH3; endo), 18.39 (CH3; exo), 12.19
(CH3; endo) ppm; HRMS-EI: m/z calcd for C15H19NO2S(mixture of):
277.1136; found 277.1133. The structures of 73b/74b were confirmed by
COSY, HMBC, HMQC, and NOESY experiments.
Dimethyl
3-(2-methylprop-1-enyl)-cyclopent-2-ene-1,1-dicarboxylate
(87): Colorless oil: 1H NMR (500 MHz, CDCl3): d = 5.73 (m, 1H), 5.52
(m, 1H), 3.65 (s, 6H), 2.58 (td, J = 6.5, 1.9 Hz, 2H), 2.40 (m, 2H), 1.77
(d, J
= =
0.9 Hz, 6H) ppm; 13C NMR (125 MHz, CDCl3; DEPT): d
172.02 (2 C), 146.13 (C), 138.04 (C), 124.86 (CH), 120.69 (CH), 65.98 (C),
52.66 (CH3), 52.72 (CH3), 34.78 (CH2), 32.14 (CH2), 27.42 (CH3), 20.51
(CH3).
3-(2-Methyl-1-propenyl)-1,1-bis(phenylsulfonyl)cyclopent-3-ene
(88):
2,7-Dimethyl-3-(toluene-4-sulfonyl)-3-azabicyclo[4.1.0]hept-4-ene (74b):
White solid: mp 167–1698C; 1H NMR (300 MHz, CDCl3): d = 7.63 (d, J
= 8.4 Hz, 2H), 7.29 (d, J = 8.1 Hz, 2H), 6.07 (dm, J = 7.7 Hz, 1H), 5.50
(dd, J = 7.8, 5.6 Hz, 1H), 4.27 (q, J = 6.4 Hz, 1H), 2.42 (s, 3H), 1.20 (d,
J = 6.4 Hz, 3H), 1.07 (ddd, J = 8.4, 5.0, 1.4 Hz, 1H), 0.83 (m, 1H), 0.79
1
Pale orange solid: mp 139–1418C; H NMR (300 MHz, CDCl3): d = 8.00
(d, J = 7.3 Hz, 4H), 7.69 (tt, J = 6.9, 1.2 Hz, 2H), 7.55 (t, J = 6.8 Hz,
4H), 5.39 (s, 1H), 5.02 (s, 1H), 3.47 (s, 2H), 3.36 (s, 2H), 1.71 (s, 3H),
1.57 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3; DEPT): d = 138.21 (C),
137.49 (C), 136.93 (C), 134.51 (CH), 130.82 (CH), 128.73 (CH), 122.73
(CH), 118.97 (CH), 91.44 (C), 41.30 (CH2), 38.54 (CH2), 27.05 (CH3),
(d, J
DEPT): d = 143.16 (C), 136.33 (C), 129.52 (CH), 126.67 (CH), 117.41
=
6.0 Hz, 3H), 0.00 (m, 1H) ppm; 13C NMR (75 MHz, CDCl3;
Chem. Eur. J. 2006, 12, 1677 – 1693
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
1691

A. M. Echavarren et al.
19.80 (CH3) ppm; HRMS-CI m/z calcd for C21H22O4S2: 403.1045; found
403.1045 [M+1]+.
Murai, Organometallics 1996, 15, 901–903; c) N. Chatani, H. Inoue,
T. Ikeda, S. Murai, J. Org. Chem. 2000, 65, 4913–4918.
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69, 8018–8023; b) R.-X. He, M. Li, X.-Y. Li, J. Mol. Struct. 2005,
717, 21–32.
[7] Hydroxycyclization catalyzed by mercuric triflate: M. Nishizawa,
V. K. Yadav, M. Skwarczynski, H. Takao, H. Imagawa, T. Sugihara,
Org. Lett. 2003, 5, 1609–1611.
3-(2-Methyl-1-propenyl)-1,1-bis(phenylsulfonyl)cyclopent-3-ene
(89):
1
Pale orange solid: mp 139–1418C; H NMR (300 MHz, CDCl3): d = 8.00
(d, J = 7.3 Hz, 4H), 7.69 (tt, J = 6.9, 1.2 Hz, 2H), 7.55 (t, J = 6.8 Hz,
4H), 5.39 (s, 1H), 5.02 (s, 1H), 3.47 (s, 2H), 3.36 (s, 2H), 1.71 (s, 3H),
1,57 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3; DEPT): d = 138.21 (C),
137.49 (C), 136.93 (C), 134.51 (CH), 130.82 (CH), 128.73 (CH), 122.73
(CH), 118.97 (CH), 91.44 (C), 41.30 (CH2), 38.54 (CH2), 27.05 (CH3),
19.80 (CH3) ppm; HRMS-CI m/z calcd for C21H22O4S2: 403.1045; found
403.1045 [M+1]+.
[8] 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.
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6785–6786; b) A. Fürstner, F. Stelzer, H. Szillat, J. Am. Chem. Soc.
2001, 123, 11863–11869.
Dimethyl 3-methyl-5-methylenecyclohex-3-ene-1,1-dicarboxylate (91):
Yellow oil: 1H NMR (300 MHz, CDCl3): d = 5.90 (s, 1H), 4.78 (s, 2H),
3.69 (s, 6H), 2.80 (s, 2H), 2.57 (s, 2H), 1.79 (s, 3H) ppm; 13C NMR
(75 MHz, CDCl3; DEPT): d = 171.38 (C), 139.30 (C), 135.48 (C), 124.38
(CH), 111.05 (CH2), 54.42 (C), 52.71 (CH3), 35.64 (CH2), 35.48 (CH2),
23.34 (CH3) ppm; HRMS-EI: m/z calcd for C12H16O4: 224.1049; found
224.1048. The corresponding reaction of deuterated enyne [D1]-18 gave
[D1]-91a (Scheme 9), in which the signal at 4.78 ppm (1H) was not ob-
served.
[11] S. Oi, I. Tsukamoto, S. Miyano, Y. Inoue, Organometallics 2001, 20,
3704–3709.
[12] 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.
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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.
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2004, 6, 1509–1511; f) G. B. Bajracharya, I. Nakamura, Y. Yamamo-
to, J. Org. Chem. 2005, 70, 892–897.
[Au(PPh3)Cl]/AgSbF6-catalyzed cyclization of [D1]-75 (Scheme 9): Cycli-
zation of the deuterated enyne [D1]-75 gave [D1]-76 and [D1]-78. In [D1]-
76 the olefinic hydrogen at 5.89 ppm was not observed [1H NMR
(300 MHz, CDCl3) for 76: d = 7.68 (d, J = 7.7 Hz, 2H), 7.31 (d, J =
7.7 Hz, 2H), 5.89 (s, 1H), 4.81 (d, J = 8.7 Hz, 2H), 3.77 (s, 2H), 3.59 (s,
2H), 2.43 (s, 3H), 1.73 (s, 3H)]. In [D1]-78 the signal at 0.92 ppm (1H)
was not observed [1H NMR (300 MHz, CDCl3): for 78: d = 7.65 (d, J =
84 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 6.28 (d, J = 7.9 Hz, 1H), 5.40 (dd,
J = 7.9, 5.6 Hz, 1H), 3.84 (d, J = 11.3 Hz, 1H), 2.72 (dd, J = 11.3,
0.7 Hz, 1H), 2.42 8 s, 3H), 1.11 (s, 3H), 0.92 (m, 1H), 0.63 (ddd, J = 8.1,
4.4, 1.2 Hz, 1H), 0.56 (t, J = 4.4 Hz, 1H)].
[14] C. Nieto-Oberhuber, S. López, A. M. Echavarren, J. Am. Chem.
Soc. 2005, 127, 6178–6179.
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Acknowledgements
[17] 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) L. Zhang, S. A. Kozmin, J.
Am. Chem. Soc. 2005, 127, 6962–6963; e) cyclization of 1,4-enynes
with AuI catalysts: X. Shi, D. J. Gorin, F. D. Toste, J. Am. Chem.
Soc. 2005, 127, 5802–5803.
This work was supported by the MEC (project CTQ2004–02869, predoc-
toral fellowships to C.N.-O., M.P.M., E.J.-N., and E.H.-G., and a Torres
Quevedo contract to S.L.), the CAM (predoctoral fellowship to C.N.),
and the ICIQ Foundation. We also thank Johnson Matthey PLC for a
loan of metal salts.
[18] C. Nieto-Oberhuber, S. López, M. P. MuÇoz, E. JimØnez-NfflÇez, E.
BuÇuel, D. J. Cµrdenas, A. M. Echavarren, Chem. Eur. J. 2006, 12,
1694–1702.
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Published online: December 16, 2005
Chem. Eur. J. 2006, 12, 1677 – 1693
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