Ligand effects in gold- and platinum-catalyzed cyclization of enynes: Chiral gold complexes for enantioselective alkoxycyclization

Article abstract of DOI:10.1021/om0491645

Phosphine and bidentate N-N ligands inhibit the Alder-ene-type cycloisomerization of enynes catalyzed by Pt(II) and favor the alkoxycyclization process. The enantioselective Pt(II)-catalyzed alkoxycyclization has been studied in the presence of chiral mono- and bidentate phosphines, as well as chiral bidentate N-N ligands. Modest levels of enantioselection (up to 50% ee) have been obtained with Tol-BINAP as ligand. The alkoxycyclizations with a catalyst formed from [Au(L)Cl]/AgX proceed more readily, and up to 94% ee's have been obtained using [(AuCl)₂(Tol-BINAP)] (47) as the precatalyst. The X-ray crystal structures of Au(I) complexes 47 and chloro-(R)-2-(tert- butylsulfenyl)-1-(diphenylphosphino)ferrocene gold(I) (39) show the AuCl fragments monocoordinated with the P centers of the chiral phosphine ligands.

Full text of DOI:10.1021/om0491645

Organometallics 2005, 24, 1293-1300
1293
Ligand Effects in Gold- and Platinum-Catalyzed
Cyclization of Enynes: Chiral Gold Complexes for
Enantioselective Alkoxycyclization
M. Paz Mun˜oz,† Javier Adrio,† Juan Carlos Carretero,† and
Antonio M. Echavarren*,†,‡
Departamento de Quı´mica Orga´nica, Universidad Auto´noma de Madrid, Cantoblanco,
28049 Madrid, Spain, and Institute of Chemical Research of Catalonia (ICIQ),
43007 Tarragona, Spain
Received October 27, 2004
Phosphine and bidentate N-N ligands inhibit the Alder-ene-type cycloisomerization of
enynes catalyzed by Pt(II) and favor the alkoxycyclization process. The enantioselective Pt(II)-
catalyzed alkoxycyclization has been studied in the presence of chiral mono- and bidentate
phosphines, as well as chiral bidentate N-N ligands. Modest levels of enantioselection (up
to 50% ee) have been obtained with Tol-BINAP as ligand. The alkoxycyclizations with a
catalyst formed from [Au(L)Cl]/AgX proceed more readily, and up to 94% ee’s have been
obtained using [(AuCl)2(Tol-BINAP)] (47) as the precatalyst. The X-ray crystal structures
of Au(I) complexes 47 and chloro-(R)-2-(tert-butylsulfenyl)-1-(diphenylphosphino)ferrocene
gold(I) (39) show the AuCl fragments monocoordinated with the P centers of the chiral
phosphine ligands.
Scheme 1
Introduction
The addition of alcohols or water to 1,6-enynes 1 in
the presence of PtCl2 as catalyst proceeds via Pt
cyclopropyl carbene intermediates 2 (MXn ) PtLCl2, L
) R′OH or H2O) to give five- or six-membered ring
alkoxy- or hydroxycyclized compounds 3 and 4 by 5-exo-
trig or 6-endo-trig pathways, respectively.1,2 The regio-
chemistry of the process is controlled by substitution
pattern on the enyne, in particular by substituents at
the alkene and the tether Z.1,2 Some of these cyclizations
are also catalyzed by AuCl3,1c Ru(II),1a,b and Pd(II)3
complexes, although the reactions with these catalysts
are more limited in scope. Similar intermediates 2 are
also involved in other transition-metal-catalyzed cy-
clization of enynes.4 For the reactions catalyzed by
Pt(II), a competing pathway is the oxidative cyclometa-
lation leading to intermediate 5, which suffers â-hydro-
gen elimination to form dienes 6 by a formal Alder-ene
process.1,2 This Alder-ene-type cycloisomerization also
proceeds with other d8 metal complexes as catalysts,
such as those based on Pd(II) and Rh(I), as well as d6
Ru(II) complexes.1-5 However, in the presence of d10
Au(I) complexes [Au(L)]+X- (L ) phosphine ligand),
prepared in situ from [Au(L)Me] and a protic acid, no
competing Alder-ene-type cycloisomerization was ob-
served.6
Here we report the effect of phosphines and oxazolines
as ligands in the selectivity of the Pt-catalyzed alkoxy-
cyclization versus Alder-ene-type cycloisomerization of
enynes 1. Modest enantioselectivities are obtained by
using chiral bidentate phosphines. We also report the
first examples of enantioselective alkoxycyclization by
using chiral Au(I) catalysts. While our work was in
† Universidad Auto´noma de Madrid.
‡ Institute of Chemical Research of Catalonia (ICIQ).
(1) (a) Me´ndez, M.; Mun˜oz, M. P.; Echavarren, A. M. J. Am. Chem.
Soc. 2000, 122, 11549-11550. (b) Me´ndez, M.; Mun˜oz, M. P.; Nevado,
C.; Ca´rdenas, D. J.; Echavarren, A. M. J. Am. Chem. Soc. 2001, 123,
10511-10520. (c) Nevado, C.; Ca´rdenas, D. J.; Echavarren, A. M.
Chem. Eur. J. 2003, 9, 2627-2635. (d) Mun˜oz, M. P.; Me´ndez, M.;
Nevado, C.; Ca´rdenas, D. J.; Echavarren, A. M. Synthesis 2003, 2898-
2902.
(2) (a) Echavarren, A. M.; Nevado, C. Chem. Soc. Rev. 2004, 33, 431-
436. (b) Echavarren, A. M.; Me´ndez, M.; Mun˜oz, M. P.; Nevado, C.;
Mart´ın-Matute, B.; Nieto-Oberhuber, C.; Ca´rdenas, D. J. Pure Appl.
Chem. 2004, 76, 453-463.
(3) Nevado, C.; Charruault, L.; Michelet, V.; Nieto-Oberhuber, C.;
Mun˜oz, M. P.; Me´ndez, M.; Rager, M.-N.; Geneˆt, J. P.; Echavarren, A.
M. Eur. J. Org. Chem. 2003, 706-713.
(4) (a) Diver, S. T.; Giessert, A. J. Chem. Rev. 2004, 104, 1317-
1382. (b) Lloyd-Jones, G. C. Org. Biomol. Chem. 2003, 215-236. (c)
Me´ndez, M.; Mamane, V.; Fu¨rstner, A. Chemtracts-Org. Chem. 2003,
16, 397-425.
(5) Fairlamb, I. J. S. Angew. Chem., Int. Ed. 2004, 43, 1048-1052.
(6) Nieto-Oberhuber, C.; Mun˜oz, M. P.; Bun˜uel, E.; Nevado, C.;
Ca´rdenas, D. J.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43,
2402-2406.
10.1021/om0491645 CCC: $30.25 © 2005 American Chemical Society
Publication on Web 02/12/2005

1294 Organometallics, Vol. 24, No. 6, 2005
Mun˜oz et al.
Table 1. Influence of Phosphine Ligands in the
PtCl2-Catalyzed Reaction of Enyne 7a
progress, the groups of Michelet, Geneˆt, and Gladiali
reported that Pt(II) cationic complexes of (R)- or (S)-
Ph-BINEPINE, a monodentate phosphine ligand, gave
up to 85% ee in this reaction.7
Results and Discussion
Pt(II) Catalysts with P- or N-Donor Ligands. We
analyzed the effect of ligands in the reaction of enyne
7, with MeOH as solvent in the presence of Pt(II)
complexes prepared in situ from PtCl2, and ligands L
(Table 1). In the absence of ligand, the reaction of 7
provided a 2:1 mixture of 8 and 9 (Table 1, entry 1).1b,d
In contrast, in the presence of mono- and bidentate
phosphines, exclusive methoxycyclization was observed
in all cases. It is interesting to note that the potentially
competitive addition of MeOH to the alkyne to form an
enol ether8 does not compete with the cyclization
process. Better results were obtained by using P(C6F5)3
or P(o-Tol)3 than PPh3 (Table 1, entries 2-4). The use
of a 2:1 ratio of phosphine to Pt(II) led only to a small
decrease in the yield of 8 (Table 1, compare entries 4
and 5). Bulky, biphenyl-based phosphine 10 gave a good
yield of 8, although the reaction was not complete after
17 h (Table 1, entry 6). The reaction was very slow with
phosphine 119 (Table 1, entry 7). Bidentate phosphines
dppe, dppp, dppb, dppf, and 12 gave satisfactory results
(Table 1, entries 8-12), dppp being the best ligand
(Table 1, entry 9).
As shown in Figure 1, a monodentate phosphine such
as P(o-Tol)3 accelerates the reaction of 7, the methoxy-
cyclization being complete in less than 1 h. On the other
hand, in the presence of [Pt(dppf)Cl2],10 formed in situ
under the conditions of entry 11 (Table 1), the meth-
oxycyclization is considerably retarded.
These results indicate that the Alder-ene-type cyclo-
isomerization reaction is inhibited by phosphine ligands,
which is somewhat surprising since that process in-
volves a formal 2-e oxidation at the metal to form a
Pt(IV) metallacycle (see 5, Scheme 1) that should be
stabilized by stronger donor ligands. The inhibition may
be explained by the displacement of weaker alkene
ligand1b by the phosphine in the initial Pt(II)-enyne
complex, thus preventing the oxidative cyclometalation.
The exclusive formation of methoxycyclization products
in the presence of phosphine ligands strongly supports
the proposal of two different mechanisms for these two
reactions.
Bidentate ligands such as 4,4′-bipyridine, 4,4′-di-
methylbipyridine, or phenantroline (Table 2, entries
1-3) gave poor results.11 Less basic quinoline led to a
mixture of 8 and 9 in moderate yield (Table 2, entry 4).
Oxazolines have shown to be excellent ligands in transi-
a All reactions were carried out in MeOH under refluxing
conditions with 5 mol % of PtCl2 for 16 h. Unless otherwise stated,
conversions were >99%. b Conversion < 90%. In this case, the yield
was determined by 1H NMR.
(7) Charruault, L.; Michelet, V.; Taras, R.; Gladialli, S.; Geneˆt, J.-
P. Chem. Commun. 2004, 850-851.
(8) Kataoka, Y.; Matsumoto, O.; Tani, K. Organometallics 1996, 15,
5246-5249.
tion metal chemistry.12 We decided to employ pyridine-
(9) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998,
120, 9722-9723.
oxazoline (13) and py-box (14)13 in the methoxycycliza-
(10) Clemente, D. A.; Pilloni, G.; Corain, B.; Longato, B.; Tiripicchio-
Camellini, M. Inorg. Chim. Acta 1986, 115, L9-L11.
(11) Complexes of the type [Pt(N-N)(alkyne)X2] (N-N ) bidentate
N-donor ligand) prefer a five-coordinate trigonal-bipyramidal structure
when the alkyne is a strong π-accepting ligand. Otherwise, even with
rigid phenantroline ligands, the resulting Pt(II) complexes are square-
planar four-coordinated. See: Fanizzi, F. P.; Maresca, L.; Natile, G.;
Lanfranchi, M.; Tiripicchio, A.; Pacchioni, G. Chem. Commun. 1992,
333-335.
(12) For Pt(II)-oxazoline complexes, see: (a) Motoyama, Y.; Mikami,
Y.; Kawakami, H.; Aoki, K.; Nishiyama, H. Organometallics 1999, 18,
3584-3588. (b) Wang, X.; Chakrapani, H.; Madine, J. W.; Keyerleber,
M. A.; Widenhoefer, R. A. J. Org. Chem. 2002, 67, 2778-2788. (c)
Motoyama, Y.; Kawakami, H.; Shimozono, K.; Aoki, K.; Nishiyama,
H. Organometallics 2002, 21, 3408-3416. (d) Fossey J. S.; Richards,
C. J. Organometallics 2004, 23, 367-373.

Gold- and Platinum-Catalyzed Cyclization of Enynes
Organometallics, Vol. 24, No. 6, 2005 1295
Figure 2. Reaction of enyne 15 in MeOH to give 17: (b)
reaction catalyzed by PtCl2; (2) reaction catalyzed by
PtCl2 preheated in MeOH; (9) reaction catalyzed by
[Pt(MeCN)2Cl2].
Figure 1. Reaction of 7 in MeOH in the absence or
presence of phosphines (refluxing conditions): (9) reaction
without phosphine to give a 67:33 mixture of 8 and 9; ([)
reaction with 5 mol % of P(o-Tol)3 to give 8; (2) reaction
with 5 mol % of dppf to give 8.
Scheme 2
Table 2. Influence of N Ligands in the
PtCl2-Catalyzed Reaction of Enyne 7a
16 should be more reactive, as the nucleophile would
approach the less hindered exo face of the bicyclic
intermediate 20.
When the reaction was carried out by mixing the
enyne and 5 mol % of PtCl2 in MeOH at 80 °C, no
conversion of the starting material was observed until
3 h. However, the reaction was complete in 17 h, giving
a sigmoid curve, showing an induction period (Figure
2).14 When the reaction was performed preheating the
PtCl2 in MeOH for 12 h before the addition of the enyne
to the reaction mixture, a similar induction period was
observed. However, from this point, the reaction was
faster than in the previous case, being complete in 10
h. The low solubility of PtCl2 in MeOH might explain
the induction period. In fact, when more soluble
[Pt(MeCN)2Cl2] was used as the catalyst, no induction
period and much faster reaction were observed. It is
important to note that it has been described that MeOH
reacts with [Pt(RCN)2Cl2] to form Pt(II) complexes with
iminoesther ligands.15
a All reactions were carried out under refluxing conditions with
5 mol % of PtCl2 for 19 h. bConversion ca. 50%. In this case, the
yield was determined by 1H NMR.
tion of the enyne 7. Although, low reactivity was found
for the PtCl2‚13 complex, excellent conversions of 7 into
methoxycyclization product 8 were obtained in the
presence of AgOTf (Table 2, entries 7 and 8).
As a last aspect, the effect of the simple MeCN ligand
was also examined in the reaction of substrates 15 and
16 in MeOH to give 17 and 18, respectively1 (Scheme
2). Qualitative comparison of the reaction rates should
shed light on the nature of the rate-determining step
in these processes. Thus, if formation of cyclopropyl
Pt(II)-carbenes 19 and 20 is rate determining, 15 should
react faster than 16 through intermediate 19 that bears
the Ph substituent at the less hindered exo face of the
bicyclo[3.1.0]heptene structure. On the other hand, in
the event that attack of methanol is the slow step, enyne
(14) Reaction of the malonate analogue of 15 takes place in aqueous
solvents to give the corresponding hydroxycyclization product.1 This
reaction proceeds similarly in aqueous acetone (86% yield after 6 days
with 5% PtCl2) or aqueous dioxane (84% yield after 6 days with 10%
PtCl2 or 53% with 5% PtCl2). In ref 7 (Table 1, entry 1), reaction of
this substrate with 10% PtCl2 in aqueous dioxane is claimed to give
only traces of hydroxycyclization product after a reaction time of 5 days.
(13) Desimoni, G.; Faita, G.; Quadrelli, P. Chem. Rev. 2003, 103,
3119-3154.

1296 Organometallics, Vol. 24, No. 6, 2005
Mun˜oz et al.
Table 3. Alkoxycyclization of Enyne 31 with
[Pt(L*)Cl2] Complexes with Chiral Ligands 21-29
and Complex 30a
entry L* additive (10 mol %) time (h) yield (%) % ee (config)
1
2
3
4
5
6
7
8
9
21
21
21
22
23
24
25
26
27
21
40
40
19
40
24
40
16
24
192
48
48
40
17
99
59
0
AgOTf
16 (+)
12 (+)
4
AgSbF6
35
100
87
0
6
97
Figure 3. Reaction of enyne 16 in MeOH to give 18
99
26 (+)
32 (-)
48 (+)
50 (+)
12 (+)
catalyzed by PtCl2.
86
97
Chart 1
10b 27
62
11
12
28
29
100
< 5
13c 30
14c 30
AgBF4
97
10 (+)
a
Unless otherwise stated all reactions were carried under
b
reflux conditions. Reaction carried out at room temperature.
Preformed complex 30 was used as precatalyst.
c
gave good yields of 32, although the enantioselectivities
were very low in all cases (Table 3, entries 1 and 4-7).
The addition of silver salts in the case of 21 led to lower
yields (Table 3, entries 2 and 3). Better results were
obtained with Tol-BINAP (27) (Table 3, entries 9 and
10). The reaction with the chiral biscationic platinum
complex, [Pt(PhCN)2-(R)-BINAP](BF4)2,16 gave a good
yield of 32, but no asymmetric induction was observed.
In the case of the monophosphine derivative (R)-MOP
(28),17 an excellent yield was obtained in 48 h, but the
enantioselectivity was low (Table 3, entry 11). In the
presence of a 2:1 ratio of 28 to PtCl2, no reaction was
observed. Reaction in the presence of a ferrocenylphos-
phine 29, with planar chirality,18 led only to traces of
the alkoxycyclization product 32 (Table 3, entry 12).
Pt(II) complex 30 gives only a productive catalyst in the
presence of AgBF4 (Table 3, entries 13 and 14), although
the enantioselectivity is low.19
We tried determining the configuration of 32 by
derivatization of the corresponding alcohol with a chiral
ester (i.e., Mosher or mandelate ester). However, at-
tempted demethylation of the methyl ether of 32 with
BBr3 at -78 °C led only to the decomposition of the
starting material.
Au(I) Catalysts with Chiral P-Ligands. A chiral
ferrocenylphosphine-Au(I) complex has been used in the
reaction of aldehydes with R-isocyanoacetate esters with
high enantioselectivities.20 This precedent in Au(I)
chemistry led us to synthesize ferrocenylphosphine-
Au(I) complexes as potential catalysts for the enantio-
selective methoxycyclization of enynes.
Enyne 16, bearing a cis-disubstituted alkene, reacted
more slowly with PtCl2 in MeOH to form 18, and a
longer induction period (ca. 10 h) was observed (Figure
3). This result supports a mechanistic scenario in which
formation of cyclopropyl Pt(II)-carbenes as intermedi-
ates is the rate-determining step.
Pt(II) Catalysts with Chiral P- or N-Ligands. We
tried chiral bidentate phosphines 21-27, monodentate
phosphine 28, potentially bidentate phosphine thioether
29, and chiral pyridyl oxazoline Pt(II) complex 30 (Chart
1) in the methoxycyclization of enyne 31 to give 32
(Table 3). The reaction in the presence of C2-symmetric
biphosphines, such us NORPHOS (21), DIPAMP (22),
Deguphos (23), or DIOP (24), as well as with BPPM (25)
(16) Oi, S.; Terada, E.; Ohuchi, K.; Kato, T.; Tachibana, Y.; Inoue,
Y. Org. Lett. 1999, 64, 8660-8667.
(17) Hayashi, T. Acc. Chem. Res. 2000, 33, 354-362.
(18) (a) Garc´ıa-Manchen˜o, O.; Priego, J.; Cabrera, S.; Go´mez Arra-
ya´s, R.; Llamas, T.; Carretero, J. C. J. Org. Chem. 2003, 68, 3679-
3686. For related ligands, see: (b) Priego, J.; Garc´ıa Manchen˜o, O.;
Cabrera, S.; Carretero, J. C. J. Org. Chem. 2002, 67, 1346-1353. (c)
Manchen˜o, O.; Arraya´s, R. G.; Carretero, J. C. J. Am. Chem. Soc. 2004,
126, 4566-457. (d) Cabrera, S.; Go´mez Arraya´s, R.; Carretero, J. C.
Angew. Chem., Int. Ed. 2004, 43, 3944-3947.
(15) (a) Casas, J. M.; Chislom, M. H.; Sicilia, M. V.; Streib, W. E.
Polyhedron 1991, 10, 1573-1578. (b) Bandoli, G.; Caputo, P. A.; Intini,
F. P.; Sivo, M. F.; Natile, G. J. Am. Chem. Soc. 1997, 119, 10370-
10376.
(19) For a recent review on applications of oxazoline-containing
ligands in asymmetric catalysis, see: McManus, H. A.; Guiry, P. J.
Chem. Rev. 2004, 104, 4151-4202.

Gold- and Platinum-Catalyzed Cyclization of Enynes
Organometallics, Vol. 24, No. 6, 2005 1297
Figure 4. Structure of Au(I) complex 39. Selected bond
distances (Å) and angles (deg): Au(1)-P(1), 2.230(2);
Au(1)-Cl(1), 2.289(2); P(1)-Au(1)-Cl(1), 174.25(10); C(1)-
P(1)-Au(1), 116.3(3); C(13)-P(1)-Au(1), 114.1(3); C(7)-
P(1)-Au(1), 111.2(3).
Figure 5. X-ray crystal structure of Au(I) complex 47.
Selected bond distances (Å) and angles (deg): Au(1)-P(1),
2.2353(8);Au(1)-Cl(1),2.2880(9);P(1)-Au(1)-Cl(1),172.69(4);
C(1)-P(1)-Au(1), 122.55(12); C(11)-P(1)-Au(1), 107.04(11);
C(18)-P(1)-Au(1), 109.73(12).
Chart 2
Chart 3
Au(I) complexes were synthesized from Na[AuCl4]‚
H2O and the corresponding chiral ligands, following the
methodology described by Parish et al.21 As ligands, we
used phosphines 26-28, Fesulphos (29, 33, and 34),18
Josiphos (35), Walphos (36), Taniaphos (37), and binol
derivative 3822 (Charts 1 and 2).
The structure of complex 39, obtained as an orange
solid in 96% yield from ligand 29 and Na[AuCl4]‚2H2O,21
is shown in Figure 4. Unlike previously reported Pd(II)
and Cu(I) complexes of the P,S-ligand 29,18 in which
both phosphorus and sulfur atoms are coordinated to
the metal, this shows that Au(I) coordinates exclusively
with the phosphorus atom.23 The same monodentate
character is proposed for complexes 40 and 41 synthe-
sized from the Fesulphos ligands 33 and 34, respectively
(Chart 3).
Although ligands 35 and 36 have two P atoms, the
31P{1H} NMR spectra of the corresponding Au(I) com-
plexes 42 and 43 (Chart 3) showed two singlet signals,
(20) (a) Ito, Y.; Sawamura, M.; Hayashi, T. J. Am. Chem. Soc. 1986,
108, 6405-6406. (b) Togni, A.; Pastor, S. D. J. Org. Chem. 1990, 55,
1649-1664. (c) Hughes, P. F.; Smith, S. H.; Olson, J. T. J. Org. Chem.
1994, 59, 5799-5802.
(21) (a) Al-Sady, A. L.; McAuliffe, C. A.; Parish, R. V.; Sandbank, J.
A. Inorg. Synth. 1985, 23, 191. For the synthesis of gold complexes
using this methodology, see: (b) Alder, M. J.; Flower, K. R.; Pritchard,
R. G. J. Organomet. Chem. 2001, 629, 153-159.
(22) de Vries, A. H. M.; Meetsma, A.; Feringa, B. Angew. Chem.,
Int. Ed. 1996, 35, 2374-2376.
(23) For Au(I) complexes dicoordination is preferred, see: Carvajal,
M. A.; Novoa, J. J.; Alvarez, S. J. Am. Chem. Soc. 2004, 126, 1465-
1477.

1298 Organometallics, Vol. 24, No. 6, 2005
Mun˜oz et al.
Table 4. Alkoxycyclization of Enyne 31 with
Chiral Phosphine Au(I)-L* Complexesa
Chart 4
entry
L*
Au(I) complex time (h) yield (%) % ee (config)
1
29
39
40
40
41
42
43
44
45
46
47
47
47
47
48
49
50
23
3
48
2
96
8
23
48
22
3
30
4
48
2
24
8
92
100
84
18 (+)
11 (+)
5 (+)
2
33
3b
4
33
34
100
100
84
8 (-)
5
35
42 (+)
38 (+)
17 (-)
< 2
6
36
7
37
99
((R)-BINAP as ligand) (Table 4, entries 9 and 10). When
the ratio of Au/Ag was 1:1, the asymmetric induction
decreased and, remarkably, the opposite enantiomer
was obtained in excess (Table 4, entry 11). For the
activation of complex 47 the best results were obtained
by less than stoichiometric amount of Ag(I), 1.6:2 (Table
4, entry 12), which presumably leads to a monocationic
complex. This experiment was performed in CH2Cl2
containing 10 equiv of MeOH. Similar reactivity was
observed in Et2O, acetone, dioxane, or nitromethane,
whereas no reaction took place with 10 equiv of MeOH
in toluene, DMF, CH3CN, or THF. The methoxycycliza-
tion proceeded in the absence of silver salt (Table 4,
entry 13), although the reaction time increased, and the
enantioselectivity decreased. Lowering the reaction
temperature to -78 °C led to a very slow conversion,
and only traces of the alkoxycyclization products were
observed. No methoxycyclization was observed with
AgSbF6 (2 mol %) and (S)-TolBINAP (2 mol %) in MeOH
at room temperature, in the absence of Au(I) after long
reaction times. The reaction with complex 48 prepared
from the (R)-MOP ligand (28) was fast, although no
enantioselection was obtained (Table 4, entry 14).
All attempts to synthesize a complex with two P
coordinated to the same Au(I) atom failed.25 The X-ray
crystal structure of complex 47 reveals that the two
atoms of Au(I) are monocoordinating to each P atom
(Figure 3). Related BINAP-Ag(I) complexes have been
isolated by Yamamoto and were shown to be excellent
Lewis acid catalysts in a variety of reactions.26 However,
for the reactions of enynes, Ag(I) complexes proved to
be rather poor catalysts.27 The coordination of Au(I) in
47 is therefore similar to that of the ferrocenyl com-
plexes 39 (Figure 1), 42, and 43.
8
38
60
9
26
98
39 (-)
43 (-)
14 (+)
53 (-)
34 (-)
< 2
10
(R)-27
(R)-27
93
11c
98
12d (R)-27
89
13e
14
(R)-27
28
26
(R)-27
100
94
15f
16
100
100
13 (-)
45 (-)
a Reactions were carried out in MeOH at room temperature with
2 mol % [Au(L*)Cl] (or 1.6 mol % [L*(AuCl)2] in entries 5, 6, 9,
and 10) and 2 mol % AgSF6. b Reaction in the absence of silver
salt. c Reaction performed in CH2Cl2 with 10 equiv of MeOH with
2 mol % 47 and 4 mol % AgSF6. d Reaction performed in CH2Cl2
with 10 equiv of MeOH with 1.6 mol % 47 and 2 mol % AgSF6.
e Reaction performed with 3 mol % 47 in the absence of Ag(I) salt.
f Reaction performed with 1.5 mol % 49 and 2 mol % phospho-
tungstic acid.
which indicates that the two phosphorus atoms are not
coordinated to the same Au atom. However, the 31P
NMR spectrum of the Au(I) complex 44, synthesized
from the Taniaphos ligand (37), showed two groups of
signals of two species in equilibrium. One of these
complexes shows a pair of doublets, which corresponds
to the two 31P atoms coordinated to the same Au atom.24
For the methoxycyclization of enynes catalyzed by
[Au(PPh3)Me], an acid HX was required as an activator
to form the cationic complex.6 Complex [Au(PPh3)Cl],
in the presence of silver salts, did not catalyze the
methoxycyclization, which indicates that complexes of
the type [Au(PPh3)(MeOH)]X are either not stable or
not sufficiently reactive in this reaction. However, in
the case of the Au(I) complexes with bulky chiral
phosphines, the Au(I)-chloride complexes in the pres-
ence of a silver salt gave cationic complexes reactive
enough to catalyze the reaction. Results on the enan-
tioselective methoxycyclization of enyne 31 with chiral
Au(I) complexes (39-50) are shown in Table 4.
Complex 39 gave the methoxycyclization product in
very good yield, but the asymmetric induction was very
low (Table 4, entry 1). Changing the phosphine to a
better electron donor in complex 40 improved the
reactivity (Table 4, entry 2), although the enantioselec-
tivity was lower. In the absence of silver salt, the
reactivity and enantioselectivity decreased (Table 4,
entry 3). A similar result was obtained with 41, al-
though the opposite enantioselection was observed
(Table 4, entry 4). Complex 42 was the less reactive,
although 32 was obtained with moderate enantioselec-
tivity (42% ee) (Table 4, entry 5). Moderate or low
enantioselection was obtained with complex 43 or 44,
respectively (Table 4, entries 6 and 7), while complex
45 prepared from monodentate ligand 38 was not
effective (Table 4, entry 8).
The dimethyl derivative 49 was also synthesized from
the chloride complex 46 following the methodology
described for [Au(PPh3)Me] (Chart 4).28 The reaction of
31 with the presumed dicationic complex resulting from
49 (1.5 mol %) and phosphotungstic acid (2 mol %) gave
32 in quantitative yield, although with lower ee than
that obtained in Table 4 (compare entries 9 and 15). A
cationic complex derived from 47 was isolated and
tentatively assigned as 50 based on the NMR data.
Reaction of 31 in MeOH with this complex gave 32
quantitatively and with similar enantiomeric excess
than that obtained when the cationic complex was
formed in situ (Table 4, compare entries 10 and 16).
(25) A trinuclear complex with two phosphorus from different
ferrocenyl ligands, coordinated to the same gold atom, has been
described: Togni, A.; Pastor, S. D.; Rihs, G. J. Organomet. Chem. 1990,
381, C21-C25.
(26) (a) Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126,
5360-5361. (b) See also: Yanagisawa, A.; Nakashima, H.; Ishiba, A.;
Yayamoto, H. J. Am. Chem. Soc. 1996, 118, 4723-4724.
(27) For an interesting side reaction catalyzed by Ag(I), see: Nevado,
C.; Echavarren, A. M. Chem. Eur. J. 2005, 11, in press.
(28) Synthesis of [Au(PPh3)Me]: Tamaki, A.; Kochi, K. J. Orga-
nomet. Chem. 1973, 61, 441-445.
Complex 47 with the (R)-TolBINAP ligand gave the
best results, being considerably more reactive than 46
(24) For a related equilibrium see ref 20b.

Gold- and Platinum-Catalyzed Cyclization of Enynes
Organometallics, Vol. 24, No. 6, 2005 1299
Table 5. Asymmetric Alkoxycyclization of Enynesa
a Reactions were carried out with 1.6 mol % 47 and 2 mol % of AgSF6.
Although the asymmetric induction obtained in the
methoxycyclization of 31 with cationic Au(I) complexes
was not high, the reaction proceeds at room tempera-
ture, in contrast with that found in the asymmetric
version catalyzed by Pt(II), which requires heating at
60-80 °C.7 We therefore decided to test the performance
of the best complex, 47, in the alkoxycyclization of
enynes with different substitution patterns. Thus, enyne
15 gave the methoxycyclization product 17 at 60 °C in
excellent yield and moderate enantioselectivity (Table
5, entry 1). Reaction of 15 with allyl alcohol at room
temperature provided 51 in 36% ee (Table 5, entry 2).
Interestingly, enyne 52, with a phenyl-substituted
alkyne, gives 53 in moderate yield but with an excellent
94% ee (Table 5, entry 3), which exceeded the best result
obtained in the Pt(II)-catalyzed hydroxycyclization (85%
ee) or methoxycyclization (78% ee) reported by Michelet,
Geneˆt, and Gladiali.7 This high enantioselectivity might
be a consequence of the more crowded nature of the
corresponding cyclopropyl Au(I)-carbene intermediate
resulting form the phenyl-substituted alkyne. On the
other hand, enyne 7 gave almost racemic 8 (Table 5,
entry 4). Enyne 54 reacts by a 6-endo-trig pathway to
afford 55 in only 30% ee (Table 5, entry 4).
of the methyl ethers was attempted using BBr3.30
However, decomposition of the starting material was
always observed. As an alternative, Pd-catalyzed deal-
lylation of 51 (36% ee) provided alcohol 56, which
reacted with (R)-(-)-MTPACl in pyridine for 2 h at room
temperature to give a 2.1:1 mixture (36% de) of two
MTPA esters. Analysis of their 1H and 13C NMR spectra
led to the assignment of the absolute configuration for
the major alcohol as shown.31
Conclusions
Our results support the proposal for two different
mechanisms for the Alder-ene-type cycloisomerization
and the alkoxycyclization of enynes as shown in Scheme
1. Thus, the Alder-ene-type cycloisomerization of enynes
catalyzed by Pt(II) is inhibited by phosphine ligands L,
probably due to displacement of the weaker alkene
ligand by the phosphine in the initial Pt(II)-enyne
complex, leading to Pt(alkyne)(L)Cl2 complexes of type
57 (or the corresponding cis isomers). Similarly, the
methoxycyclization also takes place selectively in the
presence of bidentate phosphines, although in this case
the reaction, which presumably proceeds through com-
Determination of the Configuration. For the
determination of the absolute configuration of the
carbocycles by derivatization of the corresponding al-
cohols via the Mosher esters,29 cleavage the Me-O bond
(29) (a) Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969,
34, 2543-2549. (b) Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973,
95, 512-519. (c) For application of this method see: Ohtani, I.; Kusumi,
T.; Kashman, Y.; Kakisawa, H. J. Am. Chem. Soc. 1991, 113, 4092-
4096. (d) Seco, J. M.; Quin˜oa´, E.; Riguera, R. Chem. Rev. 2004, 104,
17-117.
(30) Grieco, P. A.; Nishizawa, M.; Oguri, T.; Burke, S. D.; Marinovic,
N. J. Am. Chem. Soc. 1977, 99, 5773-5780.
(31) (a) Yamaguchi, S. In Asymmetric Synthesis; Morrison, J. D.,
Ed.; Academic Press: New York, 1983; Chapter 7. (b) Details for the
configuration assignment are given in the Supporting Information.

1300 Organometallics, Vol. 24, No. 6, 2005
Mun˜oz et al.
plexes of type 58, are slower that those via 57. With
bidentate pyridine-oxazoline (13) and py-box (14), the
reaction only proceeds satisfactorily in the presence of
AgOTf, which suggests that with N-N ligands cationic
complexes 58 are the productive intermediates in the
alkoxycyclization.
asymmetric inductions obtained are not high, the reac-
tions proceed at room temperature, in contrast with that
found in the reactions catalyzed by Pt(II), which require
heating at 60-80 °C. Enyne 52, with a less reactive
phenyl-substituted alkyne, leads to a good level of
enantioselection. Further work to establish the nature
of the active catalytic species formed from 47 is under-
way as a lead to develop more active and enantioselec-
tive Au(I) catalysts.
Acknowledgment. We are grateful to the MCyT
(Project BQU2001-0193-C02-01 to A.M.E. and BQU2003-
0508 to J.C.C.) and the ICIQ Foundation for support of
this research. We acknowledge the MEC for a Ramo´n y
Cajal contract to J.A. and a predoctoral fellowship to
M.P.M. We also thank Johnson Matthey PLC for a
generous loan of PtCl2 and Cristina Nevado (UAM) for
independently checking the experiments described in ref
14.
Achieving high levels of enantioselection in the alkoxy-
cyclization appears to be rather challenging, as these
reactions probably proceed by means of intermediates
such as 57-59, where the attacking alkene is far from
the chiral L ligand. With regard to the Pt(II)-catalyzed
reactions, the best results were obtained with Tol-
BINAP as ligand. In this, and related cases, the addition
of Ag(I) salt was not required to form catalytically active
Pt(II) complexes. Among the Au(I) complexes studied,
[Tol-BINAP(AuCl)2] (47) gives the best results in the
presence of a Ag(I) salt. Although, in general, the
Supporting Information Available: Experimental de-
tails and characterization data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OM0491645