Nitrogen acyclic gold(I) carbenes: Excellent and easily accessible catalysts in reactions of 1,6-enynes

Article abstract of DOI:10.1021/om901026m

Complexes [AuCl{C(NHR)(NHR′)}] and [AuCl{C(NHR)(NEt₂)}] (R = ^tBu, p-Tol, Xylyl, p-C₆H₄COOH, p-C ₆H₄COOEt, R′ = Me, ⁿBu, ⁱPr, ⁿheptyl, p-Tol) have been prepared by reaction of the corresponding isocyanogold complexes [AuCl(CNR)] with either primary amines or diethylamide. All the prepared carbenes are reactive and highly selective catalysts for skeletal rearrangement, methoxycyclization of 1,6-enynes, and other mechanistically related gold-catalyzed transformations. Overall, these easily accessible nitrogen acyclic carbene (NAC) gold complexes were not second to NHC complexes and were advantageous to obtain different products.

Full text of DOI:10.1021/om901026m

Organometallics 2010, 29, 951–956 951
DOI: 10.1021/om901026m
Nitrogen Acyclic Gold(I) Carbenes: Excellent and Easily Accessible
Catalysts in Reactions of 1,6-Enynes
†
Camino Bartolome, Zoraida Ramiro, Domingo Garcı
ꢀ †
´
a-Cuadrado,†
§
§
§
,§
ꢀ
ꢀ
Patricia Perez-Galan, Mihai Raducan, Christophe Bour, Antonio M. Echavarren,* and
Pablo Espinet*,†
†
´
ꢀ
IU CINQUIMA/Quımica Inorganica, Facultad de Ciencias, Universidad de Valladolid, E-47071 Valladolid,
Spain and §Institute of Chemical Research of Catalonia (ICIQ), Avenida Paısos Catalans 16,
43007 Tarragona, Spain
¨
Received November 26, 2009
Complexes [AuCl{C(NHR)(NHR0)}] and [AuCl{C(NHR)(NEt2)}] (R=tBu, p-Tol, Xylyl, p-C6H4-
n
i
n
COOH, p-C6H4COOEt, R0 =Me, Bu, Pr, heptyl, p-Tol) have been prepared by reaction of the
corresponding isocyanogold complexes [AuCl(CNR)] with either primary amines or diethylamine. All
the prepared carbenes are reactive and highly selective catalysts for skeletal rearrangement, methoxy-
cyclization of 1,6-enynes, and other mechanistically related gold-catalyzed transformations. Overall,
these easily accessible nitrogen acyclic carbene (NAC) gold complexes were not second to NHC
complexes and were advantageous to obtain different products.
Introduction
The importance of gold complexes with nitrogen hetero-
cyclic carbenes (NHCs) as catalysts in organic synthesis has
been well demonstrated.1-5
*Corresponding authors. E-mail: espinet@qi.uva.es; aechavarren@
iciq.es.
(1) (a) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180–3211. (b)
ꢀ
~
Jimenez-Nꢀunez, E.; Echavarren, A. M. Chem. Commun. 2007, 333–346.
(c) F€urstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410–3449.
ꢀ
~
(d) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395–403. (e) Jimenez-Nꢀunez,
E.; Echavarren, A. M. Chem. Rev. 2008, 108, 3326–3350. (f) Gorin, D. J.;
Sherry, B. D.; Toste, F. D. Chem. Rev. 2008, 108, 3351–3378.
(2) Marion, N.; Nolan, S. P. Chem Soc. Rev. 2008, 37, 1776–1782.
ꢀ
Díez-Gonzalez, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612–
3676.
~
~
(3) (a) Nieto-Oberhuber, C.; Munoz, M. P.; Bunuel, E.; Nevado, C.;
ꢀ
Cardenas, D. J.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43,
Figure 1. NHCs and HBHCs used as catalysts for skeletal
rearrangement of enynes.
ꢀ
~
ꢀ
2402–2406. (b) Nieto-Oberhuber, C.; Lopez, S.; Munoz, M. P.; Cardenas,
D. J.; Bunuel, E.; Nevado, C.; Echavarren, A. M. Angew. Chem., Int. Ed.
2005, 44, 6146–6148. (c) Nieto-Oberhuber, C.; Munoz, M. P.; Lopez, S.;
~
~
ꢀ
ꢀ
~
ꢀ
Jimenez-Nꢀunez, E.; Nevado, C.; Herrero-Gomez, E.; Raducan, M.;
Echavarren, A. M. Chem.;Eur. J. 2006, 12, 1677–1693. (d) Nieto-
Many heterocyclic gold carbenes (Figure 1) have been
found to be good precatalysts for reactions of enynes.2,6-9
In these reactions, the catalyst is formed in solution from
complexes such as 1a-c after chloride abstraction with a
silver salt. Alternatively, cationic complexes stabilized with
benzonitrile ligands 1d-f have also been used as catalysts.10
Similar complexes with NTf2 (Tf=trifluoromethanesulfonyl)
as a labile ligand (2a,b),11,12 are also catalytically active.
ꢀ
ꢀ
~
Oberhuber, C.; Lopez, S.; Jimenez-Nꢀunez, E.; Echavarren, A. M. Chem.;
Eur. J. 2006, 12, 5916–5923.
(4) Powell, A. B.; Bielawski, C. W.; Cowley, A. H. J. Am. Chem. Soc.
2009, 131, 18232–18233.
(5) (a) Lavallo, V.; Frey, G. D.; Kousar, S.; Donnadieu, B.; Bertrand,
G. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 13569–13573. (b) Frey, G. D.;
Dewhurst, R. D.; Kousar, S.; Donnadieu, B.; Bertrand, G. J. Organomet.
Chem. 2008, 693, 1674–1682. (c) Zeng, X.; Soleilhavoup, M.; Bertrand, G.
Org. Lett. 2009, 11, 3166–3199. (d) Aldeco-Perez, E.; Rosenthal, A. J.;
Donnadieu, B.; Parameswaran, P.; Frenking, G.; Bertrand, G. Science 2009,
326, 556–559.
ꢀ
(6) (a) Nieto-Oberhuber, C.; Lopez, S.; Echavarren, A. M. J. Am.
ꢀ
ꢀ
ꢀ
ꢀ~
Chem. Soc. 2005, 127, 6178–6179. (b) Nieto-Oberhuber, C.; Perez-Galan,
(8) Jimenez-Nunez, E.; Molawi, K.; Echavarren, A.M. Chem.
ꢀ
ꢀ
P.; Herrero-Gomez, E.; Lauterbach, T.; Rodríguez, C.; Lopez, S.; Bour, C.;
Commun. 2009, 7327–7329.
ꢀ
ꢀ
Rosellon, A.; Cardenas, D. J.; Echavarren, A. M. J. Am. Chem. Soc. 2008,
130, 269–279.
(9) Matsumoto, Y.; Selim, K. B.; Nakanishi, H.; Yamada, K.;
Yamamoto, Y.; Tomioka, K. Tetrahedron Lett. 2010, 51, 404–406.
(10) Amijs, C. H. M.; Lopez-Carrillo, V.; Raducan, M.; Perez-Galan,
P.; Ferrer, C.; Echavarren, A. M. J. Org. Chem. 2008, 73, 7721–7730.
(11) Li, G.; Zhang, L. Angew. Chem., Int. Ed. 2007, 46, 5156–5159.
(12) Ricard, L.; Gagosz, F. Organometallics 2007, 26, 4704–4707.
ꢀ
ꢀ
ꢀ
ꢀ
(7) (a) de Fremont, P.; Scott, N. M.; Stevens, E. D.; Nolan, S. P.
ꢀ
Organometallics 2005, 24, 2411–2418. (b) de Fremont, P.; Stevens, E. D.;
ꢀ
Fructos, M. R.; Díaz-Requejo, M. M.; Perez, P. J.; Nolan, S. P. Chem.
Commun. 2006, 2045–2047.
r
2010 American Chemical Society
Published on Web 01/15/2010
pubs.acs.org/Organometallics

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Bartolome et al.
952 Organometallics, Vol. 29, No. 4, 2010
Figure 2. Gold(I) complexes with NHC (A), HBHC (B), and
NAC (C and D) ligands.
Figure 3. Possible stereoisomers for the NAC complexes.
Scheme 1. Synthesis of the Gold Carbene Derivatives
The recently reported gold(I) carbene complexes of the
type AuCl{C(NHR)-(NHPy-2)}]13 (3) also turned out to be
good precatalysts in the skeletal rearrangement of enynes.14
These carbenes have been called HBHCs (hydrogen bond
supported heterocyclic carbenes) because the hydrogen-
bonded cyclic structure (Figure 2, B) is maintained in solu-
tion.13,14 These HBHCs also happened to catalyze efficiently
the alkoxycyclization of enynes in alcohols as solvent.14 As
the intramolecular hydrogen bond is split in the presence of
alcohols,14 under the reaction conditions these catalysts
should be acting as nitrogen acyclic carbene (NAC) gold
complexes (Figure 2, C and D). This observation might be
interesting for catalytic purposes because it is easier to
prepare series of gold carbene complexes with a systematic
variation of their steric and electronic properties in NAC
than in NHC or HBHC systems. For this purpose, the rather
general addition of primary or secondary amines to isocya-
nide gold complexes will yield the corresponding carbene
gold complex combining the substituents provided by the
two organic fragments.
Therefore, we decided to focus on the catalytic activity of
nitrogen acyclic gold carbenes in the skeletal rearrangement,
methoxycyclizations of 1,6-enynes, and mechanistically related
processes, to compare the catalytic behavior of these NACs
with the results obtained not only with the well-known NHCs
but also with the recently reported HBHCs. For this purpose,
we have synthesized different series of NAC gold(I) com-
plexes of the type [AuCl{C(NHR)(NHR0)}] (Figure 2, C) or
[AuCl{C(NHR)(NEt2)}] (Figure 2, D) by nucleophilic
addition of primary amines or diethylamine to isocyanogold
complexes.
which was obtained from [AuCl(tht)] (tht = tetrahydro-
thiophene)19 by substitution of tht with CN(p-C6H4-
COOEt),15 as reported for similar gold compounds.20 The
complexes [AuCl{C(NHtBu)(NEt2)}]21 (6a) and [AuCl-
{C(NHp-Tol)(NHp-Tol)}]22 (7d) have already been published.
The gold NAC complexes were identified by elemental and
spectroscopic analysis. The carbene C-N bond shows a con-
siderable multiple character, which produces an important res-
triction to rotation and can give rise to stereoisomers (Figure 3).
Two stereoisomers (E and F) are possible for carbenes
from secondary amines, but F looks clearly disfavored on the
grounds of steric factors. In fact, for the latter, the less
hindered E stereoisomer has been confirmed in the solid
state by X-ray diffraction studies in the complexes [Au-
(CtCp-R-C6H4){C(NHtBu)(NEt2)}] (R = NO2, p-NO2-
C6H4, (E)-CHdCHp-NO2-C6H4),23 [{AuC(NEt2)(NHtBu)}2-
(μ-CtCC6H4CtC)],24 [Au(C-acac){C(NEt2)(NHtBu}],24 and
[Au{C(NEt2)(NHtBu)}{CH2S(O)Me2}]ClO4,24 whereas F has
not been observed. The E stereoisomer was also confirmed in the
solid state by X-ray diffraction studies, and in solution by NOE
experiments, for the gold carbene complexes [AuCl{C(NEt2)-
(NHPy-2)}]13 and [AuR{C(NEt2)(NHPy-4)}] (R = C6F5,
Fmes).25 Stereoisomer E is also the only one observed in this
Results and Discussion
Synthesis and Structural Characterization of Gold Carbene
Complexes. The neutral gold carbene catalysts 4-8 were
synthesized by nucleophilic attack to gold alkyl or aryl
isocyanide complexes [AuCl(CNR)] (R = p-C6H4COOH,15
t
p-C6H4COOEt, Bu,16 p-Tol,17 Xylyl18) with differently hin-
dered primary amines or with a secondary amine such as die-
thylamine (Scheme 1). The starting isocyano-gold complexes had
been previously reported, except [AuCl(CNp-C6H4COOEt)],
ꢀ
(19) Uson, R.; Laguna, A.; Laguna, M. Inorg. Synth. 1989, 26, 85–91.
ꢀ
ꢀ
(20) Bayon, R.; Coco, S.; Espinet, P.; Fernandez-Mayordomo, C.;
Martin-Alvarez, J. M. Inorg. Chem. 1997, 36, 2329–2334.
(21) Vicente, J.; Chicote, M. T.; Abrisqueta, M. D.; Jones, P. G.
Organometallics 1997, 16, 5628–5636.
ꢀ
(13) Bartolome, C.; Carrasco-Rando, M.; Coco, S.; Cordovilla, C.;
Martın-Alvarez, J. M.; Espinet, P. Inorg. Chem. 2008, 47, 1616–1624.
´
(22) Bonati, F.; Minghetti, G. J. Organomet. Chem. 1973, 59, 403–
410.
(23) Vicente, J.; Chicote, M. T.; Abrisqueta, M. D.; Ramırez de
´
ꢀ
ꢀ
ꢀ
(14) Bartolome, C.; Ramiro, Z.; Perez-Galan, P.; Bour, C.; Raducan,
M.; Echavarren, A. M.; Espinet, P. Inorg. Chem. 2008, 47, 11391–11397.
(15) Coco, S.; Espinet, E.; Espinet, P.; Palape, I. Dalton Trans. 2007,
3267–3272.
(16) Elbjeirami, O.; Omary, M. A.; Stender, M.; Balch, A. L. Dalton
Trans. 2004, 3173–3175.
(17) Bonati, F.; Minghetti, G. Gazz. Chim. Ital. 1973, 373–386.
(18) Heathcote, R.; Howell, J. A. S.; Jennings, N.; Cartlidge, D.;
Cobden, L.; Coles, S.; Hursthouse, M. Dalton Trans. 2007, 1309–1315.
Arellano, M. C.; Jones, P. G.; Humphrey, M. G.; Cifuentes, M. P.;
Samoc, M.; Luther-Davies, B. Organometallics 2000, 19, 2968–2974.
ꢀ
ꢀ
(24) Vicente, J.; Chicote, M. T.; Abrisqueta, M. D.; Alvarez-Falcon,
M. M.; Ramırez de Arellano, M. C.; Jones, P. G. Organometallics 2003,
22, 4327–4333.
´
ꢀ
(25) Bartolome, C.; Carrasco-Rando, M.; Coco, S.; Cordovilla, C.;
Espinet, P.; Martın-Alvarez, J. M. Dalton Trans. 2007, 5339–5345.
´

Article
Organometallics, Vol. 29, No. 4, 2010 953
Table 1. Skeletal Rearrangement of Enyne 9a with the Series of
Catalysts 4-8.a
entry
[Au]
product(s) (yield, %)
1
2
3
4
5
6
7
8
4
5
10a (74) þ 11a (6) þ 12a (2)b
10a (51) þ 11a (12)
10a (81) þ 12a (2)b
10a (35) þ 11a (21) þ 12a (1)b
10a (50) þ 11a (15)
10a (85) þ 12a (3)
10a þ 12a (30:1) (88)c
10a (98)
6a
6b
7a
7b
7b
7c
7d
8a
8b
8c
8d
9
10a (61) þ 11a (12)
10
11
12
13
10a (100)
10a (100)
10a (8) þ 11a (17)
10a (5) þ 11a (8)
a Reactions were carried out at room temperature with 2 mol %
catalysts for 5 min. Yields were determined by GC. b Yield determined
by 1H NMR. c Isolated yield.
Figure 4. 1H-1H NOESY spectrum of 8d (NHBu region)
registered at 295 K. The NHBu shows a NOE with the methyl
hydrogen atoms of the 2,6-xylyl group at 2.24 ppm (cross-peak
in the circle), as well as with the hydrogen atoms of the
contiguous methylene of the nBu chain.
Scheme 2. Skeletal Rearrangements Catalyzed by 7b
work in the 1H NMR spectra of all the carbene gold complexes
[AuCl{C(NHR)(NEt2)}] (4, 5, and 6a-8a).
Up to four stereoisomers (G-J) are possible for com-
plexes formed from primary amines. Often, more than one
stereoisomer is observed, and these data are given in the
Experimental Section. Although J is clearly the most dis-
favored for steric reasons, it is not easy to predict which of
the other three stereoisomers should be preferred. The con-
figuration of the major stereoisomer was assigned for all the
complexes on the basis of NOE experiments (slow exchange
was observed during the experiments at room temperature in
some cases, and some NOE experiments were carried out at
243 K). Figure 4 shows the 1H-1H NOESY spectrum of 8d,
in which a NOE is observed between the hydrogen of the
NHBu group and the singlet of the methyl substituents of the
2,6-xylyl. The major stereoisomer for all the neutral com-
plexes having at least one aryl group (R1 = aryl; these are all,
except 6b) is stereoisomer I, having the aryl anti to the gold
atom, regardless of R2; moreover, I is the only stereoisomer
observed for 8c and 8d. For complex 6b (R1 = tBu; R2 = Me)
the major stereoisomer is H, with the bulky tBu group syn to
the gold atom.
Catalytic Reactions. The results obtained for the gold-
catalyzed skeletal rearrangement of 1,6-enyne 9a are sum-
marized in Table 1. All the gold carbenes 4-8 catalyze this
reaction, but the efficiency and selectivity observed change
with the substituents of the carbene. Up to three different
products have been isolated in the skeletal rearrangement
reaction of 9a: the product of exo cyclization, 10a, the
product of the endo cyclization, 12a,26 and the diene 11a
arising from the isomerization of the endo cyclic double bond
of 10a.3a,c Diene 11a has been observed in reactions of 9a
catalyzed by FeCl3 and as a minor product in reactions
catalyzed by different Au(I) complexes.3c Then, in this
respect, the new catalysts used here are more selective and
are advantageous to obtain different products. Catalysts 6a,
7b, 7c, 8a, and 8b give exclusively or almost exclusively the
exo product 10a (Table 1, entries 3, 6-11). Poor yields were
observed using complexes 8c,d, bearing bulkier substituents
(Table 1, entries 12 and 13). Previous results using HBHC-
Au(I) complexes 3a-e as catalysts led also to 10a and 12a
(g30:1 ratio) in 73-89% yield.14 All these results demon-
strate that most NAC-Au(I) complexes are, at least, as
reactive and selective as the previously reported more com-
plex carbene-Au(I) complexes.
Additional experiments were performed with complex 7b
as catalyst using 1,6-enynes 9b,c and 1,7-enyne 9d as
substrates (Scheme 2). Thus, the skeletal rearrangement
of 9b provided the exo product 10b in 79% yield, along with
5% of the product of endo-type cyclization, 12b, whereas
9c led exclusively to exo 12c in higher yield in much shorter
reaction time than that using the HBHC-Au(I) catalyst 3b.
Rearrangement of 1,7-enyne 9d was also fast, with catalyst
7b leading to diene 13 in excellent yield. This result is
comparable to that reported using the cationic catalyst
ꢀ
ꢀ~
~
ꢀ
(26) Cabello, N.; Jimenez-Nunez, E.; Bunuel, E.; Cardenas, D. J.;
Echavarren, A. M. Eur. J. Org. Chem. 2007, 4217–4223.

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Bartolome et al.
954 Organometallics, Vol. 29, No. 4, 2010
Table 2. Methoxycyclization of 1,6-Enyne 9a with the Series of
Catalysts 4-8 and 1a-ca
Scheme 3. Cyclization Reactions Catalyzed by 7b and 8a
entry
[Au]
time (h)
yield, %
1
2
3
4
5
6
7
8
4
5
2
2
2
2
2
2
2
2
2
2
2
2
1.5
5
85
74
83
65
70
83
44
72
99
92
71
85
71
87
34
6a
6b
7a
7b
7c
7d
8a
8b
8c
8d
1a
1b
1c
Scheme 4. Reactions of 1,6-Enyne 9c with Dibenzoylmethane
9
10
11
12
13
14
15
24
a Reactions were carried out at room temperature with 2 mol %
catalyst for 2 h. Yields were determined by 1H NMR.
[Au(PPh3)(NCMe)]SbF6 (2 mol %), which led to 13 in
86% yield after 5 min.27
Reactions of 1,6-enynes in alcohols or water as solvent or
cosolvent led to the cyclization of the enyne with concomi-
tant addition of a molecule of the alcohol (alkoxy- or
hydroxycyclization reaction).3,28 Interestingly, although
these processes are much slower than the skeletal rearrange-
ments, no rearrangement is usually observed in the presence
of alcohols, which suggests that the slower cyclization is due
to the immediate in situ formation of complexes [AuL-
(ROH)]X, of lower catalytic activity, in which a molecule
of alcohol or water strongly binds to the gold(I) center. These
reactions are expected to show a higher dependence on
the electronic and steric nature of the L ligands. Therefore,
we studied the methoxycyclization of 1,6-enyne 9a in
pure methanol using the new complexes 4-8 as catalysts
(Table 2). We also compared their performance with that of
known catalysts 1a-c.
The cleanest reactions and better yields were obtained
using catalysts 8a and 8b (Table 2, entries 9 and 10). The best
NHC complexes 1a-c do not outperform these results,6a and
the HBHC-Au(I) complexes 3a-e led to poorer yields
(20-79%), even using 5 mol % catalyst.14
We also carried out the cyclization of dienyne 9d using 7b
or 8a and AgSbF6 (Scheme 3). The cyclization led to the
expected tetracyclic compound 143a,29 in 83% and 57%
yield, respectively. Under these conditions, less that 1%
of the skeletal rearrangement product of 9d was detected
in the crude mixture. Skeletal rearrangement of 9d was
formed in significant amounts with some Au(I)- and Pt(II)-
phosphine complexes.29 Similarly, the [4þ2] cycloaddition of 9e
proceeded smoothly at room temperature with 7b or 8a as
precatalysts to give 15 in very good yields, comparable to those
obtained under similar conditions using phosphine-Au(I) com-
plexes.6
Finally, we probed the site selectivity of the gold(I) com-
plexes bearing NAC ligands in the reaction of 1,6-enyne 9c
with dibenzoylmethane as the nucleophile to give adducts
16a and/or 16b (Scheme 4). We have recently found that the
site of nucleophilic attack on intermediate 17 depends on the
nature of the L ligand10 and reflects the dual character,
carbene-like or carbocationic, of the intermediates involved
in the cyclizations of enynes.30,31 Thus, a highly electrophilic
complex bearing a bulky phosphite ligand gave preferentially
16b (up to 95:5 ratio) as a result of the attack at the cationic
center of 17b, whereas exclusive attack at the carbene carbon
yielding 16a occurred using the complex 1b with the IMes
ligand.10 A complex with a bulky dialkylbiarylphosphine
ligand, which is of intermediate electrophilicity, gave a 2:1
mixture of 16a and 16b.10 Therefore, we decided to probe the
site selectivity of gold(I) catalysts bearing NAC ligands in
(27) Cabello, N.; Rodrı
1753–1758.
(28) (a) Nevado, C.; Charruault, L.; Michelet, V.; Nieto-Oberhuber,
´
guez, C.; Echavarren, A. M. Synlett 2007,
~
ꢀ
^
C.; Munoz, M. P.; Mendez, M.; Rager, M.-N.; Genet, J.-P.; Echavarren,
A. M. Eur. J. Org. Chem. 2003, 706–713. (b) Charruault, L.; Michelet, V.;
^
Taras, R.; Gladiali, S.; Genet, J. P. Chem. Commun. 2004, 850–851. (c)
^
Genin, E.; Leseurre, L.; Toullec, P. Y.; Genet, J. P.; Michelet, V. Synlett 2007,
1780–1784. (d) Chao, C.-M.; Toullec, P. Y.; Michelet, V. Tetrahedron Lett.
^
2009, 50, 3719–3722. (e) Chao, C.-M.; Genin, E.; Toullec, P. Y.; Genet, J.-P.;
ꢀ
ꢀ~
ꢀ
Michelet, V. J. Organomet. Chem. 2009, 694, 538–545.
(30) Jimenez-Nunez, E.; Claverie, C. K.; Bour, C.; Cardenas, D. J.;
Echavarren, A. M. Angew. Chem., Int. Ed. 2008, 47, 7892–7895.
(31) Benitez, D.; Shapiro, N. D.; Tkatchouk, E.; Wang, Y.; Goddard,
W. A.III; Toste, F. D. Nat. Chem. 2009, 1, 482–486.
ꢀ
~
ꢀ
ꢀ~
(29) Nieto-Oberhuber, C.; Lopez, S.; Munoz, M. P.; Jimenez-Nunez,
~
ꢀ
E.; Bunuel, E.; Cardenas, D. J.; Echavarren, A. M. Chem.;Eur. J. 2006,
12, 1694–1702.

Article
Organometallics, Vol. 29, No. 4, 2010 955
this reaction. In the event, using complexes 7b and 8a, adduct
16a was obtained with high regioselectivity. The results
obtained with 8a are better than those with 1b and as good
as those obtained with the cationic complex obtained from
1b, [Au(IMes)(2,4,6-(MeO)3C6H2CN)]SbF6, which were the
best so far.10 These results reflect the highly electron-donating
character of the NAC, which leads to cyclization of enynes
through intermediates that show a significant gold-carbene
character.
ArH), 7.69 (d, J = 8.6 Hz, 2H, ArH), 4.09 (q, J = 7.1 Hz, 2H,
CH2), 3.75 (q, J = 7.2 Hz, 2H, CH2), 1.37 (t, J = 7.1 Hz, 3H,
CH3), 1.33 (t, J = 7.2 Hz, 3H, CH3). Anal. Calcd for
C12H16AuClN2O2: C, 31.84; H, 3.56; N, 6.19. Found: C,
32.01; H, 3.46; N, 6.01.
[AuCl{C(NH(p-C6H4COOEt)(NEt2)}] (5). HNEt2 (1.32
mmol, 136 μL) was added to a solution of [AuCl(CNp-
C6H4COOEt)] (0.540 g, 1.32 mmol) in CH2Cl2 (30 mL). Workup
for 4 yielded 0.472 g (98%). 1H NMR (300 MHz, acetone-d6): δ
8.00 (AA0 part of a AA0BB0 system, 2H, ArH), 7.85 (br s, 1H,
NH), 7.61 (BB0 part of a AA0BB0 system, 2H, ArH), 4.36 (q, J =
7.0 Hz, 2H, CH2), 3.99 (q, J = 7.0 Hz, 2H, CH2), 3.51 (q, J = 7.1
Hz, 2H, CH2), 1.40 (t, J = 7.0 Hz, 3H, CH3), 1.33-1.30 (m, 6H,
CH3). Anal. Calcd for C14H20AuClN2O2: C, 34.98; H, 4.19; N,
5.83. Found: C, 35.32; H, 4.25; N, 6.01.
Conclusions
The modern development of fascinating isolable NHC
ligands and the catalytic properties of their complexes have
somehow obscured so far the existence of the old, known
nitrogen acyclic carbene complexes (NACs). The latter can be
easily obtained from widespread isocyanide complexes of
transition metals and primary or secondary amines. An
advantage of this classic methodology over the NHCs is that,
at least for late transition metals, it provides an easy way to
obtain organized series of catalysts from a single isocyanide
complex precursor, by varying the amine. Moreover, these
catalysts will contain carbene ligands that are not otherwise
accessible because they do not exist as free molecules.
We have shown here that these easily accessible NACs
complexes are interesting catalysts that have been dis-
regarded in favor of the more fashionable NHC complexes
but, at least for some purposes, perform as efficiently as the
latter. Actually, complexes [AuCl{C(NHR)(NHR0)}] and
[AuCl{C(NHR)(NEt2)}] with acyclic carbene ligands (NAC
ligands) show a reactivity as catalysts in reactions of 1,6- and
1,7-enynes comparable to or higher than that displayed by
gold(I) complexes with N-heterocyclic ligands. In methanol,
these new NAC gold complexes are more reactive than
those with hydrogen bond supported heterocyclic carbenes
(HBHC). The complexes [AuCl{C(NHMe)(NHpTol)}] (7b)
and [AuCl{C(NEt2)(NHXylyl)}] (8a) have proved particularly
efficient.
[AuCl{C(NHtBu)(NHMe)}] (6b). MeNH2 (2.50 mmol, 110
μL, 40% solution in water) was added to a solution of
[AuCl(CNtBu)] (0.200 g, 0.633 mmol) in CH2Cl2 (30 mL).
Workup for 4 yielded 0.140 g (64%). 1H NMR (300 MHz,
CDCl3): δ 6.78 (br s, 1H, NH major), 6.68 (br s, 1H, NH minor),
6.30 (br s, 1H, NH minor), 5.96 (br, 1H, NHMe, major), 3.24 (d,
J = 5.2 Hz, 3H, CH3 minor), 2.78 (d, J = 5.2 Hz, 3H, CH3), 1.61
(s, 9H, C(CH3)3), 1.57 (s, 9H, C(CH3)3 minor). Stereoisomeric
ratio: 4:1. Anal. Calcd for C6H14AuClN2: C, 20.79; H, 4.07; N,
8.08. Found: C, 21.20; H, 3.80; N, 7.92.
[AuCl{C(NEt2)(NHTol-p)}](7a). Et2NH (0.60 mmol, 62 μL)
was added to a solution of [AuCl(CNTol-p)] (0.175 g, 0.50
mmol) in CH2Cl2 (30 mL). Workup as for 4 yielded 0.189 g
(89%). 1H NMR (300 MHz, CDCl3): δ 7.47 (br, 1H,
NHC6H4CH3), 7.34 (d, J = 8.3 Hz, 2H, NHC6H4CH3), 7.14
(d, J = 7.9 Hz, 2H, NHC6H4CH3), 4.01 (q, J = 7.2 Hz, 2H,
N(CH2CH3)2), 3.47 (q, J = 7.2 Hz, 2H, N(CH2CH3)2), 2.32 (t,
J = 7.2 Hz, 6H, N(CH2CH3)2) Anal. Calcd for C12H18AuClN2:
C, 34.10; H, 4.29; N, 6.63. Found: C, 33.81; H, 4.03; N, 6.25.
[AuCl{C(NHMe)(NHTol-p)}] (7b). MeNH2 (0.75 mmol, 65
μL, 40% solution in water) was added to a solution of
[AuCl(CNTol-p)] (0.193 g, 0.50 mmol) in CH2Cl2 (30 mL).
1
Workup as for 4 yielded 0.068 g (66%). H NMR (300 MHz,
CDCl3): δ 8.19 (br s, 1H, NH, major), 7.69 (br s, 1H, NH,
minor), 7.44-6.89 (m, 3H, arom, major, 3H, arom, minor, 1H,
NH, minor), 6.33 (br, 1H, NHMe, major), 3.24 (d, J = 4.6 Hz,
3H, CH3, major), 2.97 (d, J = 5.2 Hz, 3H, CH3, minor), 2.37 (s,
3H, Ar-CH3, major), 2.31 (s, 3H, Ar-CH3, minor). Stereo-
isomeric ratio: 2:1. Anal. Calcd for C9H12AuClN2: C, 28.40;
H, 3.18; N, 7.36; Found: C, 28.94; H, 2.80; N, 7.32.
It looks reasonable that this type of metal complexes of
NAC ligands should be incorporated in the armory of metal-
catalyzed reactions.
[AuCl{C(NHC7H15)(NHTol-p)}] (7c). n-Heptylamine (0.75
mmol, 112 μL) was added to a solution of [AuCl(CNTol-p)]
(0.175 g, 0.5 mmol) in CH2Cl2 (40 mL). Workup as for 4 yielded
0.168 g (72%). 1H NMR (300 MHz, CDCl3): δ 8.64 (br, 1H, NH,
minor 1), 8.00 (br, 1H, NHTol-p), 7.67 (br, 1H, NH, minor 2),
7.44 (d, J = 5.7 Hz, 2H, NHC6H4CH3, minor 1), 7.40 (d, J = 6.0
Hz, 2H, NHC6H4CH3, minor 2), 7.27 (d, J = 6.2 Hz, 2H,
NHC6H4CH3), 7.15 (d, J = 6.0 Hz, 2H, NHC6H4CH3, minor
2), 7.11 (d, J = 5.7 Hz, 2H, NHC6H4CH3, minor 1), 7.08 (d, J =
6.2 Hz, 2H, NHC6H4CH3), 6.98 (br, 1H, NH, minor 1 þ minor
2), 6,37 (br, 1H, NHC7H15), 3.73 (br, 2H, NHCH2C6H13,
minor), 3.66 (q, J = 6.3 Hz, 2H, NHCH2C6H13), 3.22 (q, J =
6.2 Hz, 2H, NHCH2C6H13, minor), 2.38 (s, 3H, NHC6H4CH3),
2.30 (s, 3H, NHC6H4CH3, minor), 2.25 (s, 3H, NHC6H4CH3,
minor), 1.58 (m, 2H, NHCH2C6H13), 1.27 (m, 8H, NH-
CH2C6H13), 0.87 (t, J = 5.2 Hz, 3H, NHCH2C6H13). Stereo-
isomeric ratio: 10:1:2. Anal. Calcd for C15H24AuClN2: C, 38.76;
H, 5.20; N, 6.03. Found: C, 39.10; H, 4.80; N, 6.19.
Experimental Section
General Conditions. All reactions were carried out under dry
N2. The solvents were purified according to standard proce-
dures.32 Enynes 9a-d were prepared according to literature
procedures.3,26 The other reagents are commercially available.
Infrared spectra were recorded in Perkin-Elmer 883 or 1720X
equipment. NMR spectra were recorded with Bruker AC300,
ARX 300, and Avance 400 Ultrashield instruments. H NMR
spectra are referred to TMS. Elemental analyses were performed
with a Perkin-Elmer 2400B microanalyzer.
Synthesis of Carbenes. [AuCl{C(NH(p-C6H4COOH)-
(NEt2)}] (4). HNEt2 (0.32 mmol, 33 μL) was added to a solution
of [AuCl(CNp-C6H4COOH)] (120 g, 0.32 mmol) in THF (30
mL). After 15 min of stirring at room temperature, the solution
did not show ν(CN) IR absorption. The volatiles were removed,
and the white residue was washed with n-hexane to remove the
excess of amine and crystallized from CH2Cl2/n-hexane. The
white solid obtained was washed with n-hexane (3 ꢀ 5 mL) and
vacuum-dried, yielding 0.134 g (92%). 1H NMR (300 MHz,
acetone-d6): δ 9.35 (br s, 1H, NH), 8.03 (d, J = 8.8 Hz, 2H,
1
[AuCl{C(NHTol-p)(NHTol-p)}] (7d). 1H NMR (300 MHz,
CDCl3): δ 9.29 (br, 2H, NHTol-p, minor), 8.73 (br, 1H, NHTol-
p, major), 7.99 (8.73 (br, 1H, NHTol-p, major), 7.50 (d, J = 8.0
Hz 4H, NHC6H4CH3, minor), 7.35 (d, J = 8.2 Hz, 2H,
NHC6H4CH3), 7.31 (d, J = 8.2 Hz, 2H, NHC6H4CH3), 7.20
(d, J = 7.9 Hz, 2H, NHC6H4CH3), 7.11 (m, 2H, NHC6H4CH3,
major þ 4H, NHC6H4CH3, minor), 2.40 (s, 3H, NHC6H4CH3,
(32) Perrin, D. D.; Armarego, W. F. F. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon Press: Oxford, U.K., 1988.

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Bartolome et al.
956 Organometallics, Vol. 29, No. 4, 2010
major), 2.30 (s, 3H, NHC6H4CH3, major), 2.27 (s, 6H,
NHC6H4CH3, minor). Stereoisomeric ratio: 10:1.
Hz, 2H, CH2), 2.24 (s, 6H, Ar-CH3), 1.52 (q, J = 6.8 Hz, 2H,
CH2), 1.33-1.25 (m, 4H, CH2), 0.90 (t, J = 7.2 Hz, 3H, CH3).
Anal. Calcd for C13H20AuClN2: C, 35.75; H, 4.62; N, 6.41.
Found: C, 35.59; H, 4.14; N, 6.16.
Catalytic Procedures. All the reactions were carried out under
N2 in solvents dried using a solvent purification system. Thin-
layer chromatography was carried out using TLC-aluminum
sheets with 0.2 mm of silica gel (Merck GF234). Chromatogra-
phy purifications were carried out using flash grade silica gel
(SDS S-2 Chromatogel 60 ACC, 40-60 μm). NMR spectra
were recorded at 25 °C on a Bruker Avance 400 Ultrashield.
Compounds 9a-14 tested in catalysis have been reported
before.3c
General Procedure for Skeletal Rearrangement of 1,6-Enynes.
Procedure with Catalysts 4-8. The enyne (0.15-0.2 mmol) and
the gold(I) complex (2-5 mol %) were dissolved with stirring in
a solution of AgSbF6 in CH2Cl2 (2 mM, 2 mL; 2-5 mol %
AgSbF6). After the indicated time (monitored by TLC), the
reaction was quenched with a solution of Et3N in hexanes
(0.1 M, 2 mL) and filtered through a pad of silica gel that was
eluted with Et2O. Isolated products were purified by flash
column chromatography (EtOAc/hexane).
General Procedure for Methoxycyclizations of 1,6-Enynes.
Procedure with Catalysts 4-8. The enyne (0.15-0.2 mmol)
and the gold(I) complex (2 mol %) were dissolved with stirring
in a solution of AgSbF6 (2 mol %) in MeOH (2 mM, 2 mL).
After 5 min, the reaction was quenched with a solution of Et3N
in hexanes (0.1 M, 2 mL) and filtered through a pad of silica gel
that was eluted with Et2O. Isolated products were purified by
flash column chromatography (EtOAc/hexane).
[AuCl{C(NHXylyl)(NEt2)}] (8a). HNEt2 (1.098 mmol, 161
μL) was added to a solution of [AuCl(CNXylyl)] (0.200 g, 0.549
mmol) in CH2Cl2 (30 mL). Workup as for 4 yielded 0.190 g
(79%). 1H NMR (300 MHz, acetone-d6): δ 8.47 (br s, 1 H, NH),
7.21-7.05 (m, 3H ArH),), 4.02 (q, J = 7.2 Hz, 2H, CH2), 3.50 (q,
J = 7.3 Hz, 2H, CH2), 2.24 (s, 6H, Ar-CH3), 1.36 (t, J = 7.3 Hz,
3H, CH3), 1.35 (t, J = 7.2 Hz, 3H, CH3). Anal. Calcd for
C13H20AuClN2: C, 35.75; H, 4.62; N, 6.41. Found: C, 35.74; H,
4.22; N, 6.53.
[AuCl{C(NHXylyl)(NHMe)}] (8b). MeNH2 (1.098 mmol, 95
μL, 40% solution in water) was added to a solution of
[AuCl(CNXylyl)] (0.200 g, 0.549 mmol) in CH2Cl2 (30 mL).
1
Workup as for 4 yielded 0.163 g (75%). H NMR (300 MHz,
CDCl3): δ 8.27 (br s, 1H, NH, minor 1), 7.67 (br s, 1H, NH,
major), 7.28-7.05 (m, 3H, major, 6H, minor 1, 6H, minor 2, 1H,
NH, minor 2), 5.83 (br, 1H, NHMe, major), 5.70 (br, 1H,
NHMe, minor 1), 5.08 (br, 1H, NHMe, minor 2), 3.24 (d, J =
4.7 Hz, 3H, CH3, major), 3.13 (d, J = 4.7 Hz, 3H, CH3, minor 1),
3.06 (d, J = 4.7 Hz, 3H, CH3, minor 2), 2.34 (s, 6H, Ar-CH3,
minor 1), 2.28 (s, 6H, Ar-CH3, minor 2), 2.24 (s, 6H, Ar-CH3,
major). Stereoisomeric ratio: 5:1:1. Anal. Calcd for
C10H14AuClN2: C, 30.43; H, 3.58; N, 7.10. Found: C, 30.93;
H, 3.48; N, 6.91.
[AuCl{C(NHXylyl)(NHiPr)}] (8c). iPrNH2 (0.825 mmol,
71 μL) was added to a solution of [AuCl(CNXylyl)] (0.200 g,
0.55 mmol) in CH2Cl2 (30 mL). Workup as for 4 yielded 0.197 g
(85%). 1H NMR (300 MHz, CDCl3): δ 7.78 (br s, 1H NH), 7.26
(t, J = 6.2 Hz, 1H, ArH), 7.17 (d, J = 6.7 Hz, 2H, ArH), 5.57 (br
d, J = 8.9 Hz, 1H, NHiPr), 4.49 (m, 1H, CH), 2.23 (s, 6H, Ar-
CH3), 1.17 (d, J = 6.6 Hz, 6H, CH3). Anal. Calcd for
C12H18AuClN2: C, 34.10; H, 4.29; N, 6.63. Found: C, 34.52;
H, 4.05; N, 6.87.
[AuCl{C(NHXylyl)(NHBu)}] (8d). BuNH2 (0.824 mmol, 82
μL) was added to a solution of [AuCl(CNXylyl)] (0.150 g, 0.412
mmol) in CH2Cl2 (30 mL). Workup as for 4 yielded 0.091 g
(51%). 1H NMR (300 MHz, CDCl3): δ 7.73 (br s, 1H NHXylyl),
7.27-7.16 (m, 3H, ArH), 5.86 (br, 1H, NHBu), 3.64 (q, J = 7.1
Acknowledgment. This work was supported by the
MICINN (CTQ2007-67411/BQU, CTQ2007-60745/BQU,
and Consolider Ingenio 2010 (Grant CSD2006-0003), pre-
doctoral fellowships to Z.R., P.P.-G., and M.R., postdoc-
toral contract to C.B., and Juan de la Cierva Contract to
D.G.-C.), the AGAUR (2009 SGR 47), the Junta de
ꢀ
Castilla y Leon (GR169), and the ICIQ Foundation.