Gold catalysis: Isolation of vinylgold complexes derived from alkynes

Article abstract of DOI:10.1002/anie.200903134

Gold plated rings: N-Propargylcarboxamides (1) when reacted with a gold complex containing the IPr N-heterocyclic carbene ligand, delivers the first isolable vinylgold intermediates obtained from alkynes. [see Scheme; IPr = 1, 3-bis(2,6diisopropylphenyl)i

Full text of DOI:10.1002/anie.200903134

Angewandte
Chemie
DOI: 10.1002/anie.200903134
Gold Catlysis
Gold Catalysis: Isolation of Vinylgold Complexes Derived from
Alkynes**
A. Stephen K. Hashmi,* Andreas M. Schuster, and Frank Rominger
Table 1: Reaction of 1a with gold complexes at room temperature.
Gold-catalyzed organic transformations still represent one of
the fast growing areas of organic chemistry.[1] The most
important reactivity pattern is the addition of nucleophiles to
Entry Complex
Base/Solvent
Product Yield [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
[Ph3PAu][NTf2][a] –/CH2Cl2
3a
–
3a
–
–
–
–
–
–
–
–
–
3a
3a
4a
38[c]
–
À
C C multiple bonds (mostly alkynes rather than allenes or
[a]
AuCl3
–/CH3CN
[Ph3PAu][NTf2][b] –/CH2Cl2
20[d]
alkenes). In 2000, we demonstrated that carbonyl oxygen
atoms of allenyl ketones can serve as nucleophiles, and form
furans by a 5-endo-trig cyclization.[2] In 2004, we reported the
use of N-propargyl carboxamides 1, having terminal alkynyl
groups (Scheme 1, R2 = H), for 5-exo-dig cyclizations,[3] and in
2007 we reported the 5-endo-dig cyclization of N-alkynyl
carbamates.[4]
[Ph3PAu][NTf2][b] 2,6-tBu2C6H3N/THF
[Ph3PAu][OTs][b] 2,6-tBu2C6H3N/THF
[Ph3PAu][OTs][b] 2,6-tBu2C6H3N/THF
[Ph3PAu][OTs][b] 2,6-tBu2C6H3N/benzene
[Ph3PAu][OTs][b] 2,6-tBu2C6H3N/toluene
[Ph3PAu][OTs][b] 2,6-tBu2C6H3N/CH3CN
[Ph3PAu][OTs][b] 2,6-tBu2C6H3N/CH2Cl2
[Ph3PAu][OTs][b] iPr2NEt/THF
–
–
–
–
–
–
–
–
[e]
[e]
[e]
[e]
[e]
[e]
[e]
[e]
[Ph3PAu][OTs][b] Et3N/THF
–
[e]
[IPrAu][OTs][b]
[IPrAu][OTs][b]
[IPrAu][OTs][b]
Et3N/benzene
Et3N/toluene
Et3N/THF
95
94
63
[a] 5 mol%. [b] 1 equiv. [c] Reaction time of 6 days; side product
detected. [d] Additionally, 70% of the new compound was detected by
in situ NMR methods. [e] Unselective reaction, the reaction mixture
turns black. Tf=trifluoromethanesulfonyl, Ts=4-toluenesulfonyl, THF=
tetrahydrofuran.
Scheme 1. Gold-catalyzed cycloisomerization of propargylamides 1
These first two papers have initiated the development of
an entire family of gold-catalyzed cyclizations involving
carbonyl groups as nucleophiles to deliver different types of
heterocycles.[5–7] Herein we report new findings on the
cyclization of N-propargyl carboxamides having internal
alkynyl groups.
heterocycle 3a (R1 = Ph, R2 = Me) in the case of gold(I). In
the 1H NMR spectrum of 2a (R1 = Ph) only an allylic coupling
constant of about J = 2.5 Hz between the vinylic and the
allylic protons could be observed, whereas in the new
compounds 3a a vicinal coupling constant of about J =
4.5 Hz between the vinylic and the allylic protons was
detected.
Different N-propargyl carboxamides 1 having internal,
À
alkyl-substituted C C triple bonds were prepared and reacted
A closer look at the NMR spectra taken in situ revealed
that for gold(I) (Table 1, entry 1) a cycloisomerization
product as well as small amounts of other compounds could
be detected. Increasing the amount of the catalyst up to
stoichiometric amounts led to increasing amounts of these
new compounds shown in the NMR spectra (stoichiometric in
Table 1, entry 3), and we suspected that a vinylgold species
could be the dominant species.[8] To obtain these as stable
compounds, we varied both the solvent [THF (Table 1,
entries 4–6, 11, 12, and 15), benzene (Table 1, entries 7 and
13), toluene (Table 1, entries 8 and 14), acetonitrile (Table 1,
entry 9), and dichloromethane (Table 1, entry 10)] and the
base, which accepts a proton and thus slows down the
protodemetallation step to conserve the organogold species
[(2,6-di(tert-butyl)pyridine (Table 1, entries 4, 5, 7–10), 2,6-
diphenylpyridine (Table 1, entry 6), Hꢀnigsꢁs base (Table 1,
entry 11), and triethylamine (Table 1, entries 12–15)]; see
Scheme 2. Efforts with gold–phosphane complexes failed
(Table 1, entries 4–12), because these experiments showed
the species in the in situ NMR reaction, but they were not
selective and it was not possible to isolate them. Finally, with
with gold catalysts. Unlike the derivatives of type 1 having
terminal alkynes, which readily lead to the alkylidenoxazo-
lines 2 or the isomeric aromatic oxazoles 2’,[3] different gold(I)
and gold(III) catalysts did not efficiently convert these
internal alkynes as exemplified for 1a (R1 = Ph, R2 = Me)
(Table 1, entries 1 and 2); very long reaction times were
observed and the products seemed to be the six-membered
[*] Prof. Dr. A. S. K. Hashmi, Dipl.-Chem. A. M. Schuster,
Dr. F. Rominger
Organisch-Chemisches Institut
Ruprecht-Karls-Universitꢀt Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
Fax: (+49)6221-54-4205
E-mail: hashmi@hashmi.de
Homepage: http://www.hashmi.de
[**] The authors thank the Deutsche Forschungsgemeinshaft (SFB 623)
for support and Umicore AG & Co. KG for the generous donation of
gold salts.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200903134.
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Communications
structure bound to the gold(I) center seems
structurally undisturbed, with 1.434(7) ꢂ for the
O15–C16 bond and 1.299(8) ꢂ for the C11–C16
double bond, the latter being slightly shorter
[11]
=
than a normal C C double bond.
Scheme 2. In the presence of base no protodeauration is observed.
One significant difference between this and
previous work is the formation of the six-
the N-heterocyclic carbene (NHC) ligand IPr [1,3-bis(2,6-
diisopropylphenyl)imidazol-2-ylidene; used in Table 1,
entries 13–15] the vinylgold compound 4a was isolated in
pure form (Table 1, entry 15) after chromatography on basic
alumina, and was fully characterized by spectroscopic meth-
ods.
Table 2 shows the substrates 1a–d used under these
reaction conditions. The amides derived from benzoic acid
(Table 2, entry 1), the bulky adamantylcarboxylic acid
(Table 2, entries 2 and 3), and the ortho-substituted furancar-
boxylic acid derivative (Table 2, entry 4) all gave the corre-
sponding vinylgold species 4a–d in good yields. The reduced
acidity of the iminium proton of intermediate A might
contribute to the exceptional fact that the intermediates 4 are
isolable.
membered 1,3-oxazine heterocycle by the 6-endo-dig cycliza-
tion. Upon screening the literature on related cyclizations, we
found some examples for the gold-catalyzed formation of six-
membered rings by 6-exo-dig cyclization,[6] but only two
examples of substrates undergoing a 6-endo-dig cyclization.
These two substrates had internal alkynes with an alkyl group
on the alkyne.[7] In two experiments we compared the reaction
of 1a, which delivered 63% of 4a (Table 2, entry 1), with the
reaction of the corresponding terminal alkyne 1e, which
under the same reaction conditions delivered 99% of the
IPrAu–vinyl complex 5 (Scheme 3). Experiments using cata-
Table 2: In situ trapping of the vinylgold species by the addition of
triethylamine.
Entry
Substrate
R1
R2
Product (Yield)
Scheme 3. The terminal alkyne 1e selectively reacts by a 5-exo-dig
cyclization.
1
2
3
1a
1b
1c
Ph
Me
Me
nBu
4a (63%)
4b (58%)
4c (71%)
1-adamantyl
1-adamantyl
lytic amounts of gold and 1e provided the known alkylidene
oxazoline 2e in 95%, 79%, and 95% yield when using
5 mol% AuCl3,[3a] 5 mol% [Ph3PAu][NTf2], and 5 mol%
[IPrAu][OTs], respectively. The structure of 5 was unambig-
uously proved by protodeauration to 2e. Thus our investiga-
tion indicates that the 6-endo-dig mode of the cyclization
seems to be general for the internal, alkyl-substituted alkynes
and the 5-exo-dig mode is general for terminal alkynes.
Similar observations have been made for the related prop-
argylic carboxylates.[12]
The other difference between this and previous work is
the stability of the organogold intermediates. In analogy to 5,
aqueous acetonitrile protodemetallated 4a to 3a at room
temperature. 4a can be used as a catalyst; under neutral
conditions the reaction is slower than the [IPrAu][OTs]-
catalyzed reaction. However when the proton, which was
previously removed by the base for the isolation of 4a, is re-
added (addition of an acid), the reaction proceeds just as fast
as the version catalyzed by [IPrAu][OTs]. The extraordinary
stability of the vinylgold intermediate obtained from allenes,
reported in the recent work of Hammond and co-workers,[13]
probably depends on the acceptor substituent which deacti-
vates the system for the electrophilic attack of the proton. The
isolation of intermediates of gold-catalyzed reactions in
general is still quite rare.[14]
4
1d
Me
4d (62%)
In addition, single crystals of compound 4a were obtained
for a crystal structure analysis (Figure 1).[9] With gold–carbon
bond lengths of 2.027(5) ꢂ for Au1–C1 and 2.038(6) ꢂ for
Au1–C11, 4a shows typical values for C(sp2)–AuI single
bonds.[10] The geometry at gold is almost linear, with the C1-
Au1-C11 angle being 176.7(2)8. The NHC ligand and the vinyl
ligand on the gold center are almost co-planar [angle between
the normal vectors of the ring planes: 7.7(5)8]. The vinyl ether
In summary, we isolated vinylgold intermediates derived
from acetylenic substrates for the first time. The results
obtained here should in principle be transferable to many
other reactions proceeding through vinylgold intermediates
Figure 1. Molecular structure of 4a. Thermal ellipsoids shown at 50%
probability.
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Chemie
Michelet, J. Am. Chem. Soc. 2006, 128, 3112 – 3113; b) S. Ritter,
and allow an exploration of additional functionalization of
these intermediates in extended catalytic cycles.
Y. Horino, J. Lex, H.-G. Schmalz, Synlett 2006, 3309 – 3313; for
very recent results, where the reaction is directed to this pathway
in special substrates showing a disubstition at the propargyl
position, see: c) V. Belting, N. Krause, Org. Biomol. Chem. 2009,
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catalyst, see: d) H. Yamamoto, M. Nishiyama, H. Imagawa, M.
Nishizawa, Tetrahedron Lett. 2006, 47, 8369 – 8373. Similar
effects of non-terminal alkynes can even be observed for
ruthenium-catalyzed reactions: e) V. Cadierno, J. Gimeno, N.
Nebra, personal communication.
Received: June 11, 2009
Revised: July 22, 2009
Published online: September 19, 2009
Keywords: alkynes · amides · gold · heterocycles ·
.
reaction mechanisms
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Mohr, L. R. Falvello, M. Laguna, Eur. J. Inorg. Chem. 2006, 833 –
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[9] CCDC 735314 (4a) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif.
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