Synthesis and structural characterization of stable organogold(I) compounds. evidence for the mechanism of gold-catalyzed cyclizations

Full text of DOI:10.1021/ja806685j

Published on Web 12/04/2008
Synthesis and Structural Characterization of Stable Organogold(I)
Compounds. Evidence for the Mechanism of Gold-Catalyzed Cyclizations
Le-Ping Liu, Bo Xu, Mark S. Mashuta, and Gerald B. Hammond*
Department of Chemistry, UniVersity of LouisVille, LouisVille, Kentucky 40292
Received August 28, 2008; E-mail: gb.hammond@louisville.edu
Table 1. Reactions of Au(PR3)OTf (in situ) with Allenoate 1a
The development of efficient and selective Au-catalyzed trans-
formations has enriched the field of organic synthesis. The
importance of these transformations is reflected in the various
reviews, highlights, and perspectives on gold catalysis that have
appeared in the literature.1 The vast majority of homogeneous Au-
catalyzed reactions have exploited the propensity of Au to activate
unsaturated carbon-carbon bonds as electrophiles. It is generally
assumedthatanucleophile(Nu)attacksaAu-activatedcarbon-carbon
multiple bond (π-complex A or B) to give an alkenyl Au
intermediate (σ-complex C or D), notwithstanding the fact that
complexes C or D are hitherto unknown (Scheme 1).2
b
entry
R1/R2/R3/R4
3, yield%
1
2
3
4
5
6
n-C6H13/H/Me/C6H5
iPr/H/Me/C6H5
Me/H/Me/C6H5
Bn/H/Me/C6H5
Me/H/H/C6H5
3a, 85
3b, 82
3c, 75
3d, 81
3e, 46
3f, 68
Scheme 1
Me/Me/Me/C6H5
7
8
9
10
11
12
Ph/H/Me/C6H5
no reaction
3g, 71
3h, 68
3i, 70
3j, 62
3k, 54
n-C6H13/H/Me/o-CH3C6H4
n-C6H13/H/Me/m-CH3C6H4
n-C6H13/H/Me/p-CH3C6H4
n-C6H13/H/Me/p-CH3OC6H4
n-C6H13/H/Me/cyclohexyl
During our recent investigations on the reactivity of allenoates,3
we found that Au(I) catalyzed the cyclization of allenoate 1a to
give the γ-lactone product 4a (eq 1).4 To our surprise, in addition
a General conditions: allenoate 1 0.24 mmol, Au(PR3)Cl 2 0.2 mmol,
AgOTf 0.2 mmol, CH2Cl2 2.0 mL. b Isolated yields.
to this cyclization product, we obtained compound 3a, a very stable
Au complex of type D, in good yield based on the amount of
catalyst used. This discovery could provide the experimental
evidence required to support the postulated mechanism of Au-
catalyzed reactions. Herein, we wish to publish the reactions of
cationic Au(I) reagents with allenoates under mild conditions, which
not only provide a synthetic entry to novel and stable γ-lactone
gold(I) complexes but also furnish experimental evidence for the
mechanism of Au-catalyzed cyclizations.5
To explore the formation of this interesting gold complex 3, we
investigated the stoichiometric reaction of Au(I) with allenoates.
Using the Au(PPh3)Cl/AgOTf system as the equivalent of
Au(PPh3)OTf, we found that the in situ generated cationic Au(I)
reagent reacted with ethyl R-methyl-γ-(n-hexyl)-allenoate 1a in
dichloromethane at room temperature to give the desired gold
complex 3a in 85% yield (Table 1, entry 1).6
Next, we studied the reactions of the cationic Au(I) reagent with
various allenoates. These results are summarized in Table 1. The
reaction took place readily with alkyl groups substituted on the
allenoates, and the corresponding products 3b-3f were obtained
in good yields (Table 1, entries 2-6). However, no reaction took
place with the phenyl-substituted allenoate (Table 1, entry 7),
perhaps due to the electronic deficiency of the double bond in the
Figure 1. ORTEP-3 (Farrugia) diagram (50% ellipsoids) illustrating one
independent molecule of the gold complex 3d. H atoms are shown as small
spheres of arbitrary radii. Selected bond lengths (Å) and angles (deg):
Au1-C1 ) 2.036(5), Au1-P1 ) 2.2955(12), C1-C2 ) 1.326(7), C1-C4
) 1.531(8), C1-Au1-P1 ) 175.61(15), C2-C1-Au1 ) 129.5(4),
C4-C1-Au1 ) 123.2(4), C2-C1-C4 ) 107.3(5).
allenoate.4a The scope of phosphine ligands was also investigated,
and these results are also outlined in Table 1. Both aromatic (Table
1, entries 8-11) and aliphatic (Table 1, entry 12) phosphines proved
to be adequate ligands for the obtention of the stable gold(I)
products 3g-3k.
1
The structure of 3 was determined by H, 13C, and 31P NMR
spectroscopic data and X-ray crystallography of complex 3d
(Figure 1).7
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17642 J. AM. CHEM. SOC. 2008, 130, 17642–17643
10.1021/ja806685j CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. Plausible Mechanism for the Formation of Gold
Complex 3
multiple bonds. Other studies related to this novel Au(I) complex,
and its chiral version, are currently ongoing in our laboratory.
Acknowledgment. We are grateful to the National Science
Foundation for financial support (CHE-0809683). M.S.M. acknowl-
edges the Kentucky Research Challenge Trust Fund for upgrade
of X-ray facilities.
Supporting Information Available: The 1H, 13C and 31P NMR
spectroscopic data of the new compounds shown in Tables 1 and eqs
1-3, and the detailed description of experimental procedures. Crystal-
lographic data for compound 3d are provided as a CIF file. This material
is available free of charge via the Internet at http://pubs.acs.org.
References
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1
In situ 31P and H NMR studies were performed to understand
the mechanism for the formation of complex 3. The 31P NMR
spectrum of the crude reaction mixture of 1g showed two new peaks
at δ 43.0 ppm (major) and 46.1 ppm8 (minor) in CDCl3. A large
downfield chemical shift of the ethyl group was also observed in
the 1H NMR spectrum of the mixture (shift from δ 1.32 to δ 1.60
ppm for CH3 and from δ 4.22 ppm to 4.94 ppm for CH2).9 This
downfield chemical shift could be ascribed to the formation of
1
oxonium intermediate F (Scheme 2). The H NMR spectrum of
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the reaction mixture, taken 12 h later, showed additional proton
signals corresponding to ethanol.10 Based on these findings, we
propose the reaction mechanism shown in Scheme 2. The double
bond of the allenoate is activated by coordination to cationic gold
to form intermediate E, which then undergoes an intramolecular
cyclization5f to give intermediate F (observed signal at δ 43.0 in
31P NMR spectrum). Complex 3 was obtained after workup, and
the ethyl group was hydrolyzed to ethanol.
To demonstrate that 3 is the actual intermediate in Au(I)-
catalyzed cyclizations, we performed two controlled reactions (eqs
2 and 3). In one experiment, γ-lactone 4a was obtained in 66%
yield when gold complex 3a was treated with TsOH in toluene at
80 °C (eq 2). In another experiment, 3a was treated with iodine in
(4) (a) Kang, J.-E.; Lee, E.-S.; Park, S.-I.; Shin, S. Tetrahedron Lett. 2005,
46, 7431. For a review of metal-catalyzed allenoate cyclizations, see: Ma,
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(6) No reaction occurred without the presence of the silver salt. Other silver
salts such as AgSbF6, AgBF4, and AgClO4 also promoted the reaction; in
all cases, the product 3a was obtained in very good yields. Moreover, this
reaction also proceeded smoothly in 1,2-dichloroethane (DCE), toluene,
tetrahydrofuran (THF), and diethyl ether. Conversely, poor yields were
obtained using acetonitrile as solvent (see Supporting Information).
(7) X-ray crystal structures of stable gold intermediates are rare. Notable
examples include: (a) Shapiro, N. D.; Toste, F. D. Proc. Natl. Acad. Sci.
U.S.A. 2008, 105, 2779. (b) Akana, J. A.; Bhattacharyya, K. X.; Muller,
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dichloromethane at room temperature to produce the γ-iodolactone
5a in 72% isolated yield (eq 3).11 The results of these two controlled
(8) The species at δ 46.1 was assigned to (Ph3P)2Au+; see: Liu, Y.; Song, F.;
Guo, S. J. Am. Chem. Soc. 2006, 128, 11332.
reactions imply that gold complex 3 is indeed the common
intermediate in Au-catalyzed cyclizations.
In summary, we have found that cationic gold compounds can
react with allenoates to form a series of room temperature stable
organogold(I) complexes and that these complexes are likely
intermediates in the Au-catalyzed reaction of carbon-carbon
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(10) The chemical shift was compared with standards from Sigma-Aldrich Co.
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