Highly efficient addition of activated methylene compounds to alkenes catalyzed by gold and silver

Article abstract of DOI:10.1021/ja0482637

A highly efficient intermolecular addition of 1,3-diketones to alkenes catalyzed by AuCl₃/AgOTf was developed. A mechanistic rationale for the reaction has been proposed via a α-C-H activation. Copyright

Full text of DOI:10.1021/ja0482637

Published on Web 05/15/2004
Highly Efficient Addition of Activated Methylene Compounds to Alkenes
Catalyzed by Gold and Silver
Xiaoquan Yao and Chao-Jun Li*
Department of Chemistry, McGill UniVersity, 801 Sherbrooke Street West, Montreal, Quebec H3A 2K6, Canada
Received March 26, 2004; E-mail: cj.li@mcgill.ca
The alkylation of 1,3-dicarbonyl compounds represents one of
the most common methodologies in organic synthesis. The standard
protocol requires the usage of a stoichiometric amount of base and
an organic halide (Figure 1, route a). On the other hand, the
development of carbon-carbon bond formation via an overall
structural isomerization such as the hydroalkylation of alkenes
(Figure 1, route b) represents the most atom-economical approach
Figure 1. Alkylation of 1,3-Dicarbonyl Compounds.
for chemical synthesis.1 Since the landmark report of the ruthenium-
catalyzed hydroarylation of alkenes by Murai and co-workers,2 there
has been great interest in hydrocarbylation of alkenes involving
Table 1. Addition of Pentane-2,4-dione to Styrene Catalyzed by
Gold
other organic substrates such as electron-deficient alkenes.3 How-
ever, most recent developments in the field have been limited to
the addition of arenes onto alkenes.4 Recently, Widenhoefer and
co-workers reported an elegant intramolecular hydroalkylation of
alkenes by carbonyl compounds catalyzed by palladium.5 To the
best of our knowledge, the intermolecular hydroalkylation of alkenes
involving such activated methylene C-H bonds has not been
reported. Herein, we wish to describe such an intermolecular
reaction catalyzed by gold and silver.
entry
catalysta
solvent
1:2 (mol:mol)
yield (%)c
1
2
3
4
5
6
7
8
AuCl3/AgOTf
AuCl3/AgOTf
AuCl3/AgBF4
AuCl3/Ag(O2CCF3)
AuCl3/AgSbF6
AuBr3/AgOTf
AgOTfb
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
1:1
49
74
12
0
65
74
trace
5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
Compared to other late transition metals, gold has not been a
common catalyst of choice in synthesis. However, recently Ito,6
Hashmi,7 and others8 have shown unique catalytic properties of
gold in several reactions. Previously, we reported the highly efficent
three-component coupling of aldehyde, alkyne, and amine (A3
Coupling) catalyzed by gold9 and silver10 in water. The reaction
was rationalized involving the activation of the sp hybridized
terminal alkyne by gold. On the other hand, Hashimi,11 Reetz,12
and Arcadi13 have recently reported the activation of sp2 hybridized
aryl C-H bonds by gold. Our continued interests in developing
C-C bond formation based on the reactivity of C-H bonds and
the unique catalytic activity of gold toward sp and sp2 C-H bonds
led us to explore the hydroalkylation of alkenes with 1,3-dicarbonyl
compounds via the reactivity of the sp3 hybridized C-H bond.14
In our initial study, 2,4-pentanedione was reacted with styrene under
a variety of conditions (Table 1) with the following conclusions:
(1) AgOTf or AuCl3 alone (entries 7 and 8, respectively) provided
only trace amounts of the desired product, (2) the combination of
AuCl3 and AgOTf provided the desired product in good yields, (3)
changing the counterion on the silver salt from OTf lowers the yield
(entries 3-5), but there is no difference when the counterion for
gold is changed (entries 2 and 6), and (4) CH2Cl2 is the solvent of
choice relative to DCE and nitromethane, and there is no amount
or trace amounts of product in THF and water (entries 9-12,
respectively). The use of (PPh3)AuCl or cyclo-hexNCAuCl, instead
of AuCl3, decreased the reactivity considerably. Therefore, the use
of catalytic AuCl3/AgOTf in CH2Cl2 (entry 2) with a slight excess
of styrene provided the best yield.
AuCl3
9d
10d
11
12
AuCl3/AgOTf
AuCl3/AgOTf
AuCl3/AgOTf
AuCl3/AgOTf
61
64
MeNO2
THF
H2O
e
-
0
a
b
5 mol % gold salt and 15 mol % silver salt. 15 mol % silver triflate.
c
d
e
Isolated yield. Under reflux. THF decomposed during the reaction.
Scheme 1. Addition of Activated Methylenes to Alkenes
effective. The use of â-ketone esters is also effective; however, it
gave a complicated mixture that is still under investigation.
Additionally, simple terminal alkenes are also reactive under the
current conditions; however, only very low conversion is observed
at the present time. The use of norbornene provided a 81% yield
of the corresponding product under the same reaction conditions
(entry 15). Esters such as dimethyl malonate and â-ketoesters
decomposed possibly because of the high Lewis acidity of the
system. The use of cyclic 1,3-diketones led to low conversions under
the present conditions.
A tentative mechanism is proposed involving the activation of
the C-H bond of the activated methylene by a Au(I) species
(generated in situ from the reduction of Au(III) by the activated
methylene). The alkylgold hydride intermediate then reacts with
the styrene to give the hydroalkyation product and regenerate the
Subsequently, the reaction was examined on various substrates
(Scheme 1). Various diketones were effectively added to styrene
and styrene derivatives under the current reaction conditions (Table
2). Note that the addition of 1,3-diketones to indene is also highly
9
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J. AM. CHEM. SOC. 2004, 126, 6884-6885
10.1021/ja0482637 CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Gold-Catalyzed Reaction of Alkenes with â-Diketone
Scheme 2. Tentative Mechanism for the Gold-Catalyzed Addition
Reaction
Acknowledgment. We are grateful to the Canada Research
Chair (Tier I) Foundation (to C.J.L.), the CFI, NSERC, and McGill
University for support of this research.
Supporting Information Available: Representative experimental
procedure and characterization of all new compounds (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
References
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a
b
c
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f
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Au(I) catalyst for further reactions (Scheme 2). Alternatively, it
may occur through an enolate addition to alkenes as in alkynes.14
In conclusion, a highly effective intermolecular addition of
activated methylene compounds to alkenes was developed by using
AuCl3/AgOTf. The scope, mechanism, and synthetic applications
of this reaction is currently under investigation.
JA0482637
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J. AM. CHEM. SOC. VOL. 126, NO. 22, 2004 6885