Highly efficient, reversible addition of activated methylene compounds to styrene derivatives catalyzed by silver catalysts

Article abstract of DOI:10.1021/jo050570n

A highly efficient inter- and intramolecular addition of 1,3-diketone/β-ketoester to alkenes was developed by using silver catalysts. Silver triflate shows the highest catalytic activity. The reaction is reversible through the cleavage of a carbon-carbon bond by silver at an elevated temperature.

Full text of DOI:10.1021/jo050570n

TABLE 1. Addition of Pentane-2,4-dione to Styrene
Catalyzed by Silver
Highly Efficient, Reversible Addition of
Activated Methylene Compounds to
Styrene Derivatives Catalyzed by Silver
Catalysts
Xiaoquan Yao and Chao-Jun Li*
entry
catalysta
conditions
yieldb (%)
Department of Chemistry, McGill University,
801 Sherbrooke Street West, Montreal,
Quebec H3A 2K6, Canada
1
2
AgI
water, 100 °C
0
AgI
CH3NO2, 100 °C
CH3NO2, 100 °C
water, 100 °C
0
3
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgNO3
AgBF4
AgSbF6
AgCO2CF3
AgCN
76c
0
4
5
CH2Cl2, 40 °C
DCE, 80 °C
<5
71c
0
cj.li@mcgill.ca
6
7
dioxane, 100 °C
[bmim]OTf, 100 °C
CH3NO2, 100 °C
CH3NO2, 100 °C
CH3NO2, 100 °C
CH3NO2, 100 °C
CH3NO2, 100 °C
CH3NO2, 100 °C
Received March 21, 2005
8
0
9
trace
0
10
11
12
13
14
trace
0
0
0
Ag2SO4
a Conditions: 10 mol % of silver salt was used. b Detected by
1H NMR. c Isolated yield.
A highly efficient inter- and intramolecular addition of
1,3-diketone/â-ketoester to alkenes was developed by using
silver catalysts. Silver triflate shows the highest catalytic
activity. The reaction is reversible through the cleavage of
a carbon-carbon bond by silver at an elevated temperature.
by using AuCl3/AgOTf as combined catalyst.5,6 In this
reaction, silver triflate was used to exchange the anion
with gold chloride to activate the gold species. We
proposed that gold(I) is the catalytic species generated
in situ from the reduction of Au(III) by the activated
methylene.
Carbon-carbon bond-forming reactions are among the
most important types of bond constructions in organic
chemistry. As one of the most common methodologies for
forming a carbon-carbon bond, the alkylation of 1,3-di-
carbonyl compounds usually requires the use of a sto-
ichiometric amount of base and an organic halide, which
has an overall low atom economy.1 An alternative reac-
tion, via a catalytic addition of 1,3-dicarbonyl compounds
to alkenes, would provide a more atom-economical ap-
proach and has attracted much interest in recent years.
Recently, Widenhoefer and Yang reported an elegant
intramolecular hydroalkylation of alkenes by carbonyl
compounds catalyzed by palladium.2 Compared with the
intramolecular addition, intermolecular hydroalkylation
of alkenes involving such activated methylene C-H
bonds have been rarely reported. Very recently, Widen-
hoefer reported a platinum- or palladium-catalyzed in-
termolecular addition of ethylene with â-diketones.3 On
the other hand, Hartwig reported a palladium-catalyzed
addition of mono- and dicarbonyl compounds to conju-
gated dienes.4
The success of the addition of diketone to styrenes
catalyzed by gold(I) species encouraged us to attempt the
reaction using silver(I) compounds as catalyst. Tradition-
ally, silver(I) and silver(II) complexes are used as sto-
ichiometeric oxidants for the oxidation of various organic
or inorganic substrates. In recent years, more and more
reports used silver(I) complexes as catalysts in oxidation
or group-transfer reactions.7 Although silver(I) was often
used as a Lewis acid,7a-c recent studies have shown that
silver species exhibited interesting catalytic activities
functioning as a transition metal catalyst.7d-j We once
reported an A3-coupling (aldehyde-alkyne-amine) reac-
tion in water or ionic liquids using silver(I) compounds
as catalysts, in which the silver(I) catalyst shows catalytic
character and reactivity similar to gold(I) catalyst.8,9
Herein, we wish to describe a silver-catalyzed inter- and
intramolecular addition of 1,3-diketone/â-ketoester to
alkenes. The silver-catalyzed reaction was found to be
(5) Yao, X. Q.; Li, C.-J. J. Am. Chem. Soc. 2004, 126, 6884.
(6) Nguyen, R.-V.; Yao, X. Q. Bohle, D. S., Li, C.-J. Org. Lett. 2005,
7, 673.
Previously, we reported a highly effective intermolecu-
lar addition of activated methylene compounds to alkenes
(7) For some recent examples, as Lewis acid: (a) Josephsohn, N.
S.; Snapper, M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 3734-
3735. (b) Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126,
5360. (c) Peddibhotla, S.; Tepe, J. J. J. Am. Chem. Soc. 2004, 126,
12766. Others: (d) Cirakovic, J.; Driver, T. G.; Woerpel, K. A. J. Am.
Chem. Soc. 2002, 124, 9370. (e) Dias, H. V. R.; Browning, R. G.; Polach,
S. A.; Diyabalanage, H. V. K.; Lovely, C. J. J. Am. Chem. Soc. 2003,
125, 9270. (f) Cui, Y.; He, C. J. Am. Chem. Soc. 2003, 125, 16202.
(g) Clark, T. B.; Woerpel, K. A. J. Am. Chem. Soc. 2004, 126, 9522.
(h) Dias, H. V. R.; Browning, R. G.; Richey, S. A.; Lovely, C. J.
Organometallics 2004, 23, 1200. (i) Cui, Y.; He, C. Angew. Chem., Int.
Ed. 2004, 43, 4210. (j) Driver, T. G.; Woerpel, K. A. J. Am. Chem. Soc.
2004, 126, 9993.
(1) (a) Trost, B. M. Science 1991, 254, 1471. (b) Trost, B. M. Angew.
Chem., Int. Ed. Engl. 1995, 34, 259. (c) Trost, B. M. Acc. Chem. Res.
2002, 35, 695.
(2) (a) Pei, T.; Widenhoefer, R. A. J. Am. Chem. Soc. 2001, 123,
11290. (b) Pei, T.; Widenhoefer, R. A. Chem. Commun. 2002, 650.
(c) Qian, H.; Widenhoefer, R. A. J. Am. Chem. Soc. 2003, 125, 2056.
(d) Pei, T.; Wang, X.; Widenhoefer, R. A. J. Am. Chem. Soc. 2003, 125,
648. (e) Wang, X.; Pei, T.; Han, X.; Widenhoefer, R. A. Org. Lett. 2003,
5, 2699. (f) Yang, D.; Li, J. H.; Gao, Q.; Yan, Y. L. Org. Lett. 2003, 5,
2869.
(3) Wang, X.; Widenhoefer, R. A. Chem. Commun. 2004, 660.
(4) Leitner, A.; Larsen, J.; Steffens, C.; Hartwig, J. F. J. Org. Chem.
2004, 69, 7552.
(8) Wei, C.; Li, Z.; Li, C.-J. Org. Lett. 2003, 5, 4473.
(9) Li, Z.; Wei, C.; Chen, L.; Varma, R. S.; Li, C.-J. Tetrahedron Lett.
2004, 45, 2443.
10.1021/jo050570n CCC: $30.25 © 2005 American Chemical Society
Published on Web 06/07/2005
5752
J. Org. Chem. 2005, 70, 5752-5755

TABLE 2. Addition of â-Diketone to Alkenes Catalyzed by AgOTf
a Conditions: 1.5 equiv or 2 equiv of styrene was added. b Isolated yield. c The ratio was determined by 1H NMR. d The conversion of
1d is 31%.
J. Org. Chem, Vol. 70, No. 14, 2005 5753

TABLE 3. Intramolecular Addition of 1,3-Dicarbonyl
Compounds to Alkenes Catalyzed by AgOTfa
a trace amount of addition product 3l was observed based
on the crude NMR analysis. Most diketone was left
unchanged while styrene 2d has been converted into
dimer 4 (entry 14 vs entry 15). However, in the gold-
catalyzed reaction, 98% of 3l was achieved in CH2Cl2 at
room temperature.5 The abnormal solvent effect attracted
our attention. By following the reaction (eq 2) with
1H NMR, rather surprising results were observed: after
4 h of stirring, 3l was generated in 60% yield; however,
after an additional 3 h, the conversion dropped down to
40%; after 11h of reaction, only 27% of 3l remained. After
the reaction, most of 1d was recovered (>95%). These
results suggested that this reaction might be reversible
under certain conditions.
a Conditions: 10 mol % of AgOTf was used. b Isolated yield. c In
these cases, only one diastereomer was observed. d The ratio was
measured by GC. e The configuration of CdC was determined by
NOESY. f The five-membered ring structure was determined by
H-H COSY.
different from the gold-catalyzed reaction. The addition
reaction is reversible under the silver-catalyzed condi-
tions.
As the first attempt, the addition of 2,4-pentadione
with styrene was selected as the prototype. Various
conditions involving different solvents and several silver-
(I) species were examined.
To verify the reversibility of the reaction, purified 3l
was treated with 10 mol % AgOTf in nitromethane at
the refluxing temperature. After 4 h, 1d and 2d were
observed in low conversions. Considering that an exces-
sive amount of styrene was usually used in the original
addition reaction, 2 equiv of 2d were introduced into the
reaction, and the mixture was heated for an additional
6 h. After separation, 84% of 3l was converted into
diketone 1d, while most 2d was converted into dimer 4
(eq 3). Clearly, the addition reaction catalyzed by silver
is a reversible reaction and silver-catalyzed carbon-
carbon bond cleavage is involved in the process.10 In eq
3, an excessive amount of styrene might promote the
equilibrium shifting to the right.
As shown in Table 1, silver catalysts exhibited good
catalytic activity toward the reaction at a temperature
higher than that for the combined AuCl3/AgOTf catalytic
system. The best result was achieved using AgOTf as the
catalyst in nitromethane (entry 3). A similar result was
observed in DCE solution with the same catalyst (entry
6). It is worth noting that there is no reaction at all when
water or ionic liquid was used as solvent (entries 4 and
8). Furthermore, the anion of the silver salt proved to be
very important for the reaction; only triflate shows good
catalytic activity.
Subsequently, the reaction was examined on a range
of substrates. Various diketones were effectively added
on to styrene and styrene derivatives under the current
reaction conditions (Table 2). It is interesting to note that
only a trace amount of the addition product was observed
when more reactive styrene derivatives were utilized,
which is completely opposite to what we have expected
(entries 4 and 6, Table 2).5 Compared with the gold
catalyzed reaction, the silver catalysis is also more
sensitive to steric effects.
Generally speaking, the results obtained with nitro-
methane or DCE as solvent are similar for most sub-
strates (entry 1 vs entry 2, entry 3 vs entry 4). However,
there is an interesting solvent effect observed during the
reaction of dibenzoylmethane (1d), which was the most
reactive substrate in the gold-catalyzed reaction. For
example, when 1d was heated with 4-chlorostyrene (2d)
in the solution of nitromethane at 100 °C overnight, only
The silver-catalyzed decomposition reaction also seems
sensitive to both electronic and steric effects. In the
presence of the corresponding styrenes, 3k and 3m were
(10) Very recently, a nickel-catalyzed carbon-carbon bond-cleavage
reaction was reported. The substrate is very similar to 3, and the
1,3-dicarbonyl structure was needed. See: Necas, D.; Tursky, M.;
Kotora, M. J. Am. Chem. Soc. 2004, 126, 10222.
5754 J. Org. Chem., Vol. 70, No. 14, 2005

SCHEME 1. Tentative Mechanism for the
Silver-Catalyzed Addition Reaction
also detected. In both cases, the desired product was
obtained with about 20% conversion upon overnight
refluxing.
Intramolecular additions of 1,3-dicarbonyl compounds
to alkenes were also investigated by using silver catalyst.
The results are summarized in Table 3.
As shown in Table 3, both 1,3-diketones and â-ke-
toesters were able to undergo additions to conjugated
alkenes to afford the corresponding six-membered-ring
products effectively. Note that the addition to form the
spiro-center is also highly effective (Table 3, entry 3). It
is also worth mentioning that the favored diastereomer
in entry 3 has been reversed relative to the gold-catalyzed
addition (75:25 vs 39:61, respectively).11 We hypothesized
that the thermodynamic isomer might be favored due to
reversible nature of the silver-catalyzed reaction, whereas
the kinetic product is favored in the gold-catalyzed
reaction. Nonconjugated alkenes were also tested in the
intramolecular reaction (Table 3, entries 5 and 6).
However, no C-alkylation product was observed. The only
O-alkylation products were obtained in low yields.
A tentative mechanism is proposed in Scheme 1. The
coordination of the alkenes with Ag(I) species activated
the alkenes, which was followed by the addition of the
1,3-diketone-Ag(I) complex to generate a silver inter-
mediate. Protonolysis of the C-silver bond generated the
final product.12 However, the exact cause of the revers-
ibility is still unclear.
reversible through the cleavage of the carbon-carbon
bond catalyzed by silver at an elevated temperature. The
scope, mechanism, and synthetic applications (including
the silver-catalyzed cleavage of carbon-carbon bond) of
this reaction are currently under investigation.
Experimental Section
Typical Procedure (Entry 1, Table 2). AgOTf (25.6 mg,
0.1 mmol) was added to 2 mL of nitromethane under N2.
2,4-Pentanedione (103 µL, 1 mmol) and styrene (172 µL,
1.5 mmol) were introduced into the solution. The mixture was
stirred and heated to 100 °C overnight, and the solvent was
removed under a reduced pressure. The residue was separated
by flash chromatography on silica to give the diketone alkylation
product 3a in 76% yield. 3a: CAS registry no. [5186-08-3]; IR
(liquid film) νmax 3027, 2964, 1723, 1700, 1602, 1494, 1356, 1185,
In conclusion, highly efficient inter- and intramolecular
hydroalkylations of 1,3-diketone/â-ketoester and alkenes
were developed by using silver catalysts. The reaction is
1154, 955, 761, 700 cm-1 1H NMR (CDCl3, 400 MHz, ppm)
;
δ 7.29-7.16 (m, 5H), 4.05 (d, J ) 11.2 Hz, 1H), 3.60 (dq, J )
11.2, 7.2 Hz, 1H), 2.26 (s, 3H), 1.83 (s, 3H), 1.21 (d, J ) 7.2 Hz,
3H); 13C NMR (CDCl3, 100 MHz, ppm) δ 203.5, 203.4, 143.2,
129.0, 127.5, 127.2, 76.9, 40.8, 30.3, 30.2, 21.3.
(11) The same reaction can be catalyzed by 5 mol % of AuCl3/
15 mol % of AgOTf at refluxing temperature in DCE. The ratio of the
two distereomers is 39:61.
(12) A similar mechanism has been studied elegantly by Reetze and
co-worker in gold-catalyzed reaction of arenes with alkynes; see:
(a) Reetze, M. T.; Sommer, K. Eur. J. Org. Chem. 2003, 3485. See
also: (b) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem.
Soc. 2004, 126, 4526. (c) Nakamura, M.; Endo, K.; Nakamura, E.
J. Am. Chem. Soc. 2003, 125, 13002. We also thank the reviewers for
their suggestions regarding this mechanism.
Supporting Information Available: General experimen-
tal method and characterization data for all new compounds
5c,d,f, 6c,d, and 7a,b. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO050570N
J. Org. Chem, Vol. 70, No. 14, 2005 5755