Bismuth triflate-catalyzed three-component Mannich-type reaction

Article abstract of DOI:10.1021/jo048617c

Bismuth triflate catalyzes the Mannich-type reaction of a variety of in situ generated aldimines using aldehydes, anilines, and silyl enol ethers in a three-component reaction. The reaction proceeds rapidly and affords the corresponding protected β-amino

Full text of DOI:10.1021/jo048617c

tions.10 Bi(OTf)3 is particularly attractive because it is
commercially available or can be easily prepared from
commercially available starting materials.11
Bismuth Triflate-Catalyzed
Three-Component Mannich-Type Reaction
We have recently reported the Bi(OTf)3-catalyzed al-
lylation of a variety of protected aldimines generated in
situ using aldehydes, primary carbamates, and allyltri-
methylsilane in a three-component reaction.5c,12 The
results encouraged us to use a similar three-component
protocol in the bismuth(III)-catalyzed Mannich-type reac-
tion. A major merit of the three-component reaction is
indeed that the reaction can be done without a separate
step for imine preparation prior to the Mannich-type
reaction.13
Herein, we report a general Bi(OTf)3-catalyzed method
for addition of silyl enol ethers to aryl imines in a three-
component process. â-Amino ketones are obtained ef-
ficiently in the presence of 1 mol % of Bi(OTf)3‚4H2O.
Thierry Ollevier* and Etienne Nadeau
De´partement de chimie, Universite´ Laval, Que´bec (Que´bec),
Canada G1K 7P4
thierry.ollevier@chm.ulaval.ca
Received August 9, 2004
Abstract: Bismuth triflate catalyzes the Mannich-type
reaction of a variety of in situ generated aldimines using
aldehydes, anilines, and silyl enol ethers in a three-
component reaction. The reaction proceeds rapidly and
affords the corresponding protected â-amino ketones in high
yields (up to 94%).
The bismuth-catalyzed Mannich-type reaction was first
studied with preformed imines. Interestingly, when
equimolar amounts of N-benzylideneaniline and (1-
phenylvinyloxy)trimethylsilane were treated with 1 mol
% Bi(OTf)3‚4H2O in acetonitrile for 2 h at 25 °C, the
corresponding â-amino ketone was isolated in low yield
(26%) because of low conversion.14 Consequently, a one-
pot sequence involving the formation of the imine and
its in situ Mannich-type reaction was investigated.
Initially, we screened various solvents for the one-pot
Mannich-type reaction of imine derived from benzalde-
hyde 1a and aniline 2a with silyl enol ether 3a in the
presence of 1 mol % of Bi(OTf)3‚4H2O. Among various
polar solvents tested, diethyl ether, dichloromethane, and
nitromethane gave moderate yields of the expected
product (Table 1, entries 1, 2, and 5). The best solvent
was found to be acetonitrile. In such solvent, 1,3-
diphenyl-3-(N-phenylamino)propan-1-one 4a was ob-
tained with the best yield (Table 1, entry 4). With further
optimization of the reaction conditions, we found that a
lower catalyst loading gave decreased yields.
â-Amino carbonyl compounds are extremely important
compounds as biologically active molecules.1 Therefore,
the development of new catalytic methods for their
preparation is of prime importance in organic synthesis.
Catalytic Mannich-type reactions have been reported by
several groups as an efficient method to prepare â-amino
carbonyl compounds.2 Lately, synthetic methods involv-
ing lanthanide triflates as catalysts for Mannich-type
reactions have been reported.3 High catalytic activity, low
toxicity, and moisture and air tolerance make lanthanide
triflates attractive catalysts. However, the high cost of
these catalysts limits their use.
Bismuth compounds too have attracted recent atten-
tion due to their low toxicity, low cost, and good stability.4
Bismuth salts have been reported as catalysts for opening
of epoxides,5 Mukaiyama-aldol reactions,6 formation and
deprotection of acetals,7 Friedel-Crafts reactions,8 Diels-
Alder reactions,9 and intramolecular Sakurai cycliza-
(1) Arend, M.; Westermann, B.; Risch, N. Angew. Chem., Int. Ed.
1998, 37, 1044-1070.
(2) For reviews of catalytic Mannich-type reactions, see: (a) Koba-
yashi, S.; Ueno, M. In Comprehensive Asymmetric Catalysis, Supple-
ment; Springer: Berlin, 2004; Vol.1, pp 143-150. (b) Cordova, A. Acc.
Chem. Res. 2004, 37, 102-112.
A possible explanation for the low yield obtained in the
Bi(OTf)3-catalyzed reaction of preformed imines would
be that the mechanism of the one-pot process is different.
Products other than imines could be the true substrates
in this process. For exemple, aminals have already been
(3) (a) Kobayashi, S.; Araki, M.; Ishitani, H.; Nagayama, S.; Hachiya,
I. Synlett 1995, 233-234. (b) Kobayashi, S.; Busujima, T.; Nagayama,
S. Synlett 1999, 545-546.
(4) (a) Organobismuth Chemistry; Suzuki, H., Matano, Y., Eds.;
Elsevier: Amsterdam, 2001. (b) Gaspard-Iloughmane, H.; Le Roux, C.
Eur. J. Org. Chem. 2004, 2517-2532. (c) Leonard, N. M.; Wieland, L.
C.; Mohan, R. S. Tetrahedron 2002, 58, 8373-8397.
(5) (a) Ollevier, T.; Lavie-Compin, G. Tetrahedron Lett. 2004, 45,
49-52. (b) Ollevier, T.; Lavie-Compin, G. Tetrahedron Lett. 2002, 43,
7891-7893. (c) Ollevier, T.; Lavie-Compin, G.; Ba, T. Recent Develop-
ment in Bismuth(III) Catalysis: Ring Opening of Epoxides with
Aromatic Amines and Allylation of in situ-Formed Imines with
Allylsilanes. Proceedings of the 13th European Symposium on Organic
Synthesis, Cavtat-Dubrovnik, 10-15 September 2003; Monduzzi: Bo-
logna, 2004; pp 51-54.
(6) Le Roux, C.; Ciliberti, L.; Laurent-Robert, H.; Laporterie, A.;
Dubac, J. Synlett 1998, 1249-1251.
(7) (a) Leonard, N. M.; Oswald, M. C.; Freiberg, D. A.; Nattier, B.
A.; Smith, R. C.; Mohan, R. S. J. Org. Chem. 2002, 67, 5202-5207. (b)
Carrigan, M. D.; Sarapa, D.; Smith, R. C.; Wieland, L. C.; Mohan, R.
S. J. Org. Chem. 2002, 67, 1027-1030.
(9) (a) Garrigues, B.; Oussaid, A. J. Organomet. Chem. 1999, 585,
253-255. (b) Laurent-Robert, H.; Garrigues, B.; Dubac, J. Synlett 2000,
1160-1162.
(10) (a) Leroy, B.; Marko´, I. E. Org. Lett. 2002, 4, 47-50. (b) Leroy,
B.; Marko´, I. E. Tetrahedron Lett. 2001, 42, 8685-8688.
(11) (a) Re´pichet, S.; Zwick, A.; Vendier, L.; Le Roux, C.; Dubac, J.
Tetrahedron Lett. 2002, 43, 993-995. (b) Labrouille`re, M.; Le Roux,
C.; Gaspard, H.; Laporterie, A.; Dubac, J.; Desmurs, J. R. Tetrahedron
Lett. 1999, 40, 285-286. (c) Torisawa, Y.; Nishi, T.; Minamikawa, J.-
i. Org. Proc. Res. Dev. 2001, 5, 84-88. (d) Peyronneau, M.; Arrondo,
C.; Vendier, L.; Roques, N.; Le Roux, C. J. Mol. Catal. A 2004, 211,
89-91. (e) Bi(OTf)3‚4H2O has been prepared from Bi2O3 according to
ref 11a.
(12) Ollevier, T.; Ba, T. Tetrahedron Lett. 2003, 44, 9003-9005.
(13) Kobayashi, S.; Araki, M.; Yasuda, M. Tetrahedron Lett. 1995,
36, 5773-5776.
(8) (a) Le Roux, C.; Dubac, J. Synlett 2002, 181-200. (b) Desmurs,
J. R.; Labrouille`re, M.; Le Roux, C.; Gaspard, H.; Laporterie, A.; Dubac,
J. Tetrahedron Lett. 1997, 38, 8871-8874. (c) Re´pichet, S.; Le Roux,
C.; Dubac, J.; Desmurs, J.-R. Eur. J. Org. Chem. 1998, 2743-2746.
(14) Interestingly, a metal chloride screening for the stoichiometric
Mannich-type reaction was studied by Kobayashi, and the â-amino
ketone was obtained with poor yield using BiCl3: Kobayashi, S.;
Busujima, T.; Nagayama, S. Chem. Eur. J. 2000, 6, 3491-3494.
10.1021/jo048617c CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/17/2004
9292
J. Org. Chem. 2004, 69, 9292-9295

TABLE 1. Three-Component Bi(OTf)3-Catalyzed
Mannich-Type Reactions Involving Benzaldehyde and
Anilinea
TABLE 3. Three-Component Bi(OTf)3-Catalyzed
Mannich-Type Reactions with Various Aldehydesa
entry
solvent
yield 4ab (%)
1
2
3
4
5
Et2O
72
60
54
82
71
CH2Cl2
PhMe
MeCN
MeNO2
a Conditions: benzaldehyde (1.0 equiv), aniline (1.0 equiv),
(1-phenylvinyloxy)trimethylsilane 3a (1.0 equiv), Bi(OTf)3‚4H2O
(0.01 equiv). b Isolated yield.
TABLE 2. Three-Component Bi(OTf)3-Catalyzed
Mannich-Type Reactions with Various Silyl Enol Ethersa
a Conditions: aldehyde (1.0 equiv), aniline (1.0 equiv),
(1-phenylvinyloxy)trimethylsilane (1.2 equiv), Bi(OTf)3‚4H2O (0.01
equiv). b Isolated yield.
The corresponding â-amino ketones 4 were obtained in
good yields (Table 2, entries 1-3). Trimethyl(prop-1-en-
2-yloxy)silane 3d afforded â-amino ketone 4d in poor
yield (Table 2, entry 4). Silyl enol ethers derived from
cyclopentanone or cyclohexanone afforded â-amino ke-
tones 4e and 4f with good yields (Table 2, entries 5 and
6).
In this one-pot protocol, the reaction involving benzal-
dehyde was further optimized using 1.2 equiv of silyl enol
ether (Table 3, entry 1). Other aldehydes were tested and
the results are summarized in Table 3. Generally, excel-
lent yields of â-amino ketone were obtained with 1.2
equiv of (1-phenylvinyloxy)trimethylsilane 3a and 0.01
equiv of Bi(OTf)3‚4H2O at 25 °C in acetonitrile. Aromatic
aldehydes as well as heterocyclic and R,â-unsaturated
aldehydes reacted smoothly to give the corresponding
â-amino ketone derivatives 4 in high yield (Table 3,
entries 1-8). The reaction worked well with a variety of
aldehydes including those bearing an electron-withdraw-
ing group, and the corresponding â-amino ketones 4 were
obtained with very good yields (Table 3, entries 2-4).
Several electron-rich aromatic aldehydes led to the
desired products in good yields (Table 3, entries 5 and
a Conditions: benzaldehyde (1.0 equiv), aniline (1.0 equiv), silyl
enol ether (1.0 equiv), Bi(OTf)3‚4H2O (0.01 equiv). b Isolated yield.
c Silyl enol ether (1.5 equiv). d Syn/anti ) 50/50. e Crude yield of
4d was 81%. After column chromatography, 4d was obtained with
a decreased yield (42%) and a double-Mannich adduct was also
isolated as a mixture of diastereoisomers (dr ) 52/48) in a 24%
yield. f Syn/anti ) 68/32. g Syn/anti ) 39/61.
characterized as intermediates in similar three-compo-
nent reactions.15
Several examples of Bi(OTf)3-catalyzed Mannich-type
reactions with various silyl enol ethers are summarized
in Table 2. Silyl enol ethers derived from aromatic
ketones and from aliphatic ketones were reacted with an
equimolar mixture of benzaldehyde 1a and aniline 2a.
(15) (a) Niimi, L.; Serita, K.-i.; Hiraoka, S.; Yokozawa, T. Tetrahe-
dron Lett. 2000, 41, 7075-7078. (b) Veenstra, S. J.; Schmid, P.
Tetrahedron Lett. 1997, 38, 997-1000.
J. Org. Chem, Vol. 69, No. 26, 2004 9293

TABLE 4. Three-Component Bi(OTf)3-Catalyzed
Mannich-Type Reactions Involving Benzaldehyde and
Various Aminesa
ates the reaction (1 equiv of PhCHO 1a, 1 equiv of PhNH2
2a, 1 equiv of (1-phenylvinyloxy)trimethylsilane 3a, 0.03
equiv of 2,6-di-tert-butylpyridinium triflate, 25 °C, 0.3 h,
80% of 4a). Other bismuth(III) salts such as BiCl3
catalyze the Mannich-type reaction albeit with a lower
yield (1 equiv of PhCHO 1a, 1 equiv of PhNH2 2a, 1 equiv
of (1-phenylvinyloxy)trimethylsilane 3a, 0.01 equiv of
BiCl3, 25 °C, 1.5 h, 59% of 4a). Competition studies
involving an excess of the aldehyde (2 equiv of PhCHO
1a, 1 equiv of PhNH2 2a, 1 equiv of (1-phenylvinyloxy)-
trimethylsilane 3a, 0.01 equiv of Bi(OTf)3‚4H2O show
complete chemoselectivity for the Mannich-type reaction
vs Mukaiyama-aldol (25 °C, MeCN, 89% of 1,3-diphenyl-
3-(N-phenylamino)propan-1-one 4a). The Mukaiyama-
aldol product is indeed formed in the absence of amines
(1 equiv of PhCHO 1a, 1.2 equiv of (1-phenylvinyloxy)-
trimethylsilane 3a, 0.01 equiv of Bi(OTf)3‚4H2O, 25 °C,
0.8 h, 93% of 3-hydroxy-1,3-diphenylpropan-1-one). This
clearly indicates coordination of the aldimine or aminal
by Bi(OTf)3 prior to the silyl enol ether attack. Moreover,
our studies clearly suggest that Bi(OTf)3 would behave
as an aldimine-selective Lewis acid.14 However, a con-
tribution of Me3SiOTf in a silicon-catalyzed mechanism
cannot be ruled out,6,17 and further mechanistic investi-
gations of the nature of the catalyst are in progress.
In summary, we have found that the Mannich-type
reaction of in situ prepared imines proceeds smoothly
with silyl enol ethers and a catalytic amount of Bi(OTf)3‚
4H2O. This method offers several advantages including
mild reaction conditions, a highly catalytic (1%) process,
and no formation of byproducts. To the best of our
knowledge, such a low catalyst loading (1%) for a metal-
catalyzed Mannich-type reaction has not been previously
reported using silyl enol ethers.18 Moreover, our protocol
does not require prior isolation of the imine. The â-amino
ketone is directly obtained, usually as a crystalline
product, in a one-pot process. Because of its numerous
benefits, the Bi(OTf)3‚4H2O protocol should find utility
in the synthesis of biologically active compounds. Devel-
opment of other Bi(OTf)3‚4H2O-catalyzed Mannich-type
reactions and related mechanistic studies will be reported
in due course.
a Conditions: benzaldehyde (1.0 equiv), amine (1.0 equiv), (1-
phenylvinyloxy)trimethylsilane 3a (1.2 equiv), Bi(OTf)3‚4H2O (0.01
equiv). b Isolated yield. c Reaction performed at 0 °C.
7). Conjugated aldehydes were good substrates as well
(Table 3, entry 8). Aliphatic aldehydes do not react under
such conditions probably due to enamine formation,
except cyclohexane carboxaldehyde, which afforded prod-
uct 4n in good yield (Table 3, entry 9). Interestingly, we
never observed side reaction products such as aldol and
deamination products.
The scope of our method could be extended to other
amines. o- and p-Anisidines gave moderate to good yield
of the corresponding â-amino carbonyl compounds (Table
4, entries 1 and 2), which are known to be easily cleavable
under oxidative conditions.16 2-Methoxy-4-nitro- and
4-methoxy-2-nitroanilines afforded the â-amino carbonyl
compounds in high yield (Table 4, entries 3 and 4). Using
Cbz-carbamate instead of an aniline gave only a moder-
ate yield of the Cbz-protected â-amino carbonyl compound
(Table 4, entry 5).
Although the precise mechanism has not been eluci-
dated, we have investigated the nature of the catalyst
as the true catalyst might be TfOH released from
hydrolysis of Bi(OTf)3‚4H2O. TfOH is indeed as effective
as Bi(OTf)3‚4H2O to catalyze the Mannich-type reaction
(1 equiv of PhCHO 1a, 1 equiv of PhNH2 2a, 1 equiv of
(1-phenylvinyloxy)trimethylsilane 3a, 0.03 equiv of TfOH,
25 °C, 0.3 h, 80% of 4a). However, the observation that
the same reaction in the presence of hindered 2,6-di-tert-
butylpyridine still occurs (1 equiv of PhCHO 1a, 1 equiv
of PhNH2 2a, 1 equiv of (1-phenylvinyloxy)trimethylsi-
lane 3a, 0.01 equiv of Bi(OTf)3‚4H2O, 0.03 equiv of 2,6-
di-tert-butylpyridine, 25 °C, 0.3 h, 80% of 4a) does not
indicate unambiguously that a Lewis acid is involved in
the process because the pyridinium salt itself also medi-
Experimental Section
General Procedures. Infrared spectra were recorded on an
FT infrared spectrometer and are reported in reciprocal centi-
1
meters (cm-1). H, 13C, and 19F NMR spectra were recorded on
1
a 400 MHz magnetic resonance spectrometer in CDCl3. For H
NMR, tetramethylsilane (TMS) served as internal standard (δ
) 0). For 13C NMR, CDCl3 was used as internal standard (δ )
77.0), and spectra were obtained with complete proton decou-
pling. For 19F NMR, CFCl3 was used as internal standard (δ )
0). Acetonitrile was distilled from calcium hydride (CaH2).
Typical Procedure for the Bismuth-Catalyzed Three-
Component Reaction. Under an inert atmosphere of argon,
the silyl enol ether (2.4 mmol) in 2 mL of dry acetonitrile was
added in one portion to a solution of Bi(OTf)3‚4H2O (0.02 mmol),
(17) (a) Hollis, T. K.; Bosnich, B. J. Am. Chem. Soc. 1995, 117, 4570-
4581. (b) Carreira, E. M.; Singer, R. A. Tetrahedron Lett. 1994, 35,
4323-4326.
(18) Snapper and Hoveyda have recently reported the use of 1 mol
% of AgOAc for selected examples of Ag-catalyzed asymmetric Mannich
reactions but generally 3-5 mol % of AgOAc was necessary: Joseph-
sohn, N. S.; Snapper, M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2004,
126, 3734-3735.
(16) Kronenthal, D. R.; Han, C. Y.; Taylor, M. K. J. Org. Chem. 1982,
47, 2765-2768.
9294 J. Org. Chem., Vol. 69, No. 26, 2004

the aldehyde (2 mmol), and the aniline (2 mmol) in 2 mL of dry
acetonitrile. The mixture was stirred at room temperature until
the reaction was completed as indicated by TLC. The reaction
was quenched with water and extracted with diethyl ether. The
organic phase was washed with water and saturated aqueous
sodium chloride, dried over magnesium sulfate, and concentrated
under vacuum (rotary evaporator). The crude product was
filtered under a glass frit and washed with hexane except for
4d,o-r, which has been purified by silica gel chromatography
(hexane/ethyl acetate). â-Amino ketones 4a-g,i-p,s accord
exactly with those that have been previously reported in the
literature.
3-Cyclohexyl-1-phenyl-3-(N-phenylamino)propan-1-
one (4n):19 77% yield.
3-[N-(2-Methoxyphenylamino)]-1,3-diphenylpropan-1-
one (4o):25 65% yield.
3-[N-(4-Methoxyphenylamino)]-1,3-diphenylpropan-1-
one (4p):19,20 79% yield.
3-[N-(2-Methoxy-4-nitrophenylamino)]-1,3-diphenylpro-
pan-1-one (4q). Reagents: benzaldehyde (203 µL, 212 mg, 2.0
mmol), 2-methoxy-4-nitroaniline (336 mg, 2.0 mmol), 3a (462
mg, 2.4 mmol), and Bi(OTf)3‚4H2O (14 mg, 0.02 mmol). The
reaction was carried out at 0 °C, stirred for 0.5 h, and quenched
according to the typical procedure. The crude product was
purified by silica gel chromatography (hexane/ethyl acetate )
80:20) to afford 642 mg (85%) of 4q as a yellow solid: mp 138-
140 °C; Rf 0.18 (hexane/ethyl acetate ) 4:1); IR (KBr) ν 3393,
1,3-Diphenyl-3-(N-phenylamino)propan-1-one (4a):19,20
89% yield.
2-Methyl-1,3-diphenyl-3-(N-phenylamino)propan-1-
one (4b):19,21 73% yield.
1
1683; H NMR (CDCl3) δ 7.90-7.92 (2H, m), 7.74 (1H, dd, J )
1-(4-Chlorophenyl)-3-phenyl-3-(N-phenylamino)propan-
1-one (4c):22 82% yield.
8.9, 2.4 Hz), 7.61 (1H, d, J ) 2.3 Hz), 7.58 (1H, t, J ) 7.5 Hz),
7.46 (2H, t, J ) 7.7 Hz), 7.32-7.40 (4H, m), 7.25-7.28 (1H, m),
6.37 (1H, d, J ) 9.0 Hz), 5.17 (1H, t, J ) 6.3 Hz), 3.95 (3H, s),
3.57 (1H, d, J ) 3.3 Hz), 3.55 (1H, d, J ) 2.0 Hz); 13C NMR
(CDCl3) δ 197.5, 145.7, 143.1, 141.6, 137.8, 136.7, 133.9, 129.3,
129.0, 128.4, 128.1, 126.4, 119.7, 108.5, 104.9, 56.2, 53.9, 46.2.
HRMS calcd for C22H20N2O4 (M+) 376.1423, found 376.1419.
3-[N-(4-Methoxy-2-nitrophenylamino)]-1,3-diphenylpro-
pan-1-one (4r). Reagents: benzaldehyde (203 µL, 212 mg, 2.0
mmol), 4-methoxy-2-nitroaniline (336 mg, 2.0 mmol), 3a (462
mg, 2.4 mmol), and Bi(OTf)3‚4H2O (14 mg, 0.02 mmol). The
reaction was carried out at 0 °C, stirred for 0.5 h, and quenched
according to the typical procedure. The crude product was
purified by silica gel chromatography (hexane/ethyl acetate )
85:15) to afford 659 mg (88%) of 4r as a orange solid: mp 106-
108 °C; Rf 0.31 (hexane/ethyl acetate ) 4:1); IR (KBr) ν 3352,
1683; 1H NMR (CDCl3) δ 8.53 (1H, br s), 7.91-7.93 (2H, m),
7.56-7.61 (2H, m), 7.41-7.47 (4H, m), 7.34 (2H, t, J ) 7.5 Hz),
7.24-7.28 (1H, m), 7.01 (1H, dd, J ) 9.4, 3.1 Hz), 6.77 (1H, d, J
) 9.4 Hz), 5.34 (1H, t, J ) 6.1 Hz), 3.75 (3H, s), 3.64 (1H, dd, J
) 16.9, 7.5 Hz), 3.50 (1H, dd, J ) 16.9, 5.4 Hz); 13C NMR (CDCl3)
δ 196.9, 150.2, 142.0, 140.3, 136.7, 133.8, 131.9, 129.3, 129.0,
128.4, 128.0, 127.1, 126.5, 116.7, 107.4, 56.0, 54.0, 47.1; HRMS
calcd for C22H20N2O4 (M+) 376.1423, found 376.1419.
4-Phenyl-4-(N-phenylamino)butan-2-one (4d):22,23 42%
yield.
2-(Phenyl-N-phenylaminomethyl)cyclopentanone (4e):
20
80% yield.
2-(Phenyl-N-phenylaminomethyl)cyclohexanone (4f):
19,21
81% yield.
3-(4-Chlorophenyl)-1-phenyl-3-(N-phenylamino)propan-
1-one (4 g):19 82% yield.
3-[4-(Trifluoromethyl)phenyl]-1-phenyl-3-(N-phenylami-
no)propan-1-one (4h). Reagents: 4-(trifluoromethyl)benzal-
dehyde (273 µL, 348 mg, 2.0 mmol), 2 (182 µL, 186 mg, 2.0
mmol), 3a (462 mg, 2.4 mmol), and Bi(OTf)3‚4H2O (14 mg, 0.02
mmol). The reaction was stirred for 0.5 h and quenched accord-
ing to the typical procedure. The crude product was washed with
hexane to afford 654 mg (88%) of 4h as a white solid: mp 144-
145 °C; Rf 0.39 (hexane/ethyl acetate ) 4:1); IR (KBr) ν ) 3403,
1671; 1H NMR (CDCl3) δ 7.89 (2H, d, J ) 7.4 Hz), 7.55-7.59
(5H, m), 7.44 (2H, t, J ) 7.7 Hz), 7.11 (2H, t, J ) 7.9 Hz), 6.71
(1H, t, J ) 7.3 Hz), 6.56 (2H, d, J ) 7.8 Hz), 5.06 (1H, t, J ) 6.3
Hz), 3.52 (1H, d, J ) 2.5 Hz), 3.50 (1H, d, J ) 3.7 Hz); 13C NMR
(CDCl3) δ 197.9, 147.3, 146.7, 136.7, 133.9, 129.8 (q, J ) 32.2
Hz), 129.5, 129.0, 128.6, 128.4, 127.1, 126.0 (q, J ) 3.8 Hz), 124.3
(q, J ) 270 Hz), 118.5, 114.2, 54.6, 46.2; 19F NMR (CDCl3) δ
-62.94; HRMS calcd for C22H18F3NO (M+) 369.1340, found
369.1336.
Benzyl 3-oxo-1,3-diphenylpropylcarbamate (4s):26 49%
yield.
3-(4-Nitrophenyl)-1-phenyl-3-(N-phenylamino)propan-
1-one (4i):19 87% yield.
Acknowledgment. This work was financially sup-
ported by the Natural Sciences and Engineering Re-
search Council of Canada (NSERC), the Fonds Que´be´-
coisde la Recherche sur la Nature et les Technologies
(FQRNT, Que´bec, Canada), the Canada Foundation for
Innovation, and Universite´ Laval. E.N. thanks NSERC
for a postgraduate scholarship. We thank Sidech s.a.
(Tilly, Belgium) for a generous gift of Bi2O3.
3-(4-Methoxyphenyl)-1-phenyl-3-(N-phenylamino)propan-
1-one (4j):24 86% yield.
3-(Furan-2-yl)-1-phenyl-3-(N-phenylamino)propan-1-
one (4k):19,22 76% yield.
1-Phenyl-3-(N-phenylamino)-3-p-tolylpropan-1-one (4l):
19
82% yield.
(E)-1,5-Diphenyl-3-(N-phenylamino)pent-4-en-1-one (4m):
72% yield.
19
Supporting Information Available: Experimental de-
tails, characterization data, and NMR spectra for compounds
4a-s. This material is available free of charge via the Internet
at http://pubs.acs.org.
(19) Akiyama, T.; Takaya, J.; Kagoshima, H. Adv. Synth. Catal.
2002, 344, 338-347.
(20) Loh, T.-P.; Liung, S. B. K. W.; Tan, K.-L.; Wei, L.-L. Tetrahedron
2000, 56, 3227-3237.
(21) Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1997, 119,
10049-10053.
JO048617C
(22) Ranu, B. C.; Samanta, S.; Guchhait, S. K. Tetrahedron 2002,
58, 983-988.
(23) Kobayashi, S.; Ishitani, H.; Nagayama, S. Synthesis 1995,
1195-1202.
(25) Manabe, K.; Mori, Y.; Wakabayashi, T.; Nagayama, S.; Koba-
yashi, S. J. Am. Chem. Soc. 2000, 122, 7202-7207.
(26) Xu, L.-W.; Xia, C.-G. Tetrahedron Lett 2004, 45, 4507-4510.
(24) Yi, L.; Lei, H.; Zou, J.; Xu, X. Synthesis 1991, 717-718.
J. Org. Chem, Vol. 69, No. 26, 2004 9295