Solvent-dependent chemoselectivities in additions of β-carbonyl imines to allyltrimethylsilane with CTAN

Article abstract of DOI:10.1021/jo048955d

The oxidative coupling of β-carbonyl imines and allyltrimethylsilane with CTAN were investigated in CH₃CN and CH₂Cl ₂. In CH₃CN allylation products were obtained predominantly, while in CH₂Cl₂, dihydropyrrole products were obtained exclusively. Solvent-assisted nucleophilic cleavage of the intermediate β-silyl cation is proposed to play a role in the solvent-dependent chemoselectivity.

Full text of DOI:10.1021/jo048955d

Solven t-Dep en d en t Ch em oselectivities in Ad d ition s of â-Ca r bon yl
Im in es to Allyltr im eth ylsila n e w ith CTAN
Yang Zhang, Andrew J . Raines, and Robert A. Flowers, II*
Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania 18105
robert.flowers@lehigh.edu
Received J une 21, 2004
The oxidative coupling of â-carbonyl imines and allyltrimethylsilane with CTAN were investigated
in CH3CN and CH2Cl2. In CH3CN allylation products were obtained predominantly, while in
CH2Cl2, dihydropyrrole products were obtained exclusively. Solvent-assisted nucleophilic cleavage
of the intermediate â-silyl cation is proposed to play a role in the solvent-dependent chemoselectivity.
SCHEME 1
In tr od u ction
During the past two decades, there has been an
increasing appreciation for the utility of Ce(IV) reagents
for generating radicals and radical cations that can
further react with other substrates to form C-C bonds.1
Among these reactions, Ce(IV)-mediated oxidative addi-
tions of enolizable carbonyl compounds to activated
olefins have received considerable attention.2 Although
ceric ammonium nitrate (CAN) is the most commonly
utilized reagent for this purpose, its application is limited
to polar organic solvents such as acetonitrile and metha-
nol. The poor solubility of CAN can be avoided through
the preparation of ceric tetra-n-butylammonium nitrate
(CTAN), which contains a more lipophilic ammonium
counterion.3 We recently described the use of CTAN in
the oxidative additions of 1,3-dicarbonyl to allyltrimeth-
ylsilane.4 Interestingly, different chemoselectivities were
observed in CH3CN and CH2Cl2 leading to the formation
of allylated and dihydrofuran products, respectively. It
was proposed that oxidation of the 1,3-dicarbonyl sub-
strate, subsequent addition to allyltrimethylsilane, and
oxidation of the intermediate â-silyl radical produces a
â-silyl cation. It was further postulated that the more
polar CH3CN provided a medium capable of affording a
pathway to elimination whereas the less polar CH2Cl2
favored cyclization, which produced an oxo-stabilized
cation (Scheme 1).
method for introducing functionality in the R position of
a â-amino acid precursor, while addition followed by
cyclization would provide a convenient route to dihydro-
pyrroles. In the latter case, this methodology would offer
an alternative and concise strategy for the synthesis of
substituted dihydropyrroles.5
Resu lts a n d Discu ssion
A series of â-carbonyl imines were synthesized in good
to high yields by reacting an equimolar amount of the
1,3-dicarbonyl and corresponding amine in the presence
of 4 Å molecular sieves and amberlyst H-15. All were
found to be stable under normal column separations and
purification with silica gel. The structures of the â-car-
bonyl imines are shown in Figure 1.
With the â-carbonyl imines in hand, we investigated
the oxidative addition reactions of allyltrimethylsilane
with CTAN in CH3CN. The results are shown in Table
1. As expected, the reactions proceed through a â-scission
pathway to afford allylation products. However, initial
Enlightened by the previous study, we extended the
work to the oxidative coupling of â-carbonyl imines.
Allylation of â-carbonyl imines potentially provides a
(1) (a) Nair, V.; Balagopal, L.; Rajan, R.; Mathew, J . Acc. Chem. Res.
2004, 37, 21. (b) Nair, V.; Mathew, J .; Prahakaran, J . J . Chem. Soc.
Rev. 1997, 127. (c) Molander, A. G. Chem. Rev. 1992, 92, 29.
(2) (a) Paolobelli, A. B.; Ceccherelli, P.; Pizzo, F.; Ruzziconi, R. J .
Org. Chem. 1995, 60, 4954. (b) Hwu, J . R.; Chen, C. N.; Shiao, S. S. J .
Org. Chem. 1995, 60, 856. (c) Nair, V.; Mathew, J .; Alexander, S. Synth.
Commun. 1995, 25, 3981. (d) Nair, V.; Mathew, J . J . Chem. Soc., Perkin
Trans. 1 1995, 187. (e) Paolobelli, A. B.; Gioacchini, R.; Ruzziconi, R.
Tetrahedron Lett. 1993, 34, 721. (f) Baciocchi, E.; Ruzziconi, R. Synth.
Commun. 1988, 18, 1841.
(3) (a) Muathen, H. A. Ind. J . Chem. 1991, 30B, 522. (b) Chen, C.;
Mariano, P. S. J . Org. Chem. 2000, 65, 3252.
(4) Zhang, Y.; Raines, A. J .; Flowers, R. A., II Org. Lett. 2003, 5,
2363.
(5) For representative recent syntheses of dihydropyrroles see: (a)
Sonesson, C.; Hallberg, A. Tetrahedron Lett. 1995, 36, 4505. (b) Ferraz,
H. M. C.; de Oliveira, E. O.; Payret-Arrua, M. E.; Brandt, C. A. J . Org.
Chem. 1995, 60, 7357. (c) Busacca, C. A.; Dong, Y. Tetrahedron Lett.
1996, 37, 3947. (d) Kawase, M.; Hirabayashi, M.; Koiwai, H.; Yama-
moto, K.; Miyamae, H. Chem. Commun. 1998, 641. (e) Knight, D. W.;
Redfern, A. L.; Gilmore, J . Chem. Commun. 1998, 2207. (f) Kawase,
M.; Hirabayashi, M.; Saito, S.; Yamamoto, K. Tetrahedron Lett. 1999,
40, 2541. (g) Prabhakaran, E. N.; Nugent, B. M.; Williams, A. L.; Nailor,
K. E.; J ohnston, J . N. Org. Lett. 2002, 4, 4197. (h) Knight, D. W.;
Redfern, A. L.; Gilmore, J . J . Chem. Soc., Perkin Trans. 1 2002, 622.
(i) Doyle, M. P.; Yan, M.; Hu, W.; Gronenberg, L. S. J . Am. Chem. Soc.
2003, 125, 4692.
10.1021/jo048955d CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/14/2004
J . Org. Chem. 2004, 69, 6267-6272
6267

Zhang et al.
TABLE 2. Cycliza tion Rea ction s in CH2Cl2
entry
substrate
product
yield (%)a
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
5a
5b
5c
5d
5e
5f
5g
5h
5i
78
71
54
65
82
72
48
76
80
74
F IGURE 1. Series of â-carbonyl imines utilized in these
studies.
10
1j
5j
TABLE 1. Exa m p les of CTAN-Med ia ted Oxid a tive
Ad d ition s of â-Ca r bon yl Im in es to Allyltr im eth ylsila n e in
CH3CN
a
Isolated yields. Reaction conditions: (D) 2 equiv of CTAN/
CH2Cl2, 4 h, Et3N, rt.
addition of triethylamine before aqueous workup (condi-
tion B in Table 1). The results of these reactions are
shown in Table 2.
The reactions proceeded as expected and no allylation
or hydrolyzed side products were observed in these
reactions in contrast to analogous reactions of â-dicar-
bonyls.4 The yields are good for those â-carbonyl imines
obtained from benzyl and propylamine while yields from
imines prepared from phenyl glycine methyl ester (1c and
1g) were modest. This indicates that sterically encum-
bered imines inhibit the cyclization to some extent.
In previous work with diketones, most reactions with
allyltrimethylsilane initiated by CTAN in CH3CN pro-
vided predominantly allylated products with a small
amount of cyclized dihydrofuran present as a side prod-
uct. The opposite distribution was found in CH2Cl2. In
the present studies with â-carbonyl imines the reactions
are more selective with allylation occurring exclusively
in CH3CN and cyclized products formed exclusively in
CH2Cl2.
yield (%)b
entry
substrate
conditionsa
product
3a
2a , 3a
2d
2e, 3e
2e, 3e
2f, 3f
2g
2g, 4g
2h , 3h
2i, 3i
2j, 3j
2k , 3k , 4k
2
3
4
1
2
3
4
5
6
7
8
9
1a
1a
1d
1e
1e
1f
1g
1g
1h
1i
A
B
B
A
B
B
B
C
B
B
B
C
62
15
52
73
10
70
71
44
56
65
54
37
46
56
8
5
12
16
7
10
9
Although selectivity in the present reactions is quite
good, the role of solvent is unclear. The initial hypothesis
was based on the supposition that solvent stabilization
of an intermediate cation determines whether â-scission
or cyclization occurs (described in Scheme 1). Another
possible scenario involves solvent as a nucleophile in the
displacement of the silyl group from the intermediate
cation. Since the seminal work of Dinnocenzo describing
the nucleophile-assisted cleavage of cation radicals,6 it
has been shown that nucleophilic solvents including
alcohols and pyridines can accelerate the rate of cleavage
10
11
12
1j
1k
11
a
Conditions: (A) 2 equiv of CTAN/CH3CN, 4 h, rt; (B) 2 equiv
of CTAN/CH3CN, 4 h, Et3N, rt; (C) 4 equiv of CTAN/CH3CN, 4 h,
b
Et3N, rt. Isolated yield.
conditions (A in Table 1, entries 1 and 4) lead to
hydrolysis upon workup, presumably through catalysis
initiated by the Ce(III) product ion. To circumvent this,
excess triethylamine (2 g) was added to the completed
reaction and the precipitated Ce salts were filtered before
aqueous workup. This protocol reduced hydrolysis of the
imine and provided allylated â-carbonyl imines in good
to moderate isolated yields. Substrates 1g and 1j were
exceptions and the overall product yields (and conversion)
were low in these two cases. The use of excess CTAN only
slightly enhanced the yields and produced some of the
diallylated products (entries 8 and 12).
of -O-SiR3 and -O-C•+ cation radicals.7,8 More re-
•+
cently, Eberlin and co-workers carried out studies that
examined â-silyl cations formed upon the addition of
N-acyliminium ions to allyltrimethylsilane in the gas
phase.9 These studies clearly showed that in the absence
(6) Dinnocenzo, J . P.; Farid, S.; Goodman, J . L.; Gould, I. R.; Todd,
W. P.; Mattes, S. L. J . Am. Chem. Soc. 1989, 111, 8973.
(7) (a) Schmittel, M.; Keller, M.; Burghart, A. J . Chem. Soc., Perkin
Trans. 2 1995, 2327. (b) Schmittel, M.; Heinze, J .; Trenkle, H. J . Org.
Chem. 1995, 60, 2726.
(8) Bockman, T. M.; Kochi, J . K. J . Chem. Soc., Perkin Trans. 2 1996,
1633.
With these initial studies complete, our attention
turned next to the oxidative addition of the â-iminocar-
bonyls to allyltrimethylsilane in the less polar CH2Cl2.
The reactions were carried out with 2 equiv of CTAN with
(9) D’Oca, M. G. M.; Moraes, L. A. B.; Pilli, R. A.; Eberlin, M. N. J .
Org. Chem. 2001, 66, 3854.
6268 J . Org. Chem., Vol. 69, No. 19, 2004

Additions of â-Carbonyl Imines to Allyltrimethylsilane
SCHEME 2
of nucleophiles, the intermediate â-silyl cations can
reform reactants through fragmentation while the pres-
ence of a nucleophile led to â-scission, which produced
allylated products.
Exp er im en ta l Section
Ma ter ia ls a n d Gen er a l Meth od s. All oxidative additions
were carried out under an inert atmosphere. Ceric tetrabutyl-
ammonium nitrate (CTAN) was prepared with ceric am-
monium nitrate and tetrabutylammonium nitrate hydrogen
sulfate and recrystalized in CH2Cl2.3a All substrates were
purchased from Aldrich and used without further purification.
CH3CN and CH2Cl2 were distilled from CaO under nitrogen.
NMR spectra were recorded on a Varian Unity Inova 500-MHz
spectrometer. Mass spectra were performed on a Thermoquest
2000 series trace ion trap GC-MS.
The studies briefly described above support a mecha-
nism where a nucleophile is necessary to effect cleavage
of a â-silyl cation to an olefin. To determine if this
mechanistic scenario is possible in the present system,
reactions of 1j and allyltrimethylsilane initiated by CTAN
were carried out in CH2Cl2 containing 15% acetonitrile
or methanol. In both cases, the addition of nucleophilic
solvent resulted in the presence of 2j, suggesting a role
for nucleophilic solvent in the allylation reaction. In the
reaction containing acetonitrile, the ratio 5j:2j was 10:1,
while the medium containing the more nucleophilic
methanol produced a product ratio of 4:1. This supports
a mechanism where the presence of a nucleophilic solvent
acts to facilitate â-scission through the nucleophilic
displacement of the silyl moiety of the â-silyl cation. In
the absence of a nucleophilic solvent, the intermediate
â-silyl cation is quenched by the presence of a proximal
nucleophilic imine (Scheme 2).
P r oced u r e for th e Oxid a tive Ad d ition Rea ction s Ca r -
r ied Ou t in CH3CN. Con d ition A: CTAN (2 equiv) in 5 mL
of CH3CN solution was added dropwise to a stirred mixture
of â-carbonyl imine compound and allyltrimethylsilane in 10
mL of CH3CN. When TLC showed the starting material was
fully consumed, the solvent was removed by rotary evapora-
tion. Next, 50 mL of 1:1 hexane/EtOAc was added to precipi-
tate Ce salts. After filtration, the filtrate was poured in water
and extracted with 4 × 25 mL of ether. The extract was washed
with brine and then dried with MgSO4. The residue obtained
after removal of solvent was chromatographed with a silica
gel column with a mixture of hexane and EtOAc as eluent.
Con d ition B: CTAN (2 equiv) in 5 mL of CH3CN solution
was added dropwise to a stirred mixture of â-carbonyl imine
compound and allyltrimethylsilane in 10 mL of CH3CN. When
TLC showed the starting material was fully consumed, the
solvent was removed by rotary evaporation. Next, 50 mL of
1:1 hexane/EtOAc was added to the crude product to remove
unreacted CTAN and filtered. Et3N (2 mL) was added to the
above solution and stirred for 30 min and then filtered. The
filtrate was poured into water and extracted with 4 × 25 mL
of ether. The extract was washed with brine and then dried
with MgSO4. The residue obtained after removal of solvent
was chromatographed by silica gel column with a mixture of
hexane and EtOAc as eluent.
Con d ition C: CTAN (4 equiv) in 10 mL of CH3CN was
added dropwise to a stirred mixture of â-carbonyl imine
compound and allyltrimethylsilane in 10 mL of CH3CN. The
rest of the procedure is identical with that shown in condition
2A.
P r oced u r e for th e Oxid a tive Ad d ition Rea ction s Ca r -
r ied Ou t in CH2Cl2. Con d ition D: CTAN (2 equiv) in 5 mL
of CH2Cl2 was added to a stirred mixture of â-carbonyl imine
compound and allyltrimethylsilane in 10 mL of CH2Cl2. After
starting material was fully consumed, the solvent was removed
by rotary evaporation and then 50 mL of 1:1 hexane/EtOAc
was added to precipitate cerium salts. Next, 2 mL of Et3N was
Con clu sion s
The experimental observations reported herein show
that solvent plays an important mechanistic role in
determining the mechanism and outcome of Ce(IV)-
mediated oxidative addition of allyltrimethylsilane to
â-carbonyl imines. The combination of allyltrimethyl-
silane, CTAN, and a â-carbonyl imine produces good
yields of highly substituted silylated pyrroles. The ease
of conversion of the silyl moiety contained in the product
into other functional groups potentially extends the
versatility of this approach.10 The generality of solvent-
controlled chemoselectivity with use of lipophilic Ce(IV)
oxidants in the synthesis of a variety of heterocycles is
currently being explored. The results of these studies will
be reported in due course.
(10) (a) Miura, K.; Hondo, T.; Nakagawa, T.; Takahashi, T.; Hosomi,
A. Org. Lett. 2000, 2, 385. (b) Colvin, E. Silicon in Organic Reactions;
Butterworth: London, UK, 1981; pp 44-133. (c) Fleming, I. Compre-
hensive Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.;
Pergamon: Oxford, UK, 1979; Vol. 3, pp 541-686.
J . Org. Chem, Vol. 69, No. 19, 2004 6269

Zhang et al.
added to the above solution with stirring for 30 min. The
solution was filtered and the filtrate was washed with water
and brine. The organic extracts were dried with MgSO4 and
then concentrated. The residue was chromatographed with a
silica gel column with a mixture of hexane and EtOAc as
eluent.
Procedure C was followed with use of 0.132 g of 3-(methoxy-
carbonylphenylmethylimino)butyric acid methyl ester (1g),
0.064 g of allyl trimethylsilane, and 2.24 g of CTAN. Purifica-
tion by flash chromatography (25 × 30 cm, EtOAc/hexane 1/4)
provided 0.086 g of product 2g and 0.021 g of product 4g (GC
tR ) 17.32 min, TLC Rf 0.50, EtOAc/hexane 1/3) as a light
1
yellow liquid. H NMR (CDCl3) of 4g: 1.91 (s, 3H), 2.62-2.80
Syn th esis of 3-(1-Ben zylim in oeth yl)h ex-5-en -2-on e (2a).
Procedure B was followed with use of 0.095 g of 4-benzylimi-
nopentan-2-one (1a ), 0.064 g of allyltrimethylsilane, and 1.12
g of CTAN. Crude NMR showed a mixture of 2a and 3a .
Purification by flash chromatography (25 × 30 cm, EtOAc/
hexane 1/5) provided 0.059 g of product 2a (GC tR ) 11.43 min,
TLC Rf 0.45, EtOAc/hexane 1/4) and 0.011 g of 3a (spectro-
(m, 4H), 3.73 (s, 3H), 3.78 (s, 3H), 4.98-5.14 (m, 4H), 5.22 (s,
1H), 5.61-5.79 (m, 2H), 7.29-7.55 (m, 5H). 13C NMR (CDCl3)
of 4g: 173.97, 171.57, 169.92, 138.35, 138.35, 133.50, 132.13,
129.16, 128.37, 127.89, 127.77, 118.16, 118.08, 67.22, 60.29,
52.33, 51.94, 37.33, 36.02, 16.83. Mass M+: 343.1 (1), 328.1
(15), 302.1 (18), 282.1 (13), 250.1 (23), 240.1 (35), 184.1 (14),
149.1 (36), 121.1 (100), 91.1 (45), 77.1 (53).
1
scopic data match the reported result4). H NMR of 2a 5b (500
Syn th esis of 2-(1-Ben zylim in oeth yl)p en t-4-en oic Acid
Eth yl Ester (2h ). Procedure B was followed with use of 0.11
g of 3-benzyliminobutyric acid ethyl ester (1h ), 0.064 g of allyl
trimethylsilane, and 1.12 g of CTAN. Purification by flash
chromatography (25 × 30 cm, EtOAc/hexane 1/4) provided
0.084 g of product 2h 5b (GC tR ) 12.47 min, TLC Rf 0.40,
EtOAc/hexane 1/4) as a colorless liquid and 0.012 g of product
3h .4 1H NMR (CDCl3) of 2h : 1.21-1.28 (t, J ) 7.0 Hz, 3H),
1.89 (s, 3H), 2.98-3.02 (d, J ) 6.3 Hz, 2H), 4.10-4.16 (q, J )
7.0 Hz, 2H), 4.40-4.44 (d, J ) 6.2 Hz, 2H), 5.02-5.12 (m, 2H),
5.72-5.84 (m, 1H), 7.11-7.43 (m, 5H), 9.33 (br s, 1H).
Syn th esis of 2-(1-Ben zylim in oeth yl)p en t-4-en oic Acid
ter t-Bu tyl Ester (2i). Procedure B was followed with use of
0.124 g of 3-benzyliminobutyric acid tert-butyl ester (1i), 0.064
g of allyl trimethylsilane, and 1.12 g of CTAN. Purification by
flash chromatography (25 × 30 cm, EtOAc/hexane 1/4) pro-
vided 0.077 g of product 2i (GC tR ) 14.30 min, TLC Rf 0.45
EtOAc/hexane 1/3) as a colorless liquid. 1H NMR (CDCl3) of
2i: 1.46 (s, 9H), 1.87 (s, 3H), 2.60-2.77 (m, 2H), 4.59 (s, 2H),
5.02-5.16 (m, 2H), 5.77-5.89 (m, 1H), 7.17-7.45 (m, 5H), 8.85
(br s, 1H). 13C NMR (CDCl3) of 2i: 172.85, 168.10, 133.83,
132.13, 129.16, 128.57, 128.25, 127.95, 126.36, 117.90, 95.88,
81.09, 54.29, 36.73, 27.95, 16.29. Mass M+: 287.1 (M+, 12),
272.1 (29), 258.1 (14), 247.1 (45), 146.1 (28), 129.1 (11), 101.1
(32), 91.1 (100), 57.1 (39).
MHz, CDCl3): δ 1.96 (s, 3H), 2.13 (s, 3H), 2.85-2.98 (m, 2H),
4.48 (s, 2H), 4.98-5.14 (m, 2H), 5.71-5.87 (m, 1H), 7.21-7.44
(m, 5H), 11.45 (br s, 1H).
Syn th esis of 2-(Ben zylim in op h en ylm eth yl)-1-p h en yl-
p en t-4-en -1-on e (2d ). Procedure B was followed with use of
0.162 g of 3-Benzylimino-1,3-diphenylpropan-1-one (1d ), 0.064
g of allyltrimethylsilane, and 1.12 g of CTAN. Purification by
flash chromatography (25 × 30 cm, EtOAc/hexane 1/3) pro-
vided 0.128 g of product 2d (GC tR ) 25.62 min, TLC Rf 0.40,
EtOAc/hexane 1/2). 1H NMR (500 MHz, CDCl3) of 2d : δ 2.71-
2.85 (m, 2H), 4.59 (s, 2H), 4.92-5.08 (m, 2H), 5.71-5.90 (m,
1H), 7.31-7.58 (m, 10H), 7.88-7.98 (m, 5H), 11.50 (s, 1H). 13
C
NMR (CDCl3) of 2d : 196.32, 164.64, 137.28, 135.48, 135.29,
135.22, 130.48, 129.71, 128.68, 128.59, 128.51, 128.43, 128.02,
127.83, 127.78, 126.35, 115.90, 100.02, 46.23, 32.67. Mass
M+: 353.1 (M+, 20), 276.1 (27), 262.1 (14), 248.1 (15), 171.1
(18), 105.1 (66), 91.1 (100), 77.1 (18).
Syn th esis of 2-(1-Ben zylim in oeth yl)p en t-4-en oic Acid
Meth yl Ester (2e). Procedure A was followed with use of
0.103 g of 3-benzyliminobutyric acid methyl ester (1e), 0.064
g of allyltrimethylsilane, and 1.12 g of CTAN. Purification by
flash chromatography (25 × 30 cm, EtOAc/hexane 1/5) pro-
vided 0.086 g of product 2e (GC tR ) 12.32 min, TLC Rf 0.40,
EtOAc/hexane 1/4) and 0.013 g of 3e as colorless liquids.4 1H
NMR (500 MHz, CDCl3) of 2e:5b 1.95 (s, 3H), 2.97-3.01 (d, J
) 6.4 Hz, 2H), 3.73 (s, 3H), 4.42-4.44 (d, J ) 6.4 Hz, 2H),
4.96-5.08 (m, 2H), 5.78-5.90 (m, 1H), 7.18-7.44 (m, 5H), 9.79
(br s, 1H).
Syn th esis of 2-(1-P r op ylim in oeth yl)p en t-4-en oic Acid
Meth yl Ester (2f). Procedure B was followed with use of 0.078
g of 3-Propylimino-butyric acid methyl ester (1f), 0.064 g allyl
trimethylsilane and 1.12 g of CTAN. Purification by flash
chromatography (25 × 30 cm, EtOAc/hexane 1/5) provided
0.071 g of product 2f (GC tR ) 11.01 min, TLC Rf 0.45, EtOAc/
hexane 1/4) as a colorless liquid. 1H NMR (CDCl3) of 2f: 0.94-
1.02 (t, J ) 7.0 Hz, 3H), 1.32-1.40 (m, 2H), 1.85 (s, 3H), 2.86-
2.92 (d, J ) 6.0 Hz, 2H), 3.14-3.26 (m, 2H), 3.71 (s, 3H), 4.93-
5.08 (m, 2H), 5.75-5.87 (m, 1H), 8.95 (s, 1H). 13C NMR (CDCl3)
of 2f: 169.82, 163.77, 135.08, 116.35, 95.40, 58.16, 47.13, 33.38,
23.81, 14.25, 11.26. Mass M+: 197.1 (M+, 7), 182.1 (35), 168.1
(29), 154.1 (100), 127.1 (49), 91.1 (78), 81.1 (36).
Syn t h esis of 2-[1-(Met h oxyca r b on ylp h en ylm et h yl-
im in o)eth yl]p en t-4-en oic Acid Meth yl Ester (2g). Proce-
dure B was followed with use of 0.132 g of 3-(methoxycarbo-
nylphenylmethylimino)butyric acid methyl ester (1g), 0.064 g
of allyl trimethylsilane, and 1.12 g of CTAN. Purification by
flash chromatography(25 × 30 cm, EtOAc/hexane 1/4) provided
0.067 g of product 2g (GC tR ) 15.98 min, Rf 0.40 EtOAc/
hexane 1/3) as a light yellow liquid. 1H NMR (CDCl3) of 2g:
1.82 (s, 3H), 2.78-2.92 (m, 2H), 3.69 (s, 3H), 3.72 (s, 3H), 4.95-
5.13 (m, 2H), 5.26 (s, 1H), 5.66-5.82 (m, 1H), 7.34-7.55 (m,
5H). 13C NMR (CDCl3) of 2g: 174.07, 171.76, 157.44, 135.55,
135.48, 128.36, 128.16, 127.74, 126.28, 126.23, 117.98, 90.33,
67.22, 55.98, 55.40, 37.84, 35.20, 27.50, 17.78. Mass M+: 303.1
(6), 288.1 (22), 272.1 (36), 262.1 (30), 242.1 (95), 210.1 (70),
149.1 (67), 121.1 (100), 91.1 (56), 77.1 (31).
Syn th esis of 2-Allyl-3-p r op ylim in ocycloh exa n on e (2k ).
Procedure B was followed with use of 0.077 g of 3-benzylimi-
nocyclohexanone (1k ), 0.064 g of allyl trimethylsilane, and 1.12
g of CTAN. Purification by flash chromatography (25 × 30 cm,
EtOAc/MeOH:20/1) provided 0.035 g of product 2k (GC tR
)
11.49 min, TLC Rf 0.35 EtOAc/MeOH 10/1) as a light yellow
1
solid. H NMR (CDCl3) of 2k :11 1.02-1.08 (t, J ) 7.0 Hz, 3H),
1.52-1.58 (m, 2H), 2.00-2.06 (t, J ) 7.0 Hz, 2H), 2.32-2.48
(m, 4H), 2.94-2.98 (d, J ) 6.2 Hz, 2H), 3.08-3.14 (m, 2H),
4.98-5.04 (m, 2H), 5.66-5.80 (m, 1H), 6.78 (s, 1H).
Syn th esis of 2,2-Dia llyl-3-p r op ylim in ocycloh exa n on e
(4k ). Procedure C was followed with use of 0.077 g of
3-benzyliminocyclohexanone (1k ), 0.064 g of allyl trimethyl-
silane, and 2.24 g of CTAN. Purification by flash chromatog-
raphy (25 × 30 cm, EtOAc/MeOH:20/1) provided 0.44 g of
product 2k and 0.018 g of product 4k (GC tR ) 13.50 min, TLC
Rf 0.50 EtOAc/MeOH 10/1) as a yellow liquid. 1H NMR (CDCl3)
of 4k : 0.92-0.95 (t, J ) 7.1 Hz, 3H), 1.52-1.58 (h, 2H), 1.98-
2.04 (t, J ) 6.2 Hz, 2H), 2.48-2.73 (m, 8H), 3.11-3.16 (q, J )
7.1 Hz, 2H), 4.98-5.11 (m, 4H), 5.56-5.80 (m, 2H). 13C NMR
(CDCl3) of 4k : 210.19, 166.42, 139.01, 138.68, 117.27, 117.11,
61.37, 50.16, 40.56, 30.62, 30.30, 24.58, 20.26, 15.73, 11.40.
Mass M+: 233.1 (M+, 3), 218.1 (24), 205.1 (33), 193.1 (100),
165.1 (18), 125.1 (16), 110.1 (20), 91.1 (24), 83.1 (12), 79.1 (35).
Syn th esis of 1-(1-Ben zyl-2-m eth yl-5-tr im eth ylsila n yl-
m eth yl-4,5-d ih yd r o-1H-p yr r ol-3-yl)eth a n on e (5a ). Proce-
dure D was followed with use of 0.095 g of 4-benzyliminopentan-
2-one (1a ), 0.065 g of allyl trimethylsilane, and 1.12 g of CTAN.
Product 5a (0.117 g) (GC tR ) 16.28 min, TLC Rf 0.65, hexane/
EtOAc 4/1) was obtained in a light red liquid and identified
Syn t h esis of 2-Allyl-2-[1-(m et h oxyca r b on ylp h en yl-
m eth ylim in o)eth yl]p en t-4-en oic Acid Meth yl Ester (4g).
(11) Iida, H.; Yuasa, Y.; Kibayashi, C. Tetrahedron Lett. 1982, 23,
3591.
6270 J . Org. Chem., Vol. 69, No. 19, 2004

Additions of â-Carbonyl Imines to Allyltrimethylsilane
without further purification. 1H NMR (CDCl3) of 5a : 0.098
(s, 9H), 1.00-1.08 (dd, J ) 14.7 and 7.2 Hz, 1H), 1.18-1.26
(dd, J ) 14.1 and 7.4 Hz,1H), 1.94 (s, 3H), 2.17 (s, 3H), 2.54-
2.62 (m, 1H), 3.03-3.11 (m, 1H), 3.48-3.60 (m, 1H), 4.64 (s,
2H), 7.19-7.48 (m, 5H). 13C NMR (125 MHz, CDCl3) of 5a : δ
195.41, 163.04, 138.04, 128.79, 128.34, 128.23, 127.39, 126.25,
100.88, 56.18, 46.89, 38.66, 27.78, 23.38, 14.87, -0.09. Mass
M+: 301.1 (M+, 7), 286.1 (62), 270.2 (10), 258.1 (12), 228.1 (25),
214.1 (18), 152.1 (22), 137.1 (13), 110.1 (14), 91.1 (85), 73.1
(100).
Syn th esis of 1-(2-Meth yl-1-p r op yl-5-tr im eth ylsila n yl-
m eth yl-4,5-d ih yd r o-1H-p yr r ol-3-yl)eth a n on e (5b). Proce-
dure D was followed with use of 0.078 g of 4-propyliminopentan-
2-one (1b), 0.065 g of allyl trimethylsilane, and 1.12 g of CTAN.
Product 5b (0.09 g) (GC tR ) 15.83 min, TLC Rf 0.7, hexane/
EtOAc 4/1) was obtained in a light red liquid. 1H NMR (CDCl3)
of 5b: 0.09 (s, 9H), 0.91-0.98 (t, J ) 7.0 Hz, 3H), 1.02-1.10
(dd, J ) 14.2 and 7.1 Hz, 1H), 1.18-1.26 (dd, J ) 14.0 and 7.4
Hz, 1H), 1.58-1.69 (q, J ) 7.0 Hz, 2H), 1.98 (s, 3H), 2.10 (s,
3H), 2.46-2.56 (dd, J ) 13.8 and 7.6, 1H), 2.94-3.04 (dd, J )
14.0 and 7.2, 1H), 3.24-3.32 (t, J ) 7.0 Hz, 2H), 3.56-3.66
(m, 1H). 13C NMR (CDCl3) of 5b: 196.52, 163.18, 108.23, 50.24,
46.22, 38.66, 27.10, 22.02, 13.50, 11.94, -0.89. Mass M+: 253.1
(M+, 4), 252.1 (18), 238.1 (85), 224.1 (32), 222.1 (12), 210.1 (25),
196.1 (12), 180.1 (14), 152.1 (21), 138.1 (14), 125.1 (12), 110.1
(17), 73.1 (100).
50.02, 43.69, 37.82, 25.46, 15.34, -0.95. Mass M+: 317.1 (M+,
0.5), 316.1 (21), 302.1 (73), 284.1 (26), 259.1 (12), 212.1 (36),
167.1 (42), 153.1 (32), 91.1 (100), 73.1 (65).
Syn t h esis of 2-Met h yl-1-p r op yl-5-t r im et h ylsila n yl-
m eth yl-4,5-d ih yd r o-1H-p yr r ole-3-ca r boxylic Acid Meth yl
Ester (5f). Procedure D was followed with use of 0.079 g of
3-propyliminobutyric acid methyl ester (1e), 0.065 g of allyl
trimethylsilane, and 1.12 g of CTAN. Product 5f (0.097 g) (GC
tR ) 16.04 min, TLC Rf 0.65 hexane/EtOAc 4/1) was obtained
in a pale yellow oil. 1H NMR (CDCl3) of 5f: 0.07 (s, 9H), 0.90-
0.98 (t, 3H), 1.02-1.10 (dd, J ) 14.0 and 7.2 Hz, 1H), 1.18-
1.26 (dd, J ) 14.5 and 6.8 Hz, 1H), 1.54-1.66 (m, 2H), 2.07 (s,
3H), 2.46-2.58 (m, 1H), 2.96-3.08 (m, 1H), 3.14-3.22 (m, 2H),
3.47-3.55 (m, 1H), 3.76 (s, 3H). 13C NMR (CDCl3) of 5f:
167.39, 160.42, 103.83, 57.92, 55.26, 49.31, 38.70, 23.42, 22.02,
14.05, 11.34, -0.65. Mass M+: 269.1 (M+, 25), 254.1 (60), 236.1
(23), 225.1 (41), 208.1 (40), 190.1 (14), 157.1 (23), 141.1 (16),
112.1 (35), 73.1 (100), 43.1 (36).
Syn t h esis of 1-(Met h oxyca r b on ylp h en ylm et h yl)-2-
m eth yl-5-tr im eth ylsilan ylm eth y l-4,5-dih ydr o-1H-pyr r ole-
3-ca r boxylic Acid Meth yl Ester (5g). Procedure D was
followed with use of 0.132 g of 3-(methoxycarbonylphenyl-
methylimino)butyric acid methyl ester (1g), 0.065 g of allyl
trimethylsilane, and 1.12 g of CTAN. Product 5g (0.091 g) (GC
tR ) 20.78 min, TLC Rf 0.45 hexane/EtOAc 4/1) was obtained
in a sticky light oil. 1H NMR (CDCl3) of 5g: 0.082 (s, 9H),
1.02-1.12 (dd, J ) 14.5 and 7.2 Hz, 1H), 1.20-1.30 (dd, J )
14.0 and 6.8 Hz 1H), 2.07 (s, 3H), 2.46-2.56 (m, 1H), 3.04-
3.14 (m, 1H), 3.53-3.65 (m, 1H), 3.70 (s, 3H), 3.76 (s, 3H), 5.26
(s, 1H), 7.18-7.45 (m, 5H). 13C NMR (CDCl3) of 5g: 171.67,
167.39, 163.15, 135.80, 130.88, 130.16, 128.67, 128.53, 127.26,
106.72, 64.97, 57.09, 47.75, 38.42, 36.82, 23.87, 14.09, -0.85.
Mass M+: 375.1 (M+, 15), 360.1 (83), 332.1 (66), 314.1 (40),
286.1 (17), 240.1 (40), 228.1 (32), 203.1 (28), 155.1 (43), 112.1
(16), 91.1 (100), 73.1 (78).
Syn th esis of 2-P h en yl-5-tr im eth ylsila n ylm eth yl-4,5-
d ih yd r o-1H-p yr r ole-3-ca r boxylic Acid Eth yl Ester (5h ).
Procedure D was followed with use of 0.125 g of 3-benzylimi-
nobutyric acid ethyl ester (1h ), 0.065 g of allyl trimethylsilane,
and 1.12 g of CTAN. Product 5h (0.126 g) (GC tR ) 16.91 min,
TLC Rf 0.65 hexane/EtOAc 4/1)was obtained in a pale red oil.
1H NMR (CDCl3) of 5h : 0.06 (s, 9H), 0.96-1.04 (dd, J ) 14.0
and 7.0 Hz 1H), 1.14-1.22 (dd, J ) 14.2 and 6.9 Hz, 1H), 1.30-
1.36 (t, J ) 7.0 Hz, 3H), 2.10 (s, 3H), 2.41-2.49 (dd, J ) 14.2
and 7.0 Hz, 1H), 2.90-2.98 (dd, J ) 14.2 and 7.1 Hz, 1H),
3.52-3.65 (m, 1H), 4.04-4.18 (q, J ) 7.0 Hz, 2H), 4.59 (s, 2H),
7.12-7.46 (m, 5H). 13C NMR (CDCl3) of 5h : 167.20, 162.48,
136.50, 128.85, 128.44, 127.75, 127.30, 126.26, 98.52, 61.88,
57.64, 45.96, 36.67, 25.68, 14.85, 13.14, -0.40. Mass M+: 331.1
(M+, 0.5), 316.1 (63), 288.1 (23), 278.1 (12), 243.1 (16), 228.1
(32), 163.1 (42), 157.1 (32), 91.1 (100), 73.1 (53).
Syn t h esis of (4-Acet yl-5-m et h yl-2-t r im et h ylsila n yl-
m eth yl-2,3-d ih yd r op yr r ol-1-yl)p h en yla cetic Acid Meth yl
Ester (5c). Procedure D was followed with use of 0.124 g of
1-methyl-3-oxobutylideneamino)phenylacetic acid methyl ester
(1c), 0.065 g of allyl trimethylsilane, and 1.12 g of CTAN.
Product 5c (0.097 g) (GC tR ) 19.92 min, TLC Rf0.5, hexane/
1
EtOAc 4:1) was obtained in a sticky pale yellow oil. H NMR
(CDCl3) of 5c: 0.057 (s, 9H), 0.98-1.06 (dd, J ) 14.0 and 7.0
Hz, 1H), 1.16-1.24 (dd, J ) 14.0 and 7.0 Hz, 1H), 2.02 (s, 3H),
2.13 (s, 3H), 2.49-2.57 (m, 1H), 2.98-3.06 (m, 1H), 3.52-3.63
(m, 1H), 3.77 (s, 3H), 5.37 (s, 1H), 7.26-7.47 (m, 5H). 13C NMR
(CDCl3) of 5c: 196.58, 171.53, 160.35, 135.30, 129.20, 129.06,
128.85, 128.64, 128.38, 128.26, 103.25, 69.27, 54.93, 48.72,
36.80, 27.55, 23.40, 13.54, -0.66. Mass M+: 359.1 (M+, 3),
344.1 (100), 316.1 (14), 300.1 (29), 286.1 (19), 272.1 (11), 258.1
(14), 228.1 (48), 210.1 (41), 186.1 (11), 167.1 (17), 149.1 (63),
137.1 (13), 96.1 (10), 87.1 (32), 73.1 (82).
Syn th esis of P h en yl(2-ph en yl-5-tr im eth ylsilan ylm eth yl-
4,5-d ih yd r o-1H-p yr r ol-3-yl)p h en ylm eth a n on e (5d ). Pro-
cedure D was followed with use of 0.157 g of 3-benzylimino-
1,3-diphenylpropan-1-one (1d ), 0.065 g of allyl trimethylsilane,
and 1.12 g of CTAN. Product 5d (0.138 g) (GC tR ) 28.97 min,
TLC Rf 0.45, hexane/EtOAc 3/1) was obtained in a sticky pale
yellow oil. 1H NMR (CDCl3) of 5d : 0.09 (s, 9H), 1.00-1.08 (dd,
J ) 14.2 and 7.8 Hz, 1H), 1.16-1.24 (dd, J ) 14.6 and 7.0 Hz,
1H), 2.40-2.48 (dd, J ) 15.0 and 7.5 Hz 1H), 2.94-3.02 (dd,
J ) 14.2 and 7.8 Hz 1H), 3.58-3.70 (m, 1H), 4.70 (s, 2H), 7.10-
7.16 (m, 5H), 7.28-7.42 (m, 8H), 7.54-7.62 (m, 2H). 13C NMR
(CDCl3) of 5d : 193.13, 161.46, 139.28, 135.65, 135.58, 134.62,
130.68, 129.58, 129.50, 128.88, 128.14, 127.54, 127.46, 126.22,
126.21, 110.10, 100.02, 57.86, 45.53, 37.54, 23.80, -0.91. Mass
M+: 425.1 (M+, 24), 410.1 (35), 394.1 (12), 366.1 (22), 334.1
(32), 245.1 (26), 206.1 (17), 159.1 (22), 105.1 (55), 91.1 (100),
77.1 (24), 73.1 (35).
Syn t h esis of 1-Ben zyl-2-m et h yl-5-t r im et h ylsila n yl-
m eth yl-4,5-d ih yd r o-1H-p yr r ole-3-ca r boxylic Acid Meth yl
Ester (5e). Procedure D was followed with use of 0.103 g of
3-benzyliminobutyric acid methyl ester, 0.065 g of allyl tri-
methylsilane, and 1.12 g of CTAN. Product 5e (0.130 g) (GC
tR ) 16.78 min, TLC Rf 0.65, hexane/EtOAc 4/1) was obtained
in a pale yellow oil. 1H NMR (CDCl3) of 5e: 0.081 (s, 9H),
1.02-1.10 (dd, J ) 14.0 and 7.1 Hz 1H), 1.20-1.28 (dd, J )
14.2 and 6.8 Hz, 1H), 2.05 (s, 3H), 2.44-2.52 (m, 1H), 2.96-
3.04 (m, 1H), 3.48-3.54 (m, 1H), 3.72 (s, 3H), 4.64 (s, 2H),
7.29-7.53 (m, 5H). 13C NMR (CDCl3) of 5e: 170.14, 166.85,
134.18, 129.38, 129.08, 128.15, 126.88, 126.36, 103.78, 59.52,
Syn th esis of 2-P h en yl-5-tr im eth ylsila n ylm eth yl-4,5-
d ih yd r o-1H-p yr r ole-3-ca r boxylic Acid ter t-Bu tyl Ester
(5i). Procedure D was followed with use of 0.123 g of 3-ben-
zyliminobutyric acid tert-butyl ester (1i), 0.065 g of allyl
trimethylsilane, and 1.12 g of CTAN. Product 5i (0.144 g) (GC
tR ) 17.86 min, TLC Rf 0.6 hexane/EtOAc 4/1) was obtained
1
in a light red oil. H NMR (CDCl3) of 5i: 0.06 (s, 9H), 0.98-
1.06 (dd, J ) 13.8 and 7.2 Hz, 1H), 1.16-1.24 (dd, J ) 14.5
and 6.6 Hz, 1H), 1.46 (s, 9H), 2.10 (s, 3H), 2.41-2.49 (dd, J )
14.8 and 7.6 Hz,1H), 2.98-3.06 (dd, J ) 14.6 and 7.6 Hz, 1H),
3.59-3.70 (m, 1H), 4.62 (s, 2H), 7.12-7.46 (m, 5H). 13C NMR
(CDCl3) of 5i: 169.72, 160.48, 137.65, 129.06, 128.61, 128.59,
127.14, 126.28, 101.98, 75.10, 56.70, 43.94, 38.60, 29.51, 23.87,
14.30, -0.77. Mass M+: 359.1 (14), 344.1 (100), 316 (15), 312.1
(24), 282.1 (18), 219.1 (32), 154.1 (35), 101.1 (27), 91.1 (86),
73.1 (80).
Syn t h esis
of
1-Ben zyl-2-t r im et h ylsila n ylm et h yl-
1,2,3,5,6,7-h exa h yd r oin d ol-4-on e (5j). Procedure D was
followed with use of 0.101 g of 3-benzyliminocyclohexanone
(1j), 0.065 g of allyl trimethylsilane, and 1.12 g of CTAN.
Product 5j (0.119 g) (GC tR ) 18.49 min, TLC Rf 0.60 EtOAc/
J . Org. Chem, Vol. 69, No. 19, 2004 6271

Zhang et al.
1
MeOH 20/1) was obtained in a slick red oil. H NMR (CDCl3)
Ack n ow led gm en t. RAF is grateful to the National
Science Foundation (CHE-0413845) and Lehigh Uni-
versity for support of this work. We also thank Drs.
Rebecca S. Miller and Edamana Prasad for their useful
comments on the manuscript.
of 5j: 0.10 (s, 9H), 0.96-1.08 (dd, J ) 14.2 and 7.4 Hz, 1H),
1.16-1.28 (dd, J ) 14.4 and 7.0 Hz, 1H), 1.90-1.98 (m, 2H),
2.30-2.44 (m, 4H), 2.55-2.63 (m, 1H), 3.10-3.18 (m, 1H),
3.60-3.74 (m, 1H), 4.73 (s, 2H), 7.18-7.47 (m, 5H). 13C NMR
(CDCl3) of 5j: 195.17, 167.99, 136.30, 128.63, 128.42, 128.06,
127.18, 126.14, 109.40, 58.96, 46.75, 37.16, 36.64, 27.37, 23.42,
20.22, -0.91. Mass M+: 313.1 (M+, 16), 298.1 (100), 280.1 (51),
265.1 (14), 252.1 (22), 219.1 (17), 205.1 (20), 168.1 (27), 135.1
(23), 91.1 (90), 73.1 (65).
Su p p or tin g In for m a tion Ava ila ble: General methods,
experimental protocols, and spectroscopic data. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O048955D
6272 J . Org. Chem., Vol. 69, No. 19, 2004