Silylated azolium salts and their applications in the synthesis of azolines and β-enaminoketones bearing allyl-, vinyl-, and acylsilane or α-silylketone units

Article abstract of DOI:10.1016/j.tet.2009.01.114

Differently silylated 3- or 4-isoxazolines and 3-pyrazolines, bearing versatile vinyl- or allylsilane moieties in various positions of the heterocyclic system, have been synthesized starting from new silylazolium salts by reduction with metal complex hydr

Full text of DOI:10.1016/j.tet.2009.01.114

Tetrahedron 65 (2009) 5472–5483
Contents lists available at ScienceDirect
Tetrahedron
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Silylated azolium salts and their applications in the synthesis of azolines
and
or
b-enaminoketones bearing allyl-, vinyl-, and acylsilane
-silylketone units
a
*
´
Ana M. Gonzalez-Nogal , Mariola Calle
´
´
´
Departamento de Qu´ımica Organica, Facultad de Ciencias and Centro de Innovacion en Quımica y Materiales Avanzados (CINQUIMA),
Universidad de Valladolid, Dr. Mergelina s/n, 47011Valladolid, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Differently silylated 3- or 4-isoxazolines and 3-pyrazolines, bearing versatile vinyl- or allylsilane moieties
in various positions of the heterocyclic system, have been synthesized starting from new silylazolium
salts by reduction with metal complex hydrides or alkylation with organolithium reagents. On the other
hand, the reductive ring-opening of silylated isoxazolium salts with lithium dimethylcuprate led to in-
Received 12 January 2009
Received in revised form 23 January 2009
Accepted 24 January 2009
Available online 14 April 2009
teresting
b
-enamino acylsilanes and
a
0-silylmethyl-
b
-enaminoketones. These polysynthetic equivalents
are useful building blocks in organic synthesis.
Keywords:
Ó 2009 Elsevier Ltd. All rights reserved.
Silicon heterocycles
Silylisoxazolines
Silylpyrazolines
b-Enaminoacylsilanes
1. Introduction
2. Results and discussion
Following on with our current research in the synthesis of sily-
lated azole derivatives, we were especially interested in the regio-
selective synthesis of azolines bearing silyl groups in different
positions of the heterocyclic ring. Previously, we have reported1 the
synthesis of monometalated and dimetalated 1- and 2-pyrazolines
by 1,3-dipolar cycloaddition of silicon and tin alkenes with N-phenyl-
sydnone or trimethylsilyldiazomethane. Moreover, although
pyrazolium salts are not reactive toward organolithium reagents, we
prepared2 5-silyl-3-pyrazolines and 3-silylindazolines by silyl lith-
iation from pyrazolium and indazolium salts. These substrates were
opened by lithium silylcuprate reagents3 to give versatile N-silylated
2.1. Synthesis of silylated azolium salts
The starting silylazolium salts have not been previously de-
scribed. We have prepared, for the first time, a variety of 4-, 5-silyl,
3-, 4-, and 5-silylmethyl isoxazolium and pyrazolium salts by
quaternization of corresponding silylated isoxazoles (Scheme 1)
and pyrazoles (Scheme 2) with tetraethyloxonio tetrafluoroborate
and occasionally with methyl iodide (Scheme 3). The necessary
silylated azoles have been synthesized by methodologies pre-
viously described by us4–7 and others.8
2.1.1. Synthesis of silyl isoxazolium tetrafluoroborates
b-enaminoimines stabilized by coordination of the silyl group with
See Scheme 1.
both nitrogen atoms.
In this paper we describe the regioselective synthesis of new
pyrazolines and isoxazolines bearing distinct silyl groups (tri-
methyl, dimethylphenyl, and tert-butyldiphenyl) by reaction of
differently silylated isoxazolium and pyrazolium salts with metal
complex hydrides and organolithium reagents. On the other hand,
the reaction of isoxazolium salts with lithium dimethylcuprate led
2.1.2. Synthesis of silyl pyrazolium tetrafluoroborates
See Scheme 2.
2.1.3. Synthesis of silylated pyrazolium iodides
See Scheme 3.
2.2. Reactions of silylated azolium salts with metal complex
hydrides
to silylated b-enaminoketones.
Isoxazolium and pyrazolium salts were reduced with sodium
borohydride in methanol and/or lithium aluminum hydride in dry
ether, giving the corresponding isoxazolines and pyrazolines.
* Corresponding author. Tel.: þ34 983423213; fax: þ34 983423013.
´
E-mail address: agn@qo.uva.es (A.M. Gonzalez-Nogal).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.114

´
A.M. Gonzalez-Nogal, M. Calle / Tetrahedron 65 (2009) 5472–5483
5473
R2
R3
R1
R2
R3
R1
R3Si
R2
R1
Et
R3Si
R2
R1
Et3O BF4
NaBH4/MeOH
or LiAlH4/Et2O
N
N
Et
BF4
N
N Et
BF4
CH2Cl2, 0 °C
O
O
O
O
2a; R1= R2= Me, R3= Me3
2b; R1= R2= Me, R3= Me2Ph
2c; R1= R2= Ph, R3= Me2Ph
1a; R1= R3= Me, R2= SiMe3
1b; R1= R3= Me, R2= SiMe2Ph
1c; R1= R3= Ph, R2= SiMe2Ph
1d; R1= Me,R3= Ph, R2= SiMe2Ph
1e; R1= Ph, R2= H, R3= SiPh2But
1f; R1= Me, R2= H, R3= SiPh2But
1g; R1= Me, R2= H, R3= SiMe3
1h; R1= Ph, R2= H, R3= SiMe2Ph
1i; R1= CH2SiPh2But, R2= H, R3= But
1j; R1= CH2SiPh2But, R2= H, R3= Ph
1k; R1= CH2SiPh2But, R2= H, R3= Ph-OMe(p)
1l; R1= Me, R2= CH2SiMe2Ph, R3= Me
1m; R1= Me, R2= H, R3= CH2SiPh2But
1n; R1= But, R2= H, R3= CH2SiPh2But
1o; R1= Ph, R2= H, R3= CH2SiPh2But
1p; R1= Ph-Cl(p), R2= H, R3= CH2SiPh2But
2a (94%)
2b (95%)
5a (87%)
5b (90%)
5c (72%)
2c (80%)
2d; R1= Me,R2= Ph, R3= Me2Ph
5d (76%)
2d (90%)
2e (95%)
2f (95%)
2g (75%)
2h (65%)
2i (95%)
Scheme 4.
R1
R1
Et
NaBH4/MeOH
2j (90%)
2k (50%)
N
Et
N
R3Si
or LiAlH4/Et2O
R3Si
O
O
BF4
2l (95%)
2e; R1= Ph, R3= Ph2But
2f; R1= Me, R3= Ph2But
2g; R1= Me, R3= Me3
2h; R1= Ph, R3= Me2Ph
5e (95%)
5f (92%)
2m (88%)
2n (94%)
2o (90%)
2p (80%)
Scheme 5.
Scheme 1.
R3
R4
R2
R3
R4
R2
SiPh2But
SiPh2But
NaBH4/MeOH
Et3O BF4
N
N
Et
or
R
Et
BF4
R
LiAlH4/Et2O
N
N
Et
BF4
CH2Cl2, 0 °C
O
O
N
N
R1
R1
2i; R= But
2j; R= Ph
2k; R= Ph-OMe(p)
5i (65%)
5j(72%)
5k(50%)
3a; R1= Ph, R2=R4= Me, R3=SiMe3
3b; R1= Ph, R2=R4= Me, R3=SiMe2Ph
4a (95%)
4b (96%)
3c; R1= R2=R4= Ph, R3=SiMe2Ph
4c (90%)
4d (94%)
4e (92%)
Scheme 6.
3d; R1= R4= Me, R2=CH2SiPh2But, R3= H
3e; R1= R2= Me, R3= H, R4=CH2SiPh2But
3f; R1= Ph,R2= Me, R3= H, R4=CH2SiPh2But
4f (90%)
isolated and recrystallized, in the reaction medium they were
decomposed because, in both cases, an identifiable mixture was
detected (Scheme 5).
Scheme 2.
Besides the synthetic utility of the vinylsilane unit,9 the silyl
group confers on these 4-isoxazolines a special reactivity. Thus, the
2.2.1. Reduction of isoxazolium salts with sodium borohydride
or lithium aluminum hydride
4-Silyl isoxazolium tetrafluoroborates 2a–d reacted easily at rt
with sodium borohydride in methanol or lithium aluminum hy-
dride in dry ether to give 4-silylated 4-isoxazolines 5a–d in the
same yields with both hydrides (Scheme 4).
The same regiochemistry was observed in the reduction of 5-
silyl isoxazolium salts with sodium borohydride or lithium alumi-
num hydride. Starting from 5-tert-butyldiphenylsilyl isoxazolium
tetrafluoroborates 2e and 2f, 5-silyl-4-isoxazolines 5e and 5f were
obtained with good yields. However, when the 5-trimethylsilyli-
soxazolium salt 2g and 5-dimethylphenylsilylisoxazolium salt 2h
were treated with the same hydrides we could not isolate any re-
duction product. Although 2g and 2h were sufficiently stable to be
MCPBA peracid oxidation of 5-silyl-4-isoxazolines afford
a,b-un-
saturated acylsilanes in excellent yields10a and the [Co2(CO)8]
promotes the rearrangement of 4- and 5-silyl-4-isoxazolines to
silylated acylaziridines.10b Moreover, the silyl group is easily elim-
inated with concomitant cleavage of N–O bond by treatment with
fluoride ion to provide
b-lactam derivatives or a,b-unsaturated
amides.11
We have also prepared for the first time 2,3-dihydroisoxazoles
5i–k, bearing the tert-butyldiphenylsilylmethyl group in C-3 from
the corresponding isoxazolium tetrafluoroborates 2i–k by re-
duction with sodium borohydride or lithium aluminum hydride
(Scheme 6).
The 4-dimethylphenylsilylmethyl-4-isoxazoline 5l was also
synthesized from the 4-silylmethylisoxazolium tetrafluoroborate 2l
by the same procedure (Scheme 7).
R1
R2
Me
R1
R2
Me
IMe
N
N Me
I
N
Ph
N
Ph
Me
Me
PhMe2Si
Me
PhMe2Si
Me
NaBH4/MeOH
3g; R1= SiMe2Ph, R2= Me
3h; R1= H, R2= SiMe2Ph
3i; R1= H, R2= SiPh2But
N
4g (45%)
4h (90%)
4i (95%)
N
Et
or
LiAlH4/Et2O
Et
BF4
O
O
2l
5l (63%)
Scheme 3.
Scheme 7.

´
5474
A.M. Gonzalez-Nogal, M. Calle / Tetrahedron 65 (2009) 5472–5483
R
R
Me
H
N Me
PhMe2Si
Me
PhMe2Si
Me
NaBH4/MeOH
N
or
Me
N
LiAlH4/Et2O
Et
N Me
Et
BF4
O
O
ButPh2Si
ButPh2Si
N
Ph
7g
N
H
Ph
8g
2m; R= Me
2n; R= But
2o; R=Ph
5m (90%)
5n (75%)
5o (70%)
5p (65%)
Scheme 11.
2p R=Ph-Cl(p)
Me
Me
Scheme 8.
1. LiAlH4/THF, r.t.
2. ClNH4+H2O
N Me
I
N Me
R3Si
R3Si
N
N
Ph
Ph
Me3Si
Me
Me
Me3Si
Me
Me
Et
LiAlH4/THF
r.t.
4h; R3= Me2Ph
4i; R3= Ph2But
8h (80%)
8i (85%)
N
Et
BF4
N
N
N
Ph
Ph
Scheme 12.
4a
t,t-6a ( 63%) + c,t-6a (14%) + t,c-6a (23%)
purification process (flash chromatography on silica gel) giving the
cis-2-ethyl-1-phenyl-3,5-dimethylpyrazolidine 6b (Scheme 10).
Surprisingly, the change of counter-ion in the pyrazolium salt
Scheme 9.
exerted
a pronounced effect on its behavior. Thus, the 4-
Finally, 5-tert-butyldiphenylsilylmethylisoxazolium salts 2m–p
were reduced to the corresponding 5-silylmethyl-4-isoxazolines
5m–p by treatment with NaBH4 or LiAlH4 (Scheme 8).
It is noteworthy that 4-isoxazolines 5l–p are versatile building
blocks in the construction of more complex molecules. The pres-
ence in these isoxazolines of allylsilane moieties allows the transfer
of the heterocyclic system to any electrophilic substrate.12
dimethylphenylsilylpyrazolium iodide 4g in the same conditions
afforded the 4-silyl-3-pyrazolines resulting from the partial re-
duction of the ring. The regiochemistry observed (attack of hydride
at C-3 or C-5) depends on the hydrolysis conditions. When the
reaction mixture of 4g with LiAlH4 in THF at rt was hydrolyzed with
water, only the 4-dimethylphenylsilyl-1-phenyl-2,3,5-trimethyl-3-
pyrazoline 7g was isolated. However, when the hydrolysis was
carried out with a saturated aqueous solution of ammonium
chloride, an equimolecular mixture of the two possible
regioisomers 3-pyrazolines 7g and 8g resulting from attack of hy-
dride at C-5 and C-3 were obtained, respectively (Scheme 10).
Moreover, the 3-pyrazoline 7g and the mixture of 7g and 8g
were converted to the 3-pyrazoline 8g after several days at rt.
Therefore, we think that the 3-pyrazoline 7g resulting from the
nucleophilic attack at C-5 is the kinetic product, probably as
a consequence of less steric hindrance in this position and the
3-pyrazoline 8g formed by attack of hydride at C-3 is the thermo-
dynamic product, because of its greater stability due to the conju-
gation of the double bond with the NPh group. This isomerization
was favored by acid medium when the hydrolysis was carried out
with an aqueous solution of ammonium chloride (Scheme 11).
On the other hand, the reduction of 5-silyl pyrazolium iodides
4h,i with LiAlH4 was shown to be regioselective, affording the
3-silyl-3-pyrazolines resulting from the attack of hydride at C-3,
exclusively (Scheme 12).
2.2.2. Reduction of silylated pyrazolium salts with lithium
aluminum hydride
Although the pyrazolium ring can be reduced by complex metal
hydrides (NaBH4 and LiAlH4), the presence of the silyl group de-
creases its reactivity, and the reduction with sodium borohydride
did not take place. Nevertheless, its total or partial reduction was
possible with lithium aluminum hydride in dry THF. Thus, the 3,5-
dimethyl-2-ethyl-1-phenyl-4-trimethylsilylpyrazolium tetrafluoro-
borate 4a by treatment with LiAlH4 in THF at rt afforded a mixture
of diastereomeric pyrazolidines resulting from the total ring-
reduction in which the trans,trans-diastereoisomer 6a was the
main product (Scheme 9).
The reaction of the 4-dimethylphenylsilylpyrazolium tetra-
fluoroborate 4b with lithium aluminum hydride in the same con-
ditions led to a complex mixture in which the only product
identified was the corresponding trans,trans-pyrazolidine that
could not be isolated because it lost the silyl group in the
Me
Et
PhMe2Si
Me
Me
PhMe2Si
Me
Me
Conversely, 3- or 5-silylmethyl substituted pyrazolium salts did
not undergo ring-reduction. The 3-(tert-butyldiphenylsilylmethyl)-
1-methylpyrazolium salt 4d was recovered. The same lack of
reactivity was observed for the 5-(tert-butyldiphenylsilylmethyl)-
1-phenylpyrazolium salt 4f, while its analogous 1-methyl 4e ex-
perienced dequaternization to give the corresponding silylated
pyrazole 3e (Scheme 13).
LiAlH4/THF
r.t.
N
N
N
Et
BF4
Et
Me
N
N
Ph
N
Ph
Ph
4b
6b
PhMe2Si
Me
Me
N Me
Me
SiPh2But
N
LiAlH4/THF
N
Et
N Et
N.R.
Ph
Me
ButPh2Si
PhMe2Si
Me
Me
or
N
Ph
N
r.t.
LiAlH4/THF
r.t.
BF4
BF4
7g (86%)
7g (42%)
Me
N Me
I
4d
4f
N
Ph
PhMe2Si
Me
N Me
Me
N
Me
N Et
+
LiAlH4/THF
r.t.
4g
Me
N
ButPh2Si
ButPh2Si
N
N
Ph
BF4
Me
Me
8g (42%)
4e
3e
Scheme 10.
Scheme 13.

´
A.M. Gonzalez-Nogal, M. Calle / Tetrahedron 65 (2009) 5472–5483
5475
Ph
Me
Et
PhMe2Si
Ph
O
NHCH(CH3)2
Ph
MeLi
THF, -78 °C
+
N
O
Ph
Ph
9a (28%)
11a (25%)
Ph
Et
10a (43%)
PhMe2Si
O
NHCH2CH3
Ph
+
ButLi
Ph
N
O
THF, -78 °C
But
PhMe2Si
Ph
Ph
11b (21%)
N Et
BF4
O
O
NHCH(CH3)Ph
Ph
PhLi
2c
Ph
THF, -78 °C
11c (44%)
Ph
Bu
Et
Ph
Et
PhMe2Si
Ph
PhMe2Si
+
BuLi
THF
Ph
Bu
N
N
O
O
10b
9b
(12%)
(35%)
(58%)
(61%)
(40%)
(21%)
-78 °C
0 °C
r.t.
Scheme 14.
2.3. Reactions of silylated azolium salts with organometallic
reagents
isoxazolium salt 2c toward methyl-, butyl-, tert-butyl-, and
phenyllithium.
The results obtained depend on the nature of the organo-
lithium reagent. When MeLi was used the nucleophilic addition
took place exclusively at C-3, giving the 4-isoxazoline 9a, while the
As described in Introduction, pyrazolium salts were shown to be
unreactive toward organolithium and Grignard reagents13 except
when they bear a nitro group14 at C-4. On the other hand, we have
not found the behavior of these substrates toward lithium carbo-
cuprates described but we have verified3 their lack of reactivity. The
2,3,5-trimethyl-1-phenylpyrazolium iodide was recovered by
treatment with lithium dimethylcuprate. Therefore, we have lim-
ited our research to the study of the reactivity of isoxazolium salts
toward organometallic reagents.
t
bulky BuLi attacked the less hindered C-5 position affording the
3-isoxazoline 10a. In both cases the
b-enaminones 11a and 11b
resulting from ring opening and loss of the silyl group were
obtained. With BuLi, a mixture of both silylated isoxazolines 9b
and 10b was isolated. Their relative ratio depends on the tem-
perature. At ꢀ78 ꢁC the majority product is the 3-isoxazoline 10b,
while at rt the principal product was the 4-isoxazoline 9b and at
0 ꢁC an equimolecular mixture was obtained. The addition of PhLi
2.3.1. Reactions of silyl isoxazolium salts with organolithium
reagents
was not observed and only the
(Scheme 14).
b
-enaminoketone 11c was isolated
We have studied the behavior of 4- and 5-silylated and 3-, 4-,
and 5-silylmethyl isoxazolium salts toward the following organo-
lithium reagents: MeLi, BuLi, tBuLi, and PhLi.
4-Silylated 3- and/or 5-methyl substituted isoxazolium salts
2a,b,d did not react with the cited organolithium. A hydrogen–
lithium exchange in the acidic methyl groups took place and the
isoxazolium salts were regenerated in the final hydrolysis. Thus,
we have used as a starting product the 3,5-diphenyl-4-silyl
The formation of desilylated b-enaminones 11a–c could be
explained by the action of the organolithium as a base extracting
a proton of the methylene attached to the quaternary nitrogen
(CH2Nþ), followed by ring opening. The addition of organolithium
at the imine group, less hindered than the carbonyl group, could
afford a lithium amide, which undergoes a 1,3-rearrangement of
silicon from carbon to nitrogen,6 followed by the easy cleavage of
the N–Si bond in the final hydrolysis (Scheme 15).
PhMe2Si
Ph
Ph
PhMe2Si
Ph
Ph
PhMe2Si
Ph
Ph
CHCH3
RLi
N CH2CH3
N CHCH3
N
O
O
O
2c
RLi
Ph
PhMe2Si
Ph
Li
Ph
H
Ph
R
R
H3O
1,3-rearr.
CHCH3
Ph
N
Ph
O
N
H
11a-c
CHCH3
N
Li
CHCH3
R
O
O
SiMe2Ph
Scheme 15.

´
5476
A.M. Gonzalez-Nogal, M. Calle / Tetrahedron 65 (2009) 5472–5483
Ph
Me
Et
MeLi
THF, -78 °C
N
ButPh2Si
ButPh2Si
ButPh2Si
ButPh2Si
O
12a(52%)
Ph
Bu
BuLi
N
Et
THF, 0 °C
O
Ph
Et
12b(63%)
N
ButPh2Si
O
Ph
Ph
Et
BF4
2e
PhLi
THF, 0 °C
N
O
12c(66%)
Ph
ButLi
THF
But
Et
O
NHEt
Ph
+
N
ButPh2Si
O
13a
12d
-78 °C
0 °C
(11%)
(61%)
(55%)
(10%)
Scheme 16.
These new silylated and highly substituted 3- and 4-isoxazo-
lines are difficult to prepare by other methods.
R1
R1
R1
RLi; -78 °C
On the other hand, 5-silylmethyl isoxazolium salts 2m–o did not
undergo nucleophilic addition of the organolithium reagents. In all
cases tested the organolithium behaves as a base, extracting
a proton from the adjacent methylene to the silicon group. The
N
Et
BF4
N Et
O
N Et
tBuPh2Si
O
tBuPh2Si
O
tBuPh2Si
2m; R1= Me
2n; R1= tBu
2o; R1= Ph
R= Me
R= Bu
R= Me
Z:E-14a (14%):(28%)
Z: E-14b (38%):(47%)
Z:E-14c (20%):(35%)
resulting intermediate carbanion stabilized by the a-silyl group led
to the corresponding silylated 5-methylen-3-isoxazolines 14a–c, as
a mixture of Z/E stereoisomers in which the E-isomer is the main
product (Scheme 17).
Scheme 17.
3-Silylmethylisoxazolium salts 2i,j showed the same behavior,
affording E-3-silylmethylen-4-isoxazolines 15a,b. The E geometry
of 15a,b was confirmed by NOE experiments.15 When 2i was treated
with BuLi at ꢀ78 ꢁC, an equimolecular mixture of the 15a and the 3-
butyl-4-isoxazoline 16a resulting from nucleophilic addition was
isolated. The PhLi was shown to be unreactive at ꢀ78 and 0 ꢁC
(Scheme 18).
The silylated methylenisoxazolines 14a–c or 15a,b are especially
interesting for their novelty and versatility due to the presence of
an exo vinylsilane moiety conjugated with the heterocyclic double
bond.
On the other hand, we have studied the behavior of 5-silylated
3-phenylisoxazolium salts 2e and 2h toward the cited organo-
lithium reagents. The 5-dimethylphenylsilyl isoxazolium tetra-
fluoroborate 2h is unstable in the reaction medium and we were
not able to obtain any product of organometallic addition in its
reaction with methyl-, butyl, tert-butyl-, and phenyllithium. Nev-
ertheless, the 5-tert-butyldiphenylsilyl isoxazolium tetrafluoro-
borate 2e reacted regioselectively with organolithium reagents,
affording the 5-silyl-4-isoxazolines 12a–d resulting from the
t
nucleophilic attack at C-3. When BuLi was used, a mixture of the
5-silyl-4-isoxazoline 12d and the silylated
b-enaminone 13a
2.3.2. Reactions of silyl isoxazolium salts with lithium
dimethylcuprate
In general, when silyl isoxazolium salts reacted with the lithium
dimethylcuprate they underwent reductive ring opening, possibly
resulting from ring opening was obtained. The product ratio de-
pends on the temperature. At ꢀ78 ꢁC the 5-silyl-4-isoxazoline 12d
was the majority product while at 0 ꢁC the
b-enaminone 13a,
bearing an acylsilane moiety, was the main product (Scheme 16).
PhMe2Si
Me
Me
Me
t
t
1. Me2CuLi/THF, 0 °C
2. H2O+ NH4Cl
SiPh2 Bu
SiPh2 Bu
N Et
Me
Me
NHEt
t
SiPh2 Bu
O
O
Bu
RLi
+
R1
N
Et
R1
N Et
R1
N
Et
2b
11d (91%)
O
O
O
THF
BF4
(SET)
H3O
2i; R1= But
2i; R1= But
2i; R1= But
2i; R1= But
2j; R1= Ph
R=Bu, -78 °C
R=Bu, 0 °C
16a (40%)
15a (40%)
PhMe2Si
PhMe2Si
Me
Me
Me
Me
15a (95%)
15a (85%)
15a (80%)
15b (82%)
H
Me
1,3-rearr.
R=Me, -78 °C
NEt
NHEt
NEt
SiMe2Ph
R=But, -78 °C
R=Me, -78 °C
O
O
O
Scheme 18.
Scheme 19.

´
A.M. Gonzalez-Nogal, M. Calle / Tetrahedron 65 (2009) 5472–5483
5477
R1
R1
3. Conclusions
1. Me2CuLi/THF, 0 °C
2. H2O+ NH4Cl
N Et
BF4
R3Si
NHEt
R3Si
For the first time, we have synthesized 3- or 4-isoxazolines and
3-pyrazolines, bearing different silyl groups (trimethyl, dimethyl-
phenyl, and tert-butyldiphenyl) in distinct positions of the het-
erocyclic ring, by reduction or alkylation of new silylated azolium
salts. These results are interesting because isoxazolines and pyr-
azolines are frequently found in a diverse array of compounds, in-
cluding biological active agents and intermediates in organic
synthesis. In addition, the presence in these azolines of vinyl- or
allylsilane moieties can be used for the transfer of heterocyclic
frameworks to electrophilic substrates. Therefore, they are versatile
building blocks in the construction of more complex molecules. On
the other hand, the reductive ring-opening of silyl isoxazolium salts
by reaction with lithium dimethylcuprate has allowed us to syn-
O
O
2e; R1 = Ph, R3 = Ph2But
2f; R1 = Me, R3 = Ph2But
2g; R1 = Me, R3 = Me3
13a (91%)
13b (52%)
13c (75%)
Scheme 20.
R
R
R
Me2CuLi
+
N
Et
BF4
NHEt
N Et
THF, 0 °C
tBuPh2Si
O
tBuPh2Si
O
O
tBuPh2Si
thesize b-enaminoketones bearing versatile acylsilane or a-silyl-
ketone units.
__
2m; R= Me
2n; R= tBu
17a (73%)
__
Z: E-14b (36%):(47%)
__
4. Experimental
4.1. General
17b (79%)
2o; R= Ph
Scheme 21.
THF was distilled from sodium benzophenone ketyl in a recy-
cling still. Dichloromethane was distilled from P2O5. All chro-
matographic and workup solvents were distilled prior to use.
LiAlH4, NaBH4, MeLi, nBuLi, tBuLi, and PhLi were commercially
available. Reactions involving LiAlH4 and organometallic reagents
were carried out under N2. 1H and 13C NMR spectra were recorded
at 300 and 75.4 MHz, respectively, in CDCl3 as an internal standard.
Carbon multiplicities were assigned by DEPT experiments. Re-
actions were monitored by TLC on a precoated plate of silica gel 60
(nano-SIL-20, Macheray-Nagel). Flash chromatography was per-
formed on silica gel 60 (230–240 mesh, M-N).
through a single-electron-transfer (SET) process, giving silylated
-enaminoketones. Nevertheless, the 4-dimethylphenylsilyl iso-
xazolium tetrafluoroborate 2b reacted with the lithium
dimethylcuprate in THF at 0 ꢁC affording the desilylated
-enamino-
ketone 11d. The loss of the silyl group occurs after the ring opening
as we had observed in the opening of 4-silyl isoxazolium salts with
catalytic hydrogenation6 and it probably takes place by Brook
1,3-rearrangement of the silyl group from carbon to nitrogen. The
labile N–Si bond is easily hydrolyzed in the final acidic workup
(Scheme 19).
b
b
4.2. Preparation of silyl isoxazolium and pyrazolium salts
When the silyl group is attached at C-5, the ring underwent
reductive opening, without the loss of the silyl group, affording the
New 4-, 5-silyl, 3-, 4-, and 5-silylmethyl isoxazolium and pyr-
azolium tetrafluoroborates or iodides were prepared by quaterni-
zation of corresponding silylated isoxazoles and pyrazoles with
tetraethyloxonio tetrafluoroborate in dry methylene chloride at rt
for 24 h or by heating with methyl iodide in a pressure tube. The
necessary silylated azoles were synthesized by methodologies
previously described by us4–7 and others.8 Their spectroscopic data
are given below.
corresponding b-enamino acylsilanes 13a–c (Scheme 20).
The behavior of this reagent toward isoxazolium salts bearing
silylmethyl substituent in C-5 is analogous to that previously in-
dicated. The 3-methyl- and 3-phenyl-5-silylmethyl derivatives
2m,o reacted with lithium dimethylcuprate yielding the silylated b-
enaminoketones 17a,b. Meanwhile, the cuprate reagent behaves as
a base toward the hindered 3-tert-butylisoxazolium 2n leading to
the 3-isoxazoline 14b resulting from a-deprotonation to the silicon
group (Scheme 21).
4.2.1. 2-Ethyl-3,5-dimethyl-4-(trimethylsilyl)isoxazolium
tetrafluoroborate (2a)
Finally, the higher acidity of the 3-silylmethyl group in the iso-
xazolium tetrafluoroborates 2i,j, determined the exclusive behavior
of the lithium dimethylcuprate as a basic reagent, giving the same
3-silylmethylen-4-isoxazolines 15a,b previously obtained by re-
action with organolithium reagents (Scheme 22).
Yield 94%; white crystal, mp 51–52 ꢁC (from acetone–ether); IR
(CHCl3) 1574, 1522, 1258, 1052 cmꢀ1; 1H NMR (CDCl3)
d
0.37 (s, 9H),
1.57 (t, J¼7.3 Hz, 3H), 2.56 (s, 3H), 2.60 (s, 3H), 4.53 (q, J¼7.3 Hz, 2H);
13C NMR (CDCl3)
ꢀ1.60, 12.04, 12.79, 46.37, 113.85, 162.01, 175.56.
d
The silylated
be interesting synthons in the creation of silyl penta- and hexa-
heterocycles.6,7 Moreover, the well-known versatility of the
b-enaminoketones 13a–c and 17a,b have proved to
4.2.2. 2-Ethyl-3,5-dimethyl-4-(dimethylphenylsilyl)isoxazolium
tetrafluoroborate (2b)
b
-
enaminoketones16 is increased by the presence of acylsilane17 and
Yield 95%; white crystal, mp 80–81 ꢁC (from acetone–ether); IR
a
-silylketone18 moieties.
(CHCl3) 1575, 1522, 1250, 1100, 1059 cmꢀ1 1H NMR (CDCl3)
; d 0.67
(s, 6H), 1.59 (t, J¼7.3 Hz, 3H), 2.31 (s, 3H), 2.44 (s, 3H), 4.55 (q,
J¼7.3 Hz, 2H), 7.44 (m, 3H), 7.55 (m, 2H); 13C NMR (CDCl3)
d
ꢀ2.43,
t
SiPh2 Bu
t
SiPh2 Bu
12.63, 12.71, 13.26, 47.15, 113.34, 128.59, 130.54, 133.78, 133.99,
162.77, 176.72.
Me2CuLi
R
N
Et
BF4
O
THF, 0 °C
R
N Et
O
4.2.3. 2-Ethyl-4-(dimethylphenylsilyl)-3,5-diphenylisoxazolium
tetrafluoroborate (2c)
2i; R= tBu
2j; R= Ph
15a (90%)
15b (56%)
Yield 80%; white crystal, mp 188–190 ꢁC (from acetone–ether);
IR (CHCl3) 1605, 1547, 1448, 1256, 1110, 1058 cmꢀ1; 1H NMR (CDCl3)
Scheme 22.
d
0.15 (s, 6H), 1.54 (t, J¼7.2 Hz, 3H), 4.54 (q, J¼7.2 Hz, 2H), 7.27–7.66

´
A.M. Gonzalez-Nogal, M. Calle / Tetrahedron 65 (2009) 5472–5483
5478
(m, 15H); 13C NMR (CDCl3)
124.69, 128.09, 128.61, 128.92, 129.38, 129.82, 130.02, 132.17, 132.56,
133.85, 134.43, 164.20, 177.50.
d
ꢀ2.28, 13.03, 48.03, 114.70, 124.10,
9H),1.54 (t, J¼7.2 Hz, 3H), 2.66 (s, 2H), 3.87 (s, 3H), 4.64 (q, J¼7.2 Hz,
2H), 7.20 (d, J¼8.9 Hz, 2H), 7.34–7.41 (m, 6H), 7.61 (s, 1H), 7.67 (m,
4H), 7.97 (d, J¼8.9 Hz, 2H).
4.2.4. 2-Ethyl-3-methyl-4-(dimethylphenylsilyl)-5-phenyl-
isoxazolium tetrafluoroborate (2d)
4.2.12. 2-Ethyl-3,5-dimethyl-4-(dimethylphenylsilylmethyl)-
isoxazolium tetrafluoroborate (2l)
Yield 90%; white crystal, mp 84–85 ꢁC (from acetone–ether); IR
Yield 95%; white crystal, mp 62–64 ꢁC (from acetone–ether); IR
(CHCl3) 1608, 1563, 1258, 1060 cmꢀ1; 1H NMR (CDCl3)
d
0.46 (s, 6H),
1.62 (t, J¼7.3 Hz, 3H), 2.45 (s, 3H), 4.63 (q, J¼7.3 Hz, 2H), 7.28–7.54
(m,10H); 13C NMR (CDCl3)
(CHCl3) 1618, 1540, 1480, 1255, 1072 cmꢀ1 1H NMR (CDCl3)
; d 0.37
(s, 6H), 1.47 (t, J¼7.3 Hz, 3H), 2.06 (s, 3H), 2.11 (s, 3H), 2.13 (s, 2H),
d
ꢀ2.06,12.31,13.11, 47.41,113.60, 124.63,
4.44 (q, J¼7.3 Hz, 2H), 7.30–7.40 (m, 5H), 7.55 (m, 2H); 13C NMR
128.33, 128.56, 129.58, 130.12, 132.38, 133.91, 134.35, 163.35, 175.89.
(CDCl3)
d
ꢀ3.90, 10.11, 10.64, 11.341, 12.47, 47.33, 117.95, 128.16,
129.87, 133.50, 133.66, 157.68, 167.28.
4.2.5. 5-(tert-Butyldiphenylsilyl)-2-ethyl-3-phenylisoxazolium
tetrafluoroborate (2e)
4.2.13. 5-(tert-Butyldiphenylsilylmethyl)-2-ethyl-3-
methylisoxazolium tetrafluoroborate (2m)
Yield 95%; white crystal, mp 102–103 ꢁC (from acetone–ether);
IR (KBr) 1601, 1566, 1470, 1110, 1051 cmꢀ1; 1H NMR (CDCl3)
d
1.29 (s,
9H), 1.68 (t, J¼7.1 Hz, 3H), 4.94 (q, J¼7.1 Hz, 2H), 6.91 (s, 1H), 7.45–
7.76 (m, 15H); 13C NMR (CDCl3)
13.16, 18.80, 27.26, 49.67, 120.55,
Yield 88%; white crystal, mp 86–88 ꢁC (from acetone–ether); IR
(KBr) 1592, 1523, 1468, 1109, 1083 cmꢀ1; 1H NMR (CDCl3)
d
1.10 (s,
9H), 1.16 (t, J¼7.2 Hz, 3H), 2.41 (s, 3H), 3.03 (s, 2H), 4.24 (q, J¼7.2 Hz,
2H), 6.16 (s, 1H), 7.37–7.55 (m, 10H); 13C NMR (CDCl3)
11.42, 12.46,
d
121.85, 128.34, 128.65, 129.40, 129.95, 131.15, 133.46, 136.01, 157.61,
161.21.
d
13.60, 18.59, 27.26, 46.93, 106.58, 128.19, 130.34, 130.71, 135.61,
159.06, 176.04.
4.2.6. 5-(tert-Butyldiphenylsilyl)-2-ethyl-3-methylisoxazolium
tetrafluoroborate (2f)
4.2.14. 3-(tert-Butyl-5-tert-butyldiphenylsilylmethyl)-2-
ethylisoxazolium tetrafluoroborate (2n)
Yield 95%; white crystal, mp 115–117 ꢁC (from acetone–ether);
IR (KBr) 1605, 1554, 1110, 1078 cmꢀ1; 1H NMR (CDCl3)
d
1.21 (s, 9H),
1.63 (t, J¼7.3 Hz, 3H), 2.72 (s, 3H), 4.71 (q, J¼7.3 Hz, 2H), 6.86 (s, 1H),
7.41–7.58 (m, 10H); 13C NMR (CDCl3)
11.67, 12.68, 18.67, 27.20,
Yield 94%; white crystal, mp 145–147 ꢁC (from acetone–ether);
IR (CHCl3) 1576, 1479, 1104, 1065 cmꢀ1
;
1H NMR (CDCl3)
d
1.11 (s,
9H), 1.22 (t, J¼7.2 Hz, 3H), 1.26 (s, 9H), 3.12 (s, 2H), 4.39 (q, J¼7.2 Hz,
2H), 5.97 (s, 1H), 7.36–7.56 (m, 10H); 13C NMR (CDCl3)
13.14, 13.86,
d
48.21, 121.62, 128.44, 128.56, 131.05, 135.90, 157.68, 179.29.
d
18.67, 27.27, 28.19, 32.71, 49.74, 104.76, 128.12, 130.31, 130.89,
135.70, 168.70, 176.96.
4.2.7. 2-Ethyl-3-methyl-5-(trimethylsilyl)isoxazolium
tetrafluoroborate (2g)
Yield 75%; white crystal, mp 68–70 ꢁC (from acetone–ether); IR
4.2.15. 5-(tert-Butyldiphenylsilylmethyl)-2-ethyl-3-
phenylisoxazolium tetrafluoroborate (2o)
(KBr) 1605, 1573, 1255, 1084 cmꢀ1
;
1H NMR (CDCl3)
d
0.43 (s, 9H),
1.62 (t, J¼7.3 Hz, 3H), 2.68 (s, 3H), 4.65 (q, J¼7.3 Hz, 2H), 7.08 (s,1H);
13C NMR (CDCl3)
ꢀ2.82, 11.14, 12.57, 47.55, 118.27, 157.35, 182.45.
Yield 90%; white crystal, mp 133–135 ꢁC (from acetone); IR
d
(CHCl3) 1575, 1491, 1464, 1100, 1058 cmꢀ1; 1H NMR (CDCl3)
d
1.12 (s,
9H), 1.19 (t, J¼7.2 Hz, 3H), 3.21 (s, 2H), 4.32 (q, J¼7.2 Hz, 2H), 6.38 (s,
1H), 7.38–7.61 (m,15H); 13C NMR (CDCl3)
12.83,13.96,18.62, 27.21,
4.2.8. 2-Ethyl-5-(dimethylphenylsilyl)-3-phenylisoxazolium
tetrafluoroborate (2h)
d
48.25, 105.87, 122.01, 128.13, 128.74, 129.84, 130.30, 130.70, 133.26,
135.64, 159.31, 177.62.
Yield 65%; white crystal, mp 148–150 ꢁC (from acetone–ether);
IR (KBr) 1605, 1588, 125o,1080 cmꢀ1; 1H NMR (CDCl3)
d
0.82 (s, 6H),
1.62 (t, J¼7.3 Hz, 3H), 4.75 (q, J¼7.3 Hz, 2H), 7.06 (s, 1H), 7.43–7.71
(m, 10H); 13C NMR (CDCl3)
4.2.16. 5-(tert-Butyldiphenylsilylmethyl)-3-(p-chlorophenyl)-2-
ethylisoxazolium tetrafluoroborate (2p)
d
ꢀ4.17, 13.18, 49.14, 117.99, 122.13,
127.95, 128.63, 129.14, 129.92, 131.50, 132.95 134.16, 157.70, 183.20.
Yield 80%; white crystal, mp 159–160 ꢁC (from acetone–ether);
IR (KBr) 1587, 1567, 1491, 1456, 1092, 1052, 830, 700 cmꢀ1; 1H NMR
4.2.9. 5-tert-Butyl-3-(tert-butyldiphenylsilylmethyl)-2-ethyl-
isoxazolium tetrafluoroborate (2i)
(CDCl3)
d
1.14 (s, 9H), 1.20 (t, J¼7.1 Hz, 3H), 3.22 (s, 2H), 4.32 (q,
J¼7.1 Hz, 2H), 6.21 (s, 1H), 7.38–7.61 (m, 14H); 13C NMR (CDCl3)
Yield 95%; white crystal, mp 156–157 ꢁC (from acetone–ether);
d 12.82, 14.13, 18.73, 27.28, 48.32, 105.88, 120.61, 128.22, 130.26,
130.39, 130.78, 135.74, 139.95, 158.47, 177.96.
IR (CHCl3) 1590, 1566, 1464, 1110, 1065 cmꢀ1; 1H NMR (CDCl3)
d
1.14
(t, J¼7.2 Hz, 3H), 1.17 (s, 9H), 1.21 (s, 9H), 3.14 (s, 2H), 3.98 (q,
J¼7.2 Hz, 2H), 5.97 (s, 1H), 7.37–7.54 (m, 10H); 13C NMR (CDCl3)
4.2.17. 2-Ethyl-3,5-dimethyl-4-(trimethylsilyl)-1-phenylpyrazolium
tetrafluoroborate (4a)
d
11.92, 13.20, 18.62, 27.22, 27.81, 33.39, 46.91, 104.68, 128.32,
130.45, 130.62, 135.80, 162.87, 181.52.
Yield 95%; white crystal, mp 126–127 ꢁC (from acetone–ether);
IR (CHCl3) 1593, 1500, 1470, 1256, 1061 cmꢀ1 1H NMR (CDCl3)
;
4.2.10. 3-(tert-Butyldiphenylsilylmethyl)-2-ethyl-5-
phenylisoxazolium tetrafluoroborate (2j)
d
0.34 (s, 9H), 1.13 (t, J¼7.2 Hz, 3H), 2.13 (s, 3H), 2.51 (s, 3H), 4.10 (q,
J¼7.2 Hz, 2H), 7.52 (m, 2H), 7.64 (m, 3H); 13C NMR (CDCl3)
d
ꢀ0.10,
Yield 90%; white crystal, mp 174–175 ꢁC (from acetone–ether);
12.54, 13.10, 14.03, 46.63, 114.11, 128.75, 130.70, 131.05, 132.45,
150.93, 151.01.
IR (KBr) 1606,1573,1462,1104,1080 cmꢀ1; 1H NMR (CDCl3)
d
1.18 (s,
9H), 1.18 (t, J¼7.2 Hz, 3H), 3.25 (s, 2H), 3.91 (q, J¼7.2 Hz, 2H), 6.73 (s,
1H), 7.39–7.64 (m, 15H); 13C NMR (CDCl3)
12.09, 13.57, 18.65,
d
4.2.18. 2-Ethyl-3,5-dimethyl-4-(dimethylphenylsilyl)-1-
phenylpyrazolium tetrafluoroborate (4b)
27.25, 46.97, 104.31, 122.79, 127.02, 128.42, 129.56, 130.45, 130.66,
133.62, 135.90, 163.52, 169.22.
Yield 96%; white crystal, mp 96–97 ꢁC (from acetone–ether); IR
(CHCl3) 1594, 1500, 1256, 1052 cmꢀ1; 1H NMR (CDCl3)
d
0.61 (s, 6H),
1.18 (t, J¼7.3 Hz, 3H), 1.96 (s, 3H), 2.38 (s, 3H), 4.09 (q, J¼7.3 Hz, 2H),
7.40–7.70 (m, 10H), 7.64 (m, 3H); 13C NMR (CDCl3)
4.2.11. 3-(tert-Butyldiphenylsilylmethyl)-2-ethyl-5-(p-methoxy-
phenyl)isoxazolium tetrafluoroborate (2k)
d
ꢀ1.34, 12.62,
Yield 50%; white crystal, mp 188–190 ꢁC (from acetone–ether);
13.15, 14.09, 42.82, 112.70, 128.36, 128.87, 129.92, 130.87, 131.16,
132.58, 133.92, 135.87, 151.61, 151.82.
IR (CHCl3) 1605, 1575, 1100, 1082 cmꢀ1 1H NMR (CDCl3)
; d 0.94 (s,

´
A.M. Gonzalez-Nogal, M. Calle / Tetrahedron 65 (2009) 5472–5483
5479
4.2.19. 2-Ethyl-4-(dimethylphenylsilyl)-1,3,5-triphenyl pyrazolium
tetrafluoroborate (4c)
until TLC indicated complete reaction. The mixture was quenched
with aqueous NH4Cl, workup with Et2O, and the ethereal layer was
dried (MgSO4). The solvents were evaporated under reduced
pressure and the residue was purified by flash chromatography to
give the following products.
Yield 90%; white crystal, mp 155–157 ꢁC (from acetone–ether);
IR (KBr) 1594, 1494, 1254, 1100, 1083, 734, 698 cmꢀ1 1H NMR
;
(CDCl3)
d
0.01 (s, 6H), 0.99 (t, J¼7.2 Hz, 3H), 4.16 (q, J¼7.2 Hz, 2H),
7.15–7.25 (m, 10H), 7.44–7.70 (m, 10H); 13C NMR (CDCl3)
d
ꢀ3.11,
19.43, 49.16, 119.52, 132.46, 132.95, 133.43, 134.24, 134.65, 134.75,
135.17, 135.59, 136.31, 136.71, 137.43, 138.75, 141.50, 158.35, 159.20.
4.3.1. 2-Ethyl-3,5-dimethyl-4-(trimethylsilyl)-4-isoxazoline (5a)
Yield 87%; oil; Rf 0.42 (CH2Cl2); 1H NMR (CDCl3)
d 0.10 (s, 9H),
1.11 (d, J¼6.3 Hz, 3H), 1.12 (t, J¼7.2 Hz, 3H), 1.82 (s, 3H), 2.57 (dq,
4.2.20. 3-(tert-Butyldiphenylsilylmethyl)-2-ethyl-1,5-
dimethylpyrazolium tetrafluoroborate (4d)
J¼12.1, 7.2 Hz, 1H), 2.85 (dq, J¼12.1, 7.2 Hz, 1H), 3.69 (q, J¼6.3 Hz,
1H); 13C NMR (CDCl3)
d
ꢀ0.28, 12.09, 12.37, 22.93, 52.60, 70.08,
Yield 94%; white crystal, mp 149–150 ꢁC (from acetone–ether);
102.19, 155.46. Anal. Calcd for C10H21NOSi: C, 60.24; H, 10.62; N,
7.03. Found: C, 60.37; H, 10.39; N, 6.86.
IR (KBr) 1563, 1460, 1110, 1059 cmꢀ1; 1H NMR (CDCl3)
d 1.12 (s, 9H),
1.13 (t, J¼7.5 Hz, 3H), 2.25 (s, 3H), 2.70 (s, 2H), 3.75 (s, 3H), 3.83 (q,
J¼7.5 Hz, 2H), 5.80 (s, 1H), 7.35–7.57 (m, 10H); 13C NMR (CDCl3)
4.3.2. 2-Ethyl-3,5-dimethyl-4-(dimethylphenylsilyl)-4-
d
10.35, 11.71, 13.61, 18.23, 27.29, 33.48, 41.36, 107.18, 128.07, 130.30,
isoxazoline (5b)
131.11, 135.63, 146.01, 147.22.
Yield 90%; oil; Rf 0.39 (CH2Cl2); IR (CHCl3) 1640,1255,1111 cmꢀ1
;
1H NMR (CDCl3)
d
0.42 (s, 3H), 0.43 (s, 3H), 1.14 (d, J¼6.5 Hz, 3H),
4.2.21. 5-(tert-Butyldiphenylsilylmethyl)-2-ethyl-1,3-
dimethylpyrazolium tetrafluoroborate (4e)
1.19 (t, J¼7.0 Hz, 3H), 1.73 (s, 3H), 2.65 (m, 1H), 2.95 (m, 1H), 3.76 (q,
J¼6.5 Hz, 1H), 7.38 (m, 3H), 7.56 (m, 2H); 13C NMR (CDCl3)
d
ꢀ1.37,
Yield 92%; white crystal, mp 181–182 ꢁC (from acetone–ether);
ꢀ1.35, 12.34, 12.44, 23.08, 52.80, 70.17, 100.54, 127.82, 128.99,
133.74, 138.67, 157.29. Anal. Calcd for C15H23NOSi: C, 68.91; H, 8.87;
N, 5.36. Found: C, 69.23; H, 9.01; N, 5.55.
IR (KBr) 1561, 1470, 1110, 1045 cmꢀ1 1H NMR (CDCl3)
; d 1.08 (t,
J¼7.2 Hz, 3H), 1.14 (s, 9H), 2.29 (s, 3H), 2.79 (s, 2H), 3.34 (s, 3H), 4.39
(q, J¼7.2 Hz, 2H), 5.93 (s, 1H), 7.33–7.47 (m, 10H); 13C NMR (CDCl3)
d
11.02, 11.41, 14.13, 18.25, 27.28, 32.73, 41.77, 106.86, 128.04, 130.19,
4.3.3. 2-Ethyl-4-(dimethylphenylsilyl)-3,5-diphenyl-4-
isoxazoline (5c)
131.26, 135.63, 144.52, 148.31.
Yield 72%; oil; Rf 0.22 (CH2Cl2); IR (CHCl3) 1635, 1596, 1490,
4.2.22. 5-(tert-Butyldiphenylsilylmethyl)-2-ethyl-3-methyl-1-
phenylpyrazolium tetrafluoroborate (4f)
1258, 1110 cmꢀ1; 1H NMR (CDCl3)
d 0.15 (s, 3H), 0.19 (s, 3H), 1.35 (t,
J¼7.2 Hz, 3H), 2.96 (dq, J¼12.2, 7.2 Hz, 1H), 3.29 (dq, J¼12.2, 7.2 Hz,
Yield 90%; white crystal, mp 165–166 ꢁC (from acetone–ether);
1H), 4.80 (s, 1H), 7.32 (m, 13H), 7.52 (m, 2H); 13C NMR (CDCl3)
IR (KBr) 1552,1495,1471,1110,1054 cmꢀ1; 1H NMR (CDCl3)
d
0.95 (s,
d
ꢀ1.87, ꢀ1.54, 12.42, 53.70, 79.84, 102.96, 127.43, 127.56, 127.84,
9H), 0.95 (t, J¼7.1 Hz, 3H), 2.42 (s, 3H), 2.51 (s, 2H), 3.96 (q, J¼7.1 Hz,
128.49, 129.06, 129.48, 130.02, 133.71, 138.20, 142.45, 159.18. Anal.
Calcd for C25H27NOSi: C, 77.88; H, 7.06; N, 3.63. Found: C, 77.65; H,
6.89; N, 3.91.
2H), 6.07 (s, 1H), 6.63 (m, 2H), 7.40–7.60 (m, 13H); 13C NMR (CDCl3)
d
11.07, 11.77, 14.43, 18.02, 27.05, 42.59, 107.25, 128.12, 128.98,
130.34, 130.42, 130.54, 131.59, 132.42, 135.97, 146.90, 149.97.
4.3.4. 2-Ethyl-3-methyl-4-(dimethylphenylsilyl)-5-phenyl-4-
isoxazoline (5d)
4.2.23. 2,3,5-Trimethyl-4-(dimethylphenylsilyl)-1-
phenylpyrazolium iodide (4g)
Yield 76%; oil; Rf 0.44 (CH2Cl2); IR (CHCl3) 1632, 1597, 1490, 1251,
Yield 45%; yellow crystal, mp 75–77 ꢁC (from acetone–ether); IR
1110 cmꢀ1 1H NMR (CDCl3)
; d 0.30 (s, 3H), 0.34 (s, 3H), 1.29 (d,
(CHCl3) 1592, 1499, 1256, 1116 cmꢀ1; 1H NMR (CDCl3)
d
0.62 (s, 6H),
1.96 (s, 3H), 2.41 (s, 3H), 3.77 (s, 3H), 7.29–7.73 (m, 10H); 13C NMR
(CDCl3)
J¼6.4 Hz, 3H), 1.29 (t, J¼7.0 Hz, 3H), 2.70 (dq, J¼12.2, 7.0 Hz, 1H),
3.11 (dq, J¼12.2, 7.0 Hz, 1H), 3.87 (q, J¼6.4 Hz, 1H), 7.23–7.56 (m,
d
ꢀ1.26, 13.21, 13.83, 36.15, 111.52, 127.13, 127.74, 128.94,
10H); 13C NMR (CDCl3)
103.56, 127.80, 128.99, 129.30, 130.42, 133.81, 138.75, 158.58. Anal.
Calcd for C20H25NOSi: C, 74.25; H, 7.79; N, 4.33. Found: C, 74.48; H,
7.92; N, 4.10.
d
ꢀ1.40, ꢀ1.28, 12.61, 22.77, 52.35, 71.21,
130.13, 132.19, 133.62, 135.29, 138.72, 150.46, 151.66.
4.2.24. 2,3-Dimethyl-5-(dimethylphenylsilyl)-1-phenylpyrazolium
iodide (4h)
Yield 90%; yellow crystal, mp 155–157 ꢁC (from acetone–ether);
4.3.5. 5-(tert-Butyldiphenylsilyl)-2-ethyl-3-phenyl-4-
isoxazoline (5e)
IR (CHCl3) 1602, 1495, 1256, 1113 cmꢀ1
;
1H NMR (CDCl3)
d
0.36 (s,
6H), 2.64 (s, 3H), 3.82 (s, 3H), 6.62 (s, 1H), 7.20–7.63 (m, 10H); 13C
NMR (CDCl3)
Yield 95%; oil, Rf 0.55 (CH2Cl2); IR (CHCl3) 1662, 1616, 1556,
d
ꢀ3.53, 13.33, 36.41, 116.30, 128.09, 129.28, 129.92,
1110 cmꢀ1; 1H NMR (CDCl3)
d
1.25 (s, 9H), 1.35 (t, J¼7.1 Hz, 3H), 3.00
130.26, 132.36, 132.62, 133.66, 147.05, 150.96.
(dq, J¼12.0, 7.1 Hz,1H), 3.32 (dq, J¼12.0, 7.1 Hz,1H), 4.81 (d, J¼2.5 Hz,
1H), 5.10 (d, J¼2.5 Hz, 1H), 7.35–7.78 (m, 15H); 13C NMR (CDCl3)
4.2.25. 5-(tert-Butyldiphenylsilyl)-2,3-dimethyl-1-
phenylpyrazolium iodide (4i)
d 12.82, 18.28, 27.68, 73.79, 116.25, 126.93, 127.69, 127.96, 128.54,
129.61, 132.86, 132.97, 136.09, 142.71, 153.35. Anal. Calcd for
C27H31NOSi:C, 78.40;H, 7.55;N, 3.39. Found:C, 78.22;H, 7.33;N, 3.61.
Yield 95%; yellow crystal, mp 205–207 ꢁC (from acetone–ether);
IR (CHCl3) 1605, 1554, 1109 cmꢀ1
;
1H NMR (CDCl3)
d
1.09 (s, 9H),
2.80 (s, 3H), 3.79 (s, 3H), 6.95 (m, 4H), 7.09 (s, 1H), 7.18–7.40 (m,
11H); 13C NMR (CDCl3)
13.93, 18.63, 27.27, 36.99, 117.79, 128.19,
4.3.6. 5-(tert-Butyldiphenylsilyl)-2-ethyl-3-methyl-4-
isoxazoline (5f)
d
129.32, 129.62, 130.15, 131.57, 132.36, 135.76, 147.27, 147.63.
Yield 92%; oil, Rf 0.60 (CH2Cl2); IR (CHCl3) 1645, 1601, 1471,
1109 cmꢀ1; 1H NMR (CDCl3)
d
1.17 (s, 9H),1.20 (d, J¼6.5 Hz, 3H),1.28
4.3. Reduction of silylated azolium salts with metal complex
hydrides. Typical procedure
(t, J¼7.0 Hz, 3H), 2.72 (dq, J¼12.2, 7.0 Hz, 1H), 3.11 (dq, J¼12.2,
7.0 Hz, 1H), 3.77 (dq, J¼2.4, 6.5 Hz, 1H), 4.96 (d, J¼2.4 Hz, 1H), 7.35–
7.46 (m, 6H), 7.68–7.65 (m, 4H); 13C NMR (CDCl3)
d 12.86, 18.17,
To a stirred solution of the silylated isoxazolium or pyrazolium
salt (0.5 mmol) in MeOH (6 mL) or THF (10 mL), NaBH4 or LiAlH4
(0.5 mmol) was added, respectively. The mixture was stirred at rt
22.65, 27.61, 53.50, 65.22, 118.07, 127.65, 129.52, 133.03, 133.17,
136.04, 152.61. Anal. Calcd for C22H29NOSi: C, 75.16; H, 8.31; N, 3.98.
Found: C, 75.32; H, 8.49; N, 4.15.

´
A.M. Gonzalez-Nogal, M. Calle / Tetrahedron 65 (2009) 5472–5483
5480
4.3.7. 5-tert-Butyl-3-(tert-butyldiphenylsilylmethyl)-2-ethyl-4-
isoxazoline (5i)
J¼1.1 Hz, 1H), 7.28–7.45 (m, 6H), 7.64–7.75 (m, 4H); 13C NMR
(CDCl3)
d 8.96, 12.37, 18.36, 25.41, 27.66, 34.78, 55.05, 80.75, 92.04,
Yield 65%; oil, Rf 0.47 (CH2Cl2); IR (CHCl3) 1663, 1601, 1105 cmꢀ1
;
127.44, 129.19, 133.63, 136.02, 136.16, 151.43. Anal. Calcd for
C26H37NOSi: C, 76.60; H, 9.15; N, 3.44. Found: C, 76.45; H, 8.96; N,
3.69.
1H NMR (CDCl3)
d
0.98 (s, 9H), 1.01 (s, 9H), 1.10 (t, J¼7.1 Hz, 3H), 1.51
(dd, J¼10.3, 14.5 Hz, 1H), 1.67 (dd, J¼10.3, 14.5 Hz, 1H), 2.36 (dq,
J¼12.3, 7.1 Hz, 1H), 2.77 (dq, J¼12.3, 7.1 Hz, 1H), 3.59 (ddd, J¼2.5,
4.2, 10.3 Hz, 1H), 3.84 (d, J¼2.5 Hz, 1H), 7.33–7.45 (m, 6H), 7.64–7.75
4.3.13. 5-(tert-Butyldiphenylsilylmethyl)-2-ethyl-3-phenyl-4-
isoxazoline (5o)
(m, 4H); 13C NMR (CDCl3)
d 12.60, 18.10, 19.94, 27.68, 27.96, 30.89,
52.68, 67.84, 94.95, 127.62, 127.86, 129.08, 134.15, 136.11, 136.36,
161.29. Anal. Calcd for C26H37NOSi: C, 76.60; H, 9.15; N, 3.44. Found:
C, 76.41; H, 8.92; N, 3.66.
Yield 70%; oil, Rf 0.48 (CH2Cl2); IR (CHCl3) 1666, 1602, 1491,
1107 cmꢀ1; 1H NMR (CDCl3)
d
1.03 (t, J¼7.0 Hz, 3H),1.09 (s, 9H), 2.28
(d, J¼15.2 Hz, 1H), 2.37 (d, J¼15.2 Hz, 1H), 2.65 (dq, J¼12.2, 7.0 Hz,
1H), 2.79 (dq, J¼12.2, 7.0 Hz, 1H), 4.23 (d, J¼2.2 Hz, 1H), 4.54 (d,
4.3.8. 3-(tert-Butyldiphenylsilylmethyl)-2-ethyl-5-phenyl-4-
isoxazoline (5j)
J¼2.2 Hz, 1H), 7.10–7.74 (m, 15H); 13C NMR (CDCl3)
d 9.51, 12.60,
18.44, 27.70, 54.34, 76.65, 95.48, 127.11, 127.52, 128.32, 129.29,
133.59, 136.09, 143.09, 151.98. Anal. Calcd for C28H33NOSi: C, 78.64;
H, 7.78; N, 3.28. Found: C, 78.43; H, 7.57; N, 3.57.
Yield 72%; oil, Rf 0.53 (CH2Cl2); IR (CHCl3) 1633,1600,1105 cmꢀ1
;
1H NMR (CDCl3)
d
1.05 (s, 9H), 1.20 (t, J¼7.1 Hz, 3H), 1.66 (dd, J¼10.3,
14.6 Hz, 1H), 1.80 (dd, J¼4.2, 14.6 Hz, 1H), 2.50 (dq, J¼12.3, 7.1 Hz,
1H), 2.91 (dq, J¼12.3, 7.1 Hz, 1H), 3.85 (ddd, J¼2.8, 4.2, 10.3 Hz, 1H),
4.62 (d, J¼2.8 Hz, 1H), 7.27–7.48 (m, 11H), 7.68–7.77 (m, 4H); 13C
4.3.14. 5-(tert-Butyldiphenylsilylmethyl)-3-(p-chlorophenyl)-2-
ethyl-4-isoxazoline (5p)
NMR (CDCl3)
d
12.68, 18.12, 19.72, 27.66, 53.01, 68.57, 98.22, 125.49,
Yield 65%; oil, Rf 0.47 (CH2Cl2); IR (CHCl3) 1605,1503,1100 cmꢀ1
;
127.52, 127.72, 128.14, 129.22, 133.92, 134.69, 134.77, 136.13, 136.36,
150.94. Anal. Calcd for C28H33NOSi: C, 78.64; H, 7.78; N, 3.28.
Found: C, 78.43; H, 7.59; N, 3.51.
1H NMR (CDCl3)
d
1.01 (t, J¼7.1 Hz, 3H), 1.07 (s, 9H), 2.26 (d,
J¼15.1 Hz, 1H), 2.33 (d, J¼15.1 Hz, 1H), 2.60 (dq, J¼12.2, 7.1 Hz, 1H),
2.78 (dq, J¼12.2, 7.1 Hz, 1H), 4.17 (d, J¼2.2 Hz, 1H), 4.49 (d, J¼2.2 Hz,
1H), 6.98 (d, J¼8.2 Hz, 2H), 7.16 (d, J¼8.2 Hz, 2H), 7.30–7.45 (m, 6H),
7.65–7.74 (m, 4H). Anal. Calcd for C28H32ClNOSi: C, 72.78; H, 6.98; N,
3.03. Found: C, 73.01; H, 7.23; N, 2.80.
4.3.9. 3-(tert-Butyldiphenylsilylmethyl)-2-ethyl-5-(p-
methoxyphenyl)-4-isoxazoline (5k)
Yield 50%; oil, Rf 0.56 (CH2Cl2); IR (CHCl3) 1655, 1608, 1510,
1464, 1253, 1106 cmꢀ1
;
1H NMR (CDCl3)
d
1.05 (s, 9H), 1.19 (t,
4.3.15. trans,trans-2-Ethyl-3,5-dimethyl-4-(trimethylsilyl)-1-
phenylpyrazolidine (t,t-6a)
J¼7.0 Hz, 3H), 1.65 (dd, J¼10.1, 14.5 Hz, 1H), 1.78 (dd, J¼4.3, 14.5 Hz,
1H), 2.50 (dq, J¼12.2, 7.0 Hz, 1H), 2.91 (dq, J¼12.2, 7.0 Hz, 1H), 3.81
(s, 3H), 3.81 (ddd, J¼2.5, 4.3, 10.1 Hz, 1H), 4.50 (d, J¼2.5 Hz, 1H),
6.82 (d, J¼8.7 Hz, 2H), 7.25 (d, J¼8.7 Hz, 2H), 7.36–7.48 (m, 6H), 7.68–
Yield 63%; oil, Rf 0.48 (hexane–CH2Cl2, 1:1); IR (CHCl3) 1493,
1252 cmꢀ1; 1H NMR (CDCl3)
d
0.02 (s, 9H), 1.22 (t, J¼7.1 Hz, 3H),1.24
(d, J¼6.7 Hz, 3H), 1.38 (dd, J¼9.5, 12.1 Hz, 1H), 1.46 (d, J¼6.3 Hz, 3H),
2.62 (dq, J¼11.2, 7.1 Hz, 1H), 2.85 (dq, J¼11.2, 7.1 Hz, 1H), 2.97 (dq,
J¼11.2, 7.1 Hz, 1H), 3.47 (dq, J¼9.5, 6.3 Hz, 1H), 6.71 (tt, J¼1.2, 7.2 Hz,
1H), 7.02 (dd, J¼1.2, 8.8 Hz, 2H), 7.19 (dd, J¼7.2, 8.8 Hz, 2H); 13C
7.77 (m, 4H); 13C NMR (CDCl3)
d12.70,18.11,19.78, 27.68, 52.96, 55.22,
68.57, 96.34, 113.55, 121.99, 126.94, 127.54, 127.69, 129.14, 129.18,
134.77, 136.13, 136.77, 150.74, 159.78. Anal. Calcd for C29H35NO2Si: C,
76.10; H, 7.71; N, 3.06. Found: C, 75.84; H, 7.87; N, 3.33.
NMR (CDCl3)
d
ꢀ2.02, 12.02, 16.18, 25.41, 41.29, 44.01, 60.87, 64.62,
112.61, 117.26, 128.50, 152.35. Anal. Calcd for C16H28N2Si: C, 69.50;
H, 10.21; N, 10.13. Found: C, 69.36; H, 10.43; N, 9.85.
4.3.10. 2-Ethyl-3,5-dimethyl-4-(dimethylphenylsilylmethyl)-4-
isoxazoline (5l)
Yield 63%; oil; Rf 0.46 (CH2Cl2); IR (CHCl3) 1622,1599,1480, 1251,
4.3.16. cis,trans-2-Ethyl-3,5-dimethyl-4-(trimethylsilyl)-1-
phenylpyrazolidine (c,t-6a)
1114 cmꢀ1
;
1H NMR (CDCl3)
d
0.32 (s, 6H), 1.07 (d, J¼6.3 Hz, 3H),
1.09 (t, J¼7.1 Hz, 3H), 1.60 (s, 3H), 1.98 (s, 2H), 2.50 (dq, J¼12.2,
7.1 Hz, 1H), 2.84 (dq, J¼12.2, 7.1 Hz, 1H), 3.33 (q, J¼6.3 Hz, 1H), 7.31–
Yield 14%; oil, Rf 0.57 (hexane–CH2Cl2, 1:1); IR (CHCl3) 1595,
1492, 1252 cmꢀ1
;
1H NMR (CDCl3)
d
0.11 (s, 9H), 0.80 (d, J¼6.8 Hz,
7.59 (m, 5H); 13C NMR (CDCl3)
d
ꢀ3.29, ꢀ2.79, 9.95, 12.34, 12.46,
3H), 1.12 (t, J¼7.1 Hz, 3H), 1.48 (d, J¼5.9 Hz, 3H), 1.80 (dd, J¼6.0,
10.6 Hz, 1H), 2.76 (m, 2H), 1.46 (d, J¼6.3 Hz, 3H), 3.29 (dq, J¼6.0,
6.8 Hz, 1H), 3.57 (dq, J¼10.6, 5.9 Hz, 1H), 6.70 (t, J¼7.5 Hz, 1H), 7.02
19.72, 53.17, 68.65, 104.71, 127.79, 129.13, 133.46, 138.69, 141.24.
Anal. Calcd for C24H33NOSi: C, 75.93; H, 8.76; N, 3.69. Found: C,
76.18; H, 8.97; N, 3.42.
(d, J¼7.5 Hz, 2H), 7.18 (t, J¼7.5 Hz, 2H); 13C NMR (CDCl3)
d
ꢀ0.97,
13.55, 19.30, 25.03, 39.08, 52.48, 60.84, 62.45, 112.08, 116.61, 128.39,
152.95. Anal. Calcd for C16H28N2Si: C, 69.50; H, 10.21; N, 10.13.
Found: C, 69.73; H, 10.39; N, 10.36.
4.3.11. 5-(tert-Butyldiphenylsilylmethyl)-2-ethyl-3-methyl-4-
isoxazoline (5m)
Yield 90%; oil, Rf 0.57 (CH2Cl2); IR (CHCl3) 1667, 1591, 1447,
1109 cmꢀ1
;
1H NMR (CDCl3)
d
0.99 (d, J¼6.0 Hz, 3H), 1.02 (t,
4.3.17. trans,cis-2-Ethyl-3,5-dimethyl-4-(trimethylsilyl)-1-
phenylpyrazolidine (t,c-6a)
J¼7.2 Hz, 3H), 1.07 (s, 9H), 2.18 (d, J¼15.2 Hz, 1H), 2.26 (d, J¼15.2 Hz,
1H), 2.45 (dq, J¼12.1, 7.2 Hz, 1H), 2.64 (dq, J¼12.1, 7.2 Hz, 1H), 3.54
(dq, J¼2.0, 6.0 Hz, 1H), 4.08 (d, J¼2.0 Hz, 1H), 7.32–7.46 (m, 6H),
Yield 26%; oil, Rf 0.55 (hexane–CH2Cl2, 1:1); IR (CHCl3) 1595,
1492, 1252 cmꢀ1
;
1H NMR (CDCl3)
d
0.05 (s, 9H), 1.04 (t, J¼7.2 Hz,
7.66–7.77 (m, 4H); 13C NMR (CDCl3)
d
9.35, 12.41, 18.28, 22.36, 27.55,
3H), 1.22 (dd, J¼6.4, 11.6 Hz, 1H), 1.29 (d, J¼6.0 Hz, 3H), 1.34 (d,
J¼7.0 Hz, 3H), 2.82 (dq, J¼11.6, 7.2 Hz, 1H), 2.91 (dq, J¼11.6, 7.2 Hz,
1H), 3.08 (dq, J¼11.6, 6.0 Hz, 1H), 3.80 (dq, J¼6.4, 7.0 Hz, 1H), 6.80
53.36, 66.51, 96.55, 127.30, 129.06, 133.62, 135.92, 150.83. Anal.
Calcd for C23H31NOSi: C, 75.56; H, 8.55; N, 3.83. Found: C, 75.36; H,
8.73; N, 4.06.
(m, 1H), 7.20 (m, 4H); 13C NMR (CDCl3)
d
ꢀ1.19, 14.36, 21.35, 21.54,
39.71, 53.42, 62.38, 67.23, 116.91, 119.29, 128.10, 155.17. Anal. Calcd
for C16H28N2Si: C, 69.50; H, 10.21; N, 10.13. Found: C, 69.79; H, 9.99;
N, 10.41.
4.3.12. 3-tert-Butyl-5-(tert-butyldiphenylsilylmethyl)-2-ethyl-4-
isoxazoline (5n)
Yield 75%; oil, Rf 0.66 (CH2Cl2); IR (CHCl3) 1670,1625,1105 cmꢀ1
;
1H NMR (CDCl3)
d
0.65 (s, 9H), 0.97 (t, J¼7.1 Hz, 3H),1.05 (s, 9H), 2.18
4.3.18. cis-2-Ethyl-3,5-dimethyl-1-phenylpyrazolidine (6b)
(d, J¼15.6 Hz, 1H), 2.29 (d, J¼15.6 Hz, 1H), 2.38 (dq, J¼12.3, 7.1 Hz,
1H), 2.59 (dq, J¼12.3, 7.1 Hz, 1H), 3.08 (d, J¼1.1 Hz, 1H), 3.96 (d,
Yield 45%; oil, Rf 0.25 (hexane–CH2Cl2, 2:1); 1H NMR (CDCl3)
d
1.13 (t, J¼7.0 Hz, 3H), 1.29 (d, J¼6.8 Hz, 3H), 1.50 (d, J¼6.4 Hz, 3H),

´
A.M. Gonzalez-Nogal, M. Calle / Tetrahedron 65 (2009) 5472–5483
5481
1.82 (dt, J¼8.5, 11.9 Hz, 1H), 2.36 (ddd, J¼11.9, 7.8, 5.7 Hz, 1H), 2.62
4.4.1. 2-Ethyl-3-methyl-4-(dimethylphenylsilyl)-3,5-diphenyl-4-
isoxazoline (9a)
Yield 28%; oil, Rf 0.58 (CH2Cl2); IR (CHCl3) 1632, 1597, 1490, 1250,
(dq, J¼11.3, 7.0 Hz, 1H), 2.90 (dq, J¼11.3, 7.0 Hz, 1H), 3.13 (ddq,
J¼11.9, 7.8, 6.8 Hz, 1H), 3.69 (ddq, J¼5.7, 8.5, 6.4 Hz, 1H), 6.75 (t,
J¼7.4 Hz, 1H), 7.07 (d, J¼8.8 Hz, 2H), 7.21 (dd, J¼8.8, 7.4 Hz, 2H).
Anal. Calcd for C13H20N2: C, 76.42; H, 9.87; N, 13.71. Found: C, 76.22;
H, 10.02; N, 13.54.
1110 cmꢀ1
;
1H NMR (CDCl3)
d
ꢀ0. 08 (s, 3H), ꢀ0.03 (s, 3H), 1.15 (t,
J¼7.0 Hz, 3H), 1.77 (s, 3H), 2.54 (m, 2H), 7.18–7.54(m, 15H); 13C NMR
(CDCl3)
d
ꢀ1.00, 13.94, 23.38, 46.45, 77.59, 110.44, 127.32, 127.58,
127.73, 127.83, 128.04, 128.51, 129.01, 130.96, 133.88, 139.19, 142.29,
160.78. Anal. Calcd for C26H29NOSi: C, 78.15; H, 7.31; N, 3.51. Found:
C, 77.93; H, 7.48; N, 3.76.
4.3.19. 2,3,5-Trimethyl-4-(dimethylphenylsilyl)-1-phenyl-3-
pyrazoline (7g)
Yield 86% (when the reaction mixture was hydrolyzed with
water) and 42% (hydrolyzed with aqueous NH4Cl); oil, Rf 0.62
4.4.2. 3-Butyl-2-ethyl-4-(dimethylphenylsilyl)-3,5-diphenyl-4-
isoxazoline (9b)
(CH2Cl2); IR (CHCl3) 1600, 1490, 1250, 1100 cmꢀ1 1H NMR (CDCl3)
;
Yield 12% (at ꢀ78 ꢁC), 35% (at 0 ꢁC), and 58% (at rt); oil, Rf 0.42
d
0.49 (s, 3H), 0.51 (s, 3H), 1.20 (d, J¼6.4 Hz, 3H), 1.80 (s, 3H), 2.63 (s,
(hexane–CH2Cl2, 1:2); IR (CHCl3) 1636, 1593, 1490, 1257, 1110 cmꢀ1
;
3H), 3.53 (q, J¼6.4 Hz, 1H), 7.10 (t, J¼7.8 Hz, 1H), 7.23 (d, J¼8.1 Hz,
2H), 7.32 (dd, J¼7.8, 8.1 Hz, 2H), 7.40–7.70 (m, 5H); 13C NMR (CDCl3)
1H NMR (CDCl3)
d
0.00 (s, 3H), 0.02 (s, 3H), 0.93 (t, J¼7.2 Hz, 3H),
d
0.15, 0.24, 14.36, 31.13, 43.22, 56.40, 112.63, 120.31, 125.31, 127.36,
1.11 (t, J¼7.0 Hz, 3H), 1.31 (m, 4H), 1.80 (m, 1H), 2.03 (m, 1H), 2.33
128.66, 129.62, 133.42, 138.65, 139.86, 151.36. Anal. Calcd for
C20H26N2Si: C, 74.48; H, 8.13; N, 8.69. Found: C, 74.30; H, 7.96; N,
8.92.
(dq, J¼13.0, 7.0 Hz, 1H), 2.53 (dq, J¼13.0, 7.0 Hz, 1H), 7.14–7.57 (m,
15H); 13C NMR (CDCl3)
d
ꢀ0.99, ꢀ0.76, 14.09, 14.27, 23.26, 27.55,
36.50, 47.76, 81.20, 108.19, 127.15, 127.24, 127.67, 127.78, 128.30,
128.45, 129.02, 129.20, 131.17, 132.94, 133.96, 138.61, 141.84, 160.55.
Anal. Calcd for C29H35NOSi: C, 78.86; H, 7.99; N, 3.17. Found: C,
79.08; H, 8.22; N, 2.89.
4.3.20. 1,3,5-Trimethyl-4-(dimethylphenylsilyl)-2-phenyl-3-
pyrazoline (8g)
Yield 42%; oil, Rf 0.61 (CH2Cl2); IR (CHCl3) 1601, 1494, 1255,
1119 cmꢀ1
;
1H NMR (CDCl3)
d
0.43 (s, 3H), 1.12 (d, J¼6.4 Hz, 3H),
4.4.3. 5-tert-Butyl-2-ethyl-4-(dimethylphenylsilyl)-3,5-diphenyl-3-
isoxazoline (10a)
2.09 (s, 3H), 2.51 (s, 3H), 3.37 (q, J¼6.4 Hz,1H), 6.79 (t, J¼7.8 Hz,1H),
6.87 (d, J¼7.8 Hz, 2H), 7.22 (t, J¼7.8 Hz, 2H), 7.31–7.75 (m, 5H); 13C
Yield 43%; oil, Rf 0.44 (hexane–AcOEt, 10:1); IR (CHCl3) 1630,
NMR (CDCl3)
d
ꢀ0.01, 15.19, 30.81, 42.01, 57.60, 113.30, 119.29,
1600, 1490, 1250 cmꢀ1; 1H NMR (CDCl3)
d 0.22 (s, 3H), 0.33 (s, 3H),
124.58, 127.65, 129.08, 129.20, 132.94, 139.24, 139.75, 148.40. Anal.
Calcd for C20H26N2Si: C, 74.48; H, 8.13; N, 8.69. Found: C, 74.66; H,
8.28; N, 8.43.
0.98 (s, 9H), 1.13 (t, J¼7.0 Hz, 3H), 2.81 (dq, J¼13.5, 7.0 Hz, 1H), 3.00
(dq, J¼13.5, 7.0 Hz, 1H), 7.28–7.47 (m, 15H). Anal. Calcd for
C29H35NOSi: C, 78.86; H, 7.99; N, 3.17. Found: C, 78.61; H, 8.19; N,
3.42.
4.3.21. 1,5-Dimethyl-3-(dimethylphenylsilyl)-2-phenyl-3-
pyrazoline (8h)
4.4.4. 5-Butyl-2-ethyl-4-(dimethylphenylsilyl)-3,5-diphenyl-3-
isoxazoline (10b)
Yield 80%; oil, Rf 0.46 (CH2Cl2); IR (CHCl3) 1591, 1489, 1255,
1118 cmꢀ1 1H NMR (CDCl3)
; d 0.16 (s, 3H), 0.25 (s, 3H), 1.12 (d,
Yield 61% (at ꢀ78 ꢁC), 40% (at 0 ꢁC), and 21% (at rt); oil, Rf 0.21
J¼6.4 Hz, 3H), 2.65 (s, 3H), 3.49 (dq, J¼2.5, 6.4 Hz, 1H), 5.30 (d,
(hexane–CH2Cl2, 1:2); IR (CHCl3) 1625, 1593, 1490, 1255, 1110 cmꢀ1
;
J¼2.5 Hz, 1H), 6.77 (t, J¼7.2 Hz, 1H), 6.90 (d, J¼7.7 Hz, 2H), 7.01 (t,
1H NMR (CDCl3)
d
0.38 (s, 3H), 0.47 (s, 3H), 0.86 (t, J¼7.0 Hz, 3H),1.19
J¼7.0 Hz, 2H), 7.09–7.68 (m, 5H); 13C NMR (CDCl3)
d
ꢀ2.40, ꢀ2.19,
(t, J¼7.0 Hz, 3H), 1.31 (m, 4H), 1.98 (m, 2H), 2.95 (dq, J¼13.6, 7.1 Hz,
1H), 3.09 (dq, J¼13.6, 7.1 Hz, 1H), 7.24–7.50 (m, 15H). Anal. Calcd for
C29H35NOSi: C, 78.86; H, 7.99; N, 3.17. Found: C, 78.53; H, 7.84; N,
3.36.
22.73, 45.31, 68.06, 114.23, 119.27, 123.10, 123.92, 127.63, 128.48,
133.90, 137.64, 145.12, 149.79. Anal. Calcd for C19H24N2Si: C, 73.97;
H, 7.84; N, 9.08. Found: C, 74.21; H, 8.01; N, 8.86.
4.3.22. 3-(tert-Butyldiphenylsilyl)-1,5-dimethyl-2-phenyl-3-
pyrazoline (8i)
4.4.5. Z-3-(Isopropylamino)-1,3-diphenylprop-2-en-1-one (11a)
Yield 25%; oil, Rf 0.34 (CH2Cl2); 1H NMR (CDCl3)
d 1.22 (d,
Yield 85%; oil, Rf 0.38 (CH2Cl2); IR (CHCl3) 1600, 1500,
1108 cmꢀ1
;
1H NMR (CDCl3)
d
1.05 (s, 9H), 1.06 (d, J¼6.5 Hz, 3H),
J¼6.4 Hz, 6H), 3.65 (d, sep, J¼7.2, 6.4 Hz, 1H), 5.70 (s, 1H), 7.31–
7.54 (m, 8H), 7.90 (m, 2H), 11.33 (br d, J¼7.2 Hz, 1H); 13C NMR
2.79 (s, 3H), 3.52 (dq, J¼2.6, 6.5 Hz, 1H), 5.85 (d, J¼2.6 Hz, 1H), 6.75
(m, 1H), 6.82 (m, 2H), 7.23–7.39 (m, 6H), 7.65 (m, 4H); 13C NMR
(CDCl3)
d 16.65, 51.32, 103.77, 120.96, 122.06, 123.89, 127.43,
128.47, 129.26, 133.46, 135.47, 159.62, 196.43. Anal. Calcd for
C18H19NO: C, 81.47; H, 7.22; N, 5.28. Found: C, 81.23; H, 6.99; N,
5.44.
(CDCl3)
d 19.04, 22.64, 28.05, 47.08, 68.19, 122.35, 122.88, 127.33,
127.50, 127.87, 129.10, 133.72, 136.05, 139.69, 150.41. Anal. Calcd for
C27H32N2Si: C, 78.59; H, 7.82; N, 6.79. Found: C, 78.84; H, 7.66; N,
7.05.
4.4.6. Z-3-(Ethylamino)-1,3-diphenylprop-2-en-1-one (11b)
Yield 21%; oil, Rf 0.46 (CH2Cl2); 1H NMR (CDCl3)
d
1.23 (t,
J¼7.2 Hz, 3H), 3.27 (q, J¼7.2 Hz, 2H), 5.77 (s, 1H), 7.35–7.98 (m, 10H),
11.37 (br s, 1H); 13C NMR (CDCl3)
14.82, 40.12, 104.31, 126.65,
4.4. Reactions of silylated isoxazolium salts with
organolithium reagents. General procedure
d
127.15, 127.62, 128.72, 130.07, 131.08, 133.21, 138.75, 172.35, 192.04.
Anal. Calcd for C17H17NO: C, 81.24; H, 6.82; N, 5.57. Found: C, 80.96;
H, 7.08; N, 5.77.
To a stirred solution of the isoxazolium salt (1 mmol) in dry THF
(10 mL) at ꢀ78, 0 ꢁC or rt, under N2, was added the organolithium
(1 mmol). The reaction mixture was stirred at this temperature
until TLC indicated complete reaction. When the reaction was
carried out at 0 ꢁC or rt, the mixture was quenched with aqueous
NH4Cl, and with methanol in the reactions at ꢀ78 ꢁC and workup
with Et2O. The ethereal layer was dried (MgSO4) and the solvents
removed. The residue was purified by flash chromatography to give
the following products.
4.4.7. Z-1,3-Diphenyl-3-(1-phenylethylamino)prop-2-en-1-
one (11c)
Yield 44%; oil, Rf 0.44 (CH2Cl2); 1H NMR (CDCl3)
d 1.55 (d,
J¼6.3 Hz, 3H), 4.60 (dq, J¼7.1, 6.3 Hz, 1H), 5.70 (s, 1H), 6.80–8.10 (m,
15H), 11.85 (br d, J¼7.1 Hz, 1H). Anal. Calcd for C23H21NO: C, 84.37;
H, 6.46; N, 4.28. Found: C, 84.63; H, 6.59; N, 4.47.

´
A.M. Gonzalez-Nogal, M. Calle / Tetrahedron 65 (2009) 5472–5483
5482
4.4.8. 5-(tert-Butyldiphenylsilyl)-2-ethyl-3-methyl-3-phenyl-4-
isoxazoline (12a)
1.70 (s, 3H), 3.25 (q, J¼7.0 Hz, 2H), 4.32 (s, 1H), 4.53 (s, 1H), 7.30–
7.75 (m, 10H); 13C NMR (CDCl3)
11.57, 17.64, 27.31, 28.83, 50.43,
68.41, 103.61, 127.68, 128.91, 134.31, 137.71, 162.43, 170.12. Anal.
Calcd for C23H29NOSi: C, 75.98; H, 8.04; N, 3.85. Found: C, 75.73;
H, 8.23; N, 3.59.
d
Yield 52%; oil, Rf 0.50 (hexane–CH2Cl2, 1:10); 1H NMR (CDCl3)
d
1.18 (s, 9H), 1.23 (t, J¼7.0 Hz, 3H), 1.64 (s, 3H), 2.51–2.69 (m, 2H),
5.24 (s, 1H), 7.25–7.73 (m, 15H); 13C NMR (CDCl3)
d
13.72, 18.28,
27.62, 47.78, 72.90, 123.05, 127.14, 127.66, 128.10, 129.54, 133.08,
136.07,153.75. Anal. Calcd for C28H33NOSi: C, 78.64; H, 7.78; N, 3.28.
Found: C, 78.86; H, 7.61; N, 2.97.
4.4.15. Z-3-tert-Butyl-5-(tert-butyldiphenylsilylmethylen)-2-ethyl-
3-isoxazoline (Z-14b)
Yield 38%; oil, Rf 0.66 (CH2Cl2); IR (CHCl3) 1609, 1106, 822 cmꢀ1
;
4.4.9. 3-Butyl-5-(tert-butyldiphenylsilyl)-2-ethyl-3-phenyl-4-
isoxazoline (12b)
1H NMR (CDCl3)
(q, J¼6.9 Hz, 2H), 3.99 (s,1H), 5.42 (s,1H), 7.35 (m, 6H), 7.74 (m, 4H);
13C NMR (CDCl3)
10.84, 18.23, 27.83, 29.49, 31.62, 50.48, 68.73,
d
0.75 (t, J¼6.9 Hz, 3H),1.05 (s, 9H),1.22 (s, 9H), 3.12
Yield 63%; oil, Rf 0.33 (hexane–CH2Cl2, 1:1); IR (CHCl3) 1625,
d
1500, 1107 cmꢀ1; 1H NMR (CDCl3)
d
0.83 (t, J¼7.0 Hz, 3H), 0.88–1.30
103.59, 127.06, 128.28, 136.05, 136.75, 164.45, 170.46. Anal. Calcd for
C26H35NOSi: C, 76.98; H, 8.70; N, 3.45. Found: C, 77.25; H, 8.83; N,
3.22.
(m, 9H), 1.20 (s, 9H), 1.25 (t, J¼7.3 Hz, 3H), 2.07 (dt, J¼14.5, 7.0 Hz,
1H), 2.19 (m, 2H), 2.52 (dq, J¼12.8, 7.3 Hz, 1H), 5.40 (s, 1H), 7.28–
7.45 (m, 11H), 7.73 (m, 4H); 13C NMR (CDCl3)
d 13.57, 13.81, 18.27,
23.07, 26.64, 27.56, 40.61, 48.03, 120.59, 127.34, 127.64, 128.04,
128.13, 129.52, 133.15, 136.04, 139.70, 154.56. Anal. Calcd for
C31H39NOSi: C, 79.26; H, 8.37; N, 2.98. Found: C, 78.93; H, 8.52; N,
3.28.
4.4.16. E-3-tert-Butyl-5-(tert-butyldiphenylsilylmethylen)-2-ethyl-
3-isoxazoline (E-14b)
Yield 47%; oil, Rf 0.66 (CH2Cl2); IR (CHCl3) 1609, 1106, 822 cmꢀ1
;
1H NMR (CDCl3)
3.37 (q, J¼6.9 Hz, 2H), 4.32 (s, 1H), 4.43 (s, 1H), 7.35 (m, 6H), 7.74 (m,
4H); 13C NMR (CDCl3)
11.39, 18.44, 27.60, 29.23, 31.54, 50.37, 67.22,
d
0.98 (s, 9H), 1.07 (s, 9H), 1.23 (t, J¼6.9 Hz, 3H),
4.4.10. 5-(tert-Butyldiphenylsilyl)-2-ethyl-3,3-diphenyl-4-
isoxazoline (12c)
d
101.62, 127.34, 128.64, 136.35, 136.75, 165.21, 169.61. Anal. Calcd for
C26H35NOSi: C, 76.98; H, 8.70; N, 3.45. Found: C, 76.74; H, 8.55; N,
3.71.
Yield 66%; oil, Rf 0.68 (hexane–CH2Cl2, 1:10); IR (CHCl3) 1593,
1471, 1109 cmꢀ1
;
1H NMR (CDCl3)
d
1.08 (s, 9H), 1.27 (t, J¼7.0 Hz,
3H), 2.31 (q, J¼7.0 Hz, 2H), 5.58 (s, 1H), 7.26–7.74 (m, 20H); 13C NMR
(CDCl3)
d
13.77, 18.31, 26.74, 49.12, 79.90, 121.26, 126.89, 127.12,
4.4.17. Z-5-(tert-Butyldiphenylsilylmethylen)-2-ethyl-3-phenyl-3-
127.21, 127.65, 127.99, 128.21, 129.03, 129.50, 133.02, 133.40, 135.48,
135.96, 141.19, 143.90, 154.20. Anal. Calcd for C33H35NOSi: C, 80.93;
H, 7.20; N, 2.86. Found: C, 81.26; H, 7.35; N, 3.11.
isoxazoline (Z-14c)
Yield 20%; oil, Rf 0.62 (CH2Cl2); IR (CHCl3) 1613, 1102, 820 cmꢀ1
;
1H NMR (CDCl3)
d
0.72 (t, J¼7.0 Hz, 3H), 1.06 (s, 9H), 3.02 (q,
J¼7.0 Hz, 2H), 4.24 (s, 1H), 5.84 (s, 1H), 7.14–7.75 (m, 15H); 13C NMR
4.4.11. 3-tert-Butyl-5-(tert-butyldiphenylsilyl)-2-ethyl-3-phenyl-4-
isoxazoline (12d)
(CDCl3) d 10.31, 18.29, 27.83, 50.46, 72.36, 105.07, 126.93, 127.17,
128.45, 128.71, 129.14, 134.80, 136.04, 156.55, 170.54. Anal. Calcd for
C28H31NOSi: C, 79.01; H, 7.34; N, 3.29. Found: C, 78.84; H, 7.49; N,
3.56.
Yield 63% (at ꢀ75 ꢁC), 10% (at 0 ꢁC); oil, Rf 0.75 (hexane–CH2Cl2,
1:10); IR (CHCl3) 1596, 1500, 1108 cmꢀ1; 1H NMR (CDCl3)
d 1.04 (s,
9H), 1.20 (t, J¼7.2 Hz, 3H), 1.20 (s, 9H), 2.30 (dq, J¼13.0, 7.2 Hz, 1H),
2.71 (dq, J¼13.0, 7.2 Hz, 1H), 5.26 (s, 1H), 7.21–7.48 (m, 10H), 7.74
4.4.18. E-5-(tert-Butyldiphenylsilylmethylen)-2-ethyl-3-phenyl-3-
(m, 5H); 13C NMR (CDCl3)
d
13.95, 18.28, 27.28, 27.63, 39.37, 51.11,
isoxazoline (E-14c)
83.42, 118.04, 126.91, 127.63, 129.50, 130.56, 133.36, 135.46, 136.21,
138.78, 152.85. Anal. Calcd for C31H39NOSi: C, 79.26; H, 8.37; N,
2.98. Found: C, 79.49; H, 8.18; N, 2.73.
Yield 35%; oil, Rf 0.62 (CH2Cl2); IR (CHCl3) 1613, 1102, 820 cmꢀ1
;
1H NMR (CDCl3)
d
1.09 (s, 9H), 1.19 (t, J¼7.0 Hz, 3H), 3.30 (q,
J¼7.0 Hz, 2H), 4.56 (s, 1H), 4.92 (s, 1H), 7.14–7.79 (m, 15H); 13C NMR
(CDCl3)
d 10.88, 18.43, 27.53, 50.39, 70.43, 102.95, 127.05, 127.50,
4.4.12. Z-1-(tert-Butyldiphenylsilyl)-3-(ethylamino)-3-phenylprop-
2-en-1-one (13a)
128.71, 128.81, 129.14, 134.80, 136.29, 157.43, 169.88. Anal. Calcd for
C28H31NOSi: C, 79.01; H, 7.34; N, 3.29. Found: C, 78.91; H, 7.18; N,
2.96.
Yield 11% (at ꢀ75 ꢁC), 61% (at 0 ꢁC); oil, Rf 0.43 (hexane–CH2Cl2,
1:10); IR (CHCl3) 3155, 1610, 1589, 1564, 1091 cmꢀ1 1H NMR
;
(CDCl3)
5.39 (s, 1H), 7.31–7.45 (m, 11H), 7.72 (m, 4H), 12.23 (br s, 1H); 13C
NMR (CDCl3) 16.00, 18.48, 28.04, 39.38, 106.79, 127.47, 127.58,
128.29, 129.06, 129.24, 133.98, 134.62, 136.38, 162.75, 217.95. Anal.
Calcd for C27H31NOSi: C, 78.40; H, 7.55; N, 3.39. Found: C, 78.65; H,
7.71; N, 3.63.
d
1.20 (t, J¼7.3 Hz, 3H), 1.21 (s, 9H), 3.20 (q, J¼7.3 Hz, 2H),
4.4.19. E-5-tert-Butyl-3-(tert-butyldiphenylsilylmethylen)-2-ethyl-
4-isoxazoline (15a)
d
Yield 40 and 95% (with BuLi at ꢀ78 and 0 ꢁC, respectively), 85%
t
(with MeLi at ꢀ78 ꢁC), 80% (with BuLi at ꢀ78 ꢁC); oil, Rf 0.67
(CH2Cl2); IR (CHCl3) 1624, 1578, 1104, 820 cmꢀ1 1H NMR (CDCl3)
;
d
0.97 (s, 9H), 1.05 (s, 9H), 1.22 (t, J¼7.0 Hz, 3H), 3.57 (q, J¼7.0 Hz,
2H), 3.98 (s, 1H), 4.43 (s, 1H), 7.28–7.45 (m, 6H), 7.80 (m, 4H); 13C
NMR (CDCl3) 9.53, 18.51, 27.68, 27.78, 31.90, 50.55, 71.06, 96.67,
4.4.13. Z-5-(tert-Butyldiphenylsilylmethylen)-2-ethyl-3-methyl-3-
d
isoxazoline (Z-14a)
127.35, 128.61, 135.32, 136.28, 164.70, 172.49. Anal. Calcd for
C26H35NOSi: C, 76.98; H, 8.70; N, 3.45. Found: C, 77.29; H, 8.88; N,
3.69.
Yield 14%; oil, Rf 0.68 (CH2Cl2); IR (CHCl3) 1610, 1105, 820 cmꢀ1
;
1H NMR (CDCl3)
d
0.74 (t, J¼7.0 Hz, 3H),1.05 (s, 9H),1.87 (s, 3H), 3.01
(q, J¼7.0 Hz, 2H), 3.97 (s, 1H), 5.38 (s, 1H), 7.30–7.75 (m, 10H); 13C
NMR (CDCl3)
d
11.03, 18.56, 27.76, 28.47, 51.63, 69.36, 104.12, 127.31,
4.4.20. E-3-(tert-Butyldiphenylsilylmethylen)-2-ethyl-5-phenyl-4-
isoxazoline (15b)
128.32, 135.45, 136.81, 163.25, 171.22. Anal. Calcd for C23H29NOSi: C,
75.98; H, 8.04; N, 3.85. Found: C, 76.20; H, 7.88; N, 4.11.
Yield 40 and 95% (with BuLi at ꢀ78 and 0 ꢁC, respectively), 82%;
oil, Rf 0.60 (CH2Cl2); IR (CHCl3) 1625, 1599, 1579, 1450, 1104,
4.4.14. E-5-(tert-Butyldiphenylsilylmethylen)-2-ethyl-3-methyl-3-
isoxazoline (E-14a)
820 cmꢀ1; 1H NMR (CDCl3)
d
1.09 (s, 9H), 1.36 (t, J¼7.0 Hz, 3H), 3.69
(q, J¼7.0 Hz, 2H), 4.20 (s, 1H), 5.19 (s, 1H), 7.31–7.43 (m, 10H), 7.80
(m, 5H); 13C NMR (CDCl3)
10.15, 18.44, 27.60, 51.05, 73.83, 98.67,
125.42, 127.52, 127.61, 128.37, 128.78, 136.02, 136.24, 160.50, 164.27.
Yield 28%; oil, Rf 0.68 (CH2Cl2); IR (CHCl3) 1610, 1105,
d
820 cmꢀ1
;
1H NMR (CDCl3)
d
1.01 (s, 9H), 1.20 (t, J¼7.0 Hz, 3H),

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A.M. Gonzalez-Nogal, M. Calle / Tetrahedron 65 (2009) 5472–5483
5483
Anal. Calcd for C28H31NOSi: C, 79.01; H, 7.34; N, 3.29. Found: C,
4.5.8. E-3-(tert-Butyldiphenylsilylmethylen)-2-ethyl-5-phenyl-4-
79.23; H, 7.48; N, 3.51.
isoxazoline (15b)
Yield 56%.
4.4.21. 3-Butyl-5-tert-butyl-3-(tert-butyldiphenylsilylmethyl)-2-
ethyl-4-isoxazoline (16a)
4.5.9. Z-1-(tert-Butyldiphenylsilyl)-4-(ethylamino)pent-3-en-2-
one (17a)
Yield 40; oil, Rf 0.45 (hexane–CH2Cl2, 1:2); 1H NMR (CDCl3)
d
0.68 (t, J¼7.1 Hz, 3H), 0.84–1.15 (m, 6H), 0.98 (s, 9H), 1.02 (s, 9H),
Yield 72%; oil, Rf 0.16 (CH2Cl2); IR (CHCl3) 3155, 1605, 1561,
1104 cmꢀ1; 1H NMR (CDCl3)
1.09 (s, 9H), 1.14 (t, J¼7.1 Hz, 3H), 1.63
(s, 3H), 2.51 (s, 2H), 3.15 (q, J¼7.1 Hz, 2H), 4.46 (s, 1H), 7.31–7.43 (m,
6H), 7.61–7.74 (m, 4H), 10.36 (br s, 1H); 13C NMR (CDCl3)
15.56,
1.19 (t, J¼6.9 Hz, 3H), 1.56 (d, J¼14.4 Hz, 1H), 1.79 (d, J¼14.4 Hz, 1H),
2.73 (q, J¼6.9 Hz, 2H), 3.94 (s, 1H), 7.32–7.42 (m, 6H), 7.68 (m, 4H);
d
13C NMR (CDCl3)
d
13.61, 13.90, 18.45, 22.91, 26.82, 27.89, 28.02,
d
29.69, 31.06, 37.40, 45.22, 72.81, 99.85, 127.17, 127.35, 128.95, 129.01,
135.16, 135.38, 136.55, 160.93. Anal. Calcd for C30H45NOSi: C, 77.69;
H, 9.78; N, 3.02. Found: C, 77.92; H, 9.95; N, 2.80.
18.47,18.68, 27.72, 30.39, 37.43, 96.54,127.32,128.99,134.70,136.21,
161.01, 195.25. Anal. Calcd for C23H31NOSi: C, 75.56; H, 8.55; N, 3.83.
Found: C, 75.78; H, 8.41; N, 4.06.
4.5. Reactions of silyl isoxazolium salts with lithium
dimethylcuprate. General procedure
4.5.10. Z-1-(tert-Butyldiphenylsilyl)-4-(ethylamino)-4-phenylbut-
3-en-2-one (17b)
Yield 79%; oil, Rf 0.30 (CH2Cl2); IR (CHCl3) 3155, 1610, 1599,
To a stirred solution of the isoxazolium salt (1 mmol) under N2,
in dry THF (3 mL) at 0 ꢁC, was added a THF solution of the lithium
dimethylcuprate reagent [prepared from Me Li and cuprous iodide]
(1 mmol). The reaction mixture was stirred at this temperature
until TLC indicated that the reaction was complete. The mixture
was quenched with aqueous NH4Cl. The organic layer was extracted
with Et2O, dried with MgSO4, and the solvents removed under re-
duced pressure. The residue was purified by flash chromatography
to give the following products.
1107 cmꢀ1; 1H NMR (CDCl3)
d
1.03 (t, J¼7.1 Hz, 3H), 1.12 (s, 9H), 2.62
(s, 2H), 3.02 (q, J¼7.1 Hz, 2H), 4.58 (s, 1H), 6.94 (m, 2H), 7.24–7.43
(m, 9H), 7.74 (m, 4H), 10.29 (br s, 1H); 13C NMR (CDCl3)
16.31,
d
18.70, 27.67, 30.95, 39.00, 98.44, 127.40, 127.58, 128.02, 128.86,
129.03, 134.48, 135.63, 136.23, 163.26, 196.20. Anal. Calcd for
C28H33NOSi: C, 78.64; H, 7.78; N, 3.28. Found: C, 78.38; H, 7.91; N,
2.93.
Acknowledgements
4.5.1. Z-4-(Ethylamino)pent-3-en-2-one (11d)
´
We thank the Ministerio de Ciencia y Tecnologıa of Spain for
supporting this work.
Yield: 91%; oil, Rf 0.57 (CH2Cl2); IR (CHCl3) 3240, 1620, 1595,
1501, 752, 680 cmꢀ1. 1H NMR (300 MHz, CDCl3)
d
1.19 (t, J¼7.1 Hz,
3H), 1.92 (s, 3H), 2.00 (s, 3H), 3.24 (dq, J¼5.9, 7.1 Hz, 2H), 4.95 (s,
1H), 10.80 (br s, 1H). Anal. Calcd for C7H13NO: C, 66.10; H, 10.30; N,
11.01. Found: C, 65.97; H, 10.11; N, 10.79.
References and notes
1. Gonza´lez-Nogal, A. M.; Calle, M.; Cuadrado, P.; Valero, R. Tetrahedron 2007, 63,
224–231.
2. (a) Cuadrado, P.; Gonza´lez-Nogal, A. M. Tetrahedron Lett. 1998, 39, 1449–1452;
4.5.2. Z-1-(tert-Butyldiphenylsilyl)-3-(ethylamino)-3-phenylprop-
2-en-1-one (13a)
´
´
(b) Gonzalez-Nogal, A. M.; Calle, M.; Calvo, L. A.; Cuadrado, P.; Gonzalez-Ortega,
A. Eur. J. Org. Chem. 2005, 4663–4669.
Yield 91%.
3. Gonza´lez-Nogal, A. M.; Calle, M.; Cuadrado, P. Eur. J. Org. Chem. 2007, 6089–
6096.
4. Calle, M.; Cuadrado, P.; Gonza´lez-Nogal, A. M.; Valero, R. Synthesis 2001, 1949–
1958.
5. Cuadrado, P.; Gonza´lez-Nogal, A. M.; Valero, R. Tetrahedron 2002, 58, 4975–
4980.
6. Calvo, L. A.; Gonza´lez-Nogal, A. M.; Gonza´lez-Ortega, A.; San˜udo, M. C. Tetra-
hedron Lett. 2001, 42, 8981–8984.
4.5.3. Z-1-(tert-Butyldiphenylsilyl)-3-(ethylamino)but-2-en-1-
one (13b)
Yield 52%; oil, Rf 0.42 (CH2Cl2); IR (CHCl3) 3150, 1592, 1517,
1105 cmꢀ1; 1H NMR (CDCl3)
d
1.20 (s, 9H), 1.27 (t, J¼7.1 Hz, 3H), 1.83
(s, 3H), 3.28 (dq, J¼6.2, 7.1 Hz, 2H), 5.27 (s, 1H), 7.33–7.46 (m, 6H),
7.68–7.76 (m, 4H); 13C NMR (CDCl3)
15.14, 18.24, 18.44, 28.08,
´
´
7. Calle, M.; Calvo, L. A.; Gonzalez-Ortega, A.; Gonzalez-Nogal, A. M. Tetrahedron
2006, 62, 611–618.
d
8. Nesi, R.; Ricci, A.; Taddei, M.; Tedeschi, P.; Seconi, G. J. Organomet. Chem. 1980,
195, 275–283.
37.78, 106.35, 127.49, 129.01, 134.25, 136.39, 161.53, 215.63. Anal.
Calcd for C22H29NOSi: C, 75.16; H, 8.31; N, 3.98. Found: C, 74.93; H,
8.45; N, 4.27.
9. Oshima, K. In Science of Synthesis. Houben-Weyl Methods of Molecular Trans-
formations; Fleming, I., Ed.; Thieme: Stuttgart, 2001; Vol. 4, pp 743–754.
10. (a) Padwa, A.; Kline, D. N.; Perumattan, J. Tetrahedron Lett. 1987, 28, 913–916; (b)
Ishikawa, T.; Kudoh, T.; Yoshida, J.; Yasuhara, A.; Manabe, S.; Saito, S. Org. Lett.
2002, 4, 1907–1910.
11. Ahn, C.; Kennington, J. W.; DeShong, P. J. Org. Chem. 1994, 59, 6282–6286.
12. (a) Fleming, I. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 2, pp 563–593; (b) Sarkar, T. K. In Science of
Synthesis. Houben-Weyl Methods of Molecular Transformations; Fleming, I., Ed.;
Thieme: Stuttgart, 2001; Vol. 4, pp 837–838 901–919.
4.5.4. Z-3-(Ethylamino)-1-(trimethylsilyl)but-2-en-1-one (13c)
Yield 75%; oil, Rf 0.10 (CH2Cl2); IR (CHCl3) 3150, 1592, 1517,
1105 cmꢀ1; 1H NMR (CDCl3)
(s, 3H), 3.29 (dq, J¼7.3, 7.1 Hz, 2H), 5.42 (s,1H),12.20 (br s,1H). Anal.
Calcd for C9H19NOSi: C, 58.32; H, 10.33; N, 7.56. Found: C, 58.55; H,
10.47; N, 7.31.
d
0.16 (s, 9H), 1.26 (t, J¼7.1 Hz, 3H), 1.95
´
13. Elguero, J.; Jacquier, R.; Tizane, D. Bull. Soc. Chim. Fr. 1970, 1121–1129.
14. Cuadrado, P.; Gonza´lez-Nogal, A. M.; Martı´nez, S. Tetrahedron 1997, 53, 8585–
8598.
15. Irradiation of the exocyclic olefinic proton showed enhancement of the CH2N
group.
4.5.5. Z-3-tert-Butyl-5-(tert-butyldiphenylsilylmethylen)-2-ethyl-
3-isoxazoline (Z-14b)
16. (a) Kuckla¨nder, U. Enaminones as Synthones. In The Chemistry of Functional
Groups; Rappoport, Z., Ed.; Wiley-Interscience: New York, NY, 1994; Part 1,
Chapter 10; (b) Lue, P.; Greenhill, J. V. Adv. Heterocycl. Chem. 1997, 67, 207–215.
17. (a) Page, P. C. B.; Mc Kenzie, M. J. In Science of Synthesis. Houben-Weyl Methods of
Molecular Transformations; Fleming, I., Ed.; Thieme: Stuttgart, 2001; Vol. 4,
pp 513–514, 543–561; (b) Linghu, X.; Potnick, J. R.; Johonson, J. S. J. Am. Chem.
Soc. 2004, 126, 3070–3071; (c) Nahm, M. R.; Linghu, X.; Potnick, J. R.; Yates, C.
M.; White, P. S.; Johnson, J. S. Angew. Chem., Int. Ed. 2005, 44, 2377–2379; (d)
Mattson, A. E.; Bharadwa, A. R.; Zuhl, A. M.; Scheidt, K. A. J. Org. Chem. 2006, 71,
5715–5724.
Yield 36%.
4.5.6. E-3-tert-Butyl-5-(tert-butyldiphenylsilylmethylen)-2-ethyl-
3-isoxazoline (E-14b)
Yield 47%.
4.5.7. E-5-tert-Butyl-3-(tert-butyldiphenylsilylmethylen)-2-ethyl-
4-isoxazoline (15a)
18. Landais, Y. In Science of Synthesis. Houben-Weyl Methods of Molecular Trans-
formations; Fleming, I., Ed.; Thieme: Stuttgart, 2001; Vol. 4, pp 757–760.
Yield 90%.