Lewis acid-mediated [3+2] cycloaddition of allyltriisopropylsilane to N-sulfonyl aldimines

Article abstract of DOI:10.1016/S0040-4039(01)00594-9

BF₃·OEt₂-mediated [3+2] cycloaddition of allyltriisopropylsilane to N-sulfonyl aldimine afforded silyl substituted pyrrolidines in good yields. Excellent cis selectivity was observed with aromatic aldimines.

Full text of DOI:10.1016/S0040-4039(01)00594-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3889–3892
Lewis acid-mediated [3+2] cycloaddition of allyltriisopropylsilane
to N-sulfonyl aldimines
Takahiko Akiyama,* Megumi Sugano and Hirotaka Kagoshima
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1, Mejiro, Toshima-ku, Tokyo 171-8588, Japan
Received 22 February 2001; revised 22 March 2001; accepted 6 April 2001
Abstract—BF ·OEt -mediated [3+2] cycloaddition of allyltriisopropylsilane to N-sulfonyl aldimine afforded silyl substituted
3
2
pyrrolidines in good yields. Excellent cis selectivity was observed with aromatic aldimines. © 2001 Elsevier Science Ltd. All rights
reserved.
Lewis acid-mediated addition reaction of allylsilane to
a carbonꢀnitrogen double bond constitutes an impor-
tant reaction for the preparation of homoallylic amines,
and a number of Lewis acids have been developed as
cycloadducts upon reaction with N-acyl aldimines
6f
(mode 3). We wish to report herein that a fourth type
of reaction took place smoothly with N-sulfonyl
aldimines under the influence of BF ·OEt to afford
3
2
1
promoter for the allylation reaction (mode 1). The
pyrrolidine derivatives in good yields (mode 4) (Scheme
1).
high nucleophilicity of allylsilane as an allylation
2
reagent originates from the b-silicon effect. Although
the synthetic utility of allylsilane as an allyl anion
equivalent has been established, Lewis acid-mediated
cycloaddition reactions of allylsilane to a,b-unsaturated
carbonyl compounds and aldehyde have attracted
attention lately as novel method for the preparation of
First of all, treatment of N-tosyl aldimine (1a) and
allyltriisopropylsilane with BF ·OEt (1.1 equiv.) in tol-
3
2
uene at 0°C for 8 h gave a cyclization product (2a) in
36% yield in addition to an allylation product (3).
Among the Lewis acids examined, BF ·OEt exhibited
3
2
3
–5
9
five- and four-membered carbocycles as well as hete-
the best results. Although lowering the reaction tem-
perature decreased the yield of 2a, the reaction at room
temperature improved the yield of 2a to 44%. On
further rise of the reaction temperature to 40°C, the
yield slightly dropped to 40%. The stereoselectivity of
the present cycloaddition is quite high judging from 400
6
,7
rocycles. With respect to the Lewis acid-mediated
addition reaction of allylsilane to a carbonꢀnitrogen
bond, we have reported the formation of tetra-
hydroquinoline derivatives with N-aryl aldimines
8
(
mode 2). Uyehara reported the formation of [2+2]
R
H
X
Mode 1
R
SiR3
+
N
NXH
Mode 2
Mode 3
Mode 4
R
X
N
R
SiR3
X
N
SiR3
HN
R
SiR3
X = Ph
X = CO R
X = Ts
2
Scheme 1.
Keywords: allylsilane; cycloaddition; pyrrolidine; imines; BF ·OEt .
3
2
*
Corresponding author. Fax: +81-3-5992-1029; e-mail: takahiko.akiyama@gakushuin.ac.jp
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00594-9

3
890
T. Akiyama et al. / Tetrahedron Letters 42 (2001) 3889–3892
1
MHz H NMR. The relative stereochemistry was
unambiguously determined to be cis by an X-ray crys-
tallographic analysis. Interestingly, dilution of the reac-
tion conditions facilitated the formation of the
cycloadducts by suppressing the formation of the
homoallylic amines, and the results are shown in Table
The present results for the formation of [3+2] cycload-
6e
duct are in sharp contrast to the Uyehara report, in
which [2+2] cycloadducts were obtained from N-acyl or
N-alkoxycarbonyl substituted aldimines. Actually,
treatment of N-benzylidenebenzamide and allyltriiso-
propylsilane with BF ·OEt in toluene under the identi-
3
2
1
. Furthermore, increase of the amount of allylsilane
cal conditions with Table 2 led to the formation of a
[2+2] cycloadduct in 72% yield (cis:trans=71:29) and
none of the [3+2] adduct was obtained. Furthermore,
the fact that we could not obtain the [2+2] cycloadduct
from aldimine (1) bearing a sulfonyl moiety at all under
various conditions, including lower reaction tempera-
ture, clearly shows that the mode of cyclization depends
on the substituents on nitrogen. The present substituent
effect can be ascribed to the difference in the nucle-
improved the yield of 2a.
Results of the BF ·OEt2 mediated cycloaddition of
allylsilane (2 equiv.) with various kinds of aromatic
imines are shown in Table 2. Pyrrolidines (2) were
obtained in good yields with excellent cis
stereoselectivity.
3
10
Next, cycloaddition reaction to aliphatic aldimines was
examined, and the results are shown in Table 3. Inter-
estingly, the cycloaddition reaction toward aliphatic
aldimines completed much quicker to afford the
cycloadducts (2) in higher yields albeit with little
stereoselectivity.
ophilicity of N-COR and N-SO Ar in the reaction
2
intermediate 4 (Scheme 2). Intramolecular attack of
strong nucleophile NCOR to b-silyl carbocation led to
the formation of azetidine by kinetic control, and the
less nucleophilic nitrogen bearing a sulfonyl moiety
gave pyrrolidine by 1,2-silicon shift under thermody-
Table 1. Effect of the concentration
(
1.1 equiv)
Ts
N
BF •OEt
NTs
3
2
Ph
Ph
+
Si(i-Pr)3
+
Toluene
r.t.
Ph
NHTs
1a
Si(i-Pr)3
2a
3
Entry
Concentration (mol/L)
Amount of allylsilane
Yield of 2a (%)
cis:trans
Yield of 3 (%)
1
2
3
4
5
0.15
0.15
0.075
0.03
0.03
1.2
2
2
2
4
44
44
57
62
73
96:6
96:6
96:6
96:6
95:5
44
44
36
25
25
Table 2. Results of the cycloannulation with aromatic imines

T. Akiyama et al. / Tetrahedron Letters 42 (2001) 3889–3892
3891
a
Table 3. Results of the cycloannulation with aliphatic imines
(
1.1 equiv)
Ts
N
BF •OEt2
NTs
3
R
+
Si(i-Pr)3
R
Toluene
r.t.
1
Si(i-Pr)3
2
Entry
R
Concentration (mol/L)
Reaction time (h)
Yield of 2 (%)
Ratiob
1
2
3
4
5
Cyclohexyl
PhCH CH
0.03
0.01
0.03
0.01
0.03
0.5
0.5
0.5
0.5
4
72
81
88
76
71
56:46
59:41
54:46
55:45
52:48
2
2
CH CH CH
3
2
2
(CH ) CH
3
2
CH OCO
3
a
2
equiv. of allylsilane was employed.
b
The relative stereochemistry has not been decided.
X
b
X
N
SiR3
N
Path a
X
R
SiR3
Path b
R
a
R
N
SiR3
X = CO R, COR
2
4
X = Ts
Scheme 2.
1
1
namic control. Although Panek already reported the
formation of pyrrolidine derivatives by the Lewis acid-
mediated annulation of functionalized allylsilane with
J. S.; Jain, N. F. J. Org. Chem. 1993, 58, 2345–2348; (c)
Murphy, W. S.; Neville, D. Tetrahedron Lett. 1997, 38,
7933–7936; (d) Jung, M. E.; D’Amico, D. C. J. Am.
Chem. Soc. 1997, 119, 12150–12158; (e) Monti, H.; Riz-
zotto, D.; L e´ andri, G. Tetrahedron 1998, 54, 6725–6738;
(f) Kn o¨ lker, H.-J.; Jones, P. G.; Wanzl, G. Synlett 1998,
6
d,6l
in situ-generated N-acyl aldimine,
example for the formation of pyrrolidine derivatives by
the reaction of parent allylsilane with aldimine.
this is the first
12,13
613–616; (g) Graning, M. D.; Brengel, G. P.; Meyers, A.
In conclusion, we have reported a formation of pyrro-
lidines by [3+2] cycloaddition reaction of allylsilane
with aldimine, in which the N-substituent of aldimine is
the control factor in the selective formation of five- or
four-membered nitrogen heterocycles.
I. J. Org. Chem. 1998, 63, 5517–5522; (h) Hojo, M.;
Murakami, C.; Nakamura, S.; Hosomi, A. Chem. Lett.
1998, 331–332; (i) Yamazaki, S.; Kumagai, H.; Yamabe,
S.; Yamamoto, K. J. Org. Chem. 1998, 63, 3371–3378
and references cited therein.
. (a) Akiyama, T.; Nakano, M.; Kanatani, J.; Ozaki, S.
Chem. Lett. 1997, 385–386; (b) Akiyama, T.; Hoshi, E.;
Fujiyoshi, S. J. Chem. Soc., Perkin Trans. 1 1998, 2121–
5
6
Acknowledgements
2122; (c) Akiyama, T.; Yamanaka, M. Tetrahedron Lett.
1998, 39, 7885–7889; (d) Akiyama, T.; Asayama, K.;
Technical assistance of Dr. Masato Nanjo (Gakushuin
University) in the X-ray analysis is greatly appreciated.
Fujiyoshi, S. J. Chem. Soc., Perkin Trans. 1 1998, 3655–
3656.
. (a) Sugimura, H. Tetrahedron Lett. 1990, 31, 5909–5912;
(
b) Panek, J. S.; Beresis, R. T. J. Am. Chem. Soc. 1993,
References
115, 7898; (c) Kiyooka, S.; Shiomi, Y.; Kira, H.; Kaneko,
Y.; Tanimori, S. J. Org. Chem. 1994, 59, 1958–1960; (d)
Panek, J. S.; Jain, N. F. J. Org. Chem. 1994, 59, 2674–
2675; (e) Stahl, A.; Steckhan, E.; Nieger, M. Tetrahedron
Lett. 1994, 35, 7371–7374; (f) Uyehara, T.; Yuuki, M.;
Masaki, H.; Matsumoto, M.; Ueno, M.; Sato, T. Chem.
Lett. 1995, 789–790; (g) Schneider, M.-S.; Mann, A.;
Taddei, M. Tetrahedron Lett. 1996, 37, 8493–8496; (h)
Schinzer, D.; Panke, G. J. Org. Chem. 1996, 61, 4496–
4497; (i) Tanino, K.; Yoshitani, N.; Moriyama, F.;
Kuwajima, I. J. Org. Chem. 1997, 62, 4206–4207; (j)
Miura, K.; Hondo, T.; Saito, H.; Ito, H.; Hosomi, A. J.
Org. Chem. 1997, 62, 8292–8293; (k) Roberson, C. W.;
Woerpel, K. A. J. Org. Chem. 1999, 64, 1434–1435; (l)
1
2
. Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
. (a) Lambert, J. B.; Zhao, Y.; Emblidge, R. W.; Salvador,
L. A.; Liu, X.; So, J.-H.; Chelius, E. C. Acc. Chem. Res.
1
999, 32, 183; (b) Lambert, J. B. Tetrahedron 1990, 46,
2
677.
3
. For reviews, see: Panek, J. S. In Comprehensive Organic
Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon
Press: Oxford, 1991; Vol. 1, p. 579. Masse, C. E.; Panek,
J. S. Chem. Rev. 1995, 95, 1293–1316. Kn o¨ lker, H.-J. J.
Prakt. Chem. 1997, 339, 304–314.
4
. (a) Danheiser, R. L.; Takahashi, T.; Bertok, B.; Dixon,
B. R. Tetrahedron Lett. 1993, 34, 3845–3848; (b) Panek,

3
892
T. Akiyama et al. / Tetrahedron Letters 42 (2001) 3889–3892
Schaus, J. V.; Jain, N.; Panek, J. S. Tetrahedron 2000, 56,
0263–10274.
. (a) Akiyama, T.; Ishikawa, K.; Ozaki, S. Chem. Lett.
994, 627–628; (b) Akiyama, T.; Yasusa, T.; Ishikawa,
K.; Ozaki, S. Tetrahedron Lett. 1994, 35, 8401–8404; (c)
Akiyama, T.; Kirino, M. Chem. Lett. 1995, 723–724; (d)
Akiyama, T.; Yamanaka, M. Synlett 1996, 1095–1096.
. Akiyama, T.; Suzuki, M.; Kagoshima, H. Heterocycles
matography (SiO , hexane: ethyl acetate=9:1, v/v) gave
2
1
2a (49.9 mg, 73%) and a homoallylic amine (11.3 mg,
1
7
25%). Spectral data of 2a; H NMR (400 MHz, CDCl ) l
3
1
7.65–7.20 (aromatic, 9H), 4.47 (dd, 1H, J=6.9, 9.7 Hz),
3.95 (dd, 1H, J=7.7, 11.3 Hz), 3.59 (dd, 1H, J=11.3,
12.1 Hz), 2.47–2.42 (m, 1H), 2.41 (s, 3H), 1.86 (ddd, 1H,
13
J=9.7, 13.3, 13.3 Hz), and 1.05–0.99 (m, 22H). C NMR
8
9
(100 MHz, CDCl ) l 143.18, 143.04, 135.40, 129.46,
3
2
000, 52, 529–532.
. Other Lewis acids examined and yields of 1a are SnCl4
11%), AlCl (17%), TiCl (11%), ZrCl (15%).
128.37, 127.44, 127.04, 126.24, 65.33, 53.58, 41.66, 24.12,
21.43, 18.88, and 11.06.
(
11. Example and discussion of the selective formation of
four- and five-membered cycloadducts, see: Ref. 5c.
3
4
4
1
0. A typical experimental procedure for the preparation of
a is described (entry 5, Table 1). To a solution of 1a
38.8 mg, 0.150 mmol) and allyltriisopropylsilane (145 ml,
.602 mmol) in toluene (5.0 ml) was added BF ·OEt
6d,l
2
(
12. In Panek’s report,
the use of lower temperature
(<−78°C) is required to obtain the cycloadducts. Raising
the reaction temperature −20°C resulted in the exclusive
formation of the homoallylic amines, which is in contrast
to our results. Furthermore, the annulation is limited to
aromatic imines.
0
3
2
(
20.5 mL, 0.167 mmol) at room temperature. After being
stirred at this temperature for 4.5 h, the reaction mixture
was quenched by addition of satd NaHCO solution. The
3
aqueous layer was extracted with ethyl acetate and the
combined organic layers were washed with brine, dried
over anhydrous Na SO , and concentrated to dryness.
13. Formation of pyrrolidine by [3+2] cycloaddition of allyl-
silane to N-acyliminoester has already been reported
though the yields of the cycloadducts are modest. See
Ref. 6e.
2
4
Purification of the crude mixture by thin-layer chro-
.