Chiral primary amino silyl ether organocatalyst for the enantioselective diels-alder reaction of 1,2-dihydropyridines with aldehydes

Article abstract of DOI:10.3987/COM-12-S(N)93

The enantioselective Diels-Alder reactions of 1,2-dihydropyridines with acroleins using a chiral primary amino silyl ether organocatalyst afforded chiral isoquinuclidines with good chemical yields and excellent enantioselectivities (up to 70% and up to 99

Full text of DOI:10.3987/COM-12-S(N)93

HETEROCYCLES, Vol. 86, No. 2, 2012
1379
HETEROCYCLES, Vol. 86, No. 2, 2012, pp. 1379 - 1389. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 7th July, 2012, Accepted, 13th August, 2012, Published online, 20th August, 2012
DOI: 10.3987/COM-12-S(N)93
CHIRAL PRIMARY AMINO SILYL ETHER ORGANOCATALYST FOR
THE
ENANTIOSELECTIVE
DIELS-ALDER
REACTION
OF
1,2-DIHYDROPYRIDINES WITH ALDEHYDES
Yuki Sakuta,a Yoshihito Kohari,a N. D. M. Romauli Hutabarat,a Koji Uwai,a
Eunsang Kwon,b Yuko Okuyama,c Chigusa Seki,a Haruo Matsuyama,a
Nobuhiro Takano,a Michio Tokiwa,d Mitsuhiro Takeshita,d and Hiroto
Nakano*a
a
Department of Applied Chemistry, Faculty of Engineering, Muroran Institute of
Technology, Muroran 050-8585, Japan, E-mail: catanaka@mmm.muroran-it.ac.jp
b
Research and Analytical Center for Giant Molecules, Graduate School of
Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578,
Japan, E-mail: ekwon@m.tohoku.ac.jp
c
Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai
981-8558, Japan, E-mail: yoku@tohoku-pharm.ac.jp
d
Tokiwakai Group, 62 Numajiri Tsuduri-chou Uchigo Iwaki 973-8053, Japan,
E-mail: m-takeshita@tokiwa.or.jp
Abstract –The enantioselective Diels-Alder reactions of 1,2-dihydropyridines with
acroleins using a chiral primary amino silyl ether organocatalyst afforded chiral
isoquinuclidines with good chemical yields and excellent enantioselectivities (up to 70%
and up to 99% ee).
INTRODUCTION
Asymmetric organocatalysis has emerged as an important and rapidly growing area of synthetic organic
chemistry, and excellent covalent and non-covalent organocatalysts have been developed for use in a
wide range of reactions.1 Recently, we also developed a covalent-type oxazolidine and !-amino alcohol
organocatalyst2 that works as an efficient catalyst in the asymmetric Diels-Alder (DA) reaction of
1,2-dihydropyridines3 with acroleins, which is an important reaction for the construction of chiral
* Dedicated to Dr. Ei-ichi Negishi on the occasion of his 77th birthday.

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HETEROCYCLES, Vol. 86, No. 2, 2012
isoquinuclidines (2-azabicyclo[2.2.2]octanes). Isoquinuclidines are found widely in natural products such
as iboga-type alkaloids, which have varied and interesting biological properties (Scheme 1).4 In
particular, there are the anti-cancer drugs, vinblastine and vincristine, which possess isoquinuclidines,
with the aspidosperma portion.5 Furthermore, it has recently been indicated that ibogaine reduces cravings
for alcohol and other drugs by means of its ability to boost the levels of a growth factor known as glial
cell line-derived neurotrophic factor (GDNF)6. Most recently it has also been shown that the
isoquinuclidines can be used as the synthetic intermediates for the synthesis of oseltamivir phosphate
(Tamiflu) which is an important anti-influenza drug.7 Therefore, it is meaningful to establish an effective
catalytic asymmetric synthetic methodology for chiral isoquinuclidines using an organocatalyst.
CO2Et
MeO
N
O
NH2
N
H
NHCOMe
. H3PO4
ibogaine
oseltamivir (tamiflu)
R
N
vinblastine
or
dienophile
R'
vincristine
N
R
DA
reaction
R'
isoquinuclidines
1,2-dihydropyridines
new drugs
Scheme 1. Utility of isoquinuclidines
We report herein that primary amino silyl ether with CF3CO2H is an efficient organocatalyst for the DA
reaction of 1,2-dihydropyridines with acroleins affording chiral isoquinuclidines at good chemical yields
(up to 65%) and excellent enantioselectivities (up to 99% ee).
Concerning the concept for catalyst design, it is suggested that the formation of the iminium ion
intermediate from the reaction of an amino silyl ether catalyst with acroleins might be able to control the
attack of a diene that was fixed by the hydrogen bonding interactions between the hydrogen on the
iminium ion intermediate and the carbonyl group on 1,2-dihydropyridines. And therefore, the steric
influence of the bulky diphenyl silyloxy group at the 1-position and a substituent at the 2-position in the
iminium ion intermediate might also effectively to afford high enantioselectivity in the reaction (Scheme
2).

HETEROCYCLES, Vol. 86, No. 2, 2012
1381
steric influence
Ph
TMS
Ph
H
R
RO2C
O
+
N
steric
influence
hydrogen
bonding
N
acrolein
O
N
N
Diels-Alder
reaction
R
X
O
CHO
Isoquinuclidines
CO2R
1,2-dihydropyridines
amino silyl ether catalyzed pathway
Scheme 2. Function of amino silyl ether organocatalyst.
RESULTS AND DISCUSSION
Catalysts 3a-i, respectively, were easily prepared by the reactions of the corresponding !-amino alcohols
with XOTf (X= TMS, TES, and TIPS) followed by treatment with an organic acid (Scheme 3). Thus, the
silylations of the !-amino alcohols 1a-g, respectively, afforded the corresponding precursor amino silyl
ethers 2a-g in good to moderate chemical yields. The treatments of 2a-g with YCO2H (Y= CF3, CCl3,
CH3) afforded the desired amino silyl ether salt catalysts 3a-i in quantitative yields. Proline-based amino
silyl ether8-CF3CO2H salt catalyst 4 was also obtained by the treatment of the precursor proline-based
amino silyl ether with CF3CO2H under the same reaction conditions.
Ph
Ph
Ph
Ph
OX
Ph
OX
Ph
OH
XOTf
Et3N
Ph
Ph
R
R
R
Y
N
H
CHCl3
CH2Cl2 or Et2O
0 °C, 1min
OTMS
�
NH2
NH2
NH2
�Y
rt, 24 h
�CF3CO2H
2a-g
4
3a-i
1a-g
a: 50% b: 76% c: 80% d: 46%,
e: 68% f: 29% g: 24%
3a-i
2a-g
R = Me, X = TMS,
a:
b:
c:
d:
e:
f:
g:
h:
i:
a:
b:
c:
d:
e:
f:
g:
R = Me, X = TMS, Y = CF3CO2H
R = iPr, X = TMS, Y = CF3CO2H
R = tBu, X = TMS, Y = CF3CO2H
R = Ph, X = TMS, Y = CF3CO2H
R = Bn, X = TMS, Y = CF3CO2H
R = tBu, X = TMS, Y = CH3CO2H
R = tBu, X = TMS, Y = CCl3CO2H
R = tBu, X = TES, Y = CF3CO2H
R = tBu, X = TIPS, Y = CF3CO2H
R = iPr, X = TMS,
R = tBu, X = TMS,
R = Ph, X = TMS,
R = Bn, X = TMS,
R = tBu, X = TES
R = tBu, X = TIPS
Scheme 3. Preparations of amino silyl ethers 2a-g and organocatalysts 3a-i.
We first examined the DA reaction of common 1-phenoxycarbonyl-1,2-dihydropyridine 5a with acrolein
6. The reaction of 5a (1 equiv) with 6 (3 equiv) was carried out at 0 °C in CH3CN-H2O (19:1)2 in the
presence of 10 mol% of catalysts 3a-i to give the DA adduct 7, and its chemical and optical yields were
determined by conversion to the alcohol 8. The results are summarized in Table 1. The reaction catalyzed

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HETEROCYCLES, Vol. 86, No. 2, 2012
by 2-methyl-1-OTMS 3a gave the DA adduct 7 in low chemical yield and with moderate
enantioselectivity (entry 1). The use of 2-isopropyl-1-OTMS 3b brought about an increase in both
chemical yield (53%) and enantioselectivity (endo-7a: 91% ee) (entry 2). Bulkier 2-tert-butyl-1-OTMS
catalyst 3c gave the endo-DA adduct 7a in good chemical yield (55%) and with excellent
enantioselectivity (95% ee) (entry 3). In contrast, the catalytic activity of sterically crowded
2-phenyl-1-OTMS 3d was low and those reactions proceeded slightly with exo-DA adduct 3b (entry 4).
On the other hand, more sterical larger 2-benzyl-1-OTMS 3e showed a high level of catalytic activity to
afford the endo-DA adduct 7a at 56% and 85% ee (entry 5), although the reasons for this are unclear.
Furthermore, the use of 2-tert-butyl-1-OTMS catalyst 3f with CH3CO2H did not show the catalytic
activity in the reaction (entry 6). In addition, the activity of 2-tert-butyl-1-OTMS catalyst 3f with
CCl3CO2H was also examined, but the chemical yield was not satisfactory, although the endo-DA adduct
7a was obtained with good enantioselectivity (entry 7). We next examined the efficiencies of the catalysts
3h,i having bulkier OTES and OTIPS at the 1-position on amino silyl ether (entries 8,9).
Table 1. Enantioselective DA reaction of 5 with 6 using catalysts 3 or 4.
RO2C
RO2C
N
N
5a (R: Ph)
5b (R: Bn)
N
CO2R
CHO
7a (R: Ph)
9a (R: Bn)
OH
catalyst
3a-i, 4
8a (R: Ph)
10a (R: Bn)
NaBH4
+
EtOH
0°C, 1 h
quant.
MeCN-H2O
(19:1)
0˚C
RO2C
N
RO2C
O
N
CHO
OH
7b (R: Ph)
9b (R: Bn)
8b (R: Ph)
10b (R: Bn)
endo/exob
endo-7a,9a
DA
(7a/7b or 9a/9b) adduct ee (%)c
Catalyst
(mol %)
Time
(h)
Yield
(%)a
Entry
Diene
24
53
55
7
13:1
20:1
endo only
6:1
20:1
62 (S)
91 (S)
95 (S)
13 (S)
85 (S)
---
92 (S)
89 (S)
85 (S)
69 (R)
92 (S)
90 (S)
95 (S)
96 (S)
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5b
7a
7a
7a
7a
7a
---
7a
7a
7a
7a
7a
7a
7a
9a
24
24
24
24
24
24
24
24
24
24
24
24
48
48
3a (10)
3b (10)
3c (10)
3d (10)
3e (10)
3f (10)
3g (10)
3h (10)
3i (10)
4 (10)
3c (5)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
56
nd
17
22
18
11
40
20
70
68
---
15 : 1
8:1
6:1
4:1
endo only
4:1
3c (2.5)
3c (10)
3c (10)
endo only
endo only
a Isolated yields.bThe endo/exo ratio was determined by 1H NMR.cThe ee of the
endo and exo isomers were determined by chiral HPLC using a Daicel AD-H
column (hexane/2-propanol : 85/15).

HETEROCYCLES, Vol. 86, No. 2, 2012
1383
Although these catalysts 3h,i brought about fairly good asymmetric inductions, the chemical yields were
poor. The catalytic activity of common proline-based organocatalyst 4 with CF3CO2H in this reaction was
also tested. However the catalyst did not afford a better result than did primary amino silyl ether 3c (entry
10). The above results indicate that primary amino silyl ether was the efficient catalyst in this DA
reaction. These results indicate that the existence of the OTMS group as a trisubstituted silyloxy group at
the 1-position on amino silyl ether is important for obtaining a satisfactory enantioselectivity and
chemical yield. To optimize the reaction conditions using superior catalysts 3c, we next examined the
effect of reducing the molar ratio of 3c. Although the reaction mixtures containing 5 mol% of 3c afforded
fairly good enantioselectivity (endo-7a: 92% ee), the chemical yield decreased to 40% (entry 11). Lower
catalytic loading to 2.5 mol% greatly decreased the chemical yield (20%) (entry 12). A dramatic increase
in chemical yield to 70% was achieved with excellent enantioselectivity (95% ee), when the reaction time
was changed from 24 h to 48 h (entry 13). Similarly, synthetically useful 1,2-dihydropyridine 5b was also
examined using superior catalyst 3c and dienophile 6 (Scheme 14). The reaction was carried out at 0 °C
for 24 h in the presence of 10 mol% of the best catalyst 3c to give the corresponding endo-DA adduct 9a.
The chemical and optical yields of the DA adduct 9 were determined by converting to the alcohol 10. As
a result, good chemical yield and enantioselectivity (68%, 96% ee) were obtained using catalyst 3c. These
results indicated that 5-tert-butyl-1-OTMS catalyst 3c with CF3CO2H were the most effective in the DA
reactions of dienes 5a,b with 6 to afford the DA adducts 7a, 9a, respectively, with good chemical yields
and excellent enantioselectivities (7a: 70%, 95% ee, 9a: 68%, 96% ee). However, the best catalyst 3c did
not afford a better result than our corresponding previously reported !-amino alcohol organꢀcatalyst 1c
with CF3CO2H2a in the same DA reaction. It might be reason that bulkier trimethylsilyloxy group on 3c
was act negatively for obtaining the DA adducts 7a or 9a with an excellent chemical yield and
enantioselectivity.
Based on both the high enantiopurity (95% ee) of the chiral DA adduct (7S)-7a that was obtained from
the reaction of diene 5a with dienophile 6 and Isihara’s detail study9 for an amino organocatalized DA
reaction mechanism, a model of the enantioselective reaction was proposed as follows (Scheme 4). Thus,
the reaction might be through the transition state A that was fixed by the hydrogen bonding interactions
between the hydrogen on the iminium ion intermediate and the carbonyl group on 1,2-dihydropyridines.
Then the diene might attack from the re-face of the olefin part on the iminium ion intermediate rather than
the sterically crowded si-face that was masked by the combination of the bulky diphenyl
trimethylsilyloxy group at the 1-position and the tert-butyl group at the 2-position in the iminium ion
intermediate (transition state B).

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HETEROCYCLES, Vol. 86, No. 2, 2012
Ph
Ph
Ph
Ph
O
TMS
TMS
O
+
+
N
N
H
catalyst
3c
H
or
O
O
5a + 6
Ph
Ph
O
O
DA
reaction
N
N
A
B
upper side attack from si-face
under side attack from re-face
95% ee
RO2C
N
CO2R
N
CHO
[S]-7a
OHC
[R]-7a
minor product
major product
Scheme 4. Prausible reaction course for DA reaction of 5a with 6 using catalyst 3c.
The effectiveness of superior 2-tert-butyl-1-OTMS catalyst 3c was then evaluated in the DA reaction
using acrolein derivative 11 (Scheme 5). The reactions of dienes 5a or 5b with dienophile 11 were carried
out at 0 °C in the presence of 10 mol% of superior catalyst 3c to give the DA adducts 12 or 13. The
chemical and optical yields of 12 or 13 were determined by conversion to alcohols 14 or 15, respectively.
In both reactions, catalyst 3c showed satisfactory asymmetric catalytic activity and the desired DA
adducts 12 or 13 were obtained in good chemical yields and with excellent enantioselectivities (12: 65%,
99% ee, 13: 60%, 97% ee).
RO2C
RO2C
MeO2C
+
N
CO2Me
N
CO2Me
(10 mol%)
3c
NaBH4
5a or 5b
MeCN-H2O (19:1)
0 °C, 24h
EtOH
rt, 1 h
quant.
O
CHO
OH
14: R = Ph, 15: R = Bn
11
12: R = Ph, endo only
65%, 99%ee
13: R = Bn, endo only
60%, 97%ee
Scheme 5. Enantioselective DA reactions of 5a or 5b with 11 using catalyst 3c.
In conclusion, new amino silyl ether organocatalyst 3 was explored. Catalyst 3 was easily prepared in two
steps. Organocatalyst 3c, in particular, showed efficient asymmetric catalytic activity in the Diels-Alder
reactions of 1,2-dihydropyridines 5a,b with acroleins 6, 11 to afford the chiral isoquinuclidines 7, 9, 12,
23, respectively. Further studies are in progress to examine the scope and limitations of this
organocatalyst for the catalytic asymmetric version of the DA reactions of 1,2-dihydropyridines.

HETEROCYCLES, Vol. 86, No. 2, 2012
1385
EXPERIMENTAL
1
IR spectra were measured with a PERKIN ELMER 1725X spectrophotometer. H-NMR spectra were
recorded on a JEOL JNM-GSX 400 and a JEOL JNM-LA 600 spectrometers with TMS as an internal
standard. MS were taken on a Hitachi RMG-6MG and a JEOL-JNM-DX 303 spectrometers. Optical
rotations was measured with a JASCO-DIP-370 digital polarimeter.
General procedure for the preparation of amino silyl ethers 2b,c,f,g
To a solution of amino alcohols 1a-e (2.0 mmol) in CH2Cl2 (30 mL) were added trisubstituted silyl
trifluoromethanesulfonates (2.4 mmol) and Et3N (2.4 mmol) at -30 °C. The mixture was stirred for 24
min at room temperature. Water (10 mL) was added, the aqueous layer was extracted with CHCl3 (2 x 30
mL) and organic phases were dried over MgSO4 and evaporated to give a crude products 2a-g. The
residue was purified by column chromatography (SiO2, CHCl3) to give a pure products 2a-g (a: 299 mg,
50%, b: 498 mg, 76%, c: 546 mg, 80%, d: 333 mg, 46%, e: 511 mg, 68%, f: 223 mg, 29%, g: 204 mg,
24%).
(S)-3-Methyl-1,1-diphenyl-1-(trimethylsilyloxy)butan-2-amine (2b)
Colorless oil. [!]D25 129.99 (c 0.30, CHCl3); IR (KBr) cm-1: 699, 836, 1069, 1250, 1493, 2954; 1H-NMR
(CDCl3) ": 7.44-7.26 (m, 10H, Ph), 3.57 (s, 1H, NCH), 1.92 (s, 1H, CH(CH3)2), 1.03 (d, J = 6.9 Hz, 6H,
13
CH(CH3)2), 0.17 (d, J = 6.9 Hz, 6H, CH(CH3)2), -0.18 (s, 9H, Si(CH3)3); C-NMR (CDCl3) ":128.7,
128.6, 127.7, 127.5, 127.1, 84.5, 61.5, 27.0, 23.6, 15.8, 1.8 ; Anal. Calcd for C20H29NOSi: C, 73.34; H,
8.92; N, 4.28. Found: C, 73.15; H, 9.10; N, 4.16. EI-MS m/z: 327 (M+).
(S)-3,3-Dimethyl-1,1-diphenyl-1-(trimethylsilyloxy)butan-2-amine (2c)
Colorless oil. [!]D26 106.66 (c 0.30, CHCl3); IR (KBr) cm-1: 700, 835, 1072, 1250, 1494, 1738, 2952;
1H-NMR (CDCl3) ": 7.58-7.26 (m, 10H, Ph), 3.61 (s, 1H, NCH), 0.72 (s, 9H, C(CH3)3), -0.21 (s, 9H,
Si(CH3)3); 13C-NMR (CDCl3) ":128.9, 128.6, 128.1, 127.5, 127.1, 126.8, 85.1, 65.1, 35.5, 28.8, 1.8; Anal.
Calcd for C21H31NOSi: C, 73.84; H, 9.15; N, 4.10. Found: C, 73.75; H, 9.21; N, 4.02. EI-MS m/z: 342
(M+).
(S)-3,3-Dimethyl-1,1-diphenyl-1-(triethylsilyloxy)butan-2-amine (2f)
Colorless oil. [!]D28 109.99 (c 0.30, CHCl3); IR (KBr) cm-1: 701, 850, 1069, 1230, 1494, 1738 2952;
1H-NMR (CDCl3) ": 7.62-7.26 (m, 10H, Ph), 3.64 (s, 1H, NCH), 0.83 (t, J = 8.0 Hz, 9H, Si(CH2CH3)3),
13
0.72 (s, 9H, C(CH3)3), 0.24 (qq, J = 7.4 Hz, J = 8.3 Hz, 6H, Si(CH2CH3)3); C-NMR (CDCl3) ":128.9,

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HETEROCYCLES, Vol. 86, No. 2, 2012
128.7, 128.0, 127.7, 127.0, 126.8, 85.0, 65.5, 35.5, 28.8, 7.3, 6.0; Anal. Calcd for C24H37NOSi: C, 75.14;
H, 9.72; N, 3.65. Found: C, 75.02; H, 9.81; N, 3.54. EI-MS m/z: 383 (M+).
(S)-3,3-Dimethyl-1,1-diphenyl-1-(triisopropylsilyloxy)butan-2-amine (2g)
Colorless oil. [!]D28 116.66 (c 0.30, CHCl3); IR (KBr) cm-1: 704, 880, 1052, 1229, 1464, 1738, 2945;
1H-NMR (CDCl3) ": 7.72-7.26 (m, 10H, Ph), 3.74 (s, 1H, NCH), 1.05 (s, 18H, Si(CH(CH3)2)3), 0.99 (d, J
= 7.4 Hz, 18H, Si(CH(CH3)2)3), 0.90 (d, J = 7.4 Hz, 18H, Si(CH(CH3)2)3), 0.72 (s, 9H, C(CH3)3), 0.66
13
(dd, J = 7.4 Hz, J = 7.7Hz, 3H, Si(CH(CH3)2)3); C-NMR (CDCl3) ":129.4, 129.1, 127.9, 126.8, 85.9,
66.2, 35.4, 28.9, 19.0, 14.2; Anal. Calcd for C27H43NOSi: C, 76.17; H, 10.18; N, 3.29. Found: C, 76.01;
H, 10.29; N, 3.14. EI-MS m/z: 425 (M+).
General procedure for the preparation of amino silyl etherꢁCF3CO2H organocatalysts 3a-i
To a CH2Cl2 (1.8 mL) solution of amino silyl ether 2a-g (0.03 mmol), trifluoroacetic acid (0.036 mmol)
was added at 0 °C. The resulting mixture was stirred at that temperature for 5 min. Solvent was
evaporated under a reduced pressure to afford the corresponding catalyst 3a-i as a colorless crystal in
quantitative yield.
(S)-1,1-Diphenyl-1-(trimethylsilyloxy)propan-2-amineꢁCF3CO2H (3a)
Colorless oil. [!]D28 73.33 (c 0.30, CHCl3); IR (KBr) cm-1: 701, 838, 1130, 1254, 1541, 1684; H-NMR
1
(CDCl3) ": 7.51-7.26 (m, 10H, Ph), 4.37 (d, J = 6.9 Hz, 1H, NCH), 1.24 (d, J = 6.9 Hz, 3H, CH3), -0.18
(s, 9H, Si(CH3)3); 13C-NMR (CDCl3) ":129.0, 128.6, 128.0, 81.9, 54.9, 14.9, 1.4; Anal. Calcd for
C20H26F3NO3Si: C, 58.09; H, 6.34; N, 3.39. Found: C, 57.91; H, 6.48; N, 3.22.
(S)-3-Methyl-1,1-diphenyl-1-(trimethylsilyloxy)butan-2-amineꢁCF3CO2H (3b)
27
White crystal (Et2O). Mp 220-221 °C; [!]D 113.33 (c 0.30, CHCl3); IR (KBr) cm-1: 702, 833, 1051,
1253, 1510, 1667; 1H-NMR (CDCl3) ": 7.77-7.26 (m, 10H, Ph), 4.10 (d, J = 3.2 Hz, 1H, NCH), 1.97 (s,
1H, CH(CH3)2), 1.05 (d, J = 6.9Hz, 6H, CH(CH3)2), 0.45 (d, J = 6.9 Hz, 6H, CH(CH3)2), -0.20 (s, 9H,
13
Si(CH3)3); C-NMR (CDCl3) ":129.2, 128.9, 128.5, 82.1, 63.4, 26.6, 22.6, 17.0, 1.4; Anal. Calcd for
C22H30 F3NO3Si: C, 59.84; H, 6.85; N, 3.17. Found: C, 59.73; H, 6.98; N, 3.05.
(S)-3,3-Dimethyl-1,1-diphenyl-1-(trimethylsilyloxy)butan-2-amineꢁꢁCF3CO2H (3c)
White crystal (Et2O). Mp 222-223 °C; [!]D24 83.33 (c 0.30, CHCl3); IR (KBr) cm-1: 702, 836, 1133, 1254,
1
1495, 1673, 2958; H-NMR (CDCl3) ": 7.58-7.09 (m, 10H, Ph), 4.19 (s, 1H, NCH), 0.75 (s, 9H,

HETEROCYCLES, Vol. 86, No. 2, 2012
1387
13
C(CH3)3), -0.14 (s, 9H, Si(CH3)3); C-NMR (CDCl3) ":129.3, 128.9, 128.7, 128.5, 128.0, 83.3, 65.2,
34.7, 28.1, 1.6; Anal. Calcd for C23H32F3NO3Si: C, 60.64; H, 7.08; N, 3.07. Found: C, 60.48; H, 7.20; N,
2.95.
(S)-1,2,2-Triphenyl-2-(trimethylsilyloxy)ethan-2-amineꢁCF3CO2H (3d)
White crystal (Et2O). Mp 189-190 °C; [!]D27 43.33 (c 0.30, CHCl3); IR (KBr) cm-1: 697, 837, 1131, 1254,
1
1507, 1684; H-NMR (CDCl3) ": 7.64-6.79 (m, 10H, Ph), 5.29 (s, 1H, NCH), -0.16 (s, 9H, Si(CH3)3);
13C-NMR (CDCl3) ":129.5, 129.4, 129.2, 128.7, 128.4, 127.6, 127.5, 83.5, 62.7, 1.6; Anal. Calcd for
C25H28 F3NO3Si: C, 63.14; H, 5.93; N, 2.95. Found: C, 62.98; H, 6.02; N, 2.82.
(S)-1,1,3-Triphenyl-1-(trimethylsilyloxy)propan-2-amineꢁCF3CO2H (3e)
28
White crystal (Et2O). Mp 173-174 °C; [!]D 246.66 (c 0.30, CHCl3); IR (KBr) cm-1: 699, 839, 1131,
1254, 1507, 1684; 1H-NMR (CDCl3) ": 7.66-7.08 (m, 10H, Ph), 4.45 (d, J = 10.9 Hz, 1H, NCH), 3.08 (d,
13
J = 14.3 Hz, 2H, CH2Ph), 2.45 (t, J = 14.0 Hz, 2H, CH2Ph), -0.10 (s, 9H, Si(CH3)3); C-NMR (CDCl3)
":129.6, 129.2, 129.0, 128.7, 128.2, 127.1, 125.6, 125.0, 81.9, 60.6, 35.1, 1.5; Anal. Calcd for
C26H30F3NO3Si: C, 63.78; H, 6.18; N, 2.86. Found: C, 63.65; H, 6.29; N, 2.75.
(S)-3,3-Dimethyl-1,1-diphenyl-1-(trimethylsilyloxy)butan-2-amineꢁꢁCH3CO2H (3f)
28
White crystal (Et2O). Mp 167-168 °C; [!]D 29.99 (c 0.30, CHCl3); IR (KBr) cm-1: 695, 837, 1074, 1179,
1
1541, 1698; H-NMR (CDCl3) ": 7.67-7.11 (m, 10H, Ph), 3.67 (s, 1H, NCH), 0.72 (s, 9H, C(CH3)3),
13
-0.32 (s, 9H, Si(CH3)3); C-NMR (CDCl3) ":129.0, 128.5, 128.2, 127.7, 127.3, 85.0, 64.9, 35.4, 28.8,
1.8; Anal. Calcd for C23H35NO3Si: C, 68.78; H, 8.78; N, 3.49. Found: C, 68.61; H, 8.92; N, 3.35.
(S)-3,3-Dimethyl-1,1-diphenyl-1-(trimethylsilyloxy)butan-2-amineꢁCCl3CO2H (3g)
29
White crystal (Et2O). Mp 177-178 °C; [!]D 119.99 (c 0.30, CHCl3); IR (KBr) cm-1: 676, 827, 1079,
1
1173, 1507, 1684; H-NMR (CDCl3) ": 7.65-7.14 (m, 10H, Ph), 4.30 (s, 1H, NCH), 0.78 (s, 9H,
13
C(CH3)3), -0.12 (s, 9H, Si(CH3)3); C-NMR (CDCl3) ":128.7, 128.1, 83.4, 65.3, 34.8, 28.2, 1.8; Anal.
Calcd for C23H32Cl3NO3Si: C, 54.71; H, 6.39; N, 2.77. Found: C, 54.61; H, 6.47; N, 2.63.
(S)-3,3-Dimethyl-1,1-diphenyl-1-(triethylsilyloxy)butan-2-amineꢁꢁCF3CO2H (3h)
Colorless oil. [!]D28 123.33 (c 0.30, CHCl3); IR (KBr) cm-1: 704, 832, 1133, 1243, 1507, 1684; 1H-NMR
(CDCl3) ": 7.51-7.26 (m, 10H, Ph), 4.23 (s, 1H, NCH), 0.77 (t, J = 7.7 Hz, 9H, Si(CH2CH3)3), 0.75 (s, 9H,
13
C(CH3)3), 0.26 (dt, J =7.5 Hz, J = 7.7 Hz, 6H, Si(CH2CH3)3); C-NMR (CDCl3) ":128.9, 128.7, 128.0,

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HETEROCYCLES, Vol. 86, No. 2, 2012
127.7, 127.0, 126.8, 85.0, 65.5, 35.5, 28.8, 7.3, 6.0; Anal. Calcd for C26H38F3NO3Si: C, 62.75; H, 7.70; N,
2.81. Found: C, 62.63; H, 7.85; N, 2.71.
(S)-3,3-Dimethyl-1,1-diphenyl-1-(triisopropylsilyloxy)butan-2-amineꢁꢁCF3CO2H (3i)
Colorless oil. [!]D28 143.33 (c 0.30, CHCl3); IR (KBr) cm-1: 706, 825, 1136, 1247, 1507, 1684; 1H-NMR
(CDCl3) ": 7.65-7.15 (m, 10H, Ph), 4.42 (s, 1H, NCH), 1.05 (s, 18H, Si(CH(CH3)2)3), 0.89 (dd, J = 8.9
Hz, J = 8.0 Hz, 18H, Si(CH(CH3)2)3), 0.73 (s, 9H, C(CH3)3), 0.60 (q, J = 7.5 Hz, 3H, Si(CH(CH3)2)3);
13C-NMR (CDCl3) ":129.4, 129.1, 128.7, 128.1, 82.7, 65.5, 34.3, 28.1, 18.7, 17.7, 13.7, 12.2; Anal. Calcd
for C29H44F3NO3Si: C, 64.53; H, 8.22; N, 2.60. Found: C, 64.41; H, 8.38; N, 2.49.
General procedure for the DA reaction of 1, 2-dihydropyridine 5a,b with acrolein 6, 11 using
catalyst 3c.
To a CH3CN:H2O (19:9, 0.5 mL) solution of catalyst 3c (0.01 mmol) and 1,2-dihydropyridines 5a,b (0.1
mmol), distillated acroleins 6, 11 (0.3 mmol) was added at 0 °C and the solution was stirred at 0 °C for 24
h. The reaction was quenched by water. The reaction mixture was diluted with water and extracted with
Et2O. The combined organic extracts were washed with brine, dried over Na2SO4, and removed under
reduced pressure to give crude DA adducts 7a, 9a, 12, 13 which was used to the next reaction without
purification.
To a stirred solution of products 7a, 9a, 12, 13 in EtOH (2.0 mL), NaBH4 (2.0 mg, 0.05 mmol) was added
and the mixture was stirred at 0 °C for 1 h. Solvent was evaporated under a reduced pressure. The
reaction mixture was diluted with water and extracted with AcOEt. The combined organic extracts were
washed with brine, dried over Na2SO4, removed under reduced pressure to give a crude DA adducts. The
residue was purified by preparative TLC (SiO2, n-hexane : AcOEt = 1 : 1) to afford the DA adducts 8a,
10a, 14, 15 in quantitative yield.
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