K. A. Jùrgensen et al.
FULL PAPER
Tol-BINAP-(R)-4b-CuClO
4
´ 4MeCN in CH
2
Cl
2
at room temperature for
196.48, 171.31, 163.50, 156.37, 156.37, 105.11, 61.61, 61.14, 57.61, 50.05, 42.47,
5
0 h produced after purification by FC (20% EtOAc in pentane) a mixture
14.54, 14.09; HRMS: exact mass calcd for C12
found: 296.1103.
H
19NO
6
[MNa] : 296.1110;
of exo-3e and endo-3e as a colorless solid (59%) with a ratio of 7:3
1
according to H NMR. The ee for exo-3e was found to be 95% and for the
N-o-methoxyphenyl-4-oxo-1,2,3,4-tetrahydro-pyridine-2-carboxlic
acid
endo-3e 37% according to HPLC using a Chiralcel OD column (iPrOH/
ethyl ester (3j): According to the general procedure, the N-o-methox-
yphenyl glyoxylate imine (1c) was reacted with diene 2a in the presence of
À1
rt
hexane 5:95, 1.0 mLmin ). M. p.: 122Ð1238C; [a]
D
À216.5 (c 0.57 in
1
CHCl
8
7
3
3
); H NMR d 7.87 (d, J 8.2 Hz, 2H, C
6
H
2
H
2
, endo-3e), 7.75 (d, J
, exo-3e), 7.29 (d, J 8.2 Hz, 2H, C , endo-3e),
.27 (d, J 8.2 Hz, 2H, C
, exo-3e), 6.53 ± 6.48 (m, 1H, HC, endo-
e), 6.23 ± 6.05 (m, 1H, HC, endo-3e; 2H, HCCH, exo-3e), 4.31 ± 4.10
CH CH Et,
m, 3H, CHCHN, CO , exo-3e; 2H, CHCHN, NCHCO
endo-3e), 4.12 (q, J 7.1 Hz, 2H, CO CH CH , endo-3e), 3.77 (brs, 1H,
NCHCO
Et, exo-3e), 3.18 ± 3.13 (m, 1H, CHCHCH, endo-3e), 2.98 ± 2.93
), 2.20 ± 2.12 (m, 1H,
, endo-3e), 1.74 ± 1.06 (m, 3H,
endo-3e exo-3e), 1.32 (t, J 7.1 Hz, 3H,
CH CH , endo-3e);
1
4 2 2
0 mol% catalyst Tol-BINAP-(R)-4b-CuClO ´ 4MeCN in CH Cl at rt.
.2 Hz, 2H, C
6
H
2
H
2
6 2 2
H H
After stirred for 40 h, the reaction mixture was directly loaded on the
column and seperated by FC (40% EtOAc in pentane) to give the title
compund as a light yellow oil (25%). The ee of the product 3j was found to
be 55% according to HPLC using a Chiralcel OJ column (hexane/iPrOH
6 2 2
H H
(
2
2
3
2
2
2
3
À1
rt
1
9
7
4
4:6, 0.5 mLmin ). [a]
D
34.6 (c 0.5 in CHCl
3
); H NMR: d 7.30 ±
2
.21 (m, 5H, CHN, C
H
), 5.14 (dd, J 1.1, 7.7 Hz, 1H, CH(CO)), 4.77 ±
6
4
(
m, 1H, CHCHCH, exo-3e), 2.42 (s, 3H, ArCH
3
.74 (m, 1H, NCHCO
CH CH
), 3.11 (dd, J 7.1, 17.0, 1H, C(O)CH
7.0, 1H, C(O)CH CH CH
), 1.19 (t, J 7.2 Hz, CO
2
CH
2
CH
3
), 4.23 (dq, J 1.7, 7.2 Hz, 2H,
CH
CH
CO
a
a
2
b a b
H , exo-3e), 2.05 ± 1.94 (m, 1H, CH CH
CO
2
2
3
a
CH
b
), 2.86 (dd, J 2.2,
13
CH
CH
b
,
a b
CH' CH' ,
1
1
6
a
b
2
2
CH
3
); C NMR: d
2
CH
3
, exo-3e), 1.25 (t, J 7.1 Hz, 3H, CO
2
2
3
89.33, 169.98, 153.06, 152.30, 133.31, 128.05, 126.25, 121.12, 111.77, 100.56,
1
3
C NMR for exo-3e: d 170.73, 143.52, 135.75, 132.80, 132.75, 129.47,
1.65, 60.45, 55.65, 38.01, 13.96; HRMS: exact mass calcd for C15
MNa] : 298.1056; found: 298.1058.
H
17NO
4
1
28.05, 61.36, 59.77, 48.36, 33.78, 25.84, 21.57, 17.96, 14.23; HRMS: exact
[
mass calcd for C17
H
21SNO
4
[MNa] : 358.1089; found: 358.1034.
N-Phenyl-4-oxo-1,2,3,4-tetrahydro-pyridine-2-carboxylic acid ethyl ester
3k): According to the general procedure, the reaction between N-phenyl
glyoxylate imine (1d) and diene 2a in the presence of 10 mol% catalyst
Tol-BINAP-(R)-4b-CuClO ´ 4MeCN in CH Cl was performed at rt. After
stirred for 20 h, the reaction was then quenched by TFA (0.1 mL) in CH Cl
15 mL), purification by FC (60% EtOAc in pentane) gave 3k (78%) with
N-Tosyl-4,5-dimethyl-1,2-dihydro-pyridine-2-carboxylic acid ethyl ester
(
(
(
3 f) and 5-methyl-2-tosylamino-4-methylene-hex-5-enoic acid ethyl ester
3g): According to the general procedure, the reaction of the N-tosyl a-
4
2
2
imino ester 1a and 2,3-dimethyl-1,3-butadiene 2 f in the presence of
0 mol% catalyst Tol-BINAP-(R)-4b-CuClO ´ 4MeCN in CH Cl at room
2
2
1
4
2
2
(
temperature for 24 h produced after purification by FC (10% EtOAc in
pentane) 3 f (64%) and 3g (7%) as light yellow oils. The ee of the major
product (aza-Diels ± Alder product) 3 f was found to be 65% according to
HPLC using a Chiralcel OJ column, and the ee of the aza-ene product 3g
was determined as 86% using a Chiralcel OD column. Product 3 f: [a]
9
9
1% ee according to HPLC using a Chiralpak AD column (hexane/i-PrOH
À1
rt
1
9:1, 0.4 mLmin ). [a]
D
36.7 (c 0.1 in CHCl
3
); H NMR: d 7.52 (d,
J 7.7 Hz, 1H, CHN), 7.41 ± 7.08 (m, 5H, Ph), 5.27 (d, J 7.7 Hz, 1H,
CH), 4.77 ± 4.74 (dd, J 1.6, 7.1 Hz, 1H, NCHCO CH CH ), 4.23 (q, J
2
2
3
rt
D
7.2 Hz, 2H, CO
2
CH
2
CH
CH
3
), 3.03 (ddd, J 7.1, 17.0, 2H, C(O)CH
a b
H ), 1.25 (t,
); C NMR: d 189.34, 169.76, 148.94, 144.56,
1
17.4 (c 0.40 in CHCl
.27 (d, J 8.2 Hz, 2H,
NCHCO CH CH
), 4.05 ± 3.61 (m, 4H, CCH
H, ArCH
), 2.55 ± 2.32 (m, 2H, CCH CH), 1.60 (s, 3H, CCH
H, CCH
3
); H NMR: d 7.69 (d, J 8.2 Hz, 2H, C
6
H
2
H
2
),
), 4.80 (dd, J 1.6 Hz, 7.1 Hz, 1H,
N, CO CH CH ), 2,41 (s,
), 1.58 (s,
13
J 7.2 Hz, 3H, CO
2
2
CH
3
7
6 2 2
C H H
1
29.68, 124.91, 119.05, 102.97, 62.34, 60.52, 38.46, 14.10; HRMS: exact mass
2
2
3
2
2
2
3
calcd for C14
H
15NO
3
[MNa] : 268.0950; found: 268.0919.
3
3
1
1
3
3
2
3
1
3
N-p-Methoxyphenyl-4-oxo-1,2,3,4-tetrahydro-pyridine-2-carboxylic acid
ethyl ester (3l): According to the general procedure, the reaction between
N-p-methoxyphenyl imine 1e with diene 2a in the presence of 10 mol%
catalyst Tol-BINAP-(R)-4b-CuClO ´ 4MeCN in CH Cl was stirred at
3
), 1.06 (t, J 7.2 Hz, 3H, CO
2
CH
2
CH
3
); C NMR: d 170.95,
43.12, 136.43, 129.33, 127.26, 122.25, 121.87, 60.97, 53.33, 45.94, 33.43, 21.48,
8.66, 15.59, 13.88; HRMS: exact mass calcd for C17
H
23SNO
4
[MNa] :
1
60.1246; found: 360.1252. 3g: H NMR: d 7.69 (d, J 8.2 Hz, 2H,
4
2
2
C
6
H
2
H
2
), 7.27 (d, J 8.2 Hz, 2H, C
NH), 4.07 (q, J 7.9 Hz, 1H, CHNHTs), 3.90 (q, J 7.2 Hz, 2H,
CO CH CH ), 2.40 (s, 3H, ArCH ), 1.82 (s,
H, CCH
); C NMR, d 171.41,
43.55, 141.81, 141.50, 136.84, 129.53, 127.29, 116.52, 113.54, 61.46, 54.97,
8.15, 21.50, 21.04, 13.92; HRMS: exact mass calcd for C17
6
H
2
H
2
), 5.14 ± 4.97 (m, 5H,CH
2
,CH
2
,
room temperature for 20 h. Purification by FC (50% EtOAc in pentane)
afforded product 3l (89%) with 72% ee according to HPLC using a
À1
rt
), 2.70 ± 2.60 (m, 2H, CCH
Chiralpak AD column (hexane/iPrOH 90:10, 1.0 mLmin ). [a]
D
181.7
2
2
3
2
3
1
3
(c 0.82 in CHCl );
1
H NMR: d 7.40 (d, J 7.7 Hz, 1H, CHN), 7.07 (d,
3
1
3
3
), 1.10 (t, J 7.2 Hz, 3H, CO
2
CH
2
CH
3
3
J 8.8 Hz, 2H, C
6
H
2
H
2
), 6.89 (d, J 8.8 Hz, 2H, C ), 5.19 (d, J
6 2 2
H H
7.7 Hz, 1H,
CHC(O)), 4.66 (brd, J 6.8 Hz, 1H, NCHCO CH CH ), 4.22
2
2
3
H
23SNO
4
(q, J 7.1 Hz, CO CH CH ), 3.19 (s, 3H, ArOCH ), 2.03 (ddd, J 6.8,
[
MNa] : 360.1246; found: 360.1278.
2
2
3
3
1
3
1
6.5 Hz, C(O)CH
a
H
b
), 1.24 (t, J 7.1 Hz, 3H, CO
2
2 3
CH CH ); C NMR:
N-Ethoxycarbonyl-4-oxo-1,2,3,4-tetrahydro-pyridine-2-carboxylic acid eth-
yl ester (3i) and 2-ethoxycarbonylamino-6-methoxy-4-oxo-hex-5-enoic
acid ethyl ester (3o): According to the general procedure, the reaction of
the N-ethyloxycarbonyl glyoxylate imine (1b) and diene 2a in the presence
d 189.12, 169.81, 157.35, 150.20, 138.21, 121.90, 114.75, 101.78, 62.23, 61.25,
5
5.57, 14.07; HRMS: exact mass calcd for C15
H17NO
4
[MNa] : 298.1056;
found: 298.1041.
-Phenyl-1-tosyl-2,3-dihydro-1H-pyridin-4-one (3m): According to the
general procedure, the reaction between N-tosyl benzaldimine (1 f) and
diene 2a in the presence of 10 mol% catalyst Tol-BINAP-(R)-4b-CuClO
MeCN in CH Cl was stirred at room temperature for 60 h. Purification
2
of 10 mol% catalyst Tol-BINAP-(R)-4b-CuClO
stirred at À788C for 20 h. The reaction mixture was quenched by TFA
0.1 mL) in CH Cl
(15 mL) at À788C and stirred at room temperature for
.5 h, followed by evaporation of the solvent. Purification of the crude
4
´ 4MeCN in THF was
4
´
(
2
2
4
2
2
0
by FC (30% EtOAc in pentane) gave product 3m (63%) with 48% ee
according to HPLC using a chiralcel OD column (hexane/iPrOH 95:5,
product by FC (gradual eluent from 20% to 35% EtOAc in pentane)
afforded aza-Diels ± Alder product 3i (10%) and Mannich-type product 3o
À1
rt
1
0
8
7
8
.8 mLmin ). [a]
D
À54.0 (c 0.50 in CHCl
3
); H NMR d 7.81 (dd, J
(
56%). The ee of 3i was found to be 79% according to HPLC using a
.2 Hz, 1H, CHN), 7.60 (d, J 8.4 Hz, 2H, SO
H, C , SO
.2 Hz, 1H, CHC(O)), 2.84 (dd, J 7.2, 16.5 Hz, 1H, C(O)CH
6 2 2
C H H ), 7.24 ± 7.14 (m,
À1
2
Chiralcel OD column (hexane/iPrOH 99:1, 0.3 mLmin ), and the ee for 3o
was determined as 37% using a Chiralcel OD column. Compound 3i:
6
H
5
2
C
6
H
2
H
2
), 5.52 (d, J 7.2 Hz, 1H, NCHPh), 5.42 (dd, J
), 2.65
); C NMR:
a
3
H
b
rt
1
[
a]
D
26.3 (c 1.0 in CHCl
3
); H NMR: d 7.88 (brd, J 7.7 Hz, 1H,
1
(
dd, J 1.6, 16.5 Hz, 1H, C(O)CH
a b 3
H ), 2.41 (s, 3H, ArCH
CHN), 5.33 (brd, J 7.7 Hz, 1H, CH(CO)), 5.14 (brd, J 7.6 Hz, 1H,
d 190.49, 145.01, 142.48, 136.97, 135.56, 130.05, 128.70, 128.09, 127.04,
NCHCO
2
CH
2
CH
3
), 4.38 ± 4.30 (q, J 7.3 Hz, 2H, NCO
2 2 3
CH CH ), 4.20 (q,
1
[
26.25, 108.33, 57.61, 41.76, 21.60; HRMS: exact mass calcd for C18
H
17SNO
3
J 7.2 Hz, 2H, CO
C(O)CH
CHCO CH
2
CH CH
2
3
), 3.03 ± 2.85 (m, J 15.6, 7.3 Hz, 2H,
MNa] : 350.0827; found: 350.0838.
2
), 1.35 (d, J 7.3 Hz, 3H, NCO
2
CH
2
CH
3
), 1.25 (t, J 7.2 Hz,
); 13C NMR: d 190.60, 168.90, 152.49, 143.47, 142.81,
Reaction with solid-supported chiral BINAP: According to the general
procedure of the catalytic reaction, the catalyst solution was prepared by
adding THF (1.5 mL) to a mixture of (R)-polymer-bound BINAP 4c
2
2
CH
3
1
07.73, 107.15, 64.00, 62.37, 55.18, 54.79, 37.48, 14.26, 14.00; HRMS: exact
mass calcd for C11
H
15NO
5
[MNa] : 264.0848; found: 264.0844. 3o:
1
H NMR: d 7.61 (d, J 13.0 Hz, 1H, CHOCH
), 5.71 (d, J 8.2 Hz, 1H,
(68 mg, ꢁ0.022 mmol) and CuClO ´ 4MeCN (6.5 mg, 0.022 mmol) under
3
4
NH), 5.56 (d, J 13.0 Hz, 1H, CHC(O)), 4.57 ± 4.52 (m, 1H,
N , and shaken for 0.5 h. The reaction between the N-tosyl a-amino ester
2
CHNHCO
2
CH
2
CH
3
), 4.23 ± 4.10 (m, 4H, 2 Â CO
2
CH
2
CH
3
), 3.72 (s, 3H,
1a and trans-1-methoxy-3-trimethylsilyloxy-1,3-butadiene (2a) was kept at
CHOCH ), 3.26 (dd, J 17.5, 4.4 Hz, 1H, C(O)CH H ), 3.01 (dd, J 17.5,
À788C for 18 h, MeOH/CH Cl 3:7 (10 mL) was added, and the suspension
3
a
b
2
2
1
3
3
.9 Hz, C(O)CH
a
H
b
), 1.29 ± 1.19 (m, 6H, 2 Â CO
2
CH
2
CH
3
); C NMR: d
was centrifugalized for 10 min. The clear upper solution phase was
2446
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
0947-6539/00/0613-2446 $ 17.50+.50/0
Chem. Eur. J. 2000, 6, No. 13