Diels–Alder Reactions
FULL PAPER
1
3
2
.8 Hz, CCHCH=CH); C NMR (100 MHz, CDCl
3
): d=23.4 (CH
3
), 26.1
with 9% 1,3-regioisomer 23b at 40% ee of unknown configuration); mol
, 208C): l = 313 (ꢀ3.70eꢀ ), 265 (5.78e ), 230 nm
3
ꢀ3
(
(
1
CH
3
), 36.0 (CH ), 42.8 (CH), 48.6 (CH ), 49.0 (CH), 56.1 (C), 133.5
CH), 139.0 (CH), 213.1 ppm (C); IR (film): n˜ =3060, 2966, 2874, 1702,
571, 1449, 1352, 1333, 1258, 1154, 1115, 860, 839, 714 cm ; GC-MS EI
positive) (HP-5MS, He, 808C for 5 min then heating 58Cmin ):
2
2
2 2
CD (0.0072m, CH Cl
ꢀ
2
(ꢀ1.76e ).
ꢀ
1
1
1
-(3-Methylcyclohex-3-enyl)-ethanone (23b; minor product): H NMR
ꢀ1
(
9
(
400 MHz, CDCl
3
): d=1.50–1.66 (m, 1H, CCH
), 1.88–2.15 (m, 5H, CH CH CHCH ), 2.15 (s, 3H, COCH
CHCH ), 5.36–5.38 ppm (m, 1H, C=CH); C NMR
): d=23.8 (CH ), 24.7 (CH ), 25.0 (CH ), 28.2 (CH ),
2
CH
2
CH), 1.63 (brs, 3H,
+
.42 min, 150 [M ], 107, 85, 66; achiral GC (OV-17, He, 808C for 5 min
CCH
2
(
3
2
2
2
3
13
), 2.47–
ꢀ
1
then heating 58Cmin ): 6.88, calibration factor=1.504; chiral GC (Lipo-
dex-E, H , 708C isothermal): 17.4*/19.6; column chromatography: pen-
tane/Et O 9.5:0.5, R
.56 (m, 1H, CH
100 MHz, CDCl
2
2
2
3
3
2
2
3
2
0
2
f
=0.32; isolated yield: 0.079 g, 80%; [a] = ꢀ608
D
31.6 (CH
), 48.6 (CH), 120.8 (CH), 132.6 (C), 211.9 ppm (C); GC-MS EI
2
ꢀ
1
20
(
CH
2
Cl
2
,
c=0.004 mgmL
,
69% ee); [a]D
=
ꢀ78 (CH
2
Cl
2
,
c=
ꢀ1
(positive) (HP-5MS, He, 808C for 1 min then heating 208Cmin ):
ꢀ
1
0
.011 mgmL , 74% ee, with 33% exo product 20b at 63% ee of un-
+
5
8
.00 min, 138 [M ], 123, 109, 105, 95, 91, 79; achiral GC (OV-17, He,
08C for 5 min then heating 58Cmin ): 7.07 min. Chiral GC (Lipodex-E,
known configuration); mol CD (0.0063m, CH
2
Cl
2
, 208C): l
=
328
ꢀ1
ꢀ7.60eꢀ ), 294 (ꢀ9.62e ), 232 nm (3.81e ).
3
ꢀ1
ꢀ2
(
H
Et
2
, 558C isothermal): 54.0/72.2 min; column chromatography: pentane/
O 95:5, R =0.26.
-(ꢀ)-(1S)-(4-Methylcyclohex-3-enyl)-propanone
400 MHz, CDCl ): d=1.05 (t, 3H, J=7.3 Hz, CH
CH), 1.65 (brs, 3H, CCH ), 1.85–2.10 (m, 5H,
), 2.41–2.65 (m, 3H, CH CHCH , COCH CH ), 5.37–
): d=7.8 (CH ),
), 33.8 (CH ), 46.3 (CH),
19.4 (CH), 133.8 (C), 214.5 ppm (C); IR (film): n˜ =2966, 2912, 2836,
endo-1-(2-Methylbicyclo
A
C
H
T
R
E
U
N
G
[2.2.1]hept-5-en-2-yl)-ethanone (20b; minor
): d=1.35 (dd, 1H, J=11.8, 3.6 Hz,
), 1.46–1.49 (m, 1H, CHCH CH), 1.63 (brd,
CH), 1.98 (dd, 1H, J=12.1, 2.7 Hz, CH C), 2.09
), 2.77 (brs, 1H, =CHCHCH ), 2.82 (brs, 1H, =CHCHC),
.00 (dd, 1H, J=5.8, 2.8 Hz, CCHCH=CH), 6.11 ppm (dd, 1H, J=8.6,
2
f
1
product): H NMR (400 MHz, CDCl
CH C), 1.36 (s, 3H, CCH
H, J=8.6 Hz, CHCH
s, 3H, COCH
3
[18]
1
1
(
(24a):
H NMR
2
3
2
CH ), 1.55–1.63 (m,
3
2
3
1
(
6
3
2
2
1
H, CCH
2
CH
CH CHCH
2
3
3
2
CH
2
2
2
2
2
2
3
1
3
5
2
1
.41 ppm (m, 1H, C=CH); C NMR (100 MHz, CDCl
3.4 (CH ), 25.1 (CH ), 27.3 (CH ), 29.6 (CH
3
3
1
3
.0 Hz, CCHCH=CH); C NMR (100 MHz, CDCl
), 36.4 (CH ), 42.7 (CH), 47.1 (CH ), 50.8 (CH), 56.7 (C), 134.2
CH), 138.1 (CH), 211.8 ppm (C); achiral GC (OV-17, He, 808C for
3 3
): d=25.4 (CH ), 26.4
3
2
2
2
2
(
CH
3
2
2
ꢀ1
(
5
7
1708, 1439, 1412, 1376, 1342, 1148, 1126, 915, 799 cm ; GC-MS EI (posi-
tive) (HP-5MS, He, 808C for 1 min then heating 208Cmin ): 5.75 min,
152 [M ], 137, 123, 109, 105, 95, 79; achiral GC (OV-17, He, 808C for
5 min then heating 58Cmin ): 9.43 min, calibration factor=1.420; chiral
GC (Hydrodex-b, H , 658C isothermal): 151.72/161.01 min; column chro-
matography: pentane/Et
ꢀ
1
ꢀ1
min then heating 58Cmin ): 7.32 (endo); ciral GC (Lipodex-E, H
08C isothermal): 22.8/28.6 (endo) min; column chromatography: pen-
O 9.5:0.5, R =0.21.
-(ꢀ)-(1S)-(3,4-Dimethylcyclohex-3-enyl)-ethanone (21):
500 MHz, CDCl ): d=1.42–1.53 (m, 1H, CCH CH), 1.56 (brs, 3H,
CCH ), 1.58 (brs, 3H, CCH ), 1.87–2.12 (m, 5H, CCH CH, CH CH ),
.12 (s, 3H, COCH ), 2.49–2.53 ppm (m, 1H, CH); C NMR (100 MHz,
CDCl ): d=19.0 (CH ), 19.2 (CH ), 25.5 (CH ), 28.1 (CH ), 31.4 (CH ),
3.3 (CH ), 48.5 (CH), 124.1 (C), 125.6 (CH), 212.1 ppm (C); IR (film):
n˜ =2910, 2833, 1707, 1437, 1378, 1351, 1231, 1166, 1123, 957 cm ; GC-
MS EI (positive) (HP-5MS, He, 808C for 1 min then heating 208Cmin ):
.81 min, 152 [M ], 137, 119, 109, 91, 79; achiral GC (OV-17, He, 808C
for 5 min then heating 58Cmin ): 10.28 min, calibration factor=1.386;
chiral GC (Lipodex-E, H , 808C isothermal): 74.4/77.0* min, column
chromatography: pentane/Et
2
,
+
ꢀ1
tane/Et
2
f
[
14]
1
1
(
H NMR
2
2
O 95:5, R
f
=0.48; isolated yield: 0.062 g, 61%;
3
2
2
D
0
ꢀ1
[a]
= ꢀ1048 (CH
2
Cl
2
, c=0.0065 mgmL , 93% ee, with 13% 1,3-regio-
3
3
2
2
2
1
3
2
3
isomer 24b at 76% ee of unknown configuration); mol CD (0.0042m,
CH
ꢀ
1
ꢀ2
ꢀ2
2
Cl
2
, 208C): l = 286 (1.23e ), 250 (1.58e ), 231 nm (ꢀ8.79e ).
3
3
3
2
3
2
1
3
2
1-(3-Methylcyclohex-3-enyl)-propanone (24b; minor product): H NMR
(400 MHz, CDCl ): d=1.06 (t, 3H, J=7.1 Hz, CH CH ), 1.55–1.63 (m,
ꢀ
1
3
2
3
ꢀ1
2 2 3
1H, CCH CH CH), 1.67 (brs, 3H, CCH ), 1.85–2.10 (m, 5H,
+
5
2 2 2 2 2 2 3
CH CH CHCH ), 2.41–2.65 (m, 3H, CH CHCH , COCH CH ), 5.37–
ꢀ1
13
3 3
5.41 ppm (m, 1H, C=CH); C NMR (100 MHz, CDCl ): d=7.8 (CH ),
2
3 2 2 2 2
23.6 (CH ), 24.6 (CH ), 24.9 (CH ), 25.3 (CH ), 31.6 (CH ), 46.9 (CH),
2
O 95:5, R
Cl
f
=0.29; isolated yield: 0.055 g,
120.5 (CH), 133.6 (C), 214.3 ppm (C); GC-MS EI (positive) (HP-5MS,
+
2
D
0
ꢀ1
ꢀ1
5
5%; [a]
=
ꢀ778 (CH
2
2
,
c=0.01 mgmL
,
67% ee); mol CD
He, 808C for 1 min then heating 208Cmin ): 5.69 min, 152 [M ], 137,
123, 109, 105, 95, 79; achiral GC (OV-17, He, 808C for 5 min then heating
ꢀ
3
ꢀ2
(
(
0.0039m, CH
ꢀ1.03eꢀ ).
2
Cl
2
, 208C): l = 322.0 (ꢀ4.71e ), 286 (8.05e ), 235 nm
1
ꢀ1
58Cmin ): 9.24 min. Chiral GC (Hydrodex-b, H , 658C isothermal):
2
[
20]
1
1
-(ꢀ)-(1S)-(3,4-Dimethylcyclohex-3-enyl)-propanone (22):
): d=1.05 (t, 3H, J=7.2 Hz, CH CH ), 1.44–1.52 (m,
CH), 1.60 (s, 3H, CCH ), 1.62 (s, 3H, CCH ), 1.75–2.21 (m,
H, CCH CH, CH CH ), 2.35–2.62 ppm (m, 3H, CH, CH CH );
C NMR (100 MHz, CDCl ): d=7.8 (CH ), 18.8 (CH ), 19.0 (CH ), 25.5
), 31.3 (CH ), 33.3 (CH ), 33.8 (CH ), 47.3 (CH), 124.1 (C), 125.3
C), 214.4 ppm (C); IR (film): n˜ =2877, 2907, 2833, 1707, 1452, 1412,
377, 1343, 1217, 1114, 992, 855 cm ; GC-MS EI (positive) (HP-5MS,
He, 808C for 1 min then heating 208Cmin ): 6.46 min, 166 [M ], 151,
67, 119, 109, 91, 79; achiral GC (OV-17, He, 808C for 5 min then heating
H NMR
143.51/168.31 min; column chromatography: pentane/Et
0.48.
2 f
O 95:5, R =
(
300 MHz, CDCl
3
2
3
1
5
H, CCH
2
3
3
1-(ꢀ)-(1S)-(1-Bromo-3,4-dimethylcyclohex-3-enyl)-ethanone
(25):
1
2
2
2
2
3
3 3
H NMR (300 MHz, CDCl ): d=1.77 (dd, 3H, J=0.8, 0.8 Hz, CCH ),
1
3
3
3
3
3
3 2 2
1.80 (dd, 3H, J=0.8, 0.8 Hz, CCH ), 2.18–2.48 (m, 4H, CH CH ), 2.56 (s,
1
3
(
(
1
CH
2
2
2
2
3 2
3H, COCH ), 2.49 ppm (dd, 2H, J=62.1, 23.1 Hz, CCH C); C NMR
3 3 3 3 2
(75 MHz, CDCl ): d=18.6 (CH ), 19.2 (CH ), 24.0 (CH ), 30.4 (CH ),
33.2 (CH ), 42.4 (CH ), 67.8 (C), 122.4 (C), 125.3 (C), 202.3 ppm (C); IR
2 2
ꢀ
1
ꢀ1
+
(film): n˜ =2910, 2859, 1711, 1431, 1353, 128e4, 1227, 1200, 1171, 1124,
+ +
ꢀ
1
1
5
H
1059, 992 cm ; MS ESI (positive): m/z: 255 [M +Na], 253 [M +Na],
179, 133, 101; GC-MS EI (positive) (HP-5MS, He, 808C for 5 min then
ꢀ
1
8Cmin ): 12.01 min, calibration factor=1.372. Chiral GC (Hydrodex-b,
, 858C isothermal): 89.63/92.72 min; column chromatography: pentane/
ꢀ
1
+
2
heating 58Cmin ): 16.69 min, 151 [M ꢀBr], 135, 107, 91, 77; HRMS-
2
0
Et
2
O 95:5, R
f
=0.43; isolated yield: 0.083 g, 76%; [a] = ꢀ1048 (CH
2
Cl
2
,
ESI (positive): m/z: calcd for C H BrNaO: 253.0203; ound: 253.0208,
D
10 15
ꢀ
1
c=0.01 mgmL , 93% ee); mol CD (0.0063m, CH
2
Cl
2
, 208C): l = 287.0
accuracy: 1.5965 ppm; achiral GC (OV-17, He, 808C for 5 min then heat-
1.96e 1), 237.0 (ꢀ9.80eꢀ2).
ꢀ
ꢀ1
(
ing 58Cmin ): 14.0 min, calibration factor=1.224; chiral GC (Lipodex-
[
32]
1
E, H , 908C isothermal): 52.3*/58.1 min; column chromatography: pen-
1
-(ꢀ)-(1S)-(4-Methylcyclohex-3-enyl)-ethanone
(23a):
CH CH), 1.66 (brs, 3H,
), 2.16 (s, 3H, COCH ), 2.56–
H NMR
2
2
D
0
tane/Et
CH Cl
2
O 20:1, R
f
=0.39; isolated yield: 0.109 g, 72%; [a]
=
ꢀ308
(
400 MHz, CDCl
3
): d=1.40–1.50 (m, 1H, CCH
), 1.88–2.15 (m, 5H, CH CH CHCH
CHCH ), 5.36–5.38 ppm (m, 1H, C=CH); C NMR
): d=23.6 (CH ), 25.1 (CH ), 27.2 (CH ), 28.2 (CH ),
), 47.4 (CH), 119.4 (CH), 134.0 (C), 212.1 ppm (C); IR (film):
2
2
ꢀ
1
(
2
2
, c=0.01 mgmL , 91% ee); mol CD (0.0049m, CH
2
Cl
2
, 208C): l
CCH
2
(
2
3
2
2
2
3
3
ꢀ
3
ꢀ2
ꢀ1
1
= 339 (ꢀ1.49e ), 301 (4.32e ), 247 nm (ꢀ3.18e ).
.64 (m, 1H, CH
100 MHz, CDCl
9.7 (CH
n˜ =2914, 2836, 1706, 1438, 1376, 1352, 1282, 1223, 1166, 911, 799 cm
GC-MS EI (positive) (HP-5MS, He, 808C for 1 min then heating
2
2
3
3
2
2
3
1-(ꢀ)-(1S)-(1-Chloro-3,4-dimethylcyclohex-3-enyl)-ethanone
(26):
1
2
3 3
H NMR (400 MHz, CDCl ): d=1.62–1.67 (m, 6H, CCH ), 2.00–2.48 (m,
ꢀ1
;
2 2 2 2 3
3H, CH CH ), 2.25–2.37 (m, 1H, CH CH ), 2.37 (s, 3H, COCH ),
1
3
2.49 ppm (brd, 2H, J=17.7 Hz, CCH C); C NMR (100 MHz, CDCl ):
2
3
ꢀ
1
+
2
(
08Cmin ): 5.05 min, 138 [M ], 123, 109, 105, 95, 91, 79; achiral GC
3 3 3 2 2
d=18.7 (CH ), 19.2 (CH ), 24.3 (CH ), 29.3 (CH ), 32.3 (CH ), 41.6
ꢀ1
OV-17, He, 808C for 5 min then heating 58Cmin ): 7.23 min, calibra-
tion factor=1.425; chiral GC (Lipodex-E, H , 558C isothermal): 43.5/
6.3* min, column chromatography: pentane/Et
ed yield: 0.043 g, 47%; [a] = ꢀ128 (CH
(CH ), 72.8 (C), 121.7 (C), 125.2 (C), 203.9 ppm (C); IR (film): n˜ =2914,
2
2
2860, 1717, 1432, 1353, 1229, 1201, 1159, 1125, 1063, 995, 887, 849,
ꢀ
1
4
2
O 95:5, R
, c=0.01 mgmL , 50% ee,
f
=0.26; isolat-
798 cm ; GC-MS EI (positive) (HP-5MS, He, 808C for 5 min then heat-
2
D
0
ꢀ1
ꢀ1
+
2
Cl
2
ing 58Cmin ): 14.3 min, 186 [M ], 151, 135, 107, 91, 77; HRMS-ESI
Chem. Eur. J. 2007, 13, 3354 – 3368
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3365