T. Ohfusa, A. Nishida / Tetrahedron 67 (2011) 1893e1906
1901
under vacuum for 20 min, a solution of dienophile (1 mmol) in PhCF3
(5 ml) was added and the mixture was stirred for 30 min at rt. To this
mixture was added aminodiene (2 mmol), and the resulting mixture
was stirred at the temperature indicated. The reaction mixture was
then filtered through a pad of CeliteÒ, the pad was washed with
CH2Cl2, and volatile material was removed under reduced pressure.
The resulting residue was purified bycolumn chromatography (SiO2,
hexane/AcOEt¼7/1) to give DielseAlder adduct.
1H), 2.45 (ddt, J¼2.4, 6.8, 16.4 Hz, 1H), 2.60 (ddt, J¼2.4, 6.8, 13.2 Hz,
1H), 3.41 (s, 3H), 3.55 (s, 3H), 3.58 (dd, J¼8.4, 17.6 Hz, 2H), 3.64 (br s,
1H), 3.79 (br d, J¼8.8 Hz, 1H), 3.89 (br d, J¼12.4 Hz, 1H), 4.34 (dd,
J¼11.6, 20.4 Hz, 1H), 4.66 (br s, 1H), 4.90 (t, J¼2.4 Hz, 1H), 5.01 (dd,
J¼1.2, 10.4 Hz, 1H), 5.08 (dd, J¼1.2, 17.2 Hz, 1H), 5.85 (ddt, J¼5.2, 5.2,
22.0 Hz, 1H), 6.80 (d, J¼8.4 Hz, 2H), 7.16 (dd, J¼8.4 Hz, 2H); 13C NMR
(C6D6, 100 MHz, 75 ꢁC):
d
ꢀ4.16, ꢀ4.14, 18.2, 25.9, 26.5, 32.1, 38.0,
38.3, 45.5, 52.1, 54.9, 56.1, 56.9, 73.6, 75.2, 114.3, 115.4, 128.5, 129.4,
131.1, 136.4, 151.6, 156.9, 160.0, 216.0; IR (ATR):
n 2929, 1736,
1702 cmꢀ1; LRMS (FAB) m/z 552 (MþNa); HRMS (FAB) m/z calcd for
C29H43NO6SiNa (MþNa) 552.2757, found 552.2737.
4.3. General procedure for the DielseAlder reaction using
microwave irradiation (1 mmol-scale experiments)
4.3.5. DA adduct 53. 1H NMR (400 MHz, CDCl3):
d
ꢀ0.01 (s, 3H),
Oven-dried powdered 4A MS (0.8 g) was added to a solution of
dienophile (1 mmol) in PhCF3 (5 mL) and the mixture was stirred for
5 min at rt. To this mixture was added aminodiene (2 mmol), and the
resulting mixture was irradiated by microwave (<300 W, 150 ꢁC, in
a sealed tube) in a CEM. Discover LabMate microwave reactor. The re-
action mixture was then filtered through a pad of CeliteÒ, the pad was
washed with CH2Cl2, and volatile material was removed under reduced
pressure. The resulting residue was purified by column chromatogra-
phy (SiO2, hexane/AcOEt¼7/1) to give DielseAlder adduct.
0.04 (s, 3H), 0.85 (s, 9H), 1.71e1.85 (m, 2H), 2.02 (dd, J¼4.8, 17.6 Hz,
1H), 2.20e2.27 (m, 1H), 2.92 (br td, J¼5.6, 11.6 Hz, 1H), 3.30 (br td,
J¼8.8, 14.4 Hz, 1H), 3.55 (s, 3H), 3.88 (d, J¼12.8 Hz, 1H), 4.03 (d,
J¼12.8 Hz, 1H), 4.12 (br d, J¼19.6 Hz, 1H), 4.39 (ddd, J¼2.0, 8.8,
13.6 Hz, 1H), 4.47 (br d, J¼2.0 Hz, 1H), 4.61 (br s, 1H), 5.02 (d,
J¼17.2 Hz, 1H), 5.19 (d, J¼10.4 Hz, 1H), 5.85 (ddt, J¼3.6, 9.6, 16.8 Hz,
1H), 7.52 (t, J¼7.6 Hz, 2H), 7.62 (t, J¼7.6 Hz, 2H), 7.97 (d, J¼7.6 Hz,
2H); 13C NMR (100 MHz, CDCl3):
34.5, 41.9, 42.2, 49.5, 53.6, 56.5, 59.2, 60.4, 100.2, 115.3, 128.4, 128.6,
d
ꢀ4.8, ꢀ4.5, 14.2, 17.8, 21.0, 33.6,
1
4.3.1. DA adduct 40. H NMR (CDCl3, 400 MHz, 55 ꢁC):
d
0.14 (s, 6H),
133.7, 136.7, 138.4, 151.0, 166.9, 166.9, 168.7, 169.3; IR (ATR): n 2991,
1754, 1724, 1698 cmꢀ1; LRMS (FAB) m/z 649 (MþK); HRMS (FAB)
m/z calcd for C28H39ClN2O7SSiK (MþK) 649.1573, found 649.1588.
0.92 (s, 9H), 1.41e1.56 (m, 2H), 1.67e1.79 (m, 4H), 2.11 (t, J¼10.0 Hz,
1H), 2.31 (dd, J¼8.0, 18.0 Hz, 1H), 2.57e2.64 (m, 1H), 3.53e3.64 (m,
1H), 3.67 (s, 3H), 3.74 (dd, J¼5.6, 16.0 Hz, 1H), 4.66 (d, J¼4.8 Hz, 1H),
5.03 (d, J¼8.4, 17.6 Hz, 1H), 5.05 (d, J¼9.6 Hz, 1H), 5.09 (br s, 1H),
5.73 (ddd, J¼5.6, 10.4, 23.2 Hz, 1H), 9.51 (s, 1H); 13C NMR (CDCl3,
4.3.6. DA adduct 54. 1H NMR (400 MHz, CDCl3, 55 ꢁC):
d 0.01 (s,
3H), 0.06 (s, 3H), 0.86 (s, 9H), 1.74e1.94 (m, 2H), 2.02 (dd, J¼6.4,
18.0 Hz, 1H), 2.15 (dt, J¼3.2, 14.0 Hz, 1H), 2.84 (ddd, J¼4.0, 6.4,
10.4 Hz, 1H), 3.40 (ddd, J¼6.8, 9.2, 13.6 Hz, 1H), 3.56 (s, 3H), 3.61 (s,
3H), 3.94e3.99 (m, 1H), 4.33 (ddd, J¼3.6, 8.4, 13.6 Hz, 1H), 4.70 (br s,
1H), 4.97 (br d, J¼17.2 Hz, 1H), 5.00 (br d, J¼10.4 Hz, 1H), 5.29 (d,
J¼2.0 Hz, 1H), 5.72 (ddd, J¼5.2, 10.4, 17.2 Hz, 1H), 7.50 (t, J¼7.6 Hz,
2H), 7.60 (t, J¼7.6 Hz, 2H), 7.98 (d, J¼7.6 Hz, 2H); 13C NMR (100 MHz,
100 MHz, 55 ꢁC):
d
ꢀ4.51, ꢀ4.28, 17.9, 19.4, 25.6, 31.1, 32.1, 32.3, 34.7,
46.9, 52.5, 54.8, 60.1,100.3,115.8,135.4,153.3, 157.2, 203.3; IR (ATR):
n
2953, 2930, 2883, 2857, 1726, 1697, 1671 cmꢀ1; HRMS (ESI) m/z
calcd for C42H70N2O8Si2Na (2MþNa) 809.4568, found 809.4545;
HPLC: DAICEL CHIRALCEL OD-H, 210 nm, flow rate 1.0 mL/min,
25
hexane/i-PrOH¼99:1, retention time: 6.4 min and 7.1 min; [
a]
D
CDCl3, 55 ꢁC):
d
ꢀ4.7, ꢀ4.5, 17.9, 25.4, 25.6, 33.8, 34.2, 42.5, 49.2,
52.4, 53.1, 57.9, 60.2, 102.0, 114.2, 128.55, 128.60, 133.5, 136.9, 139.1,
149.7, 160.8, 166.7, 169.8; IR (ATR):
2950, 1745, 1711, 1697 cmꢀ1
36.4 (c 1.00, CHCl3, 79% ee).
1
4.3.2. DA adduct 41. H NMR (C6D6, 400 MHz, 75 ꢁC):
d
0.21 (s, 6H),
n
;
HRMS (ESI) m/z calcd for C28H40N2O8SSiNa (MþNa) 615.2172, found
1.06 (s, 9H), 1.27 (br s, 4H), 1.51e1.84 (m, 4H), 2.07 (br d, J¼18.0 Hz,
1H), 2.23 (br d, J¼18.0 Hz,1H), 2.48 (br s,1H), 3.57 (br s, 3H), 3.74 (br
d, J¼16.0 Hz,1H), 3.96 (br d, J¼16.0 Hz,1H), 4.81 (br s,1H), 5.11 (br d,
J¼18.0 Hz, 3H), 5.80e5.97 (m, 1H), 9.80 (br s, 1H); 13C NMR (C6D6,
615.2162.
1
4.3.7. DA adduct 55-anti. H NMR (400 MHz, CDCl3, 55 ꢁC):
d 0.14
100 MHz, 75 ꢁC):
30.9, 31.6, 47.8, 52.3, 53.3, 57.3, 101.2, 115.2, 136.6, 153.5, 157.3,
d
ꢀ4.29, ꢀ4.13, 18.1, 21.4, 22.7, 25.8, 27.6, 28.6,
(s, 6H), 0.91 (s, 9H), 1.94e2.02 (m, 3H), 2.22e2.25 (m, 0.5H),
2.27e2.30 (m, 0.5H), 2.31e2.40 (m, 2H), 2.94e3.01 (m, 1H), 3.61 (s,
3H), 3.73 (s, 3H), 3.79e3.93 (m, 2H), 4.77 (d, J¼1.6 Hz, 1H), 5.10 (dd,
J¼1.6, 5.6 Hz, 1H), 5.13 (dt, J¼1.6, 13.2 Hz, 1H), 5.19 (br s, 1H), 5.76
204.0; IR (ATR):
n
2928, 2857, 1723, 1695, 1674 cmꢀ1; HRMS (ESI)
m/z calcd for C22H37NO4SiNa (MþNa) 430.2389, found 430.2408;
13
(ddd, J¼5.6, 10.4, 22.4 Hz, 1H); C NMR (100 MHz, CDCl3, 55 ꢁC):
HPLC: DAICEL CHIRALCEL OD-H, 210 nm, flow rate 1.0 mL/min,
25
d
ꢀ4.36, 18.0, 25.6, 26.0, 31.1, 37.6, 41.3, 50.0, 52.2, 52.9, 55.7, 62.4,
hexane/i-PrOH¼99:1, retention time: 6.1 min and 7.1 min; [
a]
D
103.6, 115.8, 135.3, 149.7, 156.6, 172.8, 211.4; IR (ATR):
n 2952, 2930,
43.7 (c 0.83, CHCl3, 81% ee).
2857, 1734, 1701, 1678 cmꢀ1
;
HRMS (ESI) m/z calcd for
C44H70N2O12Si2Na (2MþNa) 897.4365, found 897.4339; HPLC:
DAICEL CHIRALPAK IA, 210 nm, flow rate 0.5 mL/min, hexane/i-
PrOH¼95:5, retention time: 12.2 min and 13.3 min; [
a]
25 9.6 (c 1.00,
D
CHCl3, 16% ee).
1
4.3.8. DA adduct 55-syn. H NMR (CDCl3, 400 MHz, 55 ꢁC):
d 0.09
(s, 3H), 0.10 (s, 3H), 0.87 (s, 9H), 1.50e1.73 (m, 2H), 1.96e2.09 (m,
1H), 2.18 (dt, J¼9.6, 19.2 Hz, 1H), 2.37 (dt, J¼9.6, 19.2 Hz, 2H), 3.27
(dd, J¼8.4, 14.4 Hz, 1H), 3.60e3.66 (m, 1H), 3.64 (s, 3H), 3.67 (s,
3H), 3.78 (dd, J¼6.0, 16.0 Hz, 1H), 4.69 (dd, J¼1.2, 4.8 Hz, 1H), 5.06
(br d, J¼8.8 Hz, 1H), 5.09 (br d, J¼16.4 Hz, 1H), 5.36 (br s, 1H), 5.76
4.3.3. DA adduct 42. Adduct 42 was obtained as inseparable
diastereomixtures at C7 position. Good 1H and 13C NMR spectra
were difficult to obtain due to the presence of rotamers and di-
astereomers, even at elevated temperatures. The structure of 42
was determined after it was converted to 48 or 70 via 45.
13
(ddd, J¼6.0, 11.2, 22.4 Hz, 1H); C NMR (CDCl3, 100 MHz, 55 ꢁC):
d
ꢀ4.58, ꢀ4.33, 17.9, 25.6, 25.9, 31.0, 32.2, 35.0, 48.3, 52.4, 52.5,
54.0, 64.8, 101.8, 115.8, 135.32, 151.9, 156.5, 168.6, 208.7; IR (ATR):
n
1
4.3.4. DA adduct 43. H NMR (C6D6, 400 MHz, 75 ꢁC):
d
0.15 (s, 3H),
2949, 2932, 2857, 1750, 1728, 1695, 1677 cmꢀ1; HRMS (ESI) m/z
calcd for C22H35NO6SiNa (MþNa) 460.2131, found 460.2142; HPLC:
DAICEL CHIRALPAK IA, 210 nm, flow rate 0.5 mL/min, hexane/i-
0.16 (s, 3H), 0.98 (s, 9H), 1.63e1.72 (m, 1H), 1.77 (br s, 1H), 1.94 (dt,
J¼9.2, 19.2 Hz, 1H), 1.99 (br d, J¼17.6 Hz,1H), 2.26 (dd, J¼7.6, 17.6 Hz,