Enantioselective Conjugate Addition
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173.0, 164.0, 153.2, 139.8, 136.8, 134.9, 131.5, 131.3, 130.3, 130.0, 129.6,
129.2, 129.1, 128.9, 128.8, 114.0, 113.8, 63.3, 62.6, 62.4, 62.1, 62.0, 55.5,
55.0, 54.7, 53.4, 53.3, 42.9, 42.6, 40.0, 39.6, 38.8, 38.0, 32.5, 31.5, 30.8, 29.7,
3.96–3.94 (m, 2H), 3.38–3.14 (m, 2H), 2.33 (s, 3H), 1.88–1.71 (m, 4H),
1.54–1.51 (m, 12H), 0.99 ppm (s, 18H); 13C NMR (75 MHz, CDCl3): d=
208.9, 192.3 (two peaks), 190.0, 143.1, 134.0, 132.2, 128.1, 69.8, 54.8, 54.5,
53.3 (two peaks), 46.7, 39.8, 32.5, 31.6, 31.2, 29.5, 29.4, 29.3, 29.2 ppm; IR
(film): n˜ = 3019, 1520, 1213 cmꢀ1; LRMS (ESI): m/z: 539.2 [MꢀH+];
HRMS (ESI): m/z: calcd for C28H44O4NaS3: 563.2294; found: 563.2308
[M+Na+].
29.3, 29.0 ppm; IR (film): n˜
= 3019, 1778, 1686, 1601, 1522, 1423,
1215 cmꢀ1; LRMS (ESI): m/z: 624.0 [M+Na+]; HRMS
ACTHNUTRGNE(NUG ESI): m/z: calcd
for C31H36O7NClNaS: 624.1793; found: 624.1777 [M+Na+].
The ee was determined by a HPLC analyses of the Michael adduct.
CHIRALPAK IA (4.6 mm i.d.ꢁ250 mm); hexane/2-propanol 80:20; flow
; 258C; 254 nm; retention time: 25.5 min (major),
31.8 min (minor); 48.0 min (major), 68.2 min (minor).
The ee was determined by HPLC analyses of the Michael adduct. CHIR-
ALCEL OF (4.6 mm i.d.ꢁ250 mm); hexane/2-propanol 92:8; flow rate
1.0 mLminꢀ1; 258C; 254 nm; retention time: 10.2 min (major), 18.0 min
(minor).
rate 1.0 mLminꢀ1
Compound 6c: Pale yellow oil; mixture of diastereomers, 90% ee;
1H NMR (300 MHz, CDCl3): d=7.90–7.86 (m, 2H), 7.45 (d, J=8.0 Hz,
2H), 4.90–4.79 (m, 1H), 4.52–4.74 (m, 2H), 4.23 (t, J=5.9 Hz, 1H), 4.07
(t, J=8.3 Hz, 2H), 3.86–3.64 (m, 1H), 3.43–3.34 (m,1H), 1.89–1.76 (m,
2H), 1.59 (s, 6H), 1.02 (s) and 1.01 ppm (s) (together 9H); 13C NMR
(75 MHz, CDCl3): d=195.5, 194.9, 189.8, 189.3, 170.7, 170.5, 153.4, 153.2,
140.4, 140.3, 134.2, 134.1, 129.6, 129.5, 129.1, 115.0, 114.5, 62.5, 62.4, 56.0,
53.5, 53.4, 46.0, 45.8, 42.8, 42.7, 38.9, 38.8, 37.9, 37.7, 32.6, 31.6 (two
peaks), 29.7, 29.4, 29.3 (two peaks), 29.1 ppm; IR (film): n˜ = 3019, 1778,
1522, 1423, 1215 cmꢀ1; LRMS (ESI): m/z: 515.0 [M+Na+]; HRMS (ESI):
m/z: calcd for C24H29O5N2ClNaS: 515.1378; found: 515.1386 [M+Na+].
Compound 8j: Colorless oil; 93% ee; [a]2D8 =ꢀ4.5 (c = 0.44, CHCl3);
1H NMR (300 MHz, CDCl3): d=7.65 (d, J=4.3, 1H), 7.62 (d, J=4.3,
1H), 7.10 (t, J=4.3, 1H), 3.98–3.89 (m, 2H), 3.36–3.23 (m, 1H), 3.17–
3.10 (m, 1H), 2.87–2.73 (m, 1H), 2.68–2.54 (m, 1H), 1.88–1.65 (m, 4H),
1.55–1.50 (m, 12H), 1.02–0.97 ppm (m, 21H); 13C NMR (75 MHz,
CDCl3): d=211.4, 192.3, 190.1, 143.2, 133.9, 132.2, 128.1, 70.1, 54.8, 54.5,
53.3, 53.2, 46.2, 39.9, 37.2, 32.6, 32.5, 31.6, 29.4 (two peaks), 29.2,
7.45 ppm; IR (film): n˜ = 3019, 1683, 1518, 1418, 1215 cmꢀ1; LRMS (ESI):
m/z: 553.1 (M-H+); HRMS (ESI): m/z: calcd for C29H46O4NaS3:
577.2450; found: 577.2455 [M+Na+].
The ee was determined by HPLC analyses of the Michael adduct. CHIR-
ALPAK IB (4.6 mm i.d.ꢁ250 mm); hexane/2-propanol 80:20; flow rate
1.0 mLminꢀ1; 258C; 254 nm; retention time: 10.4 min (minor), 14.4 min
(major); 25.1 min (minor), 35.1 min (major).
The ee was determined by HPLC analyses of the Michael adduct. CHIR-
ALCEL ADH (4.6 mm i.d.ꢁ250 mm); hexane/2-propanol 97:3; flow rate
0.3 mLminꢀ1; 258C; 254 nm; retention time: 105.4 min (minor), 117.6 min
(major).
Compound 8a: Colorless oil; 88% ee; [a]2D9 =+11.2 (c = 2.3, CHCl3);
1H NMR (300 MHz, CDCl3): d=7.88 (d, J=7.3 Hz, 2H), 7.56 (t, J=
7.3 Hz, 1H), 7.44 (t, J=7.3 Hz, 2H), 4.02–3.90 (m, 2H), 3.45–3.36 (m,
1H), 3.27–3.21 (m, 1H), 2.36 (s, 3H), 1.89–1.72 (m, 4H), 1.55–1.51 (m,
12H), 1.00 (s, 9H), 0.98 ppm (s, 9H); 13C NMR (75 MHz, CDCl3): d=
209.2, 197.2, 192.4, 192.3, 136.0, 133.4, 128.6, 128.0, 69.8, 54.7, 54.5, 53.2,
46.7, 39.4, 32.5, 31.6, 31.2, 29.5, 29.4, 29.2, 29.1 ppm; IR (film): n˜ = 2957,
1686, 1367, 1205 cmꢀ1; LRMS (ESI): m/z: 533.3 [MꢀHꢀ] HRMS (ESI):
m/z: calcd for C30H46O4NaS2: 557.2730; found: 557.2750 [M+Na+].
Compound 8k: Colorless oil; 90% ee; [a]2D6 =ꢀ7.4 (c = 0.54, CHCl3);
1H NMR (300 MHz, CDCl3): d=7.66 (d, J=4.3, 1H), 7.63 (d, J=4.3,
1H), 7.10 (t, J=4.3, 1H), 3.98–3.89 (m, 2H), 3.36–3.22 (m, 1H), 3.17–
3.11 (m, 1H), 2.81–2.70 (m, 1H), 2.64–2.53 (m, 1H), 1.89–1.70 (m, 4H),
1.59–1.42 (m, 14H), 1.33–1.20 (m, 2H), 1.00 (s, 18H), 0.87 ppm (t, J=
7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=210.8, 192.3 (two peaks),
190.0, 143.2, 133.9, 132.2, 128.1, 70.0, 54.7, 54.5, 53.3 (two peaks), 46.4,
43.5, 39.7, 32.6, 29.4, 29.2, 25.3, 22.1, 13.9 ppm; IR (film): n˜ = 2957, 1719,
1685, 1415, 1367 cmꢀ1; LRMS (ESI): m/z: 605.1 [M+Na+]; HRMS (ESI):
m/z: calcd for C31H50O4NaS3: 605.2763; found: 605.2760 [M+Na+].
The ee was determined by HPLC analyses of the Michael adduct. CHIR-
ALPAK IA (4.6 mm i.d.ꢁ250 mm); hexane/2-propanol 92:8; flow rate
0.8 mLminꢀ1; 258C; 254 nm; retention time: 12.4 min (major), 13.5 min
(minor).
The ee was determined by HPLC analyses of the Michael adduct. CHIR-
ALPAK IA (4.6 mm i.d.ꢁ250 mm); hexane/2-propanol 90:10; flow rate
1.0 mLminꢀ1; 258C; 254 nm; retention time: 10.8 min (minor), 12.6 min
(minor).
Compound 8b: Pale yellow oil; 90% ee, [a]2D9 =+12.4 (c = 0.26, CHCl3);
1H NMR (300 MHz, CDCl3): d=7.96 (d, J=8.4 Hz, 2H), 7.66 (d, J=
8.4 Hz, 2H), 7.31 (d, J=7.3 Hz, 2H), 7.49–7.37 (m, 3H), 4.04–3.96 (m,
2H), 3.48–3.39 (m, 1H), 3.31–3.24 (m, 1H), 2.37 (s, 1H), 1.90–1.73 (m,
4H), 1.56–1.53 (m, 3H), 1.01 (s, 9H), 0.99 ppm (s, 9H); 13C NMR
(75 MHz, CDCl3): d=209.1, 196.8, 192.4, 192.3, 146.1, 139.7, 134.8, 128.9,
128.6, 128.3, 127.2, 69.8, 54.8, 54.5, 53.3, 46.8, 39.5, 32.5, 31.6, 31.1, 29.5,
29.4, 29.3, 29.2 ppm; IR (film): n˜ = 3018, 1682, 1219 cmꢀ1; LRMS (ESI):
m/z: 633.2 [M+Na+]; HRMS (ESI): m/z: calcd for C36H50O4NaS2:
633.3043; found: 633.3037 [M+Na+].
Compound 8l: Colorless oil; 90% ee; [a]2D6 =ꢀ30.6 (c = 1.19, CHCl3);
1H NMR (300 MHz, CDCl3): d=8.03 (d, J=8.4, 2H), 7.79 (d, J=8.4,
2H), 7.41 (t, J=9.1, 4H), 4.83 (dt, J=14.4, 3.5, 1H), 3.98 (d, J=10.1,
1H), 3.55 (dd, J=9.4, 7.8, 1H), 3.31 (dd, J=7.8, 3.1, 1H), 1.89–1.71 (m,
2H), 1.58–1.53 (m, 8H), 1.28 (s, 6H), 1.00 (s, 9H), 0.90 ppm (s, 9H);
13C NMR (75 MHz, CDCl3): d=199.7, 195.8, 191.9, 191.6, 140.0, 139.8,
134.9, 134.2, 130.7, 129.5, 128.9, 128.7, 70.2, 54.9, 54.6, 53.2, 53.0, 41.4,
40.0, 32.6, 32.4, 31.6, 31.5, 29.5, 29.3, 29.1, 28.6 ppm; IR (film): n˜ = 2957,
1681, 1590, 1400, 1367 cmꢀ1; LRMS (ESI): m/z: 663.3 [MꢀH+]; HRMS
(ESI): m/z: calcd for C35H46O4Cl2NaS2: 687.2107; found: 687.2125
[M+Na+].
The ee was determined by HPLC analyses of the Michael adduct. CHIR-
ALPAK IA (4.6 mm i.d.ꢁ250 mm); hexane/2-propanol 90:10; flow rate
1.0 mLminꢀ1; 258C; 254 nm; retention time: 11.7 min (major), 13.7 min
(minor).
Compound 8g: Colorless oil; 89% ee; [a]2D6 =+24.2 (c = 0.47, CHCl3);
1H NMR (300 MHz, CDCl3): d=7.56 (s, 1H), 7.16 (d, J=3.5 Hz, 1H),
6.52 (dd, J=3.5, 1.8 Hz, 1H), 3.94 (d, J=3.1 Hz, 2H), 3.30–3.06 (m, 2H),
2.33 (s, 9H), 1.88–1.72 (m, 4H), 1.58–1.47 (m, 12H), 1.00 (s, 9H),
0.99 ppm (s, 9H); 13C NMR (75 MHz, CDCl3): d=209.0, 192.3, 186.2,
152.0, 146.5, 117.3, 112.4, 69.8, 54.7, 54.5, 53.2, 46.3, 38.9, 32.5, 31.6, 31.2,
29.6, 29.5, 29.4, 29.3, 29.2 ppm; IR (film): n˜ = 2957, 1716, 1685, 1570,
1469, 1260 cmꢀ1; LRMS (ESI): m/z: 547.1 [M+Na+]; HRMS (ESI): m/z:
calcd for C28H44O5NaS2: 547.2522; found: 547.2532 [M+Na+].
The ee was determined by HPLC analyses of the Michael adduct. CHIR-
ALPAK IA (4.6 mm i.d.ꢁ250 mm); hexane/2-propanol 95:5; flow rate
0.5 mLminꢀ1; 258C; 254 nm; retention time: 31.7 min (minor), 43.7 min
(major).
Compound 8m: Colorless oil; 93% ee; [a]2D6 =ꢀ145.8 (c = 0.12, CHCl3);
1H NMR (300 MHz, CDCl3): d=7.94 (d, J=3.0, 1H), 7.67 (d, J=3.0,
1H), 7.61 (t, J=5.2, 2H), 7.13–7.08 (m, 2H), 4.73 (dt, J=10.1, 3.5, 1H),
4.04 (d, J=10.4, 1H), 3.50 (dd, J=17.1, 9.8, 1H), 3.23 (dd, J=17.1, 3.3,
1H), 1.90–1.53 (m, 10H), 1.31–1.29 (m, 6H), 1.01 (s, 9H), 0.92 ppm (s,
9H); 13C NMR (75 MHz, CDCl3): d=192.7, 191.7, 191.6, 189.5, 143.7,
143.2, 134.7, 134.6, 133.9, 132.2, 128.3, 128.1, 70.3, 54.9, 54.4, 53.2, 53.0,
43.4, 40.1, 32.6, 32.4, 31.6 (two peaks), 29.5, 29.3, 29.0, 28.6 ppm; IR
(film): n˜ = 2956, 1725, 1685, 1669, 1415 cmꢀ1; LRMS (ESI): m/z: 607.3
(M-H+); HRMS (ESI): m/z: calcd for C31H44O4NaS4: 631.2015; found.
631.2013 [M+Na+].
The ee was determined by HPLC analyses of the Michael adduct. CHIR-
ALPAK IA (4.6 mm i.d.ꢁ250 mm); hexane/2-propanol 95:5; flow rate
1.0 mLminꢀ1; 258C; 254 nm; retention time: 10.0 min (major), 11.2 min
(minor).
Compound 8i: Pale yellow oil; 93% ee; [a]2D8 =+34.2 (c = 0.62, CHCl3);
The ee was determined by HPLC analyses of the Michael adduct. CHIR-
ALPAK IA (4.6 mm i.d.ꢁ250 mm); hexane/2-propanol 90:10; flow rate
1H NMR (300 MHz, CDCl3): d=7.67–7.62 (m, 2H), 7.12–7.09 (m, 1H),
Chem. Eur. J. 2009, 15, 4925 – 4930
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4929