3180
H. Acherki et al. / Tetrahedron: Asymmetry 12 (2001) 3173–3183
4.6, NH), 4.940 (s, 1H, H-Cꢁ), 7.1–7.5 (m, 9H, Ar).
Anal. calcd for C19H23NOS%: C, 72.80; H, 7.40; N,
4.47. Found: C, 72.76; H, 7.28; N, 4.43.
Me-Ar), 2.374 (ddd, 2H, 3J=13.1, 5.0, cyclohexyl), 2.533
(dd, 1H 2J=16.1, 3J=1.7, H6), 3.006 (dd, 1H, 2J=16.1,
3J=8.2, H6’), 3.922 (dd, 1H, 3J=8.1, 1.7, H7), 5.132 (dd,
2
5
2
1H, J=13.9, J=0.9, CH2O), 5.180 (dd, 1H, J=13.9,
5J=0.9, CH2O), 6.61–6.65 (m, 2H, Ar), 6.83–6.99 (m, 5H,
Ar), 7.165 (d, 2H, 3J=8.1, Hortho-Tol). 13C NMR (50
MHz) l 21.10, 22.77, 22.88, 24.30, 31.28, 33.82, 34.31,
42.16, 65.15, 99.57, 113.18, 124.41, 126.28, 126.34, 128.32,
129.12, 136.81, 140.99, 141.06, 144.66, 165.78. MS34 (70
eV) 421 (10), 404 (100), 373 (85), 330 (23), 91 (13), 77 (7),
65 (5). Anal. calcd for C25H27NO3S%: C, 71.23; H, 6.46;
N, 3.32. Found: C, 71.37; H, 6.39; N, 3.30.
4.5. Synthesis of 4,6-disubstituted 5-(p-tolylsulfinyl)-5,6-
dehydropiperidin-2-ones, 3 and 7–12. General procedure
To a cold (−78°C) solution of sulfinyl ketimine (0.9 mmol)
in dry THF (20 mL) was added a solution of n-BuLi (1.6
M in hexane, 0.67 mL, 1.07 mmol). The solution was
stirred at −78°C for 0.5 h, the temperature was raised to
−30°C and the ene ester (2 mmol, 0.15 M solution in THF)
was added. The reaction mixture was kept to rt and was
stirred for 12 h. The mixture was diluted with H2O (1 mL)
and saturated aqueous NH4Cl solution (10 mL) and
extracted with EtAcO (3×20 mL). The combined organic
layers were washed with brine, dried over Na2SO4, con-
centrated at reduced pressure and chromatographed.
Diastereomeric ratio and conversion were determined
from analysis (1H NMR) of the reaction mixtures prior
isolation. Yields are quoted as isolated products (Table
2).
4.5.4. (SS,7R)-3,3-Pentamethylene-7-phenyl-8-(p-tolyl-
sulfinyl)-1,2,3,5,6,7-hexahydro-2-oxa-5-indolizinone 7b.
Rf=0.18 (hexane/EtOAc: 2/1 on desactivated silica gel).
1H NMR (200 MHz) l 1.58–1.84 (m, 8H, cyclohexyl),
2.182 (s, 3H, Me-Ar), 2.38 (m, 2H, cyclohexyl), 2.44 (m,
1H, H6), 3.044 (dd, 1H, 2J=15.0, 3J=8.4, H6%), 3.92 (m,
2
1H, H7), 5.184, 5.140 (AB, 2H, J=13.3, CH2O), 6.63–
6.68 (m, 2H, Ar), 6.85–7.02 (m, 5H, Ar), 7.168 (dd, 2H,
3Jortho=8.0, Hortho-Tol).
4.5.5. (SS,4R)-1-(p-Methoxyphenyl)-4-methyl-6-phenyl-
5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-one 8a. Rf=0.2
(hexane/EtAcO: 1/3, v/v). Isolated as brown oil. [h]D23
4.5.1. (SS,7R)-7-Methyl-3,3-pentamethylene-8-(p-tolyl-
sulfinyl)-1,2,3,5,6,7-hexahydro-2-oxa-5-indolizinone 3a.
Rf=0.26 (hexane/EtAcO: 1/1, v/v). Yellow solid. Mp
126–7°C. [h]2D3 −98.3 (c 0.54, CHCl3). IR (CHCl3) 1697,
1074 cm−1. 1H NMR (300 MHz) l 0.418 (d, 3H, 3J=7.1,
CH3-C7), 1.8–2.0 (m, 10H, cyclohexyl), 2.415 (s, 3H,
Me-Ar), 2.289 (dd, 1H, 2J=16.0, 3J=2.3, H6), 2.676 (dd,
1
−161.8 (c 1.0, CHCl3). IR (CHCl3) 1697, 1034 cm−1. H
NMR (200 MHz) l 0.605 (d, 3H, 3J=7.1, Me-C4), 2.445
2
3
(s, 3H, Me-Ar), 2.619 (dd, 1H, J=15.6, J=1.8, H3),
2
3
3.074 (dd, 1H, J=15.6, J=5.9, H3%), 3.219 (ddq, 1H,
3J=7.1, 5.9, 1.8, H4), 3.691 (s, 3H, OMe), 6.682 (d, 2H,
3J=9.0, Hortho-PMP), 6.862 (d, 2H, 3J=9.0, Hortho-PMP),
2
3
3
1H, J=16.0 J=6.6, H6%), 2.891 (dq, J=2.6, 6.8, H7),
3
4.991 (s, 2H, CH2O), 7.314 (d, 2H, J=7.3, Hortho-Tol),
3
7.190 (m, 5H, Ph), 7.359 (d, 2H, J=8.0, Ar), 7.628 (d,
3
7.513 (d, 2H, J=7.3, Hortho-Tol). 13C NMR (75 MHz)
3
2H, J=8.0, Ar). 13C NMR (50 MHz) l 18.39, 21.38,
l 18.7, 21.4, 22.4, 22.9, 23.6, 24.3, 31.0, 33.9, 41.5, 64.9,
99.25, 115.2, 124.4, 127.9, 129.9, 138.7, 141.5, 142.6,
166.4. MS34 (70 eV) 359 813), 342 (87), 311 (100), 296 (5),
268 (32), 91 (9), 77 (17), 65 (17). Anal. calcd for
C20H25NO3S%: C, 66.82; H, 7.01; N, 3.90. Found: C,
66.73; H, 7.05; N, 3.97%.
21.67, 40.75, 55.25, 113.94, 124.83, 127.94, 129.19, 129.72,
129.82, 130.32, 132.20, 138.57, 141.10, 147.79, 158.44,
170.02. MS34 (70 eV) 431 (6), 414 (68), 383 (100), 368 (41),
340 (28), 210 (47), 77 (28). Anal. calcd for C26H25NO3S%:
C, 72.36; H, 5.84; N, 3.25. Found: C, 72.71; H, 5.99; N,
3.21.
4.5.6. (SS,4S)-1-(p-Methoxyphenyl)-4-methyl-6-phenyl-5-
(p-tolylsulfinyl)-5,6-dehydropiperidin-2-one 8b. Rf=0.25
4.5.2. (SS,7S)-7-Methyl-3,3-pentamethylene-8-(p-tolyl-
sulfinyl)-1,2,3,5,6,7-hexahydro-2-oxa-5-indolizinone 3b.
Rf=0.47 (hexane/EtAcO: 1/1, v/v). Yellow solid. Mp
182–3°C. [h]2D3 +43.3 (c 0.21, CHCl3). IR (CHCl3) 1690,
1
(hexane/EtAcO: 1/3, v/v). Non isolated. H NMR (200
3
MHz) l 1.444 (d, 3H, J=7.1, Me-C4), 2.396 (s, 3H,
3
1
3
Me-Ar), 2.475 (d, 2H, J=4.0, H3), 2.788 (ddq, 1H,
1085 cm−1. H NMR (300 MHz) l 1.21 (d, 3H, J=7.1,
Me-C7), 1.4–1.8 (m, 8H, cyclohexyl), 2.2–2.4 (m, 3H,
cyclohexyl and H6), 2.42 (s, 3H, Me-Ar), 2.49 (m, 1H,
H6%), 4.99 (s, 2H, CH2O), 7.30 (d, 2H, 3J=7.9, Hortho-Tol),
3J=7.1, 4.3, 3.5, H4), 3.688 (s, 3H, OMe), 6.53–6.87 (m,
2H, PMP), 6.82–6.91 (m, 2H, PMP), 7.23–7.49 (m, 9H,
Ar).
3
7.43 (d, 2H, J=8.2, Hortho-Tol), 13C NMR (75 MHz) l
4.5.7.
(SS,4S)-1-(p-Methoxyphenyl)-4,6-diphenyl-5-(p-
20.9, 21.0, 21.3, 22.7, 22.8, 24.2, 26.4, 31.3, 33.6, 41.2, 64.8,
99.2, 114.5, 124.1, 129.9, 137.2, 139.7, 140.9, 142.8, 165.9.
MS34 (70 eV) 421 (10), 404 (100), 373 (85), 330 (23), 91
(13), 77 (7), 65 (5). Anal. calcd for C20H25NO3S%: C,
66.82; H, 7.01; N, 3.90. Found: C, 66.85; H, 6.98; N, 3.93.
tolyl-sulfinyl)-5,6-dehydropiperidin-2-one 9a. Rf=0.06
(hexane/EtAcO: 1/1, v/v). Isolated as white solid. Mp
185–7°C. [h]2D3 −470.6 (c 0.16, CHCl3). IR (CHCl3) 1706,
1082 cm−1. 1H NMR (200 MHz) l 2.171 (s, 3H, Me-Ar),
2
3
2.917 (dd, 1H, J=15.8, J=1.7, H3), 3.388 (dd, 1H,
2J=15.8, J=7.4, H3%), 3.693 (s, 3H, OMe), 4.370 (dd,
3
3
4.5.3. (SS,7S)-3,3-Pentamethylene-7-phenyl-8-(p-tolyl-
sulfinyl)-1,2,3,5,6,7-hexahydro-2-oxa-5-indolizinone 7a.
Rf=0.13 (hexane/EtAcO on desactivated silica gel: 2/1,
v/v). Isolated as a colourless oil. [h]2D3 +28.6 (c 0.35,
1H, J=1.7, 7.4, H4), 6.67–6.72 (m, 2H, Ar), 6.85–7.02
(m, 8H, Ar), 7.25–7.30 (m, 8H, Ar). 13C NMR (50 MHz)
l 21.08, 31.98, 41.46, 55.28, 114.00, 124.81, 126.02,
126.32, 126.49, 128.26, 128.98, 129.30, 129.97, 130.17,
132.20, 137.19, 140.27, 140.66, 149.81, 150.24, 158.52.
MS34 (70 eV) 493 (3), 476 (100), 445 (17), 210 (19), 77
1
CHCl3). IR (CHCl3) 1670, 1080 cm−1. H NMR (200
MHz) l 1.55–1.83 (m, 8H, cyclohexyl), 2.181 (s, 3H,