Full Paper
wax; [α]2D0 = +47 (c 1.0, THF). E and Z mixture: 1H NMR (300 MHz, 3.64 (d, 2H, J = 14.1 Hz), 3.55–3.33 (m, 4H), 1.49 (s, 6H), 1.46 (s, 6H),
CDCl3) δ = 8.36 and 8.31 (s, 1H), 7.84–7.81 (m, 2H), 7.55 (d, 2H, J =
7.1 Hz), 7.47–7.30 (m, 6H), 5.10 and 5.00 (d, 1H, J = 4.1 and 4.5 Hz),
4.61 and 4.57 (d, 1H, J = 4.5 and 4.1 Hz), 3.74–3.61 (m, 2H), 3.58–
1.09 (t, 6H, J = 7.3 Hz), 1.02 (t, 6H, J = 7.0 Hz) (NH proton not visible);
13C NMR (75 MHz, CDCl3) δ = 167.4 (2C), 158.9 (2C), 130.3 (2C),
129.5 (4C), 113.3 (4C), 104.6 (2C), 97.9 (2C), 75.6 (2C), 60.3 (2C), 57.9
3.42 (m, 1H), 3.38–3.31 (m, 1H), 1.52 and 1.51 (s, 3H), 1.43 (s, 3H), (2C), 56.8 (2C), 54.9 (2C), 18.7 (2C), 17. 5 (2C), 15.2 (2C), 14.9 (2C).
1.17–1.09 (m, 6H); 13C NMR (75 MHz, CDCl3) δ = 168.0, 163.3 and
162.2, 139.6, 136.2, 130.8, 128.6 (2C), 128.3 (2C), 128.2 (2C), 128.1
(2C), 127.5, 105.7, 98.5, 74.7, 74.5, 58.6 and 58.4, 57.0, 19.6, 17.7,
15.5, 15.0. MS (ESI) calcd. for C24H29NO5 [M + 1]+: m/z 412.21; found
MS (ESI) m/z 412.2 [M + 1]+, 434.2 [M + 23]+. Anal. Calcd. for
Anal. Calcd. for C36H51NO12: C, 62.68; H, 7.45; N, 2.03; found C, 62.95;
H, 7.74; N, 1.82.
(3R,3′R,5S,5′S,6S,6′S)-3,3′-{(1S,1′R)-Azanediylbis[(4-methoxy-
phenyl)methylene]}bis(5,6-diethoxy-5,6-dimethyl-1,4-dioxan-2-
one) (9c′): 82 mg (6 %); white wax; [α]2D0 = +78 (c 1.4, CHCl3). 1H
NMR (300 MHz, CDCl3) δ = 7.35 (d, 4H, J = 8.7 Hz), 6.89 (d, 4H, J =
8.7 Hz), 4.53 (d, 2H, J = 2.8 Hz), 4.40 (d, 2H, J = 2.8 Hz), 3.82 (s, 6H),
3.73–3.62 (m, 4H), 3.56–3.49 (m, 2H), 3.45–3.36 (m, 2H), 1.52 (s, 6H),
1.42 (s, 6H), 1.18–1.14 (m, 12H) (NH proton not visible); 13C NMR
(75 MHz, CDCl3) δ = 169.0 (2C), 159.0 (2C), 133.3 (2C), 128.4 (4C),
113.6 (4C), 105.3 (2C), 98.1 (2C), 74.5 (2C), 58.4 (2C), 57.3 (2C), 56.5
(2C), 55.2 (2C), 18.5 (2C), 17.6 (2C), 15.2 (2C), 15.0 (2C). Anal. Calcd.
for C36H51NO12: C, 62.68; H, 7.45; N, 2.03; found C, 62.97; H, 7.79; N,
1.83.
C
2 4 H2 9 NO5 : C, 70. 05; H, 7. 10; N, 3. 40; found C, 70. 28;
H, 7.39; N, 3.12.
Enantiomeric duals ent-9a, ent-9a′ and ent-10a were prepared us-
ing the (R,R)-TES-ketene acetal 11.
ent-9a: [α]2D0 = –196.5 (c 1.1, CHCl3). 1H NMR matches that of 9a.
Anal. Calcd. for C34H47NO10: C, 64.85; H, 7.52; N, 2.22; found C, 64.62;
H, 7.33; N, 2.47.
1
ent-9a′: [α]2D0 = –124 (c 1.0, CHCl3). H NMR matches that of 9a′.
Anal. Calcd. for C34H47NO10: C, 64.85; H, 7.52; N, 2.22; found C, 64.74;
H, 7.38; N, 2.38.
(3R,5S,6S)-5,6-Diethoxy-3-{(S)-[(4-methoxybenzylidene)amino]-
(4-methoxyphenyl)methyl}-5,6-dimethyl-1,4-dioxan-2-one
(10c): 236 mg (25 %); wax; [α]2D0 = +15.8 (c 1.0, CHCl3). E and Z
mixture: 1H NMR (300 MHz, CDCl3) δ = 8.25 and 8.22 (s, 1H), 7.74
(d, 2H, J = 8.7 Hz), 7.45 (d, 2H, J = 8.6 Hz), 6.91–6.88 (m, 4H), 5.00
and 4.95 (d, 1H, J = 4.2 and 4.5 Hz), 4.57 and 4.49 (d, 1H, J = 4.5
and 4.2 Hz), 3.82 (s, 3H), 3.80 and 3.78 (s, 3H), 3.74–3.59 (m, 2H),
3.52–3.44 (m, 1H), 3.43–3.27 (m, 1H), 1.50 (s, 3H), 1.41 (s, 3H), 1.16–
1.10 (m, 6H); 13C NMR (75 MHz, CDCl3) δ = 168.0 and 167.6, 161.9
and 161.1, 161.7, 158.9, 132.1, 130.1 (2C), 129.4, 129.2 (2C), 113.7
(2C), 113.6 (2C), 105.5, 98.5, 74.8, 73.8, 58.5, 56.9, 55.3, 55.2, 19.7,
17.7, 15.5, 15.0. Anal. Calcd. for C26H33NO7: C, 66.22; H, 7.05; N, 2.97;
found C, 66.47; H, 7.23; N, 2.74.
ent-10a: [α]2D0 = –48 (c 1.0, THF). 1H NMR matches that of 10a. Anal.
Calcd. for C24H29NO5: C, 70.05; H, 7.10; N, 3.40; found C, 70.31; H,
7.41; N, 3.22.
(3R,3′R,5S,5′S,6S,6′S)-3,3′-[(1S,1′S)-Azanediylbis(p-tolylmethyl-
ene)]bis(5,6-diethoxy-5,6-dimethyl-1,4-dioxan-2-one) (9b): Hy-
drotoluamide (4b, 680 mg). 9b (672 mg, 51 %); wax; [α]2D0 = +214
(c 1.0, CHCl3). 1H NMR (300 MHz, CDCl3) δ = 7.11 (d, 4H, J = 8.2 Hz),
7.07 (d, 4H, J = 8.2 Hz), 4.10 (d, 2H, J = 5.8 Hz), 3.87 (d, 2H, J =
5.5 Hz), 3.64 (q, 4H, J = 7.0 Hz), 3.53–3.36 (m, 4H), 2.33 (s, 6H), 1.49
(s, 6H), 1.46 (s, 6H), 1.08 (t, 6H, J = 7.0 Hz), 1.00 (t, 6H, J = 7.0 Hz)
(NH proton not visible); 13C NMR (75 MHz, CDCl3) δ = 167.5 (2C),
136.9 (2C), 135.3 (2C), 128.8 (4C), 128.5 (4C), 104.7 (2C), 98.1 (2C),
75.8 (2C), 60.8 (2C), 58.1 (2C), 57.0 (2C), 21.2 (2C), 19.0 (2C), 17. 7
(2C), 15.3 (2C), 15.1 (2C). Anal. Calcd. for C36H51NO10: C, 65.73; H,
7.81; N, 2.13; found C, 66.02; H, 8.05; N, 1.98.
(3R,3′R,5S,5′S,6S,6′S)-3,3′-{(1S,1′S)-Azanediylbis[(4-fluoro-
phenyl)methylene]}bis(5,6-diethoxy-5,6-dimethyl-1,4-dioxan-2-
one) (9d): Hydro(4-fluoro)benzamide (4d, 708 mg). 9d (572 mg,
1
43 %); white wax; [α]2D0 = +198 (c = 1.4 CHCl3). H NMR (300 MHz,
CDCl3) δ = 7.20–7.15 (m, 4H), 7.04–6.99 (m, 4H), 4.09 (d, 2H, J =
5.7 Hz), 3.90 (d, 2H, J = 5.7 Hz), 3.69 (q, 4H, J = 7.0 Hz), 3.58 (bs,
1H), 3.60–3.48 (m, 2H), 3.42–3.32 (m, 2H), 1.52 (s, 6H), 1.48 (s, 6H),
1.13–1.03 (m, 12H); 13C NMR (75 MHz, CDCl3) δ = 167.3 (2C), 162.4
(d, 2C, J = 245.4 Hz), 133.9 (2C), 130.1 (d, 4C, J = 8.1 Hz), 115.0 (d,
4C, J = 21.3 Hz), 104.9 (2C), 98.1 (2C), 75.5 (2C), 60.4 (2C), 58.2 (2C),
57.1 (2C), 18.8 (2C), 17.6 (2C), 15.3 (2C), 15.0 (2C). Anal. Calcd. for
C34H45F2NO10: C, 61.34; H, 6.81; N, 2.10; found C, 61.43; H, 6.90; N,
2.02.
(3R,3′R,5S,5′S,6S,6′S)-3,3′-[(1S,1′R)-Azanediylbis(p-tolylmethyl-
ene)]bis(5,6-diethoxy-5,6-dimethyl-1,4-dioxan-2-one) (9′b):
106 mg (8 %); white wax; [α]2D0 = +123 (c 1.0, CHCl3). 1H NMR
(300 MHz, CDCl3) δ = 7.31 (d, 4H, J = 7.9 Hz), 7.15 (d, 4H, J = 7.9 Hz),
4.51 (d, 2H, J = 1.9 Hz), 4.33 (d, 2H, J = 2.5 Hz), 3.81–3.66 (m, 4H),
3.52–3.44 (m, 2H), 3.35–3.29 (m, 2H), 2.36 (s, 6H), 1.53 (s, 6H), 1.41
(s, 6H), 1.20 (t, 6H, J = 7.0 Hz), 1.13 (t, 6H, J = 7.0 Hz) (NH proton
not visible). Anal. Calcd. for C36H51NO10: C, 65.73; H, 7.81; N, 2.13;
found C, 65.84; H, 7.79; N, 2.02.
(3R,3′R,5S,5′S,6S,6′S)-3,3′-{(1S,1′R)-Azanediylbis[(4-fluoro-
phenyl)methylene]}bis(5,6-diethoxy-5,6-dimethyl-1,4-dioxan-2-
one) (9d′): 94 mg (7 %); white wax; [α]2D0 = +48 (c 1.0, CHCl3). 1H
NMR (300 MHz, CDCl3) δ = 7.42–7.38 (m, 4H), 7.08–7.03 (m, 4H),
5.12 (d, 2H, J = 4.4 Hz), 4.27 (d, 2H, J = 4.5 Hz), 4.03 (bs, 1H), 3.83–
3.70 (m, 4H), 3.64–3.52 (m, 4H), 1.56 (s, 6H), 1.45 (s, 6H), 1.26 (t, 6H,
J = 7.1 Hz), 1.19 (t, 6H, J = 7.1 Hz); 13C NMR (75 MHz, CDCl3) δ =
166.9 (2C), 162.4 (d, 2C, J = 246.0 Hz), 134.0 (2C), 128.5 (d, 4C, J =
7.9 Hz), 114.9 (d, 4C, J = 21.4 Hz), 105.1 (2C), 98.1 (2C), 75.7 (2C),
73.9 (2C), 58.9 (2C), 57.5 (2C), 18.6 (2C), 17.5 (2C), 15.1 (4C). Anal.
Calcd. for C34H45F2NO10: C, 61.34; H, 6.81; N, 2.10; found C, 61.47;
H, 6.96; N, 2.00.
(3R,5S,6S)-5,6-Diethoxy-5,6-dimethyl-3-{(S)-[(4-methylbenzyl-
idene)amino](p-tolyl)methyl}-1,4-dioxan-2-one (10b): 212 mg
(24 %); wax; [α]2D0 = +43 (c 1.2, CHCl3). E and Z mixture: 1H NMR
(300 MHz, CDCl3) δ = 8.31 and 8.28 (s, 1H), 7.71 (d, 2H, J = 7.8 Hz),
7.42 (d, 2H, J = 7.8 Hz), 7.22–7.13 (m, 4H), 5.04 and 4.98 (d, 1H, J =
4.1 and 4.2 Hz), 4.61 and 4.55 (d, 1H, J = 4.2 and 4.1 Hz), 3.80–3.56
(m, 2H), 3.54–3.44 (m, 1H), 3.44–3.29 (m, 1H), 2.39 (s, 3H), 2.37 (s,
3H), 1.52 (s, 3H), 1.42 and 1.41 (s, 3H), 1.17–1.13 (m, 6H). Anal. Calcd.
for C26H33NO5: C, 71.05; H, 7.57; N, 3.19; found C, 70.81; H, 7.36; N,
3.38.
(3R,3′R,5S,5′S,6S,6′S)-3,3′-{(1S,1′S)-Azanediylbis[(4-methoxy-
phenyl)methylene]}bis(5,6-diethoxy-5,6-dimethyl-1,4-dioxan-2-
one) (9c): Hydro(4-methoxy)benzamide (4c, 776 mg). 9c (648 mg,
(3R,5S,6S)-5,6-Diethoxy-3-{(S)-[(4-fluorobenzylidene)amino]-
47 %); wax; [α]2D0 = +168 (c 1.3, CHCl3). 1H NMR (300 MHz, CDCl3) (4-fluorophenyl)methyl}-5,6-dimethyl-1,4-dioxan-2-one (10d):
δ = 7.11 (d, 4H, J = 8.5 Hz), 6.84 (d, 4H, J = 8.7 Hz), 4.09 (d, 2H, J = 448 mg (50 %); wax; [α]2D0 = +37 (c 1.4, CHCl3). E and Z mixture: 1H
6.0 Hz), 3.86 (d, 2H, J = 6.0 Hz), 3.81 (s, 6H), 3.66 (d, 2H, J = 14.1 Hz),
NMR (300 MHz, CDCl3) δ = 8.31 and 8.26 (s, 1H), 7.84–7.79 (m, 2H),
Eur. J. Org. Chem. 2019, 6707–6713
6711
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim