PAPER
Bioxazoline-Catalyzed Asymmetric Henry Reactions
2461
(4R,4′R)-2,2′-Bis[(1S)-1-(6-methoxy-2-naphthyl)ethyl]-
4,4′,5,5′-tetrahydro-4,4′-bi-1,3-oxazole (4c)
13C NMR (125.7 MHz, CDCl3): δ = 171.5, 157.6, 136.3, 133.7,
129.2, 128.9, 127.1, 126.1, 125.7, 118.9, 105.6, 68.7, 68.0, 55.3,
39.4, 19.1.
HRMS (EI): m/z [M + H]+ calcd for C32H33N2O4: 509.2440; found:
509.2423.
Colorless solid; yield: 1.38 g (91%); mp 129–131 °C; [α]D25 +93.17
(c 1.00, CH2Cl2); Rf = 0.7 (CH2Cl2–MeOH, 19:1).
IR (KBr): 3432, 3053, 2987, 2971, 2935, 2913, 1660, 1650, 1606,
1484, 1390, 1268, 1180, 1067, 1004, 926, 857, 817 cm–1.
N,N′-[(2S,3S)-1,4-Dihydroxybutane-2,3-diyl]bis[2-(2-naph-
1H NMR (500 MHz, CDCl3): δ = 7.67–7.63 (m, 6 H), 7.36 (dd, J =
8.5, 1.8 Hz, 2 H), 7.11 (dd, J = 8.5, 2.5 Hz, 2 H), 7.08 (d, J = 2.5 Hz,
2 H), 4.61–4.58 (m, 2 H), 4.18–4.14 (m, 2 H), 3.89 (s, 6 H), 3.86–
3.80 (m, 4 H), 1.58 (d, J = 7.0 Hz, 6 H).
13C NMR (125.7 MHz, CDCl3): δ = 171.6, 157.7, 136.2, 133.7,
129.2, 128.9, 127.1, 125.9, 125.8, 118.9, 105.7, 68.4, 68.1, 55.3,
39.5, 19.1.
thyl)acetamide] (13)
25
Colorless solid; yield: 684 mg (75%); mp 193–195 °C; [α]D
+30.00 (c 0.3, MeOH); Rf = 0.3 (CH2Cl2–MeOH, 9:1).
IR (KBr): 3196, 2818, 1731, 1618, 1398, 1282, 1217, 1143, 1051,
992, 854, 593 cm–1.
1H NMR (500 MHz, DMSO-d6): δ = 7.88–7.82 (m, 8 H), 7.74 (br s,
2 H), 7.51–7.43 (m, 6 H), 4.72 (t, J = 6.0 Hz, 2 H), 4.08–4.03 (m, 2
H), 3.60 (s, 4 H), 3.16–3.13 (m, 4 H).
HRMS (EI): m/z [M + H]+ calcd for C32H33N2O4: 509.2440; found:
509.2427.
13C NMR (125.7 MHz, DMSO-d6): δ = 171.1, 134.6, 133.5, 132.3,
(2R,2′R)-N,N′-[(2R,3R)-1,4-Bis(benzyloxy)butane-2,3-di-
yl]bis[2-(6-methoxy-2-naphthyl)propanamide] (10d)
Colorless solid; yield: 3.33 g (92%); mp 166–168 °C; [α]D25 +44.76
(c 0.5, CH2Cl2); Rf = 0.8 (CH2Cl2–MeOH, 19:1).
128.2, 128.0, 127.9, 127.8, 127.8, 126.5, 126.0, 61.3, 51.6, 43.0.
HRMS (EI): m/z [M + H]+ calcd for C28H28N2O4: 456.2049; found:
456.2049.
IR (KBr): 3749, 3451, 2936, 2867, 1800, 1643, 1605, 1539, 1392,
1366, 1264, 1210, 1100, 1030, 850, 740, 697 cm–1.
(4S,4′S)-2,2′-Bis(2-naphthylmethyl)-4,4′,5,5′-tetrahydro-4,4′-
bi-1,3-oxazole (3g)
25
Colorless solid; yield: 376 mg (81%); mp 154–156 °C; [α]D
+11.75 (c 0.25, CH2Cl2); Rf = 0.7 (CH2Cl2–MeOH, 19:1).
1H NMR (500 MHz, CDCl3): δ = 7.66 (t, J = 8.2 Hz, 4 H), 7.59 (br
s, 2 H), 7.30 (dd, J = 8.5, 1.8 Hz, 2 H), 7.21–7.12 (m, 8 H), 7.08 (d,
J = 2.5 Hz, 2 H), 6.94–6.92 (m, 4 H), 6.36 (d, J = 7.9 Hz, 2 H), 4.20–
4.19 (m, 2 H), 4.09 (dd, J = 19.3, 11.8 Hz, 4 H), 3.90 (s, 6 H), 3.53
(q, J = 7.1 Hz, 2 H), 3.37 (dd, J = 9.8, 2.8 Hz, 2 H), 3.20 (dd, J =
9.8, 4.2 Hz, 2 H), 1.50 (d, J = 7.1 Hz, 6 H).
13C NMR (125.7 MHz, CDCl3): δ = 174.6, 157.6, 137.4, 136.4,
133.7, 129.3, 129.0, 128.2, 127.7, 127.6, 127.3, 126.1, 126.0, 119.0,
105.6, 73.1, 68.7, 55.3, 50.5, 46.9, 18.3.
IR (KBr): 3466, 3273, 2512, 2250, 2124, 1997, 1827, 1769, 1661,
1372, 1222, 1055, 822, 759, 623 cm–1.
1H NMR (500 MHz, DMSO-d6): δ = 7.87–7.72 (m, 8 H), 7.50–7.45
(m, 4 H), 7.36 (dd, J = 8.5, 1.5 Hz, 2 H), 4.29–4.26 (m, 2 H), 4.21–
4.18 (m, 2 H), 4.06 (dd, J = 8.0, 6.5 Hz, 2 H), 3.67 (s, 4 H).
13C NMR (125.7 MHz, DMSO-d6): δ = 166.8, 133.7, 133.4, 128.3,
128.0, 127.9, 127.8, 127.7, 127.1, 126.7, 126.2, 69.3, 68.4, 34.4.
HRMS (EI): m/z [M + H]+ calcd for C46H49N2O6: 725.3591; found:
725.3574.
HRMS (EI): m/z [M + H]+ calcd for C28H24N2O2: 420.1837; found:
420.1842.
(2R,2′R)-N,N′-[(2R,3R)-1,4-Dihydroxybutane-2,3-diyl]bis[2-(6-
methoxy-2-naphthyl)propanamide] (11d)
(2S,2′S)-N,N′-[(2S,3S)-1,4-Bis(benzyloxy)butane-2,3-diyl]bis[2-
(4-isobutylphenyl)propanamide](10e)
Colorless solid; yield: 2.04 g (94%); mp 244–246 °C; [α]D25 +21.37
[c 0.3, CHCl3–MeOH (1:1)]; Rf = 0.3 (CH2Cl2–MeOH, 9:1).
25
Colorless solid; yield: 3.04 g (90%); mp 109 °C, [α]D –25.27 (c
1.00, CH2Cl2); Rf = 0.5 (PE–EtOAc, 4:1).
IR (KBr): 3441, 3282, 3051, 2949, 2840, 1643, 1605, 1548, 1464,
1390, 1264, 1212, 1088, 1044, 856, 733 cm–1.
IR (KBr): 3293, 3062, 2953, 1643, 1539, 1453, 1381, 1361, 1241,
1100, 1026, 738 cm–1.
1H NMR (500 MHz, DMSO-d6): δ = 7.77 (d, J = 9.0 Hz, 2 H), 7.73–
7.69 (m, 6 H), 7.45 (dd, J = 8.6, 1.7 Hz, 2 H), 7.26 (d, J = 2.5 Hz, 2
H), 7.13 (dd, J = 8.9, 2.5 Hz, 2 H), 4.62 (t, J = 6.0 Hz, 2 H), 4.02–
3.97 (m, 2 H), 3.86 (s, 6 H), 3.78 (q, J = 7.1 Hz, 2 H), 3.31–3.27 (m,
4 H), 1.43 (d, J = 7.1 Hz, 6 H).
1H NMR (500 MHz, CDCl3): δ = 7.33–7.27 (m, 6 H), 7.18–7.09 (m,
12 H), 6.39 (d, J = 7.0 Hz, 2 H), 4.26 (s, 4 H), 4.24–4.23 (m, 2 H),
3.46–3.42 (m, 4 H), 3.29 (dd, J = 10.0, 4.0 Hz, 2 H), 2.45 (d, J = 7.0
Hz, 4 H), 1.85 (m, 2 H), 1.47 (d, J = 7.0 Hz, 6 H), 0.90 (d, J = 7.0
Hz, 12 H).
13C NMR (125.7 MHz, DMSO-d6): δ = 174.6, 157.5, 137.7, 133.6,
129.6, 128.8, 127.0, 126.9, 125.8, 119.0, 106.2, 61.1, 55.6, 51.5,
45.6, 19.4.
HRMS (EI): m/z [M + H]+ calcd for C32H37N2O6: 545.2652; found:
545.2449.
13C NMR (125.7 MHz, CDCl3): δ = 174.7, 140.5, 138.5, 137.6,
129.4, 128.3, 127.7, 127.6, 127.2, 73.2, 68.7, 50.4, 46.6, 45.0, 30.1,
22.3, 18.3.
HRMS (EI): m/z [M + H]+ calcd for C44H57N2O4: 677.4318; found:
677.4318.
(4R,4′R)-2,2′-Bis[(1R)-1-(6-methoxy-2-naphthyl)ethyl]-
4,4′,5,5′-tetrahydro-4,4′-bi-1,3-oxazole (4d)
(2S,2′S)-N,N′-[(2S,3S)-1,4-Dihydroxybutane-2,3-diyl]bis[2-(4-
isobutylphenyl)propanamide] (11e)
25
Colorless solid; yield: 1.5 g (76%); mp 270–272 °C; [α]D25 +9.52 [c
0.5, CHCl3–MeOH (1:1)]; Rf = 0.4 (CH2Cl2–MeOH, 9:1).
Colorless solid; yield: 1.41 g (93%); mp 188–190 °C; [α]D
+111.97 (c 0.5, CH2Cl2); Rf = 0.7 (CH2Cl2–MeOH, 19:1).
IR (KBr): 3433, 2976, 2935, 2904, 1654, 1605, 1376, 1390, 1261,
1227, 1184, 1170, 1068, 1032, 858, 815, 475 cm–1.
IR (KBr): 3441, 3286, 2952, 2868, 1645, 1551, 1465, 1365, 1231,
1107, 1066, 1044, 736 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.67 (t, J = 8.5 Hz, 4 H), 7.63 (br
s, 2 H), 7.36 (dd, J = 8.5, 1.8 Hz, 2 H), 7.12 (dd, J = 8.5, 2.5 Hz, 2
H), 7.08 (d, J = 2.5 Hz, 2 H), 4.53–4.48 (m, 2 H), 4.14–4.10 (m, 2
H), 4.00 (dd, J = 6.5, 9.0 Hz, 2 H), 3.89 (s, 6 H), 3.80 (q, J = 7.2 Hz,
2 H), 1.50 (d, J = 7.2 Hz, 6 H).
1H NMR (500 MHz, DMSO-d6): δ = 7.60 (d, J = 8.4 Hz, 2 H), 7.21
(d, J = 8.1 Hz, 4 H), 7.07 (d, J = 8.1 Hz, 4 H), 4.61 (t, J = 6.1 Hz, 2
H), 3.98–3.93 (m, 2 H), 3.60 (q, J = 7.0 Hz, 2 H), 3.31–3.24 (m, 4
H), 2.40 (d, J = 7.1 Hz, 4 H), 1.80 (m, 2 H), 1.33 (d, J = 7.0 Hz, 6
H), 0.85 (d, J = 6.6 Hz, 12 H).
13C NMR (125.7 MHz, DMSO-d6): δ = 174.7, 139.8, 139.6, 129.2,
127.5, 61.0, 51.4, 45.3, 44.7, 30.1, 22.7, 19.5.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2455–2462