Bis(oxazoline) Ligands for Asymmetric Catalysis
(2S)-2-Am in o-2-p h en ylet h yl 2-Am in ob en zen eca r box-
Alter n a tive P r oced u r e for th e Syn th esis of 2-(o-Am i-
n op h en yl)oxa zolin es (9a-d ): Meth od b. DAST (98 µL, 0.74
mmol) was added slowly and dropwise to a solution of the
hydroxy amide (0.74 mmol) in dry CH2Cl2 (7 mL) under an
atmosphere of nitrogen at room temperature. After stirring
of the resulting yellow solution at room temperature under a
nitrogen atmosphere for 18 h, the reaction mixture was poured
on to a saturated solution of NaHCO3 (10 mL) and extracted
with CH2Cl2 (3 × 10 mL). The combined organic extracts were
dried over anhydrous Na2SO4 and evaporated in vacuo to give
a yellow/brown solid, which was purified by flash column
chromatography on silica gel [3 × 30 cm, CH2Cl2/pet. ether
(40-60 °C) 19:1] to yield product.
2-[(4S)-4-(Ben zyl)-4,5-d ih yd r o-1,3-oxa zol-2-yl]a n ilin e
(9a ). Yield: 60% (method a), 84% (method b), white solid. Mp:
56-57 °C (lit.15 mp: 56-57 °C). [R]D ) +24.7 (c ) 1.00 in
CHCl3) (lit.15 [R]D ) +24.8 (c ) 1.25 in CHCl3)). 1H NMR
(CDCl3): δ ) 7.67 (dd, J ) 7.9, 1.5 Hz, 1H),), 7.16-7.68 (m,
6H), 6.61-6.69 (m, 2H), 6.07 (s, br, 2H), 4.54-4.64 (m, 1H),
4.26 (dd, J ) 9.1, 8.5 Hz, 1H), 4.01 (dd, J ) 8.5, 7.3 Hz, 1H),
3.12 (dd, J ) 13.8, 6.2 Hz, 1H), 2.76 (dd, J ) 13.8, 8.2 Hz,
1H). 13C NMR (CDCl3): δ ) 164.4, 148.9, 138.7, 122.3, 129.9,
129.5, 128.8, 126.7, 116.3, 115.9, 109.3, 70.5, 68.4, 42.6. IR
(KBr): ν ) 3402, 3256, 1631, 1166, 1056, 968 cm-1. MS (70
eV, EI), m/z (%) 252 [M+], 161 (100), 133, 106, 91, 65, 32.
yla te (14c). Yield: 24%, white solid. Mp: 76-78 °C. [R]D
)
+19.4 (c ) 1.01 in CHCl3). 1H NMR (CDCl3): δ ) 7.84 (m,
1H), 7.24-7.47 (m. 6H), 6.61-6.67 (m, 2H), 5.69 (s, br, 2H),
4.37-4.48 (m, 2H), 4.27 (dd, J ) 10.0, 7.6 Hz, 1H). 13C NMR
(CDCl3): δ ) 167.8, 150.6, 134.2, 134.2, 131.1, 128.6, 127.7,
126.8, 116.7, 116.3, 110.6, 69.8, 54.8. IR (KBr): ν )3444, 3290,
1686, 1621, 699, 661 cm-1. MS (70 eV, EI): m/z (%) 256 [M+],
119, 120, 106 (100), 92, 79, 65. Anal. Calcd for C15H16O2N2: C
70.26, H 6.29, N 10.97. Found: C 69.94, H 6.37, N 10.59.
(2S)-2-[(2-Am in op h en yl)ca r bon yla m in o]-3-p h en yleth -
yl 2-Am in oben zen eca r boxyla te (15c). Yield: 14%, white
solid. Mp: 142-144 °C. [R]D ) -1.5 (c ) 1.00 in CHCl3). 1H
NMR (CDCl3): δ )7.77 (ddd, J ) 8.1, 1.8, 0.4 Hz, 1H), 7.22-
7.45 (m, 7H), 7.19 (ddd, J ) 8.4, 7.6, 1.8 Hz, 1H), 6.94 (d, J )
6.9 Hz, 1H), 6.60-6.66 (m, 4H), 5.67 (s, br, 2H), 5.50-5.56
(m, 3H), 4.71 (dd, J ) 11.6, 7.5 Hz, 1H), 4.55 (dd, J ) 11.6,
4.5 Hz, 1H). 13C NMR (CDCl3): δ )169.1, 168.7, 151.0, 149.3,
139.0, 134.8, 132.8, 131.5, 129.2, 128.2, 127.5, 126.9, 117.6,
117.0, 116.8, 116.7, 115.7, 110.3, 66.6, 53.6. IR (KBr): ν )
3486, 3377, 3302, 1691, 1635, 1615, 752 cm-1. MS (70 eV, EI):
m/z (%) 375 [M+], 239, 225, 120 (100), 92, 65. Anal. Calcd for
C
22H21O3N3: C 70.35, H 5.64, N 11.24. Found: C 69.96, H 5.69,
N 10.97.
N-[(1S)-1-Hyd r oxym et h yl-2,2-d im et h ylp r op yl]-2-a m i-
n oben za m id e (12d ). Yield: 40%. white solid. Mp: 100-102
°C. [R]D ) -6.3 (c ) 1.00 in EtOH). 1H NMR (CDCl3): δ )
7.35 (dd, J ) 8.5, 1.5 Hz, 1H), 7.21 (ddd, J ) 8.2, 7.0, 1.5 Hz,
1H), 6.64-6.69 (m, 2H), 6.25 (d, J ) 8.2 Hz, 1H), 5.39 (s, br,
2H), 4.01 (ddd, J ) 9.1, 7.6, 3.5 Hz, 1H), 3.93 (dd, J ) 11.0,
3.5 Hz, 1H), 3.65 (dd, J ) 11.0, 7.6 Hz, 1H), 2.65 (s, br, 1H),
1.03 (s, 9H). 13C NMR (CDCl3): δ ) 170.6, 148.5, 132.5, 127.5,
117.7, 117.2, 116.4, 63.2, 59.7, 34.1, 27.3. IR (KBr): ν ) 3343,
1632, 1590, 1368, 755, 685 cm-1. MS (70 eV, EI): m/z (%) 236
[M+], 205, 179, 161, 120 (100), 92, 65.
(2S)-2-Am in o-3,3-d im eth ylbu tyl 2-Am in oben zen eca r -
boxyla te (14d ). Yield: 19%, white solid. Mp: 82-84 °C. [R]D
) +44.55 (c ) 0.22 in CHCl3). 1H NMR (CDCl3): δ ) 7.85 (ddd,
J ) 7.9, 1.5, 0.4 Hz, 1H), 7.26 (ddd, J ) 9.8, 7.1, 1.5 Hz, 1H),
6.61-6.67 (m, 2H), 5.73 (s, br, 2H), 4.50 (dd, J ) 10.8, 3.1 Hz,
1H), 4.04 (dd, J ) 10.8, 8.9 Hz, 1H), 2.88 (dd, J ) 8.9, 3.1 Hz,
1H), 1.53 (s, br, 2H), 1.00 (s, 9H). 13C NMR (CDCl3): δ ) 168.2,
150.6, 134.1, 131.1, 116.8, 116.3, 110.8, 67.0, 58.9, 33.5, 26.5.
IR (KBr): ν ) 3416, 3369, 1686, 1628, 1242, 754 cm-1. MS
(70 eV, EI): m/z (%) 236 [M+], 179, 120 (100), 92, 86, 69. 65.
Anal. Calcd for C13H20O2N2: C 66.04, H 8.53, N 11.90. Found:
C 66.18, H 8.34, N 11.61.
(2S)-2-[(2-Am in op h en yl)ca r bon yla m in o]-3,3-d im eth yl-
bu tyl 2-Am in oben zen eca r boxyla te (15d ). Yield: 6%, white
solid. Mp: 82-84 °C. [R]D ) -63.1 (c ) 1.00 in CHCl3). 1H NMR
(CDCl3): δ )7.80 (dd, J ) 7.9, 1.6 Hz, 1H), 7.31 (dd, J ) 7.8,
1.3 Hz, 1H), 7.22 (ddd, J ) 8.2, 7.1, 1.3 Hz, 1H), 7.18 (ddd, J
) 8.2, 7.2, 1.6 Hz, 1H), 6.56-6.66 (m, 4H), 6.16 (d, J ) 8.9
Hz, 1H) 5.65 (s, br, 2H), 5.34 (s, br, 2H), 4.37-4.53 (m, 3H),
1.08 (s, 9H). 13C NMR (CDCl3): δ ) 169.3, 168.3, 150.5, 148.5,
134.3, 132.2, 131.4, 126.9, 117.2, 116.8, 116.72, 116.70, 116.4,
110.5, 63.8, 55.6, 34.2, 27.0. IR (KBr): ν ) 3467, 3360, 1691,
1651, 1618, 745 cm-1. MS (70 eV, EI): m/z (%) 355 [M+], 219,
161, 137, 120 (100), 92, 65.
2-Am in o-N-((1S)-1-ben zyl-2-[2-((4S)-4-ben zyl-4,5-d ih y-
dr ooxazol-2-yl)ph en ylam in o]eth yl)ben zam ide (16a). Yield:
7%, white solid. Mp: 130-132 °C. [R]D ) +2.21 (c ) 0.995 in
1
CHCl3). H NMR (CDCl3): δ ) 8.79 (app t, J ) 5.3 Hz, 1H),
7.72 (dd, J ) 7.9, 1.8 Hz, 1H), 7.13-7.33 (m, 13H), 6.75 (d, J
) 8.5 Hz, 1H), 6.65 (dd, J ) 5.3, 0.9 Hz, 1H), 6.62 (ddd, J )
6.2, 4.1, 0.9 Hz, 1H), 6.57 (ddd, J ) 7.9, 5.3, 1.2 Hz, 1H), 6.08
(d, J ) 8.05 Hz, 1H), 5.42 (s, br, 2H), 4.49-4.62 (m, 2H), 4.25
(app t, J ) 8.4 Hz, 1H), 3.99 (dd, J ) 8.4, 7.6 Hz, 1H), 3.30-
3.47 (m, 2H), 2.98-3.08 (m, 2H), 2.91 (dd, J ) 13.9, 7.3 Hz,
1H), 2.72 (dd, J ) 13.8, 8.1 Hz, 1H). 13C NMR (CDCl3): δ
)169.0, 164.5, 149.2, 148.7, 138.3, 137.6, 132.7, 132.2, 130.0,
129.4, 129.1, 128.6, 128.5, 127.4, 126.7, 126.5, 117.2, 116.6,
116.3, 114.9, 110.7, 108.8, 70.2, 68.0, 50.2, 44.7, 42.2, 38.2. IR
(KBr): ν ) 3303, 1633, 1587, 1523, 744, 714 cm-1. MS (70 eV,
EI): m/z (%) 504 [M+], 265 (100), 131, 120, 117, 105, 91, 77,
65. Anal. Calcd for C32H32O2N4: C 76.13, H 6.39, N 11.14.
Found: C 75.89, H 6.38, N 10.93.
2-[(4S )-4-Isop r op yl-4,5-d ih yd r o-1,3-oxa zol-2-yl]a n i-
lin e (9b). Yield: 67% (method a), 87% (method b), white solid.
Mp: 64-65 °C (lit.15 mp: 67-69 °C). [R]D ) +10.2 (c ) 1.00 in
EtOH) (lit.15 [R]D ) +8.7 (c ) 1.00 in EtOH)). 1H NMR
(CDCl3): δ ) 7.67 (dd, J ) 7.9, 1.5 Hz, 1H), 7.19 (ddd, J )
8.2, 7.3, 1.5 Hz, 1H), 6.69 (dd, J ) 8.2, 1.2 Hz, 1H), 6.65 (ddd,
J ) 7.9, 7.3, 1.2 Hz, 1H), 6.12 (s, br, 2H), 4.32 (dd, J ) 9.1, 7.6
Hz, 1H), 4.11 (ddd, J ) 9.1, 7.6, 6.7 Hz, 1H), 4.00 (app. t, J )
7.6 Hz, 1H), 1.79 (m, 1H), 1.03 (d, J ) 6.7 Hz, 3H), 0.94 (d, J
) 6.7 Hz, 3H), 13C NMR (CDCl3): δ ) 163.8, 148.9, 132.1,
129.8, 116.2, 115.9, 109.5, 73.2, 69.0, 33.5, 19.2, 18.8. IR
(KBr): ν ) 3402, 3259, 1640, 1607, 1491, 746 cm-1. MS (70
eV, EI): m/z (%) 204 [M+], 161 (100), 133, 118, 106, 92, 65, 39.
2-Am in o-N-((1S)-1-{[2-((4S)-4-isop r op yl-4,5-d ih yd r oox-
a zol-2-yl-p h en yla m in o]m et h yl}-2-m et h ylp r op yl)b en z-
a m id e (16b). Yield: 10%, brown solid. Mp: 96-98 °C. [R]D
)
1
Gen er a l P r oced u r e for th e Cycliza tion of Ch lor o
Am id es 13a -d To Give 9a -d : Meth od a . Chloroamide (23.6
mmol) was added to a suspension of NaOH pellets (1.01 g, 25.3
mmol) in EtOH (170 mL) and the resulting pale yellow mixture
was refluxed for 3 h. After cooling to room temperature, the
solvent was removed in vacuo to give a yellow residue. This
was dissolved in CH2Cl2 (100 mL) and washed with a saturated
solution of NaHCO3 (4 × 50 mL). The aqueous layers were
separated and extracted with CH2Cl2 (3 × 50 mL). The
combined organic layers were dried over anhydrous Na2SO4,
evaporated to give a yellow/brown residue, and purified by
flash column chromatography on silica gel (6 × 35 cm, hexane/
AcOEt 3:1) to give two products.
-85.8 (c ) 0.30 in CHCl3). H NMR (CDCl3): δ ) 8.74 (s, br,
1H), 7.71 (dd, J ) 7.8, 1.5 Hz, 1H), 7.28 (ddd, J ) 8.4, 7.2, 1.8
Hz. 1H), 7.23 (dd, J ) 7.9, 1.5 Hz, 1H), 7.17 (ddd, J ) 8.1, 7.3,
1.6 Hz, 1H), 6.76 (d, J ) 8.4 Hz, 1H), 6.65 (dd, J ) 8.2, 0.88
Hz, 1H), 6.55-6.63 (m, 2H), 6.11 (d, J ) 9.1 Hz, 1H), 5.44 (s,
br, 2H), 4.19-4.29 (m, 2H), 3.93-4.04 (m, 2H), 3.40-3.54 (m,
2H), 2.04-2.13 (m, 1H), 1.67-1.75 (m, 1H), 1.05 (app t, J )
7.2 Hz, 6H), 0.95 (d, J ) 6.7 Hz, 3H), 0.87 (d, J ) 6.7 Hz, 3H).
13C NMR (CDCl3): δ )169.3, 164.1, 149.5, 148.9, 132.8, 132.4,
130.2, 127.5, 117.4, 116.83, 116.76, 114.9, 110.6, 109.1, 73.0,
68.7, 54.3, 44.3, 33.3, 30.2, 19.8, 19.2, 18.9, 18.7. IR (KBr): ν
) 3455, 3397, 1633, 1530, 1250, 748 cm-1. MS (70 eV, EI):
m/z (%) 408 [M+], 257, 217 (100), 131, 120, 92, 65, 41. Anal.
J . Org. Chem, Vol. 67, No. 24, 2002 8571