Asymmetric Nitrone-Aldol Reaction
5652 5661
(q, 1J(C,F) 286 Hz), 129.31, 129.54, 129.67, 132.53, 137.45, 168.61; MS
Benzyl-(3-hydroxy-4-oxo-3-phenylpentylidene)amine
N-oxide
(3n):
3
2
(TOF ES ): m/z:370 [ MNa] ; HRMS: m/z:calcd for C 16H20F3NNaO4:
1H NMR: d 2.07 (s, 3H), 3.09 (dd, J(H,H) 6.0 Hz, J(H,H) 14.8 Hz,
1H), 3.21 (dd, 3J(H,H) 6.0 Hz, 2J(H,H) 14.8 Hz, 1H), 4.82 (s, 2H), 6.29
(s, 1H), 6.84 (t, 3J(H,H) 6.0 Hz, 1H), 7.21 7.38 (m, 8H), 7.47 (d, 2H), 7.66
(s, 1H); 13C NMR: d 24.07, 37.27, 68.98, 85.35, 125.30, 128.14, 128.81,
370.1242; found:370.1241.
Benzyl-(3-ethoxycarbonyl-4,4,4-trifluoro-3-hydroxy-1-phenylbutylidene)-
1
3
amine N-oxide (3 f): H NMR: d 0.98 (t, J(H,H) 7.0 Hz, 3H), 3.35 (d,
3J(H,H) 13.6 Hz, 1H), 3.82 (dq, 2J(H,H) 11.2 Hz, 3J(H,H) 7.2 Hz,
1H), 3.84 (d, 3J(H,H) 13.6 Hz, 1H), 3.98 (dq, 2J(H,H) 11.2 Hz,
3J(H,H) 7.2 Hz, 1H), 4.88 (d, 2J(H,H) 14 Hz, 1H), 4.95 (d, 2J(H,H)
14 Hz, 1H), 7.14 7.21 (m, 4H), 7.25 7.31 (m, 3H), 7.35 7.43 (m, 3H), 8.37
(brs, 1H); 13C NMR: d 13.84, 38.59, 62.81, 64.59, 79.56 (q, 2J(C,F)
128.84, 129.25, 129.37, 132.39, 138.45, 141.20, 209.91; MS (TOF ES ): m/z:
258 [MNa] ; HRMS: m/z:calcd for C 13H17NNaO3:258.1106; found:
258.1103.
Benzyl-(3-benzoyl-3-hydroxybutylidene)amine N-oxide (3o): 1H NMR:
d 1.32 (s, 3H), 2.22 (s, 3H), 2.76 (dd, 3J(H,H) 4.8 Hz, 2J(H,H)
1
3
2
29 Hz), 123.69 (q, J(C,F) 285 Hz), 128.02, 128.15, 128.77, 129.08, 129.47,
15.2 Hz, 1H), 2.85 (dd, J(H,H) 6.0 Hz, J(H,H) 15.2 Hz, 1H), 4.84 (s,
2H), 6.29 (s, 1H), 6.84 (dd, 3J(H,H) 6.0, 4.8 Hz, 1H), 7.32 7.39 (m, 5H);
13C NMR: d 28.36, 38.76, 68.70, 82.65, 128.118, 129.00, 129.04, 129.07,
130.66, 133.47, 134.42, 148.61, 168.05; MS (TOF ES ): m/z:395 [ MNa] ;
HRMS: m/z:calcd for C 20H20F3NNaO4:418.1242; found:418.1243.
130.41, 132.21, 132.82, 134.08, 138.66, 203.29; MS (TOF ES ): m/z:258
Benzyl-(2-(1-ethoxycarbonyl-2,2,2-trifluoro-1-hydroxyethyl)-cyclohexyli-
dene)amine N-oxide (3g):Mixture of diastereomers: 1H NMR: d 1.25 (t,
3J(H,H) 7.0 Hz), 1.23 1.44 (m, 2H), 1.61 1.71 (m, 1H), 1.72 1,87 (m,
3H), 2.52 2.71 (m, 2H), 3.97 (dd, 3J(H,H) 5.6, 8.8 Hz, 1H; minor
diastereomer), 4.25 (dt, 3J(H,H) 6.0, 2H), 4.38 (t, 3J(H,H) 6.8, 1H;
major diastereomer), 5.10 (2H, Bn; minor diastereomer), 5.14 (d,
[MNa] ; HRMS: m/z:calcd for
C 13H17NNaO3:258.1106; found:
258.1103.
Benzyl-(3-but-3-enyl-3-hydroxy-4-oxo-oct-7-enylidene)amine
N-oxide
(3p): 1H NMR: d 1.68 (ddd, 2J(H,H) 13.7, 3J(H,H) 11.3, 5.1 Hz,
2
3
1H), 1.78 (ddd, J(H,H) 13.7, J(H,H) 11.3, 4.7 Hz, 1H), 1.94 (m, 1H),
2.11 (m, 1H), 2.29 (s, 3H), 2.20 (dt, 3J(H,H) 6.7, 7.2 Hz, 2H), 2.69 (t,
3J(H,H) 7.2 Hz, 2H), 2.86 (dd, 2J(H,H) 15.0, 3J(H,H) 6.4 Hz, 3H),
2
2J(H,H) 14.6, 1H; Bn major diastereomer), 5.20 (d, J(H,H) 14.6, 1H;
Bn major diastereomer), 7.30 7.43 (m, 5H), 8.18 (brs, 1H); 13C NMR: d
14.07 (14.00), 20.63 (21.92), 23.35 (24.34), 25.19 (25.98), 28.03 (29.46), 40.61
(44.18), 63.14 (64.12), 64.68 (64.93), 82.25 (q, 2J(C,F) 28 Hz), 123.81 (q,
2J(C,F) 285 Hz), 127.54, 128.68, 129.22, 133.32, 154.01, 168,38 (167,79);
2
3
2
2.80 (dd, J(H,H) 15.0, J(H,H) 5.3 Hz, 3H), 4.82 (d, J(H,H) 15 Hz,
1H), 4.86 (d, 2J(H,H) 15 Hz, 1H), 4.97 (m, 4H), 5.73 (ddt, 3J(H,H) 17.0,
10.15, 6.6 Hz, 2H), 6.21 (brs, 1H), 6.82 (t, 3J(H,H) 6.0 Hz, 1H);
13C NMR: d 27.50, 27.70, 35.97, 36.21, 38.91, 69.35, 82.86, 115.37, 115.55,
MS (TOF ES ): m/z:396
[
MNa] ; HRMS: m/z:calcd for
C18H22F3NNaO4:396.1399; found:396.1399.
125.77, 129.28, 129.37, 132.58, 136.98, 137.31, 137.78, 215.18; MS (TOF ES ):
Benzyl-(4,4,4-trifluoro-3-hydroxy-3-phenylbutylidene)amine N-oxide (3i):
The enantiomeric excess was determined by HPLC with a Chiralpak AD
column (hexane/iPrOH 90:10; flow rate 1.0 mLminÀ1; tmajor 9.6 min; t
m/z:338 [ MNa] ; HRMS: m/z:calcd for C 19H25NNaO3:338.1732; found:
338.1732.
Benzyl-(2-benzyloxy-3-ethoxycarbonyl-4,4,4-trifluoro-3-hydroxybutylidene)-
13.2 min). 1H NMR: d 3.19 (dd, 3J(H,H) 6.2 Hz, 2J(H,H)
minor
amine N-oxide (3q):First diastereomer: 1H NMR: d 1.21 (t, 3J(H,H)
3
2
14.8 Hz, 1H), 3.44 (dd, J(H,H) 6.2 Hz, J(H,H) 14.8 Hz, 1H), 4.73 (d,
2J(H,H) 14.4 Hz, 1H), 4.78 (d, 2J(H,H) 14.4 Hz, 1H), 6.72 (t,
3J(H,H) 6.0 Hz, 1H), 7.03 7.06 (m, 2H), 7.26 7.38 (m, 6H), 7.58 7.61
(m, 2H), 7.95 (brs, 1H); 13C NMR: d 34.22, 68.88, 78.68 (q, 2J(C,F)
27 Hz), 125.32 (q, 1J(C,F) 285 Hz), 126.76, 128.60, 128.88, 129.05, 129.25,
3
2
7.2 Hz, 3H), 4.14 (dq, J(H,H) 7.2 Hz, J(H,H) 10.8 Hz, 1H), 4.32 (dq,
3J(H,H) 7.2 Hz, 2J(H,H) 10.8 Hz, 1H), 4.53 (s, 2H), 4.69 (s, 1H), 4.87
(d, 3J(H,H) 15 Hz, 1H), 4.91 (d, 3J(H,H) 15 Hz, 1H), 5.47 (d,
3
3J(H,H) 8.0 Hz, 1H), 6.89 (t, J(H,H) 8.0 Hz, 1H), 7.21 7.24 (m, 3H),
7.29 7.32 (m, 3H), 7.35 7.41 (m, 5H); 13C NMR: d 14.04, 64.23, 70.62,
71.36, 73.08, 79.96 (q, 2J(C,F) 28 Hz), 122.28 (q, 1J(C,F) 285 Hz),
128.19, 128.35, 128.67, 129.28, 129.52, 129.60, 132.32, 133.72, 137.17,
129.38, 132.02, 136.32, 138.18; MS (TOF ES ): m/z:346 [ MNa] ; HRMS:
m/z:calcd for C 17H16F3NNaO2:346.1031; found:346.1035.
Benzyl-(3,3-bis(ethoxycarbonyl)-3-hydroxypropylidene)amine
N-oxide
167.40; MS (TOF ES ): m/z:448 [ MNa] ; HRMS: m/z:calcd for
(3j): 1H NMR: d 1.16 (t, 3J(H,H) 7.2 Hz, 6H), 3.12 (d, 3J(H,H)
6.9 Hz, 2H), 4.14 (m, 3J(H,H) 7.2 Hz, 4H), 4.84 (s, 2H), 6.08 (s, 1H),
6.89 (t, 3J(H,H) 6.0 Hz, 1H), 7.24 7.38 (m, 5H); 13C NMR: d 14.13,
33.48, 62.71, 69.16, 78.91, 129.11, 129.21, 129.37, 132.69, 135.58, 169.81; MS
C21H22F3NNaO5:448.1348; found:448.1348.
Second diastereomer: 1H NMR: d 1.20 (t, 3J(H,H) 7.2 Hz, 3H), 4.14
(dq, 3J(H,H) 7.2, 2J(H,H) 10.4 Hz, 1H), 4.23 (dq, 3J(H,H) 7.2,
2J(H,H) 10.4 Hz, 1H), 4.53 (d, 3J(H,H) 12 Hz, 1H), 4.66 (d,
3J(H,H) 12 Hz, 1H), 4.76 (d, 3J(H,H) 13.6 Hz, 1H), 4.80 (d,
(TOF ES ): m/z:346 [ MNa] ; HRMS: m/z:calcd for C 16H21NNaO6:
346.1267; found:346.1270.
3
3J(H,H) 13.6 Hz, 1H), 5.43 (d, J(H,H) 6.8 Hz, 1H), 5.44 (s, 1H), 6.72
Benzyl-(3-ethoxycarbonyl-3-hydroxy-3-phenylpropylidene)amine N-oxide
(3k): 1H NMR: d 1.16 (t, 3J(H,H) 7.2 Hz, 3H), 3.22 (dd, 3J(H,H)
5.8 Hz, 2J(H,H) 16.0 Hz, 1H), 3.37 (dd, 3J(H,H) 5.8 Hz, 2J(H,H)
16.0 Hz, 1H), 4.14 (m, 3J(H,H) 7.2 Hz, 2H), 4.79 (s, 2H), 6.08 (s, 1H),
6.77 (t, 3J(H,H) 5.8 Hz, 1H), 7.20 (m, 2H), 7.24 7.38 (m, 6H), 7.53 (m,
2H); 13C NMR: d 14.19, 38.07, 62.63, 69.23, 78.88, 125.37, 128.23, 128.67,
(t, 3J(H,H) 6.8 Hz, 1H), 7.25 7.33 (m, 7H), 7.36 7.40 (m, 3H); 13C NMR:
d 13.98, 63.88, 70.04, 73.92, 74.11, 80.11 (q, 2J(C,F) 28 Hz), 123.01 (q,
1J(C,F) 285 Hz), 128.25, 128.43, 128.70, 129.29, 129.62, 129.72, 132.04,
135.35, 137.05, 166.95; MS (TOF ES ): m/z:448 [ MNa] ; HRMS: m/z:
calcd for C21H22F3NNaO5:448.1348; found:448.1352.
129.11, 129.16, 129.18, 132.72, 136.61, 141.36, 174.03; MS (TOF ES ): m/z:
Benzyl-(2-(tert-butyloxycarbonylamino)-3-ethoxycarbonyl-4,4,4-trifluoro-
3-hydroxybutylidene)amine N-oxide (3r):Mixture of diastereomers:
1H NMR: d 1.14 (t, 3J(H,H) 7.2 Hz, 3H), 1.27 (t, 3J(H,H) 7.2 Hz,
3H), 1.36 (s, 9H), 1.39 (s, 9H), 4.08 (q, 3J(H,H) 7.2 Hz, 2H), 4.26 (q,
3J(H,H) 7.2 Hz, 2H), 4.85 (s, 2H), 4.90 (s, 2H), 5.26 (dd, 3J(H,H) 4.4,
9.2 Hz, 1H), 5.92 (d, 3J(H,H) 8.8 Hz, 1H), 6.12 (d, 3J(H,H) 8.8 Hz,
1H), 7.00 (d, 3J(H,H) 4.4 Hz, 1H), 7.31 7.37 (m, 2H), 7.40 7.42 (m, 3H),
7.75 (brs, 1H); 13C NMR: d 14.02, 28.26, 50.28, 63.43, 63.90, 69.69, 81.20,
350 [MNa] ; HRMS: m/z:calcd for C 19H21NNaO4:350.1368; found:
350.1375.
Benzyl-(3-allyloxycarbonyl-3-hydroxy-3-phenylpropylidene)amine N-ox-
ide (3l): 1H NMR: d 1.32 (s, 3H), 2.22 (s, 3H), 3.25 (dd, 3J(H,H)
5.6 Hz, 2J(H,H) 16.0 Hz, 1H), 3.39 (dd, 3J(H,H) 5.6 Hz, 2J(H,H)
3
16.0 Hz, 1H), 4.59 (m, 2H), 4.81 (s, 2H), 5.15 (d, J(H,H) 10.4 Hz, 1H),
5.16 (d, 3J(H,H) 17.2 Hz, 1H), 5.78 (ddt, 3J(H,H) 6.0, 10.4, 17.2 Hz,
1H), 6.18 (s, 1H), 6.77 (t, 3J(H,H) 5.6 Hz, 1H), 7.20 7.23 (m, 2H), 7.26
7.39 (m, 6H), 7.53 7.56 (m, 2H); 13C NMR: d 38.10, 66.82, 69.24, 79.20,
119.03, 125.39, 128.30, 128.69, 129.14, 129.21, 129.22, 131.43, 132.62, 136.55,
1
122.91 (q, J(C,F) 286 Hz), 129.29, 129.51, 129.67, 131.53, 135.56, 155.60,
167.36; MS (TOF ES ): m/z:457 [ MNa] ; HRMS: m/z:calcd for
C19H25F3N2NaO6:457.1562; found:457.1564.
141.26, 173.69; MS (TOF ES ): m/z:362 [ MNa] ; HRMS: m/z:calcd for
Benzyl-(3,3-bis(ethoxycarbonyl)-2-methyl-3-hydroxypropylidene)amine
N-oxide (3s):The enantiomeric excess was determined by HPLC with a
Chiralpak AS column (hexane/iPrOH 80:20; flow rate 1.0 mLminÀ1
;
tmajor 13.8 min; tminor 18.5 min); [a]RDT À10.7 (c 11.9 g per 100 mL
in CHCl3); 1H NMR: d 1.07 (t, 3J(H,H) 7.2 Hz, 3H), 1.08 (d, 3J(H,H)
6.8 Hz, 3H), 1.18 (t, 3J(H,H) 7.2 Hz, 3H), 3.80 (dq, 3J(H,H) 6.8 Hz,
1H), 4.02 (m, 2H), 4.16 (m, 2H), 4.78 (s, 2H), 5.55 (brs, 1H), 6.84 (d,
3J(H,H) 6.8 Hz, 1H), 7.19 7.32 (m, 5H); 13C NMR: d 10.6, 13.9, 14.1,
37.1, 62.5, 62.8, 69.4, 80.8, 128.9 (2C), 128.9, 129.1 (2C), 133.1, 139.4, 169.5,
C20H21NNaO4:362.1368; found:362,1366.
Benzyl-(3-hydroxy-4-oxo-3-methylpentylidene)amine
N-oxide
(3m):
1H NMR: d 1.32 (s, 3H), 2.22 (s, 3H), 2.76 (dd, 3J(H,H) 4.8 Hz,
2J(H,H) 15.2 Hz, 1H), 2.85 (dd, 3J(H,H) 6.0 Hz, 2J(H,H) 15.2 Hz,
3
1H), 4.84 (s, 2H), 6.29 (s, 1H), 6.84 (dd, J(H,H) 6.0, 4.8 Hz, 1H), 7.32
7.39 (m, 5H); 13C NMR: d 24.11, 26.35, 36.88, 69.28, 80.41, 129.26, 129.33,
129.41, 132.59, 137.26, 213.61; MS (TOF ES ): m/z:258 [ MNa] ; HRMS:
m/z:calcd for C 13H17NNaO3:258.1106; found:258.1103.
Chem. Eur. J. 2002, 8, No. 24
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0947-6539/02/0824-5659 $ 20.00+.50/0
5659