116
M. Lamblin et al. / Tetrahedron: Asymmetry 19 (2008) 111–123
(CH), 131.7 (C), 148.2, (C), 149.6 (C), 159.6 (CH@N) ppm.
Anal. Calcd for C13H17NO3: C, 66.36; H, 7.28; N, 5.95.
Found: C, 66.31; H, 7.25; N, 6.11.
1.76 (sext, J = 6.8 Hz, 1H, CH), 2.33 (m, 1H, CH), 3.36
(dd, J = 5.6, 10.6 Hz, 1H, CH2), 3.64 (dd, J = 4.2,
10.6 Hz, 1H, CH2), 3.88 (q, J = 6.6 Hz, 1H, ArCH),
7.26–7.35 (m, 5H, Harom) ppm; 13C NMR (75 MHz,
CDCl3): d 18.7 (CH3), 19.5 (CH3), 24.2 (CH3), 29.4 (CH),
60.1 (CH2), 55.4 (CH), 61.1 (CH), 126.5 (2 · CH), 127.1,
128.5 (2 · CH), 145.8 (C) ppm. Anal. Calcd for
C13H21NO: C, 75.32; H, 10.21; N, 6.76. Found: C, 75.45;
H, 10.22; N, 6.69.
4.2.4. (S)-2-{[1-(3,4-Dimethoxyphenylmethylidene)]amino}-
3-methylbutan-1-ol 14. Mp 105–106 ꢁC (lit.:15c 102–
25
25
104 ꢁC); ½aꢁD ¼ ꢀ41:0 (c 1.06, CHCl3) {lit.:15c ½aꢁD
¼
ꢀ42:0, (c 0.2, MeOH)}.
4.2.5. 3-Methyl-2-{[1-(3,4,5-trimethoxyphenyl) meth-(Z)-yl-
25
idene]amino}butan-1-ol 15. Oil; ½aꢁD ¼ ꢀ13:0 (c 1.11,
4.3.2. (S)-3-Methyl-2-((S)-2-methyl-1-phenylpropyl-amino)-
25
CHCl3); 1H NMR (300 MHz, acetone-d6): d 0.91 (d,
J = 6.7 Hz, 3H, CH3), 0.92 (d, J = 6.7 Hz, 3H, CH3),
1.94 (sext, J = 6.7 Hz, 1H, CH), 2.96–3.02 (m, 1H, CH),
3.15 (br s, 1H, OH), 3.64–3.85 (m, 2H, CH2), 3.77 (s, 3H,
OCH3), 3.87 (s, 6H, 2 · OCH3), 7.10 (s, 2H, Harom), 8.16
(s, 1H, CH@N) ppm; 13C NMR (75 MHz, acetone-d6): d
18.3 (CH3), 19.4 (CH3), 29.9 (CH), 55.5 (2 · OCH3), 59.8
(O CH3), 63.8 (CH2), 78.8 (CH), 105.4 (2 · CH), 132.1
(C), 140.1, (C), 153.5 (2 · C), 160.6 (CH@N) ppm. Anal.
Calcd for C15H23NO4: C, 64.04; H, 8.24; N, 4.98. Found:
C, 63.82; H, 8.07; N, 4.73.
butan-1-ol 21b. ½aꢁD ¼ ꢀ28:8 (c 1.03, CHCl3); H NMR
(300 MHz, CDCl3): d 0.74 (d, J = 6.7 Hz, 3H, CH3),
0.80–0.86 (m, 6H, 2 · CH3), 1.06 (d, J = 6.7 Hz, 3H,
CH3), 1.68 (sext, J = 6.7 Hz, 1H, CH), 1.87 (sext,
J = 6.7 Hz, 1H, CH), 2.13 (m, 1H, CH), 3.31 (d,
J = 7.6 Hz, 1H, ArCH), 3.44 (dd, J = 3.1, 10.8 Hz, 1H,
CH2), 3.62 (dd, J = 4.0, 10.8 Hz, 1H, CH2), 7.19 (d,
J = 6.7 Hz, 2H, Harom), 7.24–7.35 (m, 3H, Harom) ppm;
13C NMR (75 MHz, CDCl3): d 19.1 (CH3), 19.4 (CH3),
19.8 (CH3), 20.2 (CH3), 29.3 (CH), 34.5 (CH), 59.1
(CH2), 61.0 (CH), 66.5 (CH), 126.8 (CH), 127.1 (2 · CH),
128.1 (2 · CH), 143.1 (C) ppm. Anal. Calcd for
C15H25NO: C, 76.55; H, 10.71; N, 5.95. Found: C, 76.71;
H, 10.69; N, 5.78.
1
4.2.6. (S)-2-{[1-(4-Isopropoxy-3,5-dimethoxyphenyl)-meth-
ylidene]amino}-3-methylbutan-1-ol 16. Mp 101–102 ꢁC;
25
½aꢁD ¼ ꢀ80:1 (c 0.40, CHCl3); 1H NMR (300 MHz,
CDCl3): d 0.86 (d, J = 6.9 Hz, 3H, CH3), 0.94 (d,
J = 6.6 Hz, 3H, CH3), 1.29 (d, J = 6.1 Hz, 3H, CH3),
1.31 (d, J = 6.1 Hz, 3H, CH3), 1.94 (sept, J = 6.7 Hz, 1H,
CH), 2.92 (dt, J = 3.1, 8.2 Hz, 1H, CH), 3.79 (dd,
J = 3.1, 11.3 Hz, 1H, CH2), 3.84 (s, 6H, 2 · OCH3), 3.90
(br s, 1H, OH), (sext, J = 6.7 Hz, 1H, CH), 3.92 (dd,
J = 3.2, 11.3 Hz, 1H, CH2), 4.41 (sext, J = 6.1 Hz, 1H,
CH), 6.84 (s, 2H, Harom), 7.95 (s, 1H, CH@N) ppm; 13C
NMR (75 MHz, CHCl3): d 19.4 (CH3), 19.7 (CH3), 22.4
(CH3), 22.5 (CH3), 30.1 (CH), 56.1 (2 · OCH3), 64.5
(CH2), 75.5 (CH), 79.3 (CH), 105.2 (2 · CH), 130.8 (C),
138.2, (C), 153.8 (2 · C), 162.0 (CH@N) ppm. Anal. Calcd
for C17H27NO4: C, 65.99; H, 8.80; N, 4.53. Found: C,
65.87; H, 8.98; N, 4.77.
4.3.3. (S)-2-[(S)-1-(3-Methoxyphenyl)ethylamino]-3-methyl-
25
1
butan-1-ol 21c. ½aꢁD ¼ ꢀ22:1 (c 1.09, CHCl3); H NMR
(300 MHz, CDCl3): d 0.86 (d, J = 6.8 Hz, 3H, CH3), 0.92
(d, J = 6.8 Hz, 3H, CH3), 1.36 (d, J = 6.5 Hz, 3H, CH3),
1.75 (sext, J = 6.8 Hz, 1H, CH), 2.32 (q, J = 5.1 Hz, 1H,
CH), 3.36 (dd, J = 5.1, 10.5 Hz, 1H, CH2), 3.63 (dd,
J = 4.1, 10.5 Hz, 1H, CH2), 3.82 (s, 3H, OCH3), 3.85 (q,
J = 6.8 Hz, 1H, ArCH), 6.80 (d, J = 8.1 Hz, 1H, Harom),
6.85–6.90 (m, 2H, Harom), 7.26 (t, J = 8.2 Hz, 1H, Harom
)
ppm; 13C NMR (75 MHz, CDCl3): d 18.7 (CH3), 19.6
(CH3), 24.3 (CH3), 29.4 (CH), 55.2 (CH), 55.4 (OCH3),
60.0 (CH2), 61.1 (CH), 112.2 (CH), 112.25 (CH), 118.8
(CH), 129.5 (CH), 147.6 (C), 159.7 (C) ppm. Anal. Calcd
for C14H23NO2: C, 70.85; H, 9.77; N, 5.90. Found: C,
70.62; H, 10.02; N, 5.74.
4.3. Synthesis of aminoalcohols 21a–i
4.3.4. (S)-2-[(S)-1-(3-Methoxyphenyl)pentylamino]-3-meth-
25
A solution of the appropriate organolithium (MeLi, n-
BuLi or PhLi) derivative (31 mmol) was added dropwise
to a solution of imines 11–16 (10 mmol) in Et2O (60 mL)
at 0 ꢁC. The solution was then stirred at rt for 20 h. For
21b and 21i, i-PrMgBr (2 M solution in THF, 31 mmol,
15.5 mL) was added dropwise to a solution of imines 11,
15 (10 mmol) in THF (60 mL) at 0 ꢁC and the solution
was then stirred at 50 ꢁC for 20 h. The reaction mixture
was carefully quenched with water, and the ethereal layer
washed with water (30 mL) and brine (20 mL). Evapora-
tion of the solvents in vacuo left an oily residue, which
was purified by flash column chromatography using a mix-
ture of Et2O–Et3N–hexanes (50:10:40) as eluent to furnish
a pale yellow oil.
ylbutan-1-ol 21d. ½aꢁD ¼ ꢀ17:1 (c 1.01, CHCl3); 1H
NMR (300 MHz, CDCl3): d 0.84–0.91 (m, 9H, 3 · CH3),
1.05–1.37 (m, 4H, 2 · CH2), 1.50–1.83 (m, 3H, CH + CH2),
2.45 (m, 1H, CH), 3.38 (dd, J = 4.1, 10.6 Hz, 1H, CH2),
3.56–3.64 (m, 2H, CH + CH2), 3.82 (s, 3H, OCH3), 6.79–
6.84 (m, 3H, Harom), 7.25 (t, J = 8.0 Hz, 1H, Harom) ppm;
13C NMR (75 MHz, CDCl3): d 14.0 (CH3), 18.9 (CH3),
19.6 (CH3), 55.1 (OCH3), 22.7 (CH2), 28.8 (CH2), 29.4
(CH), 38.0 (CH2), 59.7 (CH2), 60.5 (CH), 60.9 (CH),
112.0 (CH), 112.8 (CH), 119.4 (CH), 129.4 (CH), 146.4
(C), 159.7(C) ppm. Anal. Calcd for C17H29NO2: C,
73.07; H, 10.46; N, 5.01. Found: C, 72.98; H, 10.41; N,
5.22.
4.3.5. (S)-2-((S)-1-Benzo[1,3]dioxol-5-ylethylamino)-3-meth-
25
4.3.1.
(S)-3-Methyl-2-((S)-1-phenylethylamino)butan-1-ol
ylbutan-1-ol 21e. ½aꢁD ¼ ꢀ51:8 (c 1.00, CHCl3); 1H NMR
25
1
21a. ½aꢁD ¼ ꢀ12:6 (c 1.04, CHCl3); H NMR (300 MHz,
CDCl3): d 0.86 (d, J = 6.8 Hz, 3H, CH3), 0.92 (d,
J = 6.8 Hz, 3H, CH3), 1.38 (d, J = 6.6 Hz, 3H, CH3),
(300 MHz, CDCl3): d 0.84 (d, J = 6.8 Hz, 3H, CH3), 0.89
(d, J = 6.8 Hz, 3H, CH3), 1.30 (d, J = 6.5 Hz, 3H, CH3),
1.73 (sext, J = 6.8 Hz, 1H, CH), 2.29 (m, 1H, CH), 3.17