N,N-Dicyclohexyl-2-[(2S,4S,5R)-3,4-dimethyl-5-
phenyloxazolidin-2-yl]-6-formyl-p-anisamide (20)
135.9, 159.6, 165.5 (C, CON(cHex)2), 189.1 (C, 2 × CHO). m/z
(CI) 372 (MH+, 100%).
A solution of aldehyde 19 (2.469 g, 7.19 mmol) and (1R,2S)-(−)-
ephedrine (2.376 g, 14.38 mmol) in toluene (90 mL) was heated
at reflux for 20 h. After cooling to room temperature, the mixture
was poured on a column of neutral alumina and eluted (5–20%
EtOAc–petroleum ether solvent gradient) to yield the oxazolidine
20 as yellow oil (3.502 g, 99%). dH (300 MHz, C6D6) 0.35 (3H,
d, J 6.3 Hz, NCHCH3), 0.48 (3H, br m), 1.02 (8H, br m), 1.30
(2H, br), 1.44 (1H, br d, J 12.1 Hz), 1.59 (3H, br), 1.72 (1H, br d,
J 11.3 Hz), 1.88 (3H, s, NCH3), 2.39 (1H, q, J 6.5 Hz, NCHCH3),
2.74 (1H, br m), 2.94 (2H, br m), 3.09 (3H, s, OCH3), 3.18 (1H,
br m), 4.68 (1H, d, J 8.1 Hz, OCHPh), 4.94 (1H, s, CH(O)N),
6.53 (1H, dd, J 2.6, 8.4 Hz, H-5), 6.83 (4H, m, 3 × Har, H-6), 7.12
(2H, d, J 6.9 Hz), 7.55 (1H, d, J 2.5 Hz, H-3). dC (75 MHz, C6D6)
14.9, 24.9, 25.1, 25.4, 25.5, 26.7, 29.9, 30.0, 30.8, 31.2, 35.7, 54.3,
55.7, 59.3, 63.7, 82.3, 94.4, 112.8, 114.8, 126.0, 133.8, 136.4, 140.2,
159.6, 169.5.
N,N-Dicyclohexyl-2-[(2S,4S,5R)-3,4-dimethyl-5-
phenyloxazolidin-2-yl]-6-[(S)-p-toluenesulfinyl]-p-anisamide (28)
sec-BuLi (1.00 mL, 1.30 mmol) was added to a solution of
oxazolidine 20 (0.531 g, 1.08 mmol) in dry THF (11 mL) at
−78 ◦C and the solution was stirred for 1 h. (−)-Menthyl p-
toluenesulfinate23 (0.636 g, 2.16 mmol) was slowly added at
−78 ◦C. After 1 h, water (10 mL) was added and the mixture
was extracted with EtOAc. The combined organic fractions were
washed with water (20 mL) and brine (10 mL), dried over MgSO4
and concentrated under reduced pressure. Purification by flash
chromatography (10% EtOAc–petroleum ether) gave the sulfoxide
28 as a colourless oil (0.476 g, 70% yield). dH (300 MHz, C6D6) 0.33
(3H, d, J 6.5 Hz, NCHCH3), 0.47 (3H, br m), 1.04 (9H, br m), 1.30
(3H, br), 1.52 (4H, br), 1.62 (3H, s, ArCH3), 1.80 (3H, s, NCH3),
1.83 (1H, br), 2.03 (1H, br), 2.37 (1H, q, J 6.4 Hz, NCHCH3),
2.88 (4H, s, Hcyclohex and OCH3), 3.37 (1H, br m), 4.67 (2H, d,
J 8.1 Hz, OCHPh), 4.81 (1H, s, CH(O)N), 6.65 (1H, d, J 8.1),
6.83 (3H, m, 3 × H ar), 7.10 (2H, d, J 6.9), 7.42 (1H, d, J 2.6, H-3),
7.58 (1H, d, J 2.6), 7.92 (2H, d, J 8.2). dC (75 MHz, C6D6) 13.8,
14.9, 20.6, 24.9, 25.1, 25.4, 25.5, 26.5, 26.6, 29.4, 30.0, 30.9, 31.4,
35.5, 54.4, 56.5, 59.6, 60.3, 63.6, 82.4, 93.9, 109.8, 118.0, 124.3,
129.6, 131.4 136.9, 139.6, 139.9, 143.8, 146.1, 160.5, 166.5.
N,N-Dicyclohexyl-2,6-diformyl-p-anisamide (21)
sec-BuLi (1.08 mL, 1.40 mmol) was added to a solution of
oxazolidine 20 (0.577 g, 1.17 mmol) in dry THF (11 mL) at −78 ◦C
and the solution was stirred for 1 h. DMF (0.127 mL, 1.64 mmol)
was slowly added at −78 ◦C. After 1 h, water (10 mL) was added
and the mixture was extracted with EtOAc. The combined organic
phases were washed with water (20 mL) and brine (10 mL),
dried over MgSO4 and concentrated under reduced pressure.
Purification by flash chromatography (10% EtOAc–petroleum
ether) gave the oxazolidinoaldehyde as a yellow oil (0.362 g, 60%)
as a mixture of endo and exo oxazolidines dH (300 MHz, C6D6)
0.33 (6H, m, 3 × Hcyclohex, NCHCH3), 0.95 (9H, br m), 1.30 (3H,
br), 1.54 (4H, br), 1.84 (1H, br), 1.85 (3H, s, exo NCH3), 1.88
(3H, s, endo NCH3), 2.34 (1H, q, J 6.4, NCHCH3), 2.76 (2H, br),
2.92 (3H, s, OCH3), 4.64 (1H, d, J 8.2, exo OCHPh), 4.68 (1H,
d, J 8.2, exo OCHPh), 4.84 (1H, s, endo CH(O)N), 4.94 (1H, s,
endo CH(O)N), 6.84 (3H, m, 3 × Har), 7.09 (2H, d, J 7.0), 7.31
(1H, d, J 2.7 Hz, H-3), 7.79 (1H, d, J 2.7, H-5), 10.08 (1H, s, endo
CHO), 10.17 (1H, s, exo CHO). dC (75 MHz, C6D6) 14.9, 24.7,
25.0, 25.2, 25.4, 26.6, 26.6, 26.7, 29.4, 29.8, 30.7, 30.9, 35.5, 54.5,
56.4, 59.9, 63.7, 82.4, 93.6, 112.2, 120.9, 127.0, 133.6, 136.2, 137.5,
139.6, 159.7, 166.5, 189.3.
N,N-Dicyclohexyl-2-formyl-6-[(S)-p-toluenesulfinyl]-p-anisamide
(29)
Trifluoroacetic acid (0.770 mL, 10.00 mmol) and water (0.180 mL,
10.00 mmol) were added to a solution of oxazolidine 28 (0.318 g,
0.50 mmol) in THF (5 mL). The mixture was stirred for 2 h and
concentrated under reduced pressure. Rapid filtration thrrough
silica (EtOAc–petroleum ether 1 : 1) removed the ephedrine. The
residue was dissolved in EtOAc and the solution was washed with
saturated sodium carbonate, dried over MgSO4 and concentrated
under reduced pressure. Purifiation by flash chromatography (20%
EtOAc–petroleum ether) gave the aldehyde 29 as pale yellow oil
(0.156 g, 65%). dH (300 MHz, CDCl3) 0.91 (3H, br m), 1.21 (3H, br
m), 1.53 (8H, br m), 1.75 (3H, br m), 1.97 (1H, br m), 2.25 (3H, s,
ArCH3), 2.63 (2H, br m), 3.12 (2H, br m), 3.74 (3H, s, OCH3),
7.11 (3H, m), 7.41 (1H, d, J 2.7 Hz, H-3), 7.52 (1H, d, J 2.7 Hz,
H-5), 7.60 (1H, d, J 8.2 Hz), 9.97 (1H, s, CHO).
Trifluoroacetic acid (0.732 mL, 9.5 mmol) and water (0.171 mL,
9.5 mmol) were added to a solution of this oxazolidinoaldehyde
(0.246 g, 0.47 mmol) in THF (5 mL). The reaction mixture was
stirred for 2 h and concentrated under reduced pressure. The
residue was quickly purified by flash chromatography (EtOAc–
petroleum ether 1 : 1) to remove the ephedrine. The resulting
residue was dissolved in EtOAc and the solution was washed
saturated sodium carbonate, dried over MgSO4 and concentrated
under reduced pressure. Purification by flash chromatography
(20% EtOAc–petroleum ether) gave the dialdehyde 21 as colourless
oil (0.148 g, 85% yield). mmax/cm−1 2931, 2856, 1700, 1629, 1436,
1364, 1317, 1285, 732. dH (300 MHz, CDCl3) 0.83 (3H, m), 1.22
(3H, br m), 1.46 (5H, br m), 1.61 (5H, br m), 1.80 (2H, br m), 2.65
(2H, br m), 2.93 (1H, m), 3.08 (1H, br m), 3.87 (3H, s, OCH3), 7.61
(2H, s, H-3 and H-5), 10.08 (2H, s, CHO). dC (75 MHz, CDCl3)
24.8, 25.1, 25.4, 26.4, 29.5, 30.7, 55.9, 56.9, 60.6, 118.8, 133.9,
N,N-Dicyclohexyl-2–[(2ꢀR,4ꢀS)-2-phenylperhydropyrrolo-(1,2c)-
imidazol-3-yl]-6-[(S)-p-toluenesulfinyl]-p-anisamide (30)
A solution of aldehyde 29 (0.120 g, 0.28 mmol) and (S)-diamine 12
(0.070 g, 0.4 mmol) in toluene (3 mL) was heated at reflux for 20 h.
After cooling to room temperature, the mixture was poured onto a
column of neutral alumina and eluted (5–20% EtOAc–petroleum
ether solvent gradient) to produce the imidazolidine 30 as waxy
yellow solid (0.172 g, quantitative yield). dH (300 MHz, C6D6) 0.62
(3H, br m), 0.80–1.48 (20H, m), 1.55 (3H, s, ArCH3), 1.72 (2H,
m), 2.00 (1H, q, J 8.9 Hz), 2.33 (1H, br m), 2.58 (1H, t, J 8.9 Hz),
2.65 (3H, s, OCH3), 2.86 (2H, br m), 3.26 (2H, br m), 5.75 (1H, s),
6.37 (2H, d, J 8.2 Hz), 6.66 (1H, d, J 2.6 Hz, H-3), 6.87 (5H, br
m), 7.23 (1H, d, J 2.6 Hz, H-5), 7.89 (2H, d, J 8.2). dC (75 MHz,
CDCl3) 20.5, 23.4, 25.2, 25.5, 25.7, 25.8, 26.6, 27.4, 29.0, 30.8, 30.9,
This journal is
The Royal Society of Chemistry 2006
Org. Biomol. Chem., 2006, 4, 444–454 | 453
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