1988
Helvetica Chimica Acta – Vol. 96 (2013)
reaction, and the mixture was extracted with CH2Cl2. The combined org. extracts were washed with
brine, dried (Na2SO4), concentrated in vacuo, and the resulting aldehyde was purified by FC for
immediate use in the next reaction. To a soln. of the above aldehyde (5.0 g, 19 mmol) in anh. DMSO
(75 ml), were added PhNO (2.3 g, 21 mmol, 1.1 equiv) and l-proline (1.02 g, 8.9 mmol, 0.45 equiv.)
consecutively at 208 under N2. The mixture was stirred vigorously for 25 min (the color of the mixture
changed from green to yellow during this time), then cooled to 08, and diluted with MeOH (380 ml). To
this soln., NaBH4 (2.2 g, 59 mmol) was added portionwise, and stirring was continued for another 1 h at
r.t., and then the mixture was cooled to 08. At this temp., NH4Cl (0.29 g, 6 mmol) and Cu(OAc)2 (0.36 g,
2 mmol) were added sequentially. The resulting mixture was stirred for 24 h at r.t., and then MeOH was
evaporated under vacuum. The mixture was diluted with H2O (100 ml) and extracted with Et2O (3 ꢁ
200 ml). The combined org. layers were washed with H2O and sat. NaCl soln., dried (Na2SO4) and
concentrated in vacuum. The residue was purified by FC to give 3 (3.48 g, 65%). Yellowish liquid. Rf
(AcOEt/hexane 1:1) 0.2. [a]2D7 ¼ þ0.65 (c ¼ 0.46, CHCl3). IR (neat): 3438, 2924, 2855, 1644, 1456, 1202,
1092. 1H-NMR (CDCl3, 300 MHz): 5.32 – 5.28 (m, 2 H); 3.71 – 3.57 (m, 2 H); 3.42 – 3.36 (m, 1 H); 2.04 –
1.95 (m, 4 H); 1.45 – 1.20 (m, 20 H); 0.89 (t, J ¼ 6.8, 3 H). 13C-NMR (CDCl3, 75 MHz): 130.1; 129.5; 72.3;
66.8; 33.1; 31.8; 29.7; 29.6; 29.5; 29.4; 29.3; 29.2; 27.2; 27.1; 25.4; 22.6; 14.0. ESI-MS: 270 (Mþ).
(2R,8Z)-2-Hydroxyheptadec-8-en-1-yl 2,2-Dimethylpropanoate (7). A mixture of 3 (2.0 g 7.4 mmol),
dry pyridine (5 ml) and 4-(dimethylamino)pyridine (DMAP; 150 mg, 1.4 mmol) in dry CH2Cl2 (15 ml)
was stirred under N2. The mixture was cooled to 08, and pivaloyl chloride (0.97 g, 1 ml, 8.1 mmol) was
added dropwise over 15 min. The resulting mixture was further stirred for 1 h at r.t., then the reaction was
quenched with sat. NaHCO3 (10 ml), and the mixture was extracted with CH2Cl2 (3 ꢁ 25 ml). The
combined org. layers were washed with sat. CuSO4 soln. and brine. The org. layer was dried (Na2SO4),
filtered, and concentrated under reduced pressure. The crude product was purified by CC (SiO2) to give
the 7 (2.3 g, 88% yield). Colorless oil. Rf (AcOEt/hexane 2 :8) 0.5. [a]2D5 ¼ ꢀ1.05 (c ¼ 0.66, CHCl3). IR
(neat): 3451, 2924, 2854, 1728, 1660, 1158, 1032, 757. 1H-NMR (CDCl3, 300 MHz): 5.34 – 5.22 (m, 2 H);
4.06 (dd, J ¼ 11.3, 3.0, 1 H ); 3.90 (dd, J ¼ 11.3, 6.7, 1 H); 3.81 – 3.66 (m, 1 H); 2.02 – 1.83 (m, 4 H); 1.46 –
1.17 (m, 21 H); 1.16 (s, 9 H); 0.81 (t, J ¼ 6.7, 3 H). 13C-NMR (CDCl3, 75 MHz): 178.7; 130.0; 129.5; 70.1;
68.5; 34.0; 33.3; 31.8; 29.7; 29.6; 29.5; 29.29; 29.20; 27.1; 27.0; 25.2; 24.8; 22.6; 14.1. ESI-MS: 355 ([M þ
H]þ); 377 ([M þ Na]þ).
(2R,8Z)-2-(Methoxymethoxy)heptadec-8-en-1-yl 2,2-Dimethylpropanoate (8). To a stirred soln. of 7
(500 mg, 1.4 mmol) in anh. CH2Cl2 (10 ml) was added EtNiPr2 (728 mg, 0.97 ml, 5.6 mmol) dropwise at
08, and stirring was continued for 15 min. Then, methoxymethyl chloride (MOMCl) (0.35 ml, 4.2 mmol)
was added slowly at 08 under N2, and the mixture was stirred at r.t. for 6 h. The reaction was quenched
with ice flakes, and the mixture was extracted with CH2Cl2. The org. extracts were washed with brine,
dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by CC (SiO2) to give
8 (528 mg, 94%). Colorless oil. Rf (AcOEt/hexane, 1:9) 0.6. [a]2D5 ¼ þ5.74 (c ¼ 0.36, CHCl3). IR (neat):
2927, 1733, 1453, 1377, 1161, 1036, 760, 537. 1H-NMR (CDCl3, 300 MHz): 5.34 – 5.22 (m, 2 H); 4.63 (dd,
J ¼ 27.1, 6.7, 2 H); 4.11 – 4.04 (m, 1 H); 4.00 – 3.93 (m, 1 H); 3.72 – 3.64 (m, 1 H); 3.32 (s, 3 H); 2.01 – 1.85
(m, 4 H); 1.58 – 1.15 (m, 20 H); 1.14 (s, 9 H); 0.81 (t, J ¼ 6.7, 3 H). 13C-NMR (CDCl3, 75 MHz): 178.0;
130.0; 129.5; 95.9; 75.2; 66.3; 55.5; 38.7; 31.9; 31.8; 29.7; 29.6; 29.5; 2 ꢁ 29.3; 29.0; 2 ꢁ 27.1; 25.1; 22.6; 14.0.
ESI-MS: 421 ([M þ Na]þ).
(2R,8Z)-2-(Methoxymethoxy)heptadec-8-en-1-ol (9). To a stirred soln. of 8 (400 mg, 1.0 mmol) in
dry CH2Cl2 (15 ml) in a 50-ml round-bottom two-neck flask, under N2 at ꢀ 788, was added DIBAL-H;
(2.1 ml, 25% soln. in hexane, 4.0 mmol) dropwise. After 30 min, the reaction (monitored by TLC) was
quenched with MeOH (1.0 ml), and the mixture was transferred to a 250-ml separating funnel containing
a sat. soln. of sodium potassium tartrate (25 ml) and CH2Cl2 (30 ml). The org. layer was separated and
dried (Na2SO4). Evaporation of the solvent, followed by purification by CC (SiO2) afforded pure 9
(277 mg, 88%). Colorless liquid. Rf (AcOEt/hexane 2 :8) 0.3. [a]2D5 ¼ ꢀ13.25 (c ¼ 0.16, CHCl3). IR
(neat): 3382, 2924, 2854, 1647, 1274, 1173, 1119. 1H-NMR (CDCl3, 300 MHz): 5.40 – 5.31 (m, 2 H); 4.71
(dd, J ¼ 24.9, 6.9, 2 H); 3.64 – 3.47 (m, 3 H); 3.43 (s, 3 H); 2.99 (br. s, 1 H); 2.06 – 1.95 (m, 4 H); 1.61 – 1.50
(m, 2 H); 1.48 – 1.23 (m, 18 H); 0.88 (t, J ¼ 6.9, 3 H). 13C-NMR (CDCl3, 75 MHz): 130.0; 129.5; 96.9; 82.4;
65.7; 55.6; 31.8; 31.6; 29.7; 29.69; 29.61; 29.5; 29.3; 29.2; 27.2; 27.0; 25.4; 22.6; 14.1. ESI-MS: 337 ([M þ
Na]þ).