F
R. Pemha et al.
Paper
Synthesis
IR (KBr): 3463, 2929, 2921, 2852, 1740, 1470, 1368, 1279, 1257, 1165,
HRMS (ESI): m/z calcd for C20H38O4Na [M + Na]+: 365.2783; found:
365.2779.
1097, 795 cm–1
.
Anal. Calcd for C20H38O4: C, 70.13; H, 11.18. Found: C, 70.20; H, 11.09.
15
1H NMR (400 MHz, CDCl3): = 4.83 (dddd, J =7.4, 6.8, 5.5, 5.4 Hz, 1 H),
3.07–2.98 (m, 2 H), 1.88–1.78 (m, 2 H), 1.71–1.60 (m, 4 H), 1.49 (s, 9
H), 1.32–1.25 (m, 25 H), 0.88 (pseudo t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): = 153.4 (C=O), 81.9 (C), 75.5 (CH), 54.0
(CH), 52.5 (CH), 34.6 (CH2), 34.0 (CH2), 32.9 (2 × CH2), 32.3 (CH2), 31.9
(2 × CH2), 29.7 (2 × CH2), 29.6 (CH2), 29.5 (CH2), 29.4 (CH2), 29.3 (CH2),
27.8 (3 × CH3), 25.4 (CH2), 22.2 (CH2), 14.1 (CH3), 13.3 (CH3).
18
White crystals (minor amount); mp 97–98 °C; Rf = 0.28 (PE/acetone
80:20) [α]D +3.0; [α]578 +2.8; [α]546 +3.0; [α]436 +5.4; [α]365
21
21
21
21
21
21
21
21
21
+8.9 (c 2.7, CH2Cl2) [α]D +6.4; [α]578 +6.1; [α]546 +6.7; [α]436
+11.5; [α]36521 +17.8 (c 1.4, THF).
IR (KBr): 3523, 2918, 2851, 1757, 1471, 1380, 1221, 1059, 782, 718
cm–1
.
1H NMR (400 MHz, CDCl3): = 4.42 (ddd, J = 8.9, 6.9, 3.8 Hz, 1 H), 4.26
(dq, J = 6.9, 6.1 Hz, 1 H), 3.82–2.78 (m, 1 H), 2.49 (s, 1 H), 1.98 (ddd,
J = 14.4, 4.1, 3.8 Hz, 1 H), 1.83–1.70 (m, 3 H), 1.62 (ddd, J = 14.4, 4.1,
3.8 Hz, 1 H), 1.50–1.34 (m, 3 H), 1.32–1.25 (m, 23 H), 0.88 (pseudo t,
J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): = 149.3 (C=O), 82.5 (CH), 78.5 (CH), 69.1
(CH), 52.5 (CH2), 35.2 (CH2), 31.9 (CH2), 29.8 (CH2), 29.67 (CH2), 29.6
(2 × CH2), 29.5 (CH2), 29.4 (CH2), 29.3 (CH2), 29.2 (CH2), 29.1 (CH2),
24.4 (CH2), 22.8 (CH2), 18.2 (CH3), 14.1 (CH3).
16
1H NMR (400 MHz, CDCl3): = 4.83 (dddd, J = 7.4, 6.8, 5.5, 5.4 Hz, 1 H),
3.07–2.98 (m, 2 H), 1.88–1.78 (m, 2 H), 1.71–1.60 (m, 4 H), 1.49 (s, 9
H), 1.32–1.25 (m, 25 H), 0.88 (pseudo t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): = 153.3 (C=O), 81.8 (C), 75.3 (CH), 53.4
(CH), 52.0 (CH), 34.6 (CH2), 34.0 (CH2), 32.8 (2 × CH2), 32.2 (CH2), 31.9
(2 × CH2), 29.7 (CH2), 29.6 (2 × CH2), 29.5 (CH2), 29.4 (CH2), 29.4 (CH2),
27.8 (3 × CH3), 25.4 (CH2), 22.2 (CH2), 14.1 (CH3), 13.3 (CH3).
HRMS (ESI): m/z calcd for C24H46O4Na [M + Na]+: 421.3283; found:
421.3288; m/z calcd for C20H38O4Na [M – C4H8 + Na]+: 365.2662;
found: 365.2659.
HRMS (ESI): m/z calcd for C20H38O4Na [M + Na]+: 365.2783; found:
365.2774.
Anal. Calcd for C24H46O4: C, 72.31; H, 11.63: Found: C, 70.16; H, 11.64.
(2R)-1-[(4R,6R)-2-Oxo-6-tetradecyl-1,3-dioxan-4-yl]ethyl Meth-
anesulfonate (21)
(4R,6R)-4-[(R)-1-Hydroxyethyl]-6-tetradecyl-1,3-dioxan-2-one
(17) and (4S,6R)-4-[(S)-1-Hydroxyethyl]-6-tetradecyl-1,3-dioxan-
2-one (18)
To a cooled solution (–20 °C) of 17 (153 mg, 0.45 mmol) in DCM (2.7
mL) was added Et3N (129 L, 0.92 mmol, 2.05 equiv) and a solution of
MsCl (56 L, 0.72 mmol, 1.6 equiv) in DCM (0.5 mL). The resulting
white suspension was left with stirring for 3 h 30 min at –20 °C. TLC
monitoring showed completion of the reaction and distilled H2O (120
mL) was added when the temperature had reached –5 °C. Extraction
was done with DCM and the combined organic layers were dried
(Na2SO4). DCM was evaporated under reduced pressure to provide 21
as a colorless oil and was used without further purification; yield:
175.7 mg (94%); Rf = 0.69 (PE/acetone 80:20).
To a cooled solution (–40 °C) of a mixture of epoxycarbonate 15/16
(780.6 mg, 1.95 mmol) in DCM (39 mL) was slowly added a solution of
BF3·OEt2 (279 mg, 1.966 mmol, 1.01 equiv) in CH2Cl2 (10 mL) under N2
and the stirring was continued for 15 min at the same temperature.
TLC monitoring showed completion of the reaction and sat. aq
NaHCO3 (15.1 mL) was added to the mixture. Extraction was done
with EtOAc/PE (80:20). The combined organic layers were washed
with brine and dried (Na2SO4). The solvent was evaporated under re-
duced pressure and the crude purified by column chromatography on
silica gel (0 → 2% MeOH in DCM) to provide successively compounds
17 (270.86 mg, 72%) and 18 (105.34 mg, 28%) in an enantiomeric ratio
72:28 as white crystals in 56% overall yield, along with a small
amount of the starting material.
1H NMR (400 MHz, CDCl3): = 4.86 (dq, J = 6.9, 6.1 Hz, 1 H), 4.45–4.37
(m, 2 H), 3.06 (s, 3 H), 2.04–2.01 (m, 2 H), 1.83–1.73 (m, 2 H), 1.49 (d,
J = 6.1 Hz), 3 H), 1.44–1.26 (m, 24 H), 0.88 (pseudo t, J = 6.9 Hz, 3 H).
(4R,6R)-4-[(S)-1-Azidoethyl]-6-tetradecyl-1,3-dioxan-2-one (22)
In a dried flask were introduced compound 21 (175.7 mg, 0.42 mmol),
NaN3 (136 mg, 2.1 mmol, 5 equiv), and DMSO (2.1 mL). The flask was
purged under N2 and the contents were refluxed at 80 °C. The color
changed from cream at the beginning to orange after stirring for 20 h
at 80 °C. TLC monitoring showed completion of the reaction and ex-
traction was done with EtOAc/PE (80:20). The combined organic lay-
ers were washed with brine, filtered over a short plug of silica gel, and
dried (Na2SO4). The solvent was evaporated under reduced pressure to
provide 22 as a yellow oil; yield: 140.7 mg (94%); Rf = 0.47 (PE/acetone
90:10); []D21 –4.3, []57821 –4.7, []54621 –5.1, []43621 –7.2 (c 1.5,
CH2Cl2); []D21 –8.5, []57821 –9.4, []54621 –10.4, []43621 –15.8 (c 1.47,
THF).
17
White crystals (major amount); mp 70 °C; Rf = 0.35 (PE/acetone
80:20); []D21 –31.9, []57821 –33.3, []54621 –37.6, []43621 –62.2,
[]36521 –93,7 (c 1,5, CH2Cl2); []D21 –33.9, []57821 –35,6, []54621 –40.3,
[]43621 –66.2, []36521 –98.8 (c 1.5, THF).
IR (KBr): 3447, 2920, 2851, 1712, 1473, 1406, 1376, 1268, 1257, 1242,
1223, 1170, 1104, 1082, 774, 719, 684, 485 cm–1
.
1H NMR (400 MHz, CDCl3): = 4.42 (dddd, J = 11.6, 7.2, 5.4, 2.9 Hz, 1
H), 4.26 (ddd, J = 11.9, 7.2, 5.4, 2.9 Hz, 1 H), 3.92–3.82 (m, 1 H), 1.90
(ddd, J = 14.3, 3.5, 2.9 Hz, 1 H), 1.71 (ddd, J = 14.1, 3.4, 2.9 Hz, 1 H),
1.68–1.60 (m, 2 H), 1.47 (d, J = 6.5 Hz, 3 H), 1.45–1.37 (m, 1 H), 1.32–
1.27 (m, 24 H), 0.88 (pseudo t, J = 6.9 Hz, 3 H).
IR (KBr): 2925, 2854, 2103 (N3), 1805, 1466, 1459, 1376, 1187, 1074,
774 cm–1
.
1H NMR (400 MHz, CDCl3): = 4.46 (dq, J = 7.0, 6.2 Hz, 1 H), 4.34 (ddd,
J = 7.2, 7.0, 5.5 Hz, 1 H), 3.48 (dddd, J = 7.2, 6.6, 6.5, 5.6 Hz, 1 H), 2.02
(ddd, J = 14.6, 7.3, 7.2 Hz, 1 H), 1.84 (ddd, J = 14.6, 5.5, 5.4 Hz, 1 H),
1.65–1.60 (m, 4 H), 1.49 (d, J = 4.8 Hz, 3 H), 1.44–1.33 (m, 2 H), 1.31–
1.26 (m, 20 H), 0.88 (pseudo t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): = 154.6 (C=O), 81.0 (CH), 79.0 (CH), 68.0
(CH), 40.7 (CH2), 38.2 (CH2), 31.9 (CH2), 29.7 (CH2), 29.6 (3 × CH2), 29.5
(2 × CH2), 29.4 (2 × CH2), 29.3 (CH2), 25.2 (CH2), 22.7 (CH2), 18.8 (CH3),
14.1 (CH3).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G