The Journal of Organic Chemistry
Note
hexanes). After 2 h, sat. aqueous Na2SO4 (8.5 mL) was added and the
resulting mixture was adjusted to rt. When precipitation appeared, the
mixture was diluted with Et2O, Celite was added, and stirring was
continued for 1 h. Solids were filtered off and washed with Et2O. The
organic solutions were dried over anhydr. Na2SO4, and solvents were
removed under diminished pressure to afford a mixture of
diastereomeric allyl alcohols 6 (10.3 g, 75%, overall after 3 steps)
pure enough to use in the next step. The analytically pure sample was
obtained by short pad chromatography on silica gel (15% AcOEt in
Method B. To a cooled to −50 °C solution of allylic alcohol 3 (1 g,
8.6 mmol) in 20 mL of THF was added 0.82 mL of CSI (1.34 g, 9.5
mmol). After 1 h, the reaction was carefully quenched with water (10
mL). Extractive workup, filtration through a silica gel pad, and
concentration gave 1.07 g of carbamate 8 (78%).
(S,E)-N-(1-Methoxypent-3-en-2-yl)acetamide (9). To a cooled
to 0 °C solution of allyl carbamate 8 (1.6 g, 10 mmol) and Et3N (8.35
mL, 60 mmol) in 100 mL of THF was added 2.8 mL of TFAA (20
mmol). After 30 min, the reaction mixture was cooled to −20 °C and
20 mL of 3 M soln. of MeMgBr in THF was added. After 4 h, reaction
was quenched carefully by addition of aq. NH4Cl. The organic phase
was separated, and the aqueous one was extracted with EtOAc (6 × 50
mL). The combined organic solutions were dried over Na2SO4, and
solvent was removed under diminished pressure. The residue was
chromatographed on silica gel (CH2Cl2/MeOH 50:1) to afford 1.17 g
1
hexanes). H NMR (400 MHz, CDCl3, mixture of diastereoisomers)
δ: 5.85 (dt, J 16.4, 6.4 Hz, 2 × 1H), 5,60 (dd, J 16.4, 7.2 Hz, 2 × 1H),
4.75 (t, J 3.2 Hz, 1H), 4.60 (t, J 3 Hz, 1H), 4.36−4.32 (m, 2H), 4.20−
4,14 (m, 4H), 3.93−3.90 (m, 2H), 3.52−3.46 (m, 2H), 1.95−1.65 (m,
14H), 1.30 (d, J 6.6 Hz, 3H), 1.22 (d, J 6.3 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ: 133.4, 131.9, 131.3, 129.0, 96.1, 95.3, 71.5, 71.3, 62.5,
62.3, 62.1, 30.7, 30.5, 25.3, 25.2, 19.6, 19.4, 19.3; IR (film) v: 3415,
1022 cm−1; HRMS (ESI-TOF) m/z calcd for C10H18O3Na [M + Na+]
209.1154. Found: 209.1151.
1
of acetamide 9 (74%) as a brown oil. [α]2D0 +6.3 (c 1, CHCl3); H
NMR (500 MHz, CDCl3) δ: 5.80 (s, 1H, NH), 5.72−5.63 (m, 1H,
CH3CHCH), 5.46 (ddd, J 15.4, 6.1, 1.6 Hz, 1H, CH3CHCH),
4.58−4.56 (m, 1H, CHNHAc), 3.46−3.42 (m, 2H, CH2OMe), 3.36 (s,
3H, OCH3), 2.01 (s, 3H, CH3CO), 1.71−1.68 (br d, J 6.1 Hz, 3H,
CH3CHCH); 13C NMR (126 MHz, CDCl3) δ: 169.8, 128.5, 127.8,
74.81, 59.3, 50.7, 23.5, 17.9; IR (film) v: 3284, 1651, 1548, 1126, 966
cm−1; HRMS (ESI-TOF) m/z calcd for C8H15NO2Na [M + Na+]
180.1000. Found 180.0995.
(S,E)-5-Methoxypent-3-en-2-ol (3). Method A. To a suspension
of NaH (45.1 mmol, 1.8 g of 60% disp. in mineral oil) in dry THF
(150 mL) was added a solution of alcohol 6 (37.6 mmol, 7 g) in dry
THF (60 mL). When evolution of hydrogen was finished (ca. 2−3 h),
MeI (45.1 mmol, 6.4 g, 2.8 mL) was added. After stirring for 3 h, the
reaction was quenched carefully with water (50 mL), and the mixture
was stirred for 30 min. Solvent was removed under diminished
pressure, and the aqueous residue was extracted with AcOEt. The
combined organic phases were dried over anhydr. Na2SO4. Removal of
solvent under diminished pressure gave crude methyl ether 7
(diastereomeric mixture), which was used directly in the next step
(yield 90% according to 1H NMR with internal standard). Crude ether
7 was dissolved in dry MeOH (100 mL), and AcCl (5 mol %, 160 μL)
was added dropwise. After 1.5 h, acid was neutralized by addition of
Et3N (1 mL) and stirring was continued for 30 min. After removal of
solvent, the residue was chromatographed on silica gel (50% AcOEt in
hexanes) to afford 3.8 g of alcohol 3 (87%, 2 steps). [α]2D4 +2 (c 1.5,
CH2Cl2); 1H NMR (500 MHz, CDCl3) δ: 5.85−5.66 (m, 2H), 4.38−
4.28 (m, 1H), 3.91 (d, J 5.0 Hz, 2H), 3.34 (s, 3H), 1.28 (d, J 6.4 Hz,
3H); 13C NMR (126 MHz, CDCl3) δ: 137.1, 126.1, 72.4, 68.2, 58.0,
23.2; IR (film) v: 3404, 1123 cm−1; HRMS (ESI-TOF) m/z calcd for
C6H12O2Na [M + Na+] 139.0735. Found: 139.0735.
Method B. To a suspension of NaH (45.1 mmol, 1.8 g of 60% disp.
in mineral oil) in dry THF (150 mL) was added a solution of alcohol 6
(37.6 mmol, 7 g) in dry THF (60 mL). When evolution of hydrogen
was finished (ca. 2−3 h), Me2SO4 (45.1 mmol, 5.8 mL) was added.
After stirring for 4 h, the reaction was quenched as in method A and
the crude product was submitted to the deprotection step. Product 3
was obtained in 75% yield (3.2 g) after 2 steps.
Method C. A two-phase mixture of 50% aq. NaOH (1 g), alcohol 6
(2.1 g, 11.27 mmol), Me2SO4 (1.6 mL, 22 mmol), and TBABr (320
mg, 1 mmol) in 10 mL of CH2Cl2 was stirred vigorously for 20 h. After
extractive workup, the crude ether 8 was directly submitted to the
deprotection step. Product 3 was obtained in 60% yield (0.79 g) after
2 steps.
N-Acetyl-O-methyl-D-serine (10). To a solution of allyl amide 2
(1.15 g, 7.3 mmol) in an acetone/water mixture (5:1, 60 mL) were
added solid NaIO4 (3.2 g, 15 mmol) and RuCl3·H2O (20 mg, 0.09
mmol, 1.5 mol %). After 8 h, the reaction mixture was filtered through
a Celite pad and collected solids were washed with acetone (4 × 10
mL). After removal of solvent, the residue was dissolved in CH2Cl2
(50 mL) and dried over anhydrous Na2SO4, and solvent was removed
under diminished pressure to afford crude amino acid 10 (0.93 g, 79%
1
yield determined by H NMR), which was used directly in the next
step. The analytical sample was obtained by chromatography on silica
gel (CH2Cl2/MeOH 50:1 v/v) as a white solid; mp 108−109 °C
[Lit.6b mp 108−109 °C]. [α]D20 −16.3 (c 1.78, MeOH) [Lit.6a [α]D25
−16.9 (c 1.2, MeOH)]; 1H NMR (600 MHz, CDCl3) δ: 6.50 (d, J 7.5
Hz, 1H), 4.75−4.69 (m, 1H), 3.87 (dd, J 9.5, 3.3 Hz, 1H), 3.63 (dd, J
9.6, 3.6 Hz, 1H), 3.37 (s, 3H), 2.07 (s, 3H); 13C NMR (151 MHz,
CDCl3) δ: 173.5, 171.4, 71.8, 59.5, 52.7, 23.1; IR (film) v: 3334, 1732,
1658, 1546, 1197, 1118 cm−1; HRMS (ESI-TOF) m/z calcd for
C6H11NO4Na [M + Na+] 184.0586. Found: 184.0581. Anal. Calcd for
C6H11NO4 C, 44.72, H, 6.88, N, 8.69. Found C, 44.67, H, 6.82, N,
8.67.
(S,E)-5-Methoxypent-3-en-2-yl 2,2,2-Trichloroacetimidate
(11). To a cooled solution of allyl alcohol 3 (300 mg, 1.15 mmol)
and DBU (30 μL, 30 mg, 0.2 mmol) in CH2Cl2 (15 mL) was added
neat CCl3CN (188 mg, 130 μL, 1.3 mmol). After 30 min, solvent was
removed under reduced pressure and the residue was chromato-
graphed on silica gel (30% AcOEt in hexanes) to afford 11 as a yellow
oil (80%, 240 mg). [α]2D0 −14.2 (c 1.1, CHCl3); H NMR (500 MHz,
1
C6D6) δ: 8.32 (s, 1H), 5.84−5.69 (m, 2H), 5.60−5.52 (m, 1H), 3.70−
3.61 (m, 2H), 3.06 (s, 3H), 1.23 (d, J 6.4 Hz, 3H); 13C NMR (126
MHz, C6D6) δ: 161.8, 130.7, 129.4, 92.4, 75.5, 72.1, 57.6, 19.5; IR
(film) v: 3344, 1660, 1082, 795 cm−1; HRMS (ESI-TOF) m/z calcd
for C8H12NO2Cl3Na [M + Na+] 281.9831; Found 281.9828.
(S,E)-5-Methoxypent-3-en-2-yl Carbamate (8). Method A. To
a cooled to −10 °C solution of allyl alcohol 3 (4 g, 34.4 mmol) in 50
mL of CH2Cl2 was added 5.2 mL of TCA-NCO (8.4 g, 44.7 mmol).
After 1 h, solvent was removed. The residue was dissolved in a mixture
of MeOH/H2O (4:1 v/v, 200 mL), and 19.2 g of K2CO3 was added in
one portion. After 1.5 h, MeOH was removed and the aqueous residue
was extracted with AcOEt. The combined organic extracts were dried
over Na2SO4 and filtered through a silica gel pad, and solvent was
removed under diminished pressure. Carbamate 8 was obtained in
N-Trichloroacetyl-O-methyl-D-serine (12). To a solution of
imidate 11 (100 mg, 0.38 mmol) in xylene (5 mL) was added K2CO3
(55 mg, 0.38 mmol), and the reaction mixture was put into a
preheated oil bath (140 °C). After 6 h, the reaction mixture was
diluted with CH2Cl2 (10 mL) and filtered, and solvents were removed
under diminished pressure. The residue was purified by chromatog-
raphy on silica gel to afford 30 mg of amide 12 (30%) as a colorless oil.
82% yield (4.5 g) as a colorless oil. [α]2D1 −14.4 (c 2.1, CHCl3); H
1
1
[α]2D0 −16.5 (c 1.3, CHCl3); H NMR (500 MHz, CDCl3) δ: 7.00 (s,
NMR (500 MHz, CDCl3) δ: 5.83−5.69 (m, 2H), 5.29−5.21 (m, 1H),
4.75 (s, 2H), 3.94−3.86 (m, 2H), 3.32 (s, 3H), 1.32 (d, J 6.5 Hz, 3H);
13C NMR (125 MHz, CDCl3) δ: 156.5, 132.6, 128.0, 72.4, 71.1, 58.2,
20.4; IR (film) v: 3443, 3350, 3203, 1714, 1376, 1051 cm−1; HRMS
(ESI-TOF) m/z calcd for C7H13NO3Na [M + Na+] 182.0793. Found:
182.0788.
1H, NH), 5.81−5.71 (m, 1H, CH3CHCH), 5.53−5.46 (m, 1H,
CH3CHCH), 4.57−4.42 (m, 1H, CHNH), 3.56−3.48 (m, 2H,
CH2OMe), 3.39 (s, 3H, CH3O), 1.72 (br d, J 6.5 Hz, 3H, CH3CH
CH); IR (film) v: 3420, 3335, 1703, 1514, 1119, 821 cm−1; HRMS
(ESI-TOF) m/z calcd for C8H12NO2Cl3Na [M + Na+] 281.9831;
Found 281.9830.
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dx.doi.org/10.1021/jo500857t | J. Org. Chem. 2014, 79, 6342−6346