The Journal of Organic Chemistry
Article
[(benzyloxy)carbonyl]-L-serine methyl ester (5.06 g, 20 mmol) was
added dropwise to the reaction mixture. The ice−water bath was
removed, and the mixture was then stirred for 4 h at room
temperature. After addition of 3 N HCl (100 mL) to the reaction
mixture at 0 °C, the resulting mixture was extracted with ethyl acetate
(50 mL × 3). The combined organic phase was washed with brine,
dried over MgSO4, filtered, and concentrated under reduced pressure.
The obtained crude material was purified by column chromatography
(silica gel; hexane/ethyl acetate, 1:1) to give (S)-2-[[(benzyloxy)-
carbonyl]amino]-3-methyl-1,3-butanediol in 50% yield (2.53 g, 10
mmol). To a solution of (S)-2-[[(benzyloxy)carbonyl]amino]-3-
methyl-1,3-butanediol (2.53 g, 10 mmol) in MeCN (40 mL) were
added phosphate buffer solution (pH 6.7, 30 mL) and TEMPO
(2,2,6,6-tetramethylpiperidine-1-oxyl; 1.56 g, 1 mmol) at room
temperature. After the reaction mixture was warmed to 35 °C, a
H2O solution (10 mL) of NaClO2 (1.8 g, 20 mmol) and an aqueous
NaClO solution (0.83%, 6 mL) were added to the reaction mixture at
the same time with stirring for 1 h. The reaction mixture was
additionally stirred for 4 h at 35 °C, and then the resulting solution
was acidified to pH 2 with citric acid. The obtained mixture was
extracted with ethyl acetate (50 mL × 3). The combined organic phase
was washed with brine, dried over MgSO4, filtered, and concentrated
under reduced pressure. To the obtained crude N-[(benzyloxy)-
carbonyl]-3-hydroxy-D-valine in a flask were added DMF (50 mL),
K2CO3 (2.76 g, 20 mmol), KI (166 mg, 1 mmol), and benzyl bromide
(2.56 g, 15 mmol). After being stirred for 15 h at room temperature,
the resulting solution was poured into water (200 mL) and extracted
with ethyl acetate (50 mL × 3). The combined organic phase was
washed with brine, dried over MgSO4, filtered, and concentrated under
reduced pressure. The obtained crude material was purified by column
chromatography (silica gel; hexane/ethyl acetate, 4:1) to give N-
[(benzyloxy)carbonyl]-3-hydroxy-D-valine benzyl ester in 63% yield
(two steps, 2.25 g, 6.3 mmol). To a solution of N-[(benzyloxy)-
carbonyl]-3-hydroxy-D-valine benzyl ester (0.36 g, 1 mmol) in dry
DMF (4 mL) were added 2,6-lutidine (0.75 g, 7 mmol) and
(TBS)OTf (0.63 g, 3 mmol) at 0 °C under a nitrogen atmosphere.
The reaction mixture was stirred for 3 h at 0 °C and then additionally
for 8 h at room temperature. The resulting solution was poured into
water (20 mL) and extracted with Et2O (20 mL × 3). The combined
organic phase was washed with brine, dried over MgSO4, filtered, and
concentrated under reduced pressure. After the obtained crude
material was roughly purified by column chromatography (silica gel;
hexane/ethyl acetate, 8:1), the obtained N-[(benzyloxy)carbonyl]-3-
(tert-butyldimethylsiloxy)-D-valine benzyl ester was dissolved in
MeOH (8 mL), and the solution was added onto Pd/C (10%, 60
mg) under a nitrogen atmosphere in a round-bottomed flask. After the
atmosphere in the flask was replaced with hydrogen, the reaction
mixture was stirred for 6 h under a hydrogen atmosphere at room
temperature. Pd/C was filtered with Celite, and the filtrate was
concentrated under reduced pressure. The obtained white solid was
washed with Et2O and hexane and dried in air to give pure 3-(tert-
butyldimethylsiloxy)-D-valine (3j) in 70% yield (two steps, 173 mg, 0.7
mmol) as a white solid: mp 114−115 °C; [α]2D1 = +11.5° (c = 1.0,
MeOH); NMR (CD3OD) δH 0.17 (3H, s), 0.18 (3H, s), 0.91 (9H, s),
1.31 (3H, s), 1.54 (3H, s), 3.38 (1H, s); NMR (CD3OD) δC 18.9,
25.4, 26.4, 29.4, 65.8, 74.8, 171.6; IR (KBr) ν/cm−1 1637 (CO); HR
ESI-MS m/z calcd for C11H25NO3Si + H (M + H) 248.1677, found
(M+ + H) 248.1675.
yield (67.9 mg) as a clear oil. The enantioselectivity was determined by
chiral HPLC analysis (86% ee). The absolute configuration was
determined by comparison of the specific rotation with that of the
literature:9b,c,14b [α]D20.0 = −69.5° (c = 1.0, CHCl3, 86% ee), −35.0° (c
= 1.0, MeOH, 86% ee). NMR (CDCl3) data for 5a: δH 1.44 (3H, s),
2.60−2.72 (2H, m), 5.01−5.08 (2H, m), 5.49−5.60 (1H, m), 7.24−
7.31 (3H, m), 7.37−7.41 (2H, m), 9.52 (1H, s); δC18.7, 40.5, 53.5,
118.5, 127.0, 127.2, 128.7, 133.1, 139.3, 201.7. The spectroscopic data
of 5b,9b 5c,9b 5e,9c 5i,9b 5j,9b and 69b are in agreement with the
published data.
Data for 2-methyl-2-(4-methylphenyl)pent-4-enal (5b):9b
79% yield (74.3 mg); clear oil; [α]2D0.0 = −55.7° (c = 1.0, CHCl3,
84% ee); NMR (CDCl3) δH 1.42 (3H, s), 2.34 (3H, s), 2.58−2.71
(2H, m), 5.01−5.08 (2H, m), 5.50−5.60 (1H, m), 7.13−7.14 (2H, m),
7.19−7.21 (2H, m), 9.50 (1H, s); NMR (CDCl3) δC 18.8, 20.9, 40.5,
53.2, 118.5, 127.1, 129.6, 133.3, 136.3, 137.1, 202.0.
Data for 2-methyl-2-(3-methylphenyl)pent-4-enal (5c):9b
89% yield (83.7 mg); clear oil; [α]2D5.0 = −72.8° (c = 1.0, CHCl3,
82% ee); NMR (CDCl3) δH 1.43 (3H, s), 2.36 (3H, s), 2.59−2.72
(2H, m), 5.02−5.09 (2H, m), 5.50−5.61 (1H, m), 7.05−7.12 (3H, m),
7.28−7.30 (1H, m), 9.50 (1H, s); NMR (CDCl3) δC 18.8, 21.6, 40.5,
53.5, 118.5, 124.1, 127.9, 128.1, 128.7, 133.3, 138.5, 139.3, 202.0.
Data for 2-(4-chlorophenyl)-2-methylpent-4-enal (5e):9c 85%
yield (88.7 mg); clear oil; [α]2D4.8 = −66.9° (c = 1.0, CHCl3, 87% ee);
NMR (CDCl3) δH 1.43 (3H, s), 2.58−2.69 (2H, m), 5.03−5.08 (2H,
m), 5.46−5.57 (1H, m), 7.17−7.19 (2H, m), 7.34−7.37 (2H, m), 9.49
(1H, s); NMR (CDCl3) δC 18.8, 40.6, 53.3, 119.0, 128.6, 129.0, 132.7,
133.4, 137.9, 201.4.
Data for 2-(3-chlorophenyl)-2-methylpent-4-enal (5f): 82%
yield (85.6 mg); clear oil; [α]2D4.7 = −65.0° (c = 1.0, CHCl3, 86% ee);
NMR (CDCl3) δH 1.44 (3H, s), 2.58−2.70 (2H, m), 5.04−5.10 (2H,
m), 5.47−5.58 (1H, m), 7.11−7.14 (1H, m), 7.24−7.34 (3H, m), 9.51
(1H, s); NMR (CDCl3) δC 18.8, 40.6, 53.6, 119.1, 125.5, 127.4, 127.6,
130.0, 132.6, 134.9, 141.6, 201.2; IR (neat) ν/cm−1 1726 (CO); HR
EI-MS m/z calcd for C12H13ClO (M) 208.0655, found (M+) 208.0651.
Data for 2-(4-fluorophenyl)-2-methylpent-4-enal (5h): 80%
yield (76.9 mg); clear oil; [α]2D2.2 = −68.0° (c = 1.0, CHCl3, 84% ee);
NMR (CDCl3) δH 1.44 (3H, s), 2.58−2.70 (2H, m), 5.03−5.08 (2H,
m), 5.48−5.58 (1H, m), 7.05−7.09 (2H, m), 7.21−7.25 (2H, m), 9.49
(1H, s); NMR (CDCl3) δC 20.3, 42.1, 54.5, 117.1 (d, J 21.7 Hz),
120.2, 130.3 (d, J 7.9 Hz), 134.3, 136.5 (d, J 3.0 Hz), 163.4 (d, J 246.3
Hz), 203.0; IR (neat) ν/cm−1 1725 (CO); HR ESI-MS m/z calcd
for C12H13FO + H (M + H) 193.1023, found (M+ + H) 193.1024.
Data for 2-methyl-2-(naphthalen-2-yl)pent-4-enal (5i):9b
76% yield (85.2 mg); clear oil; [α]2D4.7 = −107.0° (c = 1.0, CHCl3,
85% ee); NMR (CDCl3) δH 1.56 (3H, s), 2.70−2.85 (2H, m), 5.02−
5.11 (2H, m), 5.52−5.62 (1H, m), 7.36−7.38 (1H, m), 7.48−7.52
(2H, m), 7.71−7.72 (1H, m), 7.83−7.87 (3H, m), 9.59 (1H, s); NMR
(CDCl3) δC 18.9, 40.5, 53.8, 118.7, 125.0, 126.26, 126.28, 126.4, 127.5,
128.0, 128.6, 132.4, 133.1, 133.4, 136.8, 202.0.
Data for 2-methyl-2-(thiophene-2-yl)pent-4-enal (5j):9b 88%
yield (79.0 mg); clear oil; [α]2D2.3 = −13.2° (c = 1.0, CHCl3, 70% ee);
NMR (CDCl3) δH 1.51 (3H, s), 2.69 (2H, d, J 7.2 Hz), 5.09−5.16
(2H, m), 5.60−5.71 (1H, m), 6.92 (1H, dd, J 1.2, 3.6 Hz), 7.04 (1H,
dd, J 3.6, 5.2 Hz), 7.31 (1H, dd, J 1.2, 5.2 Hz), 9.49 (1H, s); NMR
(CDCl3) δC 19.9, 41.4, 52.1, 119.2, 125.2, 125.4, 127.4, 132.5, 144.1,
199.6.
Data for 2-ethyl-2-phenylpent-4-enal (5k): 36% yield (33.9
mg); clear oil; [α]2D0.0 = −46.5° (c = 1.0, CHCl3, 84% ee); NMR
(CDCl3) δH 0.82 (3H, t, J 7.3 Hz), 1.96−2.06 (2H, m), 2.66−2.79
(2H, m), 5.03−5.12 (2H, m), 5.49−5.60 (1H, m), 7.23−7.42 (5H, m),
9.52 (1H, s); NMR (CDCl3) δC 7.9, 24.5, 36.1, 57.4, 118.3, 127.3,
127.6, 128.7, 132.9, 138.4, 202.4; IR (neat) ν/cm−1 1724 (CO); HR
ESI-MS m/z calcd for C13H16O + H (M + H) 189.1274, found (M+ +
H) 189.1275.
Typical Procedure for the Allylation Reaction. Pd(OAc)2 (4b;
5.6 mg, 0.025 mmol), PPh3 (19.7 mg, 0.075 mmol), O-TBS-L-
threonine (3h; 23.3 mg, 0.1 mmol), MgSO4 (12 mg, 0.1 mmol), and
CHCl3 (1 mL) were placed in a 7 mL vial, and the atmosphere in the
vial was replaced with argon. After addition of 2-phenylpropionalde-
hyde (1a; 67 mg, 0.5 mmol) and allyl pivalate (2h; 85 mg, 0.6 mmol)
to the reaction mixture with stirring, the vial was charged with argon
again and capped tightly. Then the reaction mixture was stirred for 72
h at 25 °C. The resulting mixture was filtered through a small plug of
silica gel, eluted with Et2O (2 mL × 3), and concentrated under
reduced pressure. (R)-2-Methyl-2-phenylpent-4-enal (5a) was isolated
by column chromatography (silica gel, hexane−Et2O, 19:1) in 78%
Data for 2-methoxy-2-phenylpent-4-enal (5l): 48% yield (45.6
mg); clear oil; [α]2D0.0 = −59.5° (c = 1.0, CHCl3, 46% ee); NMR
(CDCl3) δH 2.83−2.89 (1H, m), 3.03−3.09 (1H, m), 3.34 (3H, s),
5.08−5.18 (2H, m), 5.59−5.70 (1H, m), 7.30−7.41 (5H, m), 9.52
(1H, s); NMR (CDCl3) δC 35.4, 51.5, 86.1, 118.8, 126.9, 128.3, 128.8,
10857
dx.doi.org/10.1021/jo4018414 | J. Org. Chem. 2013, 78, 10853−10859