D
Z.-b. Luo et al.
PSP
Synthesis
1H NMR (400 MHz, CDCl3): δ = 4.15 (t, J = 4.0 Hz, 1 H), 3.83 (dd, J =
12.0, 12.0 Hz, 2 H), 2.82 (br s, 2 H), 1.51 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 173.6 (CO), 137.6 (Ar–C), 130.1 (Ar–C),
129.1 (Ar–C), 126.7 (Ar–C), 73.6 (C–O), 72.0 (C–O), 62.1 (–OCH2CH3),
40.1 (–CPh), 14.1 (–OCH2CH3).
Methyl cis-2,3-Dihydroxy-2-methylpropanoate (4b)13
HRMS (ESI): m/z [M + Na]+ calcd for C12H16NaO4: 247.0946; found:
247.0943.
Colorless oil; yield: 0.61 g (92%).
1H NMR (400 MHz, CDCl3): δ = 3.80 (m, 4 H), 3.57 (m, 1 H), 3.29 (br s,
2 H), 1.35 (s, 3 H).
Ethyl cis-2,3-Dihydroxy-3-methyl-4-phenylbutanoate (12b)
White solid; yield: 0.98 g (82%); mp 65–67 °C.
Ethyl cis-2,3-Dihydroxybutanoate (5b)14
IR: 3050–3530 (br, m), 1750 (s), 1125 (m) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.31 (m, 5 H), 4.27 (m, 2 H), 4.01 (dd,
J = 2.0, 8.0 Hz, 1 H), 3.03 (dd, J = 2.0, 12.0 Hz, 1 H), 2.75 (m, 1 H), 1.47
(s, 3 H), 1.32 (t, J = 8.0 Hz, 3 H).
Colorless oil; yield: 0.63 g (88%).
1H NMR (400 MHz, CDCl3): δ = 4.27 (q, J = 8.0 Hz, 2 H), 4.08 (m, 1 H),
4.00 (d, J = 4.0 Hz, 1 H), 3.00 (br s, 2 H), 1.30 (m, 6 H).
13C NMR (100 MHz, CDCl3): δ = 175.9 (CO), 138.2 (Ar–C), 129.4 (Ar–C),
128.6 (Ar–C), 126.6 (Ar–C), 76.3 (C–O), 62.2 (–OCH2CH3), 36.9 (PhC–),
21.8 (CH3), 14.2 (–OCH2CH3).
HRMS (ESI): m/z [M + Na]+ calcd for C13H18NaO4: 261.1103; found:
261.1100.
Butyl cis-2,3-Dihydroxypropanoate (6b)15
Colorless oil; yield: 0.72 g (90%).
1H NMR (400 MHz, CDCl3): δ = 4.28–4.22 (m, 3 H), 3.83 (m, 2 H), 3.39
(br s, 2 H), 1.65 (m, 2 H), 1.39 (m, 2 H), 0.94 (t, J = 8.0 Hz, 3 H).
Benzyl cis-2,3-Dihydroxybutanoate (13b)19
Ethyl cis-2,3-Dihydroxyoctanoate (7b)16
White solid; yield: 0.88 g (84%); mp 45–46 °C.
White solid; yield: 0.77 g (75%); mp 41–42 °C.
1H NMR (400 MHz, CDCl3): δ = 7.37 (m, 5 H), 5.24 (q, J = 12.0 Hz, 2 H),
3.85 (d, J = 12.0 Hz, 1 H), 3.61 (d, J = 12.0 Hz, 1 H), 3.52 (br s, 2 H), 1.37
(s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 4.31 (q, J = 8.0 Hz, 2 H), 4.10 (d, J = 2.0
Hz, 1 H), 3.90 (m, 1 H), 2.79 (br s, 2 H), 1.70–1.57 (m, 2 H), 1.56–1.20
(m, 9 H), 0.91 (t, J = 8.0 Hz, 3 H).
Methyl cis-2,3-Dihydroxypropanoate (14b)20
Ethyl cis-2,3-Dihydroxy-3-methyloctanoate (8b)17
Colorless oil; yield: 0.53 g (90%).
White solid; yield: 0.78 g (72%); mp 45–46 °C.
1H NMR (400 MHz, CDCl3): δ = 4.30 (t, J = 4.0 Hz, 1 H), 3.88 (m, 5 H),
3.01 (br s, 2 H).
1H NMR (400 MHz, CDCl3): δ = 4.27 (m, 2 H), 3.72 (d, J = 12.0 Hz, 1 H),
1.62 (m, 2 H), 1.35 (m, 9 H), 0.90 (t, J = 8.0 Hz, 3 H).
Ethyl cis-3-Cyclohexyl-2,3-dihydroxypropanoate (9b)18
Ethyl (2S*,3R*)-3-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2,3-dihy-
droxy-2-methylpropanoate (1b); Scaled-Up Synthesis
White solid; yield: 0.86 g (80%); mp 50–51 °C.
A 5 L three-necked round-bottomed flask was charged with TEBAC
(273.6 g, 1.2 mol), KMnO4 (189.6 g, 1.2 mol), and acetone (2.14 L), and
the mixture was stirred at r.t. for 3 h under N2 then cooled to –5 to 0
°C. A solution of enoate 1a (214 g, 1.0 mol) in acetone (214 mL) was
added dropwise over 15 min while the internal temperature was kept
at 5 °C or below. After completion of the addition, the mixture was
stirred for a further 30 min at the same temperature until the enoate
was completely consumed (TLC). A solution of NaHSO3 (107 g) in H2O
(214 mL) was added over 5 min to quench the reaction; during the
addition the internal temperature was kept at 35 °C or below. The
mixture was stirred for 1 h then filtered through Celite, which was
washed thoroughly with acetone (3 × 300 mL). The combined filtrates
were concentrated under reduced pressure to remove the acetone,
and the residue was extracted with EtOAc (3 × 600 mL). The organic
phases were combined, washed with brine (2 × 200 mL), dried
(Na2SO4), filtered, and evaporated to dryness to afford a crude oily
product (211 g) that solidified on standing. A 10 g sample of the crude
oil was purified by column chromatography (silica gel, 25% EtOAc in
PE) to give 9.5 g (81% yield) of the analytically pure product.
1H NMR (400 MHz, CDCl3): δ = 4.30 (m, 3 H), 3.57 (d, J = 8.0 Hz, 1 H),
2.77 (br s, 2 H), 2.07 (m, 1 H), 0.97–1.48 (m, 13 H).
Ethyl cis-3-Cyclohexyl-2,3-dihydroxy-2-methylpropanoate (10b)
Colorless oil; yield: 0.9 g (78%);
IR: 3280–3650 (br, m), 2980 (s), 1740 (s), 1250 (m) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 4.27 (m, 2 H), 4.0–4.5 (br s, 2 H), 3.62
(d, J = 4.0 Hz, 1 H), 1.08–1.92 (m, 17 H).
13C NMR (100 MHz, CDCl3): δ = 176.9 (CO), 78.5 (C–O), 77.6 (C–O),
62.3 (–OCH2CH3), 42.8 (Cy–C), 38.7 (Cy–C), 28.8 (Cy–C), 26.2 (Cy–C),
26.0 (Cy–C), 25.3 (Cy–C), 22.6 (CH3), 14.1 (–OCH2CH3).
HRMS (ESI): m/z [M + Na]+ calcd for C12H22NaO4: 253.1416; found:
253.1414.
Ethyl cis-2,3-Dihydroxy-4-phenylbutanoate (11b)
White solid; yield: 0.92 g (86%); mp 60–61 °C.
IR: 3060–3550 (br, s), 1750 (s), 1250 (s) cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.29 (m, 5 H), 4.27 (m, 2 H), 4.18 (m, 1
H), 4.08 (d, J = 2.0 Hz, 1 H), 2.98 (m, 2 H), 2.76 (br s, 2 H), 1.31 (t, J = 8.0
Hz, 3 H).
Acknowledgment
The authors acknowledge the financial support of Jiangsu University
scientific research funding (13JD062) and the National Natural Sci-
ence Foundation of China (No. 21402067).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–E