D
I. Khan et al.
PSP
Synthesis
1H NMR (400 MHz, CDCl3): δ = 4.3–3.7 (m, 5 H), 2.36 (br, 2 H), 1.68 (m,
2 H), 1.34–1.28 (m, 16 H), 0.90 (t, J = 8.0 Hz, 3 H).
Ethyl 2,3-Dihydroxy-4-phenylbutanoate (2m)8
White solid; yield: 1.90 g (85%); mp 60–61 °C.
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, 2 H), 1.31 (t, J = 8.0
Hz, 3 H).
Butyl 2,3-Dihydroxypropanoate (2c)8
Colorless oil; yield: 1.54 g (95%).
1H NMR (400 MHz, CDCl3): δ = 4.22–4.28 (m, 3 H), 3.83 (m, 2 H), 3.39
(br, 2 H), 1.65 (m, 2 H), 1.39 (m, 2 H), 0.94 (t, J = 8.0 Hz, 3 H).
Ethyl 2,3-Dihydroxy-2-methyl-4-phenylbutanoate (2n)8
White solid; yield: 1.93 g (81%), mp 65–67 °C.
tert-Butyl 2,3-Dihydroxypropanoate (2d)8
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: 1.50 g (93%).
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, 2 H), 1.51 (s, 9 H).
Benzyl 2,3-Dihydroxy-2-methylpropanoate (2p)8
Ethyl 2,3-Dihydroxypropanoate (2e)8
White solid; yield: 1.74 g (83%); mp 45–46 °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, 2 H), 1.37
(s, 3 H).
Colorless oil; yield: 1.18 g (88%).
1H NMR (400 MHz, CDCl3): δ = 4.28 (m, 3 H), 3.88 (m, 2 H), 3.17 (br, 2
H), 1.30 (m, 3 H).
Benzyl 2,3-Dihydroxypropanoate (2q)12
Methyl 2,3-Dihydroxypropanoate (2f)8
Colorless oil; yield: 1.70 g (87%).
Colorless oil; yield: 1.09 g (91%).
1H NMR (400 MHz, CDCl3): δ = 7.40 (m, 5 H), 5.27 (m, 2 H), 4.33 (t,
J = 4.0 Hz, 1 H), 3.91 (m, 2 H), 2.83 (br, 2 H).
1H NMR (400 MHz, CDCl3): δ = 4.30 (t, J = 4.0 Hz, 1 H), 3.88 (m, 5 H),
3.01 (br, 2 H).
Phenyl 2,3-Dihydroxypropanoate (2r)13
Methyl 2,3-Dihydroxy-2-methylpropanoate (2g)8
White solid; yield: 1.25 g (69%); mp 85–86 °C.
Colorless oil; yield: 1.20 g (90%).
1H NMR (400 MHz, CDCl3): δ = 7.43 (m, 2 H), 7.30 (m, 1 H), 7.15 (m, 2
H), 4.56 (t, J = 4.0 Hz, 1 H), 4.09 (m, 2 H), 2.51 (br, 2 H).
1H NMR (400 MHz, CDCl3): δ = 3.80 (m, 4 H), 3.57 (m, 1 H), 3.29 (br, 2
H), 1.35 (s, 3 H).
Methyl 2,3-Dihydroxy-3-phenylpropanoate (2s)14
Ethyl 2,3-Dihydroxybutanoate (2h)8
Colorless oil; yield: 1.49 g (76%).
Colorless oil; yield: 1.31 g (89%).
1H NMR (400 MHz, CDCl3): δ = 7.42–7.28 (m, 5 H), 5.06 (d, J = 4.0 Hz, 1
H), 4.41 (d, J = 4.0 Hz, 1 H), 3.84 (s, 3 H).
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), 1.30 (m, 6 H).
Ethyl 2,3-Dihydroxyoctanoate (2i)8
Ethyl (2S,3R)-3-[(R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2,3-dihy-
droxy-2-methylpropanoate (2t);8 Scaled Up Synthesis
White solid; yield: 1.85 g (91%); mp 41–42 °C.
To a 1000-mL three-necked flask was charged 1t (54.0 g, 0.25 mol)
and acetone (500 mL); QAS-2 (11.4 g, 25.0 mmol) was added. The
mixture was cooled to 0–5 °C. Solid KMnO4 (47.5 g, 0.3 mol) was add-
ed in 10 portions within 10 min. The mixture was stirred at the same
temperature for 2 h, and TLC indicated complete consumption of 1t. A
solution of NaHSO3 (25.0 g) in water (50 mL) was added in one por-
tion to quench the reaction. The mixture was stirred for 15 min and
then filtered on Celite, which was washed thoroughly with acetone
(3 × 100 mL). The combined filtrates were concentrated to remove ac-
etone under reduced pressure and the residue was extracted with
EtOAc (3 × 150 mL). The combined organic phases were washed with
sat. brine (3 × 50 mL), dried (Na2SO4), filtered, and evaporated to dry-
ness to afford a colorless oil (57.5 g, 93%), which was recrystallized
(petroleum ether, 200 mL) to afford the product as a white solid;
yield: 51.3 g (83%); mp 75–76 °C.
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, 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).
Ethyl 2,3-Dihydroxy-2-methyloctanoate (2j)8
White solid; yield: 1.92 g (88%); mp 45–46 °C.
1H NMR (400 MHz, CDCl3): δ = 4.27 (m, 2 H), 3.72 (d, J = 12.0 Hz, 1 H),
1.64-1.26 (m, 16 H), 0.90 (t, J = 8.0 Hz, 3 H).
Ethyl 3-Cyclohexyl-2,3-dihydroxypropanoate (2k)8
White solid; yield: 1.77 g (82%), mp 50–51 °C.
1H NMR (400 MHz, CDCl3): δ = 4.30 (m, 3 H), 3.57 (d, J = 8.0 Hz, 1 H),
2.77 (br, 2 H), 2.07 (m, 1 H), 0.97–1.48 (m, 13 H).
1H NMR (400 MHz, CDCl3): δ = 4.20–4.31 (m, 3 H), 4.09 (m, 2 H), 3.93
(d, J = 8.0 Hz, 1 H), 2.52 (br, 2 H), 1.31–1.49 (m, 12 H).
Ethyl 3-Cyclohexyl-2,3-dihydroxy-2-methylpropanoate (2l)8
Colorless oil; yield: 1.84 g (80%).
1H NMR (400 MHz, CDCl3): δ = 4.27 (m, 2 H), 4.0–4.5 (br, 2 H), 3.62 (d,
J = 4.0 Hz, 1 H), 1.08–1.92 (m, 17 H).
Funding Information
The authors acknowledge the financial support of National Natural
Science Foundation (No. 21676129), Jiangsu University scientific re-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–E