The Journal of Organic Chemistry
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determined by GC analysis using a Agilent J&W GC column (CP-
Chirasil-V-Val for Optical Isomers 25 m 0.25 mm 0.12 μm P/N:
CP7495), conditions: tmajor = 20.4 min, tminor = 21.6 min.
(R)-(R)-Methyl 2-Acetylamino-3-(2-thienyl)propanoate (2j).
White solid, purified by silica gel column chromatography (ethyl
acetate/petroleum ether, 1/2), 42.2 mg, 94% yield, 93% ee. 1H NMR
(400 MHz, DMSO-d6) δ 7.90 (d, J = 7.7 Hz, 1H), 7.02 (dd, J = 4.9,
3.0 Hz, 1H), 6.80 (dd, J = 2.9, 1.2 Hz, 1H), 6.57 (dd, J = 4.9, 1.3 Hz,
1H), 4.02 (ddd, J = 9.1, 7.7, 5.5 Hz, 1H), 2.65−2.56 (m, 1H), 2.49
(dd, J = 14.4, 9.1 Hz, 1H), 1.39 (s, 3H). 13C NMR (101 MHz,
DMSO-d6) δ 172.1, 169.3, 137.4, 128.5, 125.8, 122.4, 53.0, 51.8, 31.3,
22.2. The ee of 2j was determined by GC analysis using a Agilent
J&W GC column (CP-Chirasil-V-Val for Optical Isomers 25 m 0.25
Methyl (R)-2-Acetamido-3-(4-methoxyphenyl)propanoate (2d).
White solid, purified by silica gel column chromatography (ethyl
acetate/petroleum ether, 1/2), 45.7 mg, 91% yield, 96% ee. 1H NMR
(400 MHz, DMSO-d6) δ 8.26 (d, J = 7.7 Hz, 1H), 7.21 (ddd, J = 8.2,
7.4, 1.8 Hz, 1H), 7.10 (dd, J = 7.4, 1.8 Hz, 1H), 6.95 (dd, J = 8.3, 1.1
Hz, 1H), 6.85 (td, J = 7.4, 1.1 Hz, 1H), 3.78 (s, 3H), 3.55 (s, 3H),
1.77 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 172.5, 169.3, 157.3,
130.6, 128.2, 124.9, 120.1, 110.6, 55.3, 52.0, 51.6, 31.9, 22.2. The ee
of 2d was determined by GC analysis using a Agilent J&W GC
column (CP-Chirasil-V-Val for Optical Isomers 25 m 0.25 mm 0.12
μm P/N: CP7495), conditions: tmajor = 24.9 min, tminor = 25.8 min.
(R)-Methyl 2-acetylamino-3-(3-methoxyphenyl)propanoate (2e).
White solid, purified by silica gel column chromatography (ethyl
acetate/petroleum ether, 1/2), 49.2 mg, 90% yield, 98% ee. 1H NMR
(400 MHz, chloroform-d) δ 8.33 (d, J = 7.8 Hz, 1H), 7.19 (td, J = 7.5,
1.0 Hz, 1H), 6.78 (dt, J = 9.0, 1.4 Hz, 3H), 4.44 (ddd, J = 9.4, 7.7, 5.4
Hz, 1H), 3.72 (s, 3H), 3.60 (s, 3H), 2.98 (dd, J = 13.7, 5.5 Hz, 1H),
2.84 (dd, J = 13.7, 9.4 Hz, 1H), 1.79 (s, 3H). 13C NMR (101 MHz,
chloroform-d) δ 172.2, 169.4, 159.2, 138.8, 129.3, 121.2, 114.7, 112.1,
54.9, 53.6, 51.9, 36.7, 22.2. The ee of 2e was determined by GC
analysis using a Agilent J&W GC column (CP-Chirasil-V-Val for
Optical Isomers 25 m 0.25 mm 0.12 μm P/N: CP7495), conditions:
tmajor = 20.4 min, tminor = 21.6 min.
Methyl (R)-2-Acetamido-3-(2-methoxyphenyl)propanoate (2f).
White solid, purified by silica gel column chromatography (ethyl
acetate/petroleum ether, 1/2), 46.2 mg, 92% yield, 92% ee. 1H NMR
(400 MHz, DMSO-d6) δ 8.26 (d, J = 7.7 Hz, 1H), 7.21 (ddd, J = 8.2,
7.4, 1.8 Hz, 1H), 7.10 (dd, J = 7.4, 1.8 Hz, 1H), 6.95 (dd, J = 8.3, 1.1
Hz, 1H), 6.85 (td, J = 7.4, 1.1 Hz, 1H), 3.78 (s, 3H), 3.55 (s, 3H),
1.77 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 172.5, 169.3, 157.3,
130.6, 128.2, 124.9, 120.1, 110.6, 55.3, 52.0, 51.6, 31.9, 22.2. The ee
of 2f was determined by GC analysis using a Agilent J&W GC column
(CP-Chirasil-V-Val for Optical Isomers 25 m 0.25 mm 0.12 μm P/N:
CP7495), conditions: tmajor = 23.3 min, tminor = 23.7 min.
mm 0.12 μm P/N: CP7495), conditions: tmajor = 19.3 min, tminor
=
20.0 min.
Methyl (R)-2-Acetamido-3-(furan-3-yl)propanoate (2k). White
solid, purified by silica gel column chromatography (ethyl acetate/
1
petroleum ether, 1/2), 39.2 mg, 93% yield, 98% ee. H NMR (400
MHz, DMSO-d6) δ 8.40 (d, J = 7.9 Hz, 1H), 7.35 (dd, J = 5.1, 1.3 Hz,
1H), 7.23−6.73 (m, 2H), 4.46 (ddd, J = 8.9, 7.9, 5.3 Hz, 1H), 3.62 (s,
3H), 3.26 (ddd, J = 14.9, 5.2, 0.8 Hz, 1H), 3.12 (ddd, J = 14.8, 8.9, 0.9
Hz, 1H), 1.84 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 171.6,
169.4, 139.0, 126.9, 126.4, 124.8, 53.6, 52.0, 31.0, 22.3. The ee of 2k
was determined by GC analysis using a Agilent J&W GC column
(CP-Chirasil-V-Val for Optical Isomers 25 m 0.25 mm 0.12 μm P/N:
CP7495), conditions: tmajor = 13.9 min, tminor = 15.0 min.
(R)-2-tert-Butoxycarbonylamino-3-phenylpropanoic Acid Meth-
yl Ester (2l). White solid, purified by silica gel column chromatog-
raphy (ethyl acetate/petroleum ether, 1/2), 50.2 mg, 90% yield,96%
ee. 1H NMR (400 MHz, chloroform-d) δ 7.33−7.24 (m, 1H), 7.15−
7.08 (m, 1H), 4.97 (d, J = 8.3 Hz, 0H), 4.58 (q, J = 7.1, 6.6 Hz, 0H),
3.70 (s, 3H), 3.07 (qd, J = 13.9, 6.0 Hz, 2H), 1.41 (s, 9H). 13C NMR
(101 MHz, chloroform-d) δ 172.5, 155.2, 136.2, 129.4, 128.7, 127.2
80.1, 54.6, 52.3, 38.51, 28.4. The ee of 2l was determined by HPLC
analysis using a Daicel Chiralcel OJ-H column (25 cm × 0.46 cm ID),
conditions: n-hexane/i-PrOH = 97/3, 1.0 mL/min, 220 nm; tmajor
10.2 min, tminor = 12.2 min.
=
Isopropyl (R)-α-Acetylamido-3-phenylpropanoate (2m). White
solid, purified by silica gel column chromatography (ethyl acetate/
1
Methyl (R)-2-Acetamido-3-(4-fluorophenyl)propanoate (2g).
White solid, purified by silica gel column chromatography (ethyl
acetate/petroleum ether, 1/2), 45.4 mg, 95% yield, 75% ee. 1H NMR
(400 MHz, DMSO-d6) δ 8.34 (d, J = 7.8 Hz, 1H), 7.29−7.04 (m,
4H), 3.59 (s, 3H), 2.89−2.78 (m, 1H), 1.79 (s, 3H). 13C NMR (101
MHz, DMSO-d6) δ 172.1, 169.2, 162.3, 159.9, 133.4 (d, J = 3.1 Hz),
130.9 (d, J = 8.1 Hz), 115.0, 114.92 (d, J = 20.9 Hz), 53.6, 51.8, 35.9,
22.2. The ee of 2g was determined by GC analysis using a Agilent
J&W GC column (CP-Chirasil-V-Val for Optical Isomers 25 m 0.25
petroleum ether, 1/2), 45.3 mg, 91% yield, 93% ee. H NMR (400
MHz, DMSO-d6) δ 8.35 (d, J = 7.7 Hz, 1H), 7.09 (s, 4H), 4.40 (ddd,
J = 9.3, 7.7, 5.5 Hz, 1H), 3.59 (s, 3H), 2.95 (dd, J = 13.7, 5.6 Hz, 1H),
2.81 (dd, J = 13.7, 9.3 Hz, 1H), 2.25 (s, 3H), 1.79 (s, 3H). 13C NMR
(101 MHz, DMSO-d6) δ 172.3, 169.4, 135.6, 134.2, 128.9, 128.9,
53.8, 51.8, 36.4, 22.3, 20.7. The ee of 2m was determined by GC
analysis using a Agilent J&W GC column (CP-Chirasil-V-Val for
Optical Isomers 25m 0.25 mm 0.12 μm P/N: CP7495), conditions:
tmajor = 21.0 min, tminor = 21.9 min.
2a′: White solid, purified by silica gel column chromatography
(ethyl acetate/petroleum ether, 1/2), 41.1 mg, 93% yield, 91% ee. 1H
NMR (400 MHz, chloroform-d) δ 7.38−7.19 (m, 3H), 7.14−7.07
(m, 2H), 6.13 (d, J = 5.1 Hz, 1H), 4.88 (dd, J = 7.8, 5.8 Hz, 0.1H),
3.72 (s, 3H), 3.09 (d, J = 24.2 Hz, 1H), 1.98 (s, 3H). 13C NMR (101
MHz, chloroform-d) δ 172.2, 169.8, 135.9, 129.3, 128.7, 127.2, 52.4,
23.2.
mm 0.12 μm P/N: CP7495), conditions: tmajor = 16.3 min, tminor
=
17.3 min.
Methyl (R)-2-Acetamido-3-(2-fluorophenyl)propanoate (2h).
White solid, purified by silica gel column chromatography (ethyl
acetate/petroleum ether, 1/2), 44.9 mg, 94% yield, 93% ee. 1H NMR
(400 MHz, DMSO-d6) δ 8.41 (d, J = 8.0 Hz, 1H), 7.47−7.37 (m,
1H), 7.41−7.18 (m, 3H), 3.59 (s, 3H), 3.20 (dd, J = 13.8, 5.8 Hz,
1H), 2.95 (dd, J = 13.8, 9.5 Hz, 1H), 1.78 (s, 3H). 13C NMR (101
MHz, DMSO-d6) δ 171.9, 169.3, 134.7, 133.3, 131.6, 129.2, 128.6,
127.0, 51.9, 51.6, 34.6, 22.2. The ee of 2h was determined by GC
analysis using a Agilent J&W GC column (CP-Chirasil-V-Val for
Optical Isomers 25 m 0.25 mm 0.12 μm P/N: CP7495), conditions:
tmajor = 22.2 min, tminor = 23.2 min.
Methyl (R)-2-Acetamido-3-(2-chlorophenyl)propanoate (2i).
White solid, purified by silica gel column chromatography (ethyl
acetate/petroleum ether, 1/2), 48.9 mg, 96% yield, 91% ee. 1H NMR
(400 MHz, DMSO-d6) δ 8.38 (d, J = 7.9 Hz, 1H), 7.39−7.25 (m,
3H), 7.23−7.12 (m, 1H), 4.46 (ddd, J = 9.6, 7.8, 5.4 Hz, 1H), 3.60 (s,
3H), 3.03 (dd, J = 13.7, 5.4 Hz, 1H), 2.86 (dd, J = 13.8, 9.6 Hz, 1H),
1.78 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 172.0, 169.4, 139.9,
132.8, 130.1, 129.0, 127.8, 126.6, 53.3, 51.9, 36.2, 22.2. The ee of 2i
was determined by GC analysis using a Agilent J&W GC column
(CP-Chirasil-V-Val for Optical Isomers 25 m 0.25 mm 0.12 μm P/N:
CP7495), conditions: tmajor = 27.3 min, tminor = 28.2 min.
2d′: White solid, purified by silica gel column chromatography
(ethyl acetate/petroleum ether, 1/2), 45.1 mg, 90% yield, 96% ee. 1H
NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 7.12 (d, J = 8.6 Hz, 2H),
6.84 (d, J = 8.6 Hz, 2H), 3.71 (s, 3H), 3.58 (s, 3H), 2.77 (s, 1H), 1.79
(s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 172.4, 169.4, 130.1,
129.0, 113.7, 55.0, 51.8, 22.3.
2h′: White solid, purified by silica gel column chromatography
(ethyl acetate/petroleum ether, 1/2), 44.5 mg, 93% yield, 93% ee. 1H
NMR (400 MHz, DMSO-d6) δ 8.44 (s, 1H), 7.42 (dd, J = 5.7, 3.6 Hz,
1H), 7.35−7.22 (m, 3H), 3.59 (s, 3H), 2.92 (s, 1H), 1.77 (s, 3H). 13C
NMR (101 MHz, DMSO-d6) δ 172.0, 169.4, 134.7, 133.3, 131.8,
129.3, 128.8, 127.1, 52.0, 22.3.
(R)-2-Amino-3-phenylpropanoic acid (3a). White solid. 1H NMR
(400 MHz, deuterium oxide) δ 7.41−7.23 (m, 5H), 3.93 (dd, J = 7.9,
5.1 Hz, 1H), 3.25 (s, 1H), 3.06 (dd, J = 14.5, 8.0 Hz, 1H), 2.89−2.81
(m, 1H), 1.70 (dtd, J = 10.8, 8.1, 5.3 Hz, 1H), 0.59−0.55 (m, 1H).
7144
J. Org. Chem. 2021, 86, 7141−7147