H
Synthesis
P. Spránitz et al.
Paper
1
3-(4-Chlorobenzoyl)-5-methoxy-5-oxopentanoic Acid (22)
H NMR (500 MHz, CDCl ): δ = 7.74–7.69 (m, 1 H), 7.40–7.34 (m, 1 H),
3
7
(
2
.29–7.22 (m, 2 H), 4.09 (quint., J = 6.8 Hz, 1 H), 3.62 (s, 3 H), 2.81
ddd, J = 33.8, 16.8, 6.9 Hz, 2 H), 2.54 (ddd, J = 19.7, 16.8, 6.6 Hz, 2 H),
.42 (s, 3 H).
Yield: 241 mg (85%); colourless oil; ee: 93%; t = 9.0 (major), 10.0 (mi-
nor) min (Chiralpak IB; 85% hexane/15% EtOH; 1 mL/min; 20 °C; λ =
R
256 nm; 20 μL).
13
1
C NMR (125 MHz, CDCl ): δ = 203.7, 177.3, 171.8, 138.6, 136.6,
H NMR (500 MHz, CDCl ): δ = 7.91 (d, J = 8.7 Hz, 2 H), 7.43 (d, J =
3
3
131.8, 131.4, 128.3, 125.8, 51.9, 41.8, 34.9, 34.8, 20.6.
8
3
.6 Hz, 2 H), 4.20 (quint., J = 6.9 Hz, 1 H), 3.61 (s, 3 H), 2.82 (ddd, J =
1.5, 16.8, 7.2 Hz, 2 H), 2.53 (td, J = 17.2, 6.6 Hz, 2 H).
HRMS (ESI): m/z [M + H]+ calcd for C14H17ClO : 265.1076; found:
5
13
265.1068.
C NMR (125 MHz, CDCl ): δ = 199.5, 177.1, 171.7, 139.9, 133.9,
3
130.0, 129.1, 52.0, 38.5, 35.7, 35.4.
HRMS (ESI): m/z [M + H]+ calcd for C13H14ClO : 285.0530; found:
3-(3-Fluorobenzoyl)-5-methoxy-5-oxopentanoic Acid (27)
5
285.0522.
Yield: 206 mg (77%); colourless oil; ee: 89%; t
= 18.5 (minor), 23.5
R
(major) min (Chiralpak AD; 50% hexane/50% IPA; 1 mL/min; 20 °C; λ =
2
44 nm; 20 μL).
3
-(2-Fluorobenzoyl)-5-methoxy-5-oxopentanoic Acid (23)
1
H NMR (500 MHz, CDCl ): δ = 10.28 (s, 1 H), 7.73 (d, J = 7.8 Hz, 1 H),
Yield: 225 mg (84%); colourless oil; ee: 75%; tR = 12.3 (minor), 17.3
major) min (Chiralpak AD; 50% hexane/50% IPA; 1 mL/min; 20 °C; λ =
3
7.62 (d, J = 9.4 Hz, 1 H), 7.42 (td, J = 7.9, 5.3 Hz, 1 H), 7.24 (ddd, J =
(
10.8, 6.6, 2.5 Hz, 1 H), 4.17 (t, J = 6.9 Hz, 1 H), 3.59 (s, 3 H), 2.80 (ddd,
239 nm; 20 μL).
J = 16.6, 12.9, 6.9 Hz, 2 H), 2.51 (dd, J = 16.9, 6.6 Hz, 2 H).
1
H NMR (500 MHz, CDCl ): δ = 7.81 (td, J = 7.6, 1.8 Hz, 1 H), 7.51
3
13
C NMR (125 MHz, CDCl ): δ = 199.7, 177.0, 171.8, 162.9 (d, J =
(
(
dddd, J = 8.6, 7.1, 5.0, 1.8 Hz, 1 H), 7.22 (td, J = 7.6, 1.1 Hz, 1 H), 7.12
ddd, J = 11.2, 8.3, 1.0 Hz, 1 H), 4.08 (quint., J = 6.7 Hz, 1 H), 3.63 (s,
3
2
3
3
47.9 Hz), 137.7 (d, J = 6.2 Hz), 130.4 (d, J = 7.6 Hz), 124.2 (d, J =
.1 Hz), 120.4 (d, J = 21.4 Hz), 115.3 (d, J = 22.5 Hz), 52.0, 38.9, 35.6,
5.5.
3
H), 2.88 (dddd, J = 22.5, 16.7, 6.8, 1.4 Hz, 2 H), 2.63–2.48 (m, 2 H).
13
C NMR (125 MHz, CDCl ): δ = 198.6, 177.2, 171.8, 161.2 (d, J =
3
HRMS (ESI): m/z [M + H]+ calcd for C13H14FO : 269.0825; found:
254.1 Hz), 134.7 (d, J = 9.2 Hz), 131.2 (d, J = 2.4 Hz), 124.7 (d, J =
3.2 Hz), 124.7 (d, J = 13.9 Hz), 116.6 (d, J = 23.9 Hz), 51.9, 43.2 (d, J =
6.6 Hz), 34.8 (d, J = 16.7 Hz).
5
269.08177.
HRMS (ESI): m/z [M + H]+ calcd for C13H14FO : 269.0825; found:
3-(3-Chlorobenzoyl)-5-methoxy-5-oxopentanoic Acid (28)
Yield: 170 mg (60%); colourless oil; ee: 94%; t = 19.5 (minor), 25.5
major) min (Chiralpak AD; 50% hexane/50% IPA; 1 mL/min; 20 °C; λ =
5
269.0817.
R
(
2
43 nm; 20 μL).
3
-(2-Chlorobenzoyl)-5-methoxy-5-oxopentanoic Acid (24)
1
H NMR (500 MHz, CDCl ): δ = 7.93 (s, 1 H), 7.85 (dt, J = 7.8, 1.4 Hz,
Yield: 219 mg (77%); colourless oil; ee: 49%; tR = 12.2 (minor), 23.5
major) min (Chiralpak AD; 50% hexane/50% IPA; 1 mL/min; 20 °C; λ =
3
1
7
2
H), 7.61–7.50 (m, 1 H), 7.41 (t, J = 7.9 Hz, 1 H), 4.20 (quint., J =
.0 Hz, 1 H), 3.63 (s, 3 H), 2.83 (ddd, J = 28.7, 16.9, 7.1 Hz, 2 H), 2.64–
.48 (m, 2 H).
(
263 nm; 20 μL).
1
H NMR (500 MHz, CDCl ): δ = 10.15 (s, 1 H), 7.69–7.51 (m, 1 H),
3
13
C NMR (125 MHz, CDCl ): δ = 199.5, 176.9, 171.6, 137.2, 135.2,
7.42–7.30 (m, 3 H), 4.06 (quint., J = 6.8, 6.0 Hz, 1 H), 3.64 (s, 3 H),
3
133.3, 130.1, 128.6, 126.6, 52.0, 38.7, 35.6, 35.4.
2.94–2.79 (m, 2 H), 2.66–2.53 (m, 2 H).
HRMS (ESI): m/z [M + H]+ calcd for C13H14ClO : 285.0530; found:
13
C NMR (125 MHz, CDCl ): δ = 202.0, 177.0, 171.7, 137.7, 131.9,
5
3
285.0522.
131.1, 130.5, 129.5, 127.0, 52.0, 43.1, 34.3, 34.2.
HRMS (ESI): m/z [M + H]+ calcd for C13H14ClO : 285.0530; found:
5
5-Methoxy-3-(3-methylbenzoyl)-5-oxopentanoic Acid (29)
285.0521.
Yield: 200 mg (76%); colourless oil; ee: 91%; tR = 18.5 (minor), 25.5
major) min (Chiralpak AD; 50% hexane/50% IPA; 1 mL/min; 20 °C; λ =
(
3
-(2-Bromobenzoyl)-5-methoxy-5-oxopentanoic Acid (25)
254 nm; 20 μL).
Yield: 183 mg (56%); colourless oil; ee: 37%; tR = 13.1 (minor), 25.5
major) min (Chiralpak AD; 50% hexane/50% IPA; 1 mL/min; 20 °C; λ =
1
H NMR (500 MHz, CDCl ): δ = 7.78 (d, J = 6.2 Hz, 2 H), 7.45–7.32 (m,
(
3
2
1
H), 4.27 (quint., J = 7.0 Hz, 1 H), 3.64 (s, 3 H), 2.86 (ddd, J = 27.5,
6.8, 6.9 Hz, 2 H), 2.54 (td, J = 16.3, 6.9 Hz, 2 H), 2.41 (s, 3 H).
247 nm; 20 μL).
1
H NMR (500 MHz, CDCl ): δ = 10.19 (s, 1 H), 7.59 (ddd, J = 7.6, 5.1,
3
13
C NMR (125 MHz, CDCl ): δ = 200.6, 177.0, 171.8, 138.7, 135.4,
1
4
6
.4 Hz, 2 H), 7.37 (td, J = 7.5, 1.1 Hz, 1 H), 7.29 (td, J = 7.7, 1.7 Hz, 1 H),
.05 (quint., J = 6.7 Hz, 1 H), 3.63 (s, 3 H), 2.85 (ddd, J = 31.8, 17.0,
.6 Hz, 2 H), 2.58 (ddd, J = 18.8, 17.0, 6.8 Hz, 2 H).
3
134.2, 129.0, 128.7, 125.7, 51.9, 38.7, 35.6, 35.3, 21.3.
HRMS (ESI): m/z [M + H]+ calcd for C14H17O : 265.1076; found:
5
13
265.1069.
C NMR (125 MHz, CDCl ): δ = 202.6, 177.2, 171.7, 139.7, 133.8,
3
131.9, 129.3, 127.4, 119.3, 52.0, 43.0, 34.2, 34.2.
HRMS (ESI): m/z [M – H]– calcd for C13H12BrO : 326.9868; found:
3-Acetyl-5-methoxy-5-oxopentanoic Acid (30)
5
326.9874
Yield: 112 mg (60%); white crystals; decomposition at 89–96 °C; ee:
78%; tR = 51.0 (minor), 57.5 (major) min (Chiralpak OJ; 70% hex-
ane/30% IPA; 1 mL/min; 20 °C; λ = 265 nm; 20 μL).
5
-Methoxy-3-(2-methylbenzoyl)-5-oxopentanoic Acid (26)
1
H NMR (500 MHz, DMSO-d ): δ = 3.56 (s, 3 H), 3.12 (t, J = 6.8 Hz, 1 H),
Yield: 201 mg (76%); colourless oil; ee: 74%; tR = 10.4 (minor), 23.2
major) min (Chiralpak AD; 50% hexane/50% IPA; 1 mL/min; 20 °C; λ =
47 nm; 20 μL).
6
2.60 (ddd, J = 30.6, 16.8, 7.5 Hz, 2 H), 2.42 (ddd, J = 25.6, 16.8, 5.9 Hz,
(
2
2
H), 2.15 (s, 3 H).
Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–J