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yield 53 mg (0.22 mmol, 75 %), yellowish oil. 1H NMR (400 MHz,
2-Fluoro-1-phenyl-3-(p-tolylthio)propan-1-one (16d): From 2-
fluoro-1-phenylprop-2-en-1-one (7d; 25 mg, 0.17 mmol), yield
CDCl ): δ = 1.30 (m, 4 H), 1.46 (m, 2 H), 1.56 (m, 4 H), 1.69 (m, 2 H),
3
1
1
.82 (m, 4 H), 2.50 (m, 4 H), 2.74 (m, 1 H), 2.83 (m, 2 H), 5.01 (ddd,
36 mg (0.13 mmol, 83 %), brown oil. H NMR (400 MHz CDCl ): δ =
,
3
1
3
J = 3.9, J = 5.5, J = 50.8 Hz, 1 H, CHF) ppm. C NMR (400 MHz,
CDCl ): δ = 24.0 (CH ), 25.6 (2 CH ), 25.8 (CH ), 26.0 (2 CH ), 27.8,
2.34 (s, 3 H), 2.85 (m, 1 H), 3.33 (ddd, J = 7.8, J = 14.7 Hz, J = 17.7 Hz,
1 H), 3.48 (ddd, J = 4.3, J = 14.7 Hz, J = 26.0 Hz, 1 H), 5.61 (ddd, J =
4.3, J = 7.7 Hz, J = 48.4 Hz, 1 H, CHF), 7.13 (d, J = 7.8 Hz, 1 H), 7.35
(d, J = 7.8 Hz, 1 H), 7.42–7.47 (m, 2 H), 7.57–7.62 (m, 1 H), 7.87 (m,
2 H) ppm. 13C NMR (101 MHz, CDCl ): δ = 21.1 (CH ), 37.1 (d, J =
3
3
2
2
2
2
7.9 (2 CH ), 46.3 (CH), 55.1 (2 CH ), 60.4 (d, J = 19.4 Hz, CH ), 94.8
2 2 2
1
9
(d, J = 187.5 Hz, CHF), 211.9 (d, J = 22.7 Hz) ppm. F NMR (282 MHz,
CDCl ): δ = –190.1 (ddt, J = 3.0, J = 27.4 Hz, J = 50.8 Hz) ppm. HRMS
3
3
3
+
(
ESI): calcd. for C H FNONa [M + Na] 264.1740; found 264.1734.
22.8 Hz, CH ), 91.2 (d, J = 186.8 Hz, CHF), 128.7 (CH), 129.0 (C), 130.0
14
24
2
(
CH), 130.7 (CH), 131.8 (CH), 134.0 (C), 134.2 (CH), 137.6 (C), 211.1
2
-Fluoro-1-phenyl-3-(piperidin-1-yl)propan-1-one (15d): From 2-
19
(d, J = 23.1 Hz) ppm. F NMR (282 MHz, CDCl ): δ = –196.8 (ddd,
3
fluoro-1-phenylprop-2-en-1-one (7d; 53 mg, 0.20 mmol), yield
J = 17.7, J = 25.8 Hz, J = 48.3 Hz) ppm. HRMS (ESI): calcd. for
C H FOSNa [M + Na] 297.0725; found 297.0727.
1
5
3 mg (0.22 mmol, 75 %), yellowish oil. H NMR (101 MHz, CDCl ):
+
3
16 15
δ = 1.43 (m, 2 H), 1.57 (m, 4 H), 2.54 (m, 4 H), 2.89 (m, 1 H), 2.99
Methyl (2S)-2-[(tert-Butoxycarbonyl)amino]-3-[(2-fluoro-3-oxo-
decyl)thio]propanoate (17a): From 2-fluorodec-1-en-3-one (7a;
6
(m, 1 H), 5.80 (ddd, J = 4.0, J = 5.9 Hz, J = 50.4 Hz, 1 H, CHF), 7.49
1
3
(m, 2 H), 7.59 (m, 1 H), 7.97 (m, 2 H) ppm. C NMR (75 MHz, CDCl3):
3 mg, 0.37 mmol), yield 82 mg (0.20 mmol, 54 %), yellow solid,
δ = 23.9 (CH ), 25.9 (2 CH ), 54.9 (2 CH ), 60.6 (d, J = 20.9 Hz, CH ),
2
2
2
2
1
m.p. 38 °C. H NMR (400 MHz, CDCl ): δ = 0.88 (t, J = 7.0 Hz, 3 H),
9
1
4.1 (d, J = 185.4 Hz, CHF), 128.7 (2 CH), 127.8 (2 CH), 134.5 (CH),
34.6 (C), 196.1 (d, J = 19.2 Hz) ppm. F NMR (282 MHz, CDCl3):
3
1
9
1.24–1.30 (m, 8 H), 1.45 (s, 9 H), 1.55–1.63 (m, 2 H), 2.61–2.66 (m, 2
H), 2.94 (m, 2 H), 3.04 (m, 2 H), 3.77 (s, 3 H), 4.54–4.56 (m, 1 H), 4.92
(ddd, J = 3.7, J = 6.7 Hz, J = 49.2 Hz, 1 H, CHF), 5.34–5.36 (m, 1 H,
NH) ppm. 13C NMR (101 MHz, CDCl ): δ = 14.1 (CH ), 22.5 (CH ),
28.3–29.0 (3 CH ), 28.7 (3 CH ), 33.9 (d, J = 21.5 Hz, CH ), 35.6 (d,
J = 9.4 Hz, CH ), 39.0 (d, J = 5.3 Hz, CH ), 45.7 (CH ), 52.6 (CH ),
2 2 2 3
δ = –186.9 (dm, J = 50.5 Hz) ppm. HRMS (ESI): calcd. for
C H FNONa [M + Na] 258.1270; found 258.1271.
+
14 18
3
3
2
2
-Fluoro-1-(p-tolylthio)decan-3-one (16a): From 2-fluorodec-1-
2 2 2
en-3-one (7a; 36 mg, 0.21 mmol), yield 53 mg (0.18 mmol, 86 %),
colorless oil. H NMR (300 MHz, CDCl ): δ = 0.88 (t, J = 6.9 Hz, 3 H),
1
1
3
52.2/53.3 (CH), 80.2 (C), 95.5 (d, J = 187.8 Hz, CHF), 155.1 (C), 171.3
.24–1.31 (m, 8 H), 1.53–1.65 (m, 2 H), 2.33 (s, 3 H), 2.63 (td, J = 3.1, (C), 208.6 (d, J = 24.4 Hz) ppm. 19F NMR (282 MHz, CDCl ): δ =
3
+
J = 7.3 Hz, 2 H), 3.19 (ddd, J = 7.2, J = 14.6 Hz, J = 22.7 Hz, 1 H),
–190.1 (m) ppm. HRMS (ESI): calcd. for C H FNO SNa [M + Na]
430.2039; found 430.2036.
19
34
5
3
.37 (ddd, J = 3.7, J = 14.6 Hz, J = 24.7 Hz, 1 H), 4.84 (ddd, J = 3.7,
J = 7.2 Hz, J = 49.2 Hz, 1 H, CHF), 7.10–7.14 (m, 2 H), 7.30–7.37 (m,
H) ppm. 13C NMR (75 MHz, CDCl ): δ = 14.1 (CH ), 21.1 (CH ), 22.5
Methyl (2S)-2-[(tert-Butoxycarbonyl)amino]-3-[(2-fluoro-3-oxo-
hexadecyl)thio]propanoate (17b): From 2-fluorohexadec-1-en-3-
one (7b; 50 mg, 0.20 mmol), yield 56 mg (0.11 mmol, 58 %), yellow
solid, m.p. 47 °C. H NMR (400 MHz, CDCl ): δ = 0.87 (t, J = 6.9 Hz,
3
(
(
5
2
2
3
3
3
(CH ), 22.7 (CH ), 29.0–31.7 (3 CH ), 36.9 (d, J = 19.7 Hz, CH ), 38.9
2 2 2 2
(CH ), 93.9 (d, J = 188.4 Hz, CHF), 129.9 (2 CH), 130.8 (C), 131.4 (2
2
1
1
9
3
CH), 137.4 (C), 208.9 (d, J = 25.4 Hz) ppm. F NMR (282 MHz, CDCl3):
δ = –190.0 to –190.2 (dm, J = 49.1 Hz) ppm. HRMS (ESI): calcd. for
C H FSONa [M + Na] 319.1508; found 319.1507.
H), 1.26–1.33 (m, 20 H), 1.45 (s, 9 H), 1.55–1.63 (m, 2 H), 2.58–2.71
m, 2 H), 2.87–3.00 (m, 2 H), 2.99 (m, 2 H), 3.77 (s, 3 H), 4.52–4.59
+
17 25
m, 1 H), 4.92 (ddd, J = 3.5, J = 6.9 Hz, J = 49.2 Hz, 1 H, CHF), 5.33–
.35 (m, 1 H) ppm. 13C NMR (101 MHz, CDCl ): δ = 14.1 (CH ), 22.5,
2
-Fluoro-1-(p-tolylthio)hexadecan-3-one (16b): From 2-fluoro-
3 3
2.7 (2 CH ), 28.7 (3 CH ), 29.1–29.6 (9 CH ), 33.9 (d, J = 21.6 Hz,
hexadec-1-en-3-one (7b; 50 mg, 0.20 mmol), yield 63 mg
2
3
2
1
CH ), 35.5 (d, J = 1.8 Hz, CH ), 39.0 (d, J = 5.3 Hz, CH ), 45.3 (CH ),
5
(
0.18 mmol, 88 %), yellow solid, m.p. 45 °C. H NMR (300 MHz,
2 2 2 2
2.6 (CH ), 52.2/53.3 (CH), 80.3 (C), 95.5 (d, J = 187.5 Hz, CHF), 155.1
CDCl ): δ = 0.87 (t, J = 6.9 Hz, 3 H), 1.21–1.33 (m, 20 H), 1.49–1.57
3
3
19
(C), 171.3 (C), 208.6 (d, J = 24.6 Hz) ppm. F NMR (282 MHz, CDCl3):
(m, 2 H), 2.32 (s, 3 H), 2.62 (m, 2 H), 3.18 (ddd, J = 7.2, J = 14.6 Hz,
δ = –190.1 (m) ppm. HRMS (ESI): calcd. for C H FNO SNa [M +
Na] 514.2978; found 514.2970.
J = 22.5 Hz, 1 H), 3.37 (ddd, J = 3.7, J = 14.6 Hz, J = 24.7 Hz, 1 H),
25 46
5
+
4
.84 (ddd, J = 3.7, J = 7.2 Hz, J = 49.2 Hz, 1 H, CHF), 7.11–7.13 (m,
1
3
2
H), 7.32–7.35 (m 2 H) ppm. C NMR (75 MHz, CDCl ): δ = 14.1
3
Methyl (2S)-2-[(tert-Butoxycarbonyl)amino]-3-[(3-cyclohexyl-2-
fluoro-3-oxopropyl)thio]propanoate (17c): From 1-cyclohexyl-2-
fluoroprop-2-en-1-one (7c; 31 mg, 0.20 mmol), yield 42 mg
(CH ), 21.0 (CH ), 22.5 (CH ), 22.7 (CH ), 29.1–29.8 (9 CH ), 31.9 (t,
3 3 2 2 2
C-4), 45.6 (d, J = 21.0 Hz), 94.4 (d, J = 186.4 Hz, CHF), 113.5 (2 CH),
1
18.6 (2 CH), 129.4 (C), 146.9 (C), 209.4 (d, J = 24.2 Hz) ppm. 19
F
1
(
0.11 mmol, 54 %), yellow oil. H NMR (400 MHz, CDCl ): δ = 1.22–
3
NMR (282 MHz, CDCl ): δ = –190.1 (dtt, J = 3.0, J = 23.7 Hz, J =
3
1.37 and 1.66–1.90 (m, 10 H), 1.45 (s, 9 H), 2.82–2.88 (m, 1 H), 2.90–
3.10 (m, 4 H), 3.77 (s, 3 H), 4.54–4.56 (m, 1 H), 5.00 (ddt, J = 3.5, J =
6
+
5
4
0.3 Hz) ppm. HRMS (ESI): calcd. for C23H37FOSNa [M + Na]
03.2447; found 403.2448.
13
.9 Hz, J = 49.0 Hz, 1 H, CHF), 5.32–5.35 (m, 1 H) ppm. C NMR
(
101 MHz, CDCl ): δ = 25.4, 25.6 (2 CH ), 25.8 (CH ), 27.3, 28.1 (2
3 2 2
1
-Cyclohexyl-2-fluoro-3-(p-tolylthio)propan-1-one (16c): From 1-
CH ), 28.7 (3 CH ), 34.0 (d, J = 21.5 Hz, CH ), 35.6 (d, J = 10.5 Hz,
CH), 46.3 (CH
1
NMR (282 MHz, CDCl ): δ = –191.3, –191.4 (m) ppm. HRMS (ESI):
calcd. for C H FNO SNa [M + Na] 414.1726; found 414.1716.
2
2
2
cyclohexyl-2-fluoroprop-2-en-1-one (7c; 36 mg, 0.23 mmol), yield
1
2
), 52.7 (CH
3
), 52.2/53.3 (CH), 80.2 (C), 95.1 (dd, J =
4
9 mg (0.17 mmol, 88 %), colorless oil. H NMR (400 MHz, CDCl ):
3
1
9
87.7 Hz, CHF), 155.1 (C), 171.3 (C), 210.9 (d, J = 23.1 Hz) ppm.
F
δ = 1.17–1.87 (m, 10 H), 2.33 (s, 3 H), 2.85 (m, 1 H), 3.18 (ddd, J =
3
7
1
4
.5, J = 14.5 Hz, J = 21.4 Hz, 1 H, 1-CH ), 3.38 (ddd, J = 3.6, J =
4.6 Hz, J = 26.0 Hz, 1 H, 1-CH ), 4.92 (ddd, J = 3.6, J = 7.6 Hz, J =
9.9 Hz, 1 H, CHF), 7.09–7.30 (m, 2 H), 7.30–7.39 (m, 2 H) ppm.
2
+
18
30
5
2
13
C
Methyl (2S)-2-[(tert-Butoxycarbonyl)amino]-3-[(2-fluoro-3-oxo-
3-phenylpropyl)thio]propanoate (17d): From 2-fluoro-1-phenyl-
NMR (101 MHz, CDCl ): δ = 21.6 (CH ), 25.4, 25.6, 25.7 (3 CH ), 26.9
3
3
2
(
(
(
CH ), 27.4, 28.0 (2 CH ), 37.0 (d, J = 21.8 Hz, CH ), 46.4 (CH), 93.5
prop-2-en-1-one (7d; 26 mg, 0.17 mmol), yield 36 mg (0.15 mmol,
2
2
2
1
d, J = 188.9 Hz, CHF), 128.5 (2 CH), 129.9 (C), 131.3 (2 CH), 137.3
83 %), yellow oil. H NMR (400 MHz, CDCl ): δ = 1.45 (s, 9 H), 3.02–
3
1
9
C), 211.1 (d, J = 23.1 Hz) ppm. F NMR (282 MHz, CDCl ): δ = 3.19 (m, 4 H), 3.76 (s, 3 H), 4.56 (m, 1 H), 5.63–5.80 (m, 1 H, CHF),
3
–
196.8 (dddd, J = 3.3, J = 21.4 Hz, J = 25.4 Hz, J = 50.2 Hz) ppm.
HRMS (ESI): calcd. for C16H21FOSNa [M + Na]+ 303.1195; found
03.1188.
5.34–5.36 (m, 1 H), 5.63–5.80 (m, 1 H), 7.49–7.52 (m, 2 H), 7.61–7.65
13
(m, 1 H), 7.97–7.99 (m, 2 H) ppm. C NMR (101 MHz, CDCl ): δ =
3
3
28. 3 (3 CH ), 34.0 (d, J = 21.5 Hz, CH ), 35.6 (d, J = 10.7 Hz, C), 41.7
2
2
Eur. J. Org. Chem. 2016, 1751–1759
www.eurjoc.org
1757
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim