10.1002/ejoc.201801363
European Journal of Organic Chemistry
FULL PAPER
2-ammonio-2-((methylthio)methyl)pent-4-enoate (11)
recovered with AcOEt and washed two times with water. The organic
layer was dried with anhydrous Na2SO4, filtered and evaporated in vacuo.
The crude mixture was purified by flash chromatography to give 10b as a
yellow solid (57 mg, 75%). Rf = 0.20 (hexane/AcOEt 80:20); IR (neat, cm-
1): 3030, 2951, 2854, 1734, 1660, 1512, 1338, 1221; 1H NMR (CDCl3,
400 MHz, mixture of E/Z diastereoisomers). The integral of the isolated
signal at 6.22 ppm, belonging to the major diastereoisomer, was
arbitrarily assigned the value of one proton: δ 2.98 (dd, J = 7.5, 14.1 Hz,
1 H), 3.10 (ddd, J = 1.3, 8.1, 15.1 Hz, 0.5 H), 3.18 (d, J = 13.5 Hz, 0.5 H),
3.27 (d, J = 13.5 Hz, 1 H), 3.72 (s, 1.5 H), 3.81–3.94 (m, 4.5 H), 3.98 (d,
J = 13.5 Hz, 0.5 H), 4.03 (d, J = 13.5 Hz, 1 H), 5.75 (ddd, J = 6.6, 8.1,
11.9 Hz, 0.5 H), 6.22 (dt, J = 7.6, 15.4 Hz, 1 H), 6.54–6.61 (m, 1.5 H),
6.97–7.03 (m, 2.5 H), 7.05–7.10 (m, 2 H), 7.17–7.25 (m, 4.5 H), 7.36–
7.47 (m, 6 H), 7.49–7.56 (m, 1.5 H), 7.65–7.72 (m, 3 H), 8.12 (d, J = 8.8
Hz, 2 H), 8.22 (d, J = 8.8 Hz, 1 H); 13C{1H} NMR (CDCl3, 100 MHz,
mixture of E/Z diastereoisomers) δ 34.5 (t), 39.3 (t), 40.8 (t), 41.1 (t), 53.2,
53.4, 66.5 (s), 67.0 (s), 124.0, 124.3, 127.1, 127.2 (2C), 127.5, 127.6,
128.7, 128.8, 129.0, 129.1, 129.3, 129.6, 129.8, 129.9, 130.0, 130.8,
132.1 (2C), 132.6, 135.2 (s), 135.5 (s), 136.1 (s), 136.2 (s), 143.8 (s),
144.0 (s), 147.3 (s), 167.2 (s), 167.5 (s), 173.5 (s); HRMS (ESI) calcd. for
C26H24N2O5Na [M + Na]+ 467.1583; found 467.1586 (Δ = 0.6 ppm).
The title compound was prepared from compound 3d (163 mg, 0.592
mmol) according to the general procedure for the ring-opening of
azlactone ring under acidic conditions. The crude mixture was purified by
ion-exchange chromatography with Amberlite IR-120 (Plus)® resin as the
stationary phase. After the crude mixture was loaded onto the column,
the resin was washed with H2O until the eluted solution turned neutral,
then it was eluted with NH3 (10% aqueous solution). The fractions
containing the product were evaporated in vacuo to give 11 (110 mg,
98%) as a white solid. The product was crystalized from EtOH/H2O
(10:1.5) to afford the estimated optically pure (S)-enantiomer (65 mg, 59
22
22
%). [α]D = -4.1 (0.5 c, H2O, before crystallization), [α]D = -6.6 (0.5 c,
H2O, after crystallization). Melting point: 175-178 °C. IR (neat, cm-1):
3075, 2975, 2916, 1591, 1518, 1439, 1384, 1310; 1H NMR (D2O, 400
MHz) δ 1.99 (m, 1H), 2.05 (s, 3H), 2.13 (m, 1H), 2.37–2.47 (m, 2H),
2.48–2.68 (m, 2H), 5.17–5.28 (m, 2H), 5.58 (m, 1H); 13C{1H} NMR (D2O,
50 °C, 100 MHz) δ 14.8, 28.1 (t), 35.8 (t), 41.0 (t), 65.0 (s), 122.3 (t),
131.0, 175.1 (s); HRMS (ESI) calcd. for C8H16NO2S [M + H]+ 190.0902;
found 190.0904 (Δ = 1.1 ppm).
Synthesis of (E)-7-(4-benzyl-5-oxo-2-phenyl-4,5-dihydrooxazol-4-
yl)hept-5-enenitrile (12)
Acknowledgements
Financial support from Italian Ministry of Education, University
and Research (MIUR) is gratefully acknowledged (PRIN2015
prot. 20157WW5EH). The authors thank Enrico Torregrossa,
Francesco Zerilli and Nicola Ranalli for their valuable contributes.
Compound 3b (50 mg, 0,17 mmol) and 5-hexenenitrile (49 mg, 0.51
mmol) were dissolved in dry toluene (1.7 mL, 0.10 M) under nitrogen
atmosphere. Afterward, Hoveyda-Grubbs II generation catalyst (11 mg,
10% mol) was added and the reaction mixture was heated at 60 °C.
Reaction completion was monitored by TLC analysis, Rf
= 0.25
(hexane/AcOEt 80:20). After 5 hours the solvent was evaporated in
vacuo and the crude mixture was purified by flash chromatography to
give 9b as a pale yellow oil (50 mg, 81%). Rf = 0.19 (hexane/AcOEt
80:20); IR (neat, cm-1): 3031, 2922, 2851, 2246, 1814, 1654; 1H NMR
(CDCl3, 400 MHz, mixture of E/Z diastereoisomers). The integral of the
isolated quartet at 2.19 ppm, belonging to the major diastereoisomer,
was arbitrarily assigned the value of two protons: δ 1.63 (quintuplet, J =
7.1 Hz, 2 H), 1.72 (quintuplet, J = 7.2 Hz, 0.6 H), 2.11 (q, J = 7.1 Hz, 2 H),
2.19 (t, J = 7.1 Hz, 2 H), 2.26 (q, J = 7.2 Hz, 0.6 H), 2.34 (t, J = 7.2 Hz,
0.6 H), 2.65–2.87 (m, 2.6 H), 3.12–3.32 (m, 2.6 H), 5.37–5.50 (m, 1.6 H),
5.55 (dt, J = 7.0, 15.2 Hz, 1 H), 7.14–7.23 (m, 6.5 H), 7.42–7.49 (m, 2.6
H), 7.52–7.58 (m, 1.3 H), 7.84–7.90 (m, 2.6 H); 13C{1H} NMR (CDCl3, 75
MHz, mixture of E/Z diastereoisomers) δ 16.4 (t), 16.9 (t), 25.1 (t), 25.5
(t), 26.7 (t), 31.5 (t), 35.3 (t), 40.7 (t), 43.5 (t), 43.7 (t), 75.2 (s), 75.3 (s),
119.7 (s), 119.9 (s), 123.9, 124.9, 125.7 (s), 125.8 (s), 127.7, 128.2,
128.6, 129.1, 129.2, 130.5, 132.9, 133.1, 133.2, 134.5, 134.6 (2C), 160.5
(s, 2C), 179.2 (s), 179.4 (s); HRMS (ESI) calcd. for C23H22N2O2Na [M +
Na]+ 381.1579; found 381.1581 (Δ = 0.5 ppm).
Keywords: • quaternary amino acids • asymmetric synthesis•
allylation • asymmetric catalysis • palladium
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Synthesis of methyl 2-benzamido-2-benzyl-5-(4-nitrophenyl)pent-4-
enoate (13)
To a solution of 3b (50 mg, 0,17 mmol) in dry MeOH (1.7 mL, 0.10 M)
under nitrogen atmosphere, 1-bromo-4-nitrobenzene (38 mg, 0.19 mmol),
tetrabutylammonium acetate (0.16 g, 0.52 mmol) and Pd EnCat 30® (43
mg, 10% mmol) were added. The reaction mixture was heated at 120°C
for 15 minute by microwave irradiation. Reaction completion was
monitored by TLC analysis, Rf = 0.26 (hexane/AcOEt 80:20). The
reaction mixture was filtered with a Gooch apparatus to remove Pd
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