PAPER
C–C Bond Formation via Tandem Aldol Reaction/Hydrogenation
2581
Ethyl 2-Cyano-3-[4-(methylthio)phenyl]propanoate (5d)
1H NMR (300 MHz, CDCl3): d = 1.29 (t, J = 7.1 Hz, 3 H), 3.12–3.28
(m, 2 H), 3.67–3.72 (m, 1 H), 4.27 (q, J = 7.1 Hz, 2 H), 7.18–7.27
(m, 4 H).
13C NMR (75 MHz, CDCl3): d = 13.8, 15.5, 35.0, 39.5, 62.9, 116.0,
126.6, 129.4, 131.8, 138.0, 165.3.
HRMS (ESI): m/z calcd for C12H12NO2 [M – H]–: 202.0868; found:
202.0849.
Ethyl 2-Cyano-5-phenylpentanoate (5l)
1H NMR (300 MHz, CDCl3): d = 1.27–1.34 (m, 3 H), 1.81–1.98 (m,
3 H), 2.66–2.71 (m, 2 H), 3.45–3.50 (m, 2 H), 3.66–3.69 (m, 1 H),
4.22–4.30 (m, 2 H), 7.31–7.32 (m, 5 H).
HRMS (ESI): m/z calcd for C13H14NO2S [M – H]–: 248.0745;
found: 247.0765.
13C NMR (75 MHz, CDCl3): d = 14.0, 28.3, 29.241, 34.91, 37.4,
62.8, 116.4, 128.5, 128.5, 140.7, 166.0.
Ethyl 2-Cyano-3-(2-methoxyphenyl)propanoate (5e)
1H NMR (300 MHz, CDCl3): d = 1.28 (t, J = 7.2 Hz, 3 H), 3.08–3.15
(m, 1 H), 3.86 (s, 3 H), 3.33–3.40 (m, 1 H), 4.20–4.27 (q, J = 7.2 Hz,
2 H), 7.53–8.20 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 13.9, 31.5, 37.3, 55.2, 62.6, 110.3,
116.5, 120.6, 123.5, 129.7, 131.1, 157.3, 165.9.
HRMS (ESI): m/z calcd for C14H17NO2 [M – H]–: 230.1249; found:
230.1243.
tert-Butyl 2-Cyano-3-(4-nitrophenyl)propanoate (5m)
1H NMR (300 MHz, CDCl3): d = 1.47 (s, 9 H), 3.68–3.73 (m, 1 H),
3.25–3.38 (m, 2 H), 7.45 (d, J = 8.7 Hz, 2 H), 8.21 (d, J = 8.7 Hz, 2
H).
13C NMR (75 MHz, CDCl3): d = 27.6, 34.9, 39.6, 84.9, 115.9, 123.9,
130.1, 142.8, 147.4, 163.6.
HRMS (ESI): m/z calcd for C13H15NO3 [M – H]–: 232.1038; found:
232.1042.
Ethyl 3-(3-Chlorophenyl)-2-cyanopropanoate (5f)
1H NMR (300 MHz, CDCl3): d = 1.29 (t, J = 7.2 Hz, 3 H), 3.14–3.30
(m, 2 H), 3.70–3.75 (m, 1 H), 4.27 (q, J = 7.2 Hz, 2 H), 7.19–7.20
(m, 1 H), 7.29–7.30 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 13.9, 35.1, 39.2, 63.0, 115.7, 127.2,
127.9, 129.1, 130.1, 134.5, 137.1, 165.1.
HRMS (ESI): m/z calcd for C14H15N2O4 [M – H]–; 275.1032; found:
275.1032.
Benzyl 2-Cyano-3-(4-nitrophenyl)propanoate (5n)
1H NMR (300 MHz, CDCl3): d = 3.82–3.84 (m, 1 H), 3.32–3.35 (m,
2 H), 5.22 (s, 2 H), 7.30–7.39 (m, 7 H), 8.10–8.14 (d, J = 8.7 Hz, 2
H).
13C NMR (75 MHz, CDCl3): d = 35.0, 38.8, 68.8, 115.3, 124.0,
128.7, 128.7, 129.0, 130.1, 134.1, 142.1, 147.5, 164.6.
HRMS (ESI): m/z calcd for C12H11ClNO2 [M – H]–: 236.0478;
found: 236.0457.
Ethyl 2-Cyano-3-(3,4,5-trimethoxyphenyl)propanoate (5g)
1H NMR (300 MHz, CDCl3): d = 1.28 (t, J = 7.2 Hz, 3 H), 3.09–3.20
(m, 2 H), 3.68–3.73 (m, 1 H), 3.83 (s, 3 H, CH3), 3.86 (s, 6 H, CH3),
4.26 (q, J = 7.2 Hz, 2 H), 6.49 (s, 2 H).
13C NMR (75 MHz, CDCl3): d = 13.9, 36.0, 39.7, 56.0, 60.7, 62.9,
105.8, 116.2, 130.8, 137.3, 153.2, 165.4.
HRMS (ESI): m/z calcd for C17H13N2O4 [M – H]–: 309.0875; found:
309.0871.
Furan-2-ylmethyl 2-Cyano-3-(4-nitrophenyl)propanoate (5o)
1H NMR (300 MHz, CDCl3): d = 3.28 (m, 2 H), 3.82–3.88 (m, 1 H),
5.18 (m, 2 H), 6.38–6.39 (m, 1 H), 6.46–6.49 (m, 1 H), 7.38–7.48
(m, 3 H), 8.14–8.17 (d, J = 6.4 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 34.8, 38.7, 59.9, 110.7, 112.0,
115.2, 123.8, 130.0, 142.2, 143.7, 147.3, 164.5.
HRMS (ESI): m/z calcd for C15H18NO5 [M – H]–: 292.1185; found:
292.1180.
Ethyl 2-Cyano-3-(furan-2-yl)propanoate (5h)
HRMS (ESI): m/z calcd for C15H11N2O5 [M – H]–: 299.0668; found:
299.0665.
1H NMR (300 MHz, CDCl3): d = 1.31 (t, J = 7.2 Hz, 3 H, CH3),
3.23–3.36 (m, 2 H), 3.81–3.86 (m, 1 H), 4.29 (q, J = 7.2 Hz, 2 H),
6.25–6.26 (m, 1 H), 6.32–6.34 (m, 1 H), 7.37 (m, 1 H).
Thiophen-2-ylmethyl 2-Cyano-3-(4-nitrophenyl)propanoate
(5p)
13C NMR (75 MHz, CDCl3): d = 13.8, 28.4, 37.0, 63.0, 108.3, 110.5,
115.8, 142.5, 148.8, 165.1.
HRMS (ESI): m/z calcd for C10H11NO3 [M – H]–: 192.0661; found:
192.0645.
1H NMR (300 MHz, CDCl3): d = 3.17–3.34 (m, 2 H), 3.81–3.85 (m,
1 H), 5.36 (m, 2 H), 6.97–7.01 (m, 1 H), 7.10–7.11 (m, 1 H), 7.34–
7.37 (m, 3 H), 8.10–8.12 (d, J = 6.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 35.0, 38.7, 62.5, 115.205, 124.0,
127.0, 127.9, 129.7, 130.1, 135.7, 142.0, 147.5, 164.6.
HRMS (ESI): m/z calcd for C15H11N2O4S [M – H]–: 315.0440;
found: 315.0437.
Ethyl 2-Cyano-3-(thiophen-2-yl)propanoate (5i)
1H NMR (300 MHz, CDCl3): d = 1.3 (t, J = 6.9 Hz, 3 H), 3.4–3.5
(m, 2 H), 3.75–3.77 (m, 1 H), 4.24–4.31 (q, J = 6.9 Hz, 2 H), 6.97–
7.00, 7.22–7.24 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 13.9, 29.8, 39.8, 63.1, 115.9, 125.3,
Supporting Information for this article is available online at
127.2, 127.3, 136.6, 165.0.
HRMS (ESI): m/z calcd for C10H10NO2S [M – H]–: 208.0432;
found: 208.0447.
Acknowledgment
Ethyl 2-Cyano-3-phenylpropanoate (5j)
1H NMR (300 MHz, CDCl3): d = 1.27 (t, J = 7.2 Hz, 3 H), 3.16–3.32
(m, 2 H), 3.90–3.74 (m, 1 H), 4.20–4.27 (q, J = 7.2 Hz, 2 H), 7.26–
7.38 (m, 5 H).
We gratefully acknowledge the financial support from the National
Natural Science Foundation of China (Grants 20721003 and
20872153), International Collaboration Projects (Grants
20720102040), the 863 Hi-Tech Program of China (Grant
2006AA020602), and National
(2009ZX09501-001 and 2009ZX09501-010).
13C NMR (75 MHz, CDCl3): d = 13.9, 35.7, 39.6, 62.9, 116.1, 127.7,
128.8, 129.0, 135.2, 165.5.
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Synthesis 2010, No. 15, 2577–2582 © Thieme Stuttgart · New York