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0.80 (m, 3H). 13C NMR (75.46 MHz, CDCl3) d (ppm): 209.6, Boc-D-phenylalaninal 14 (149 mg, 0.6 mmol) and the distillated
198.4, 138.3, 136.7, 133.3, 130.0, 130.0, 129.2, 128.7, 128.5, DBU (22 mL, 0.15 mmol), then chalcone (104 mg, 0.5 mmol).
ꢀ
128.2, 127.6, 53.4, 42.5, 42.0 32.1, 29.6, 29.5, 29.5, 29.4, 29.1, Reaction was stirred 20 hours at 75 C. The crude was puried
27.0, 22.5, 14.2. IR (ATR) n (cmꢁ1): 2927, 2855, 1713, 1683, 1598, by ash chromatography over silica-gel (pentane/EtOAc 95/5 to
+
1450, 1400, 1202, 753, 690. HRMS (ESI) m/z calcd for C31H43O2
90/10) to provide product 23 as a yellow oil (84 mg, 37%). A
[M + H]+ 447.32576, found 447.32574. NMR spectra for mixture of two diastereoisomeres d1 and d2 (d.r. ¼ 59 : 41) was
compound 20 are reported in the ESI.†
obtained which were not separated.
1
Compound 21. Synthesized according to the general proce-
Rf: 0.2 (EP/AcOEt: 95/5). H NMR (300 MHz, CDCl3) d (ppm)
dure for Stetter reaction in water. Azolium salt 8 (113 mg, 8.02–7.87 (m, 2H, d1 + d2), 7.63–6.89 (m, 13H, d1 + d2), 5.21 (d, J
30 mol%) was added to water (0.6 mL) in a Schlenk tube, then ¼ 9 Hz, 1H, d1), 5.08 (d, J ¼ 9 Hz, 1H, d2), 4.79–4.52 (m, 2H, d1 +
tetrahydro-2H-pyran-2-ol 12 (111 mL, 1.2 mmol) and the dis- d2), 4.08–3.86 (m, 1H, d1 + d2), 3.44–2.98 (m, 2.4H, d1 + d2),
tillated DBU (45 mL, 0.3 mmol), then chalcone (208 mg, 1 2.76 (dd, J ¼ 7.5 Hz, 13.8 Hz, 0.6H, d1) 1.54–1.12 (m, 9H, d1 +
mmol). Reaction was stirred 20 hours at 75 C. The crude was d2). 13C NMR (75.5 MHz, CDCl3) d (ppm) 207.7, 206.9 (d1 and
ꢀ
puried by ash chromatography over silica-gel (CH2Cl2/MeOH d2), 198.1, 197.7 (d1 and d2), 155.4, 154.8 (d1 and d2), 137.3,
from 100/0 to 99/1) to provide product 21 as a yellow oil (216 mg, 137.1, 136.7, 136.5, 136.4, 133.4, 133.4, 129.8, 129.5, 129.3,
70%).
129.2, 128.7, 128.5, 128.2, 127.9, 127.7, 126.8, 126.4 (d1 and d2),
Rf: 0.43 (CH2Cl2). 1H NMR (300 MHz, CDCl3) d (ppm) 7.88 (d, 79.9, 79.5 (d1 and d2), 59.2, 58.7 (d1 and d2), 50.9, 50.0 (d1 and
J ¼ 8.1 Hz, 2H), 7.58–7.06 (m, 8H), 4.36 (dd, J ¼ 3.6 Hz, 10.5 Hz, d2), 43.1, 42.4 (d1 and d2), 38.0, 36.7 (d1 and d2), 29.8, 28.4,
1H), 3.98 (dd, J ¼ 10.5 Hz, 18 Hz, 1H), 3.44 (t, J ¼ 6.3 Hz, 2H), 28.4, 28.0 (d1 and d2). IR (ATR) n (cmꢁ1) 3379, 3063, 3030, 3005,
3.07 (dd, J ¼ 3.3 Hz, 18 Hz, 1H), 2.76 (brs, 1H), 2.71–2.36 (m, 2977, 2929, 1706, 1684, 1599, 1582, 1494, 1452, 1392, 1366,
2H), 1.70–1.29 (m, 4H). 13C NMR (75.5 MHz, CDCl3) d (ppm) 1333, 1286, 1245, 1206, 1164, 1076, 1054, 1004, 987, 946, 911,
209.5, 198.2, 137.9, 136.3, 133.2, 129.0, 128.4, 128.2, 128.0, 860, 751, 732, 697, 648, 618, 558, 522. HRMS (ESI) m/z calcd for
127.5, 61.9, 53.1, 42.3, 41.2, 31.7, 19.6. IR (ATR) n (cmꢁ1) 3402,
C
29H32NO4+ [M + H]+ 458.23258, found 458.23274. NMR spectra
2935, 2864, 1712, 1681, 1598, 1581, 1494, 1450, 1073, 754, 696. for compound 23 are reported in the ESI.†
HRMS (ESI) m/z calcd for C20H21O3ꢁ [M ꢁ H+] 309.14962, found
Compound 24. Synthesized according to the general proce-
309.14921. NMR spectra for compound 21 are reported in the dure for Stetter reaction in water. Azolium salt 8 (57 mg, 0.15
ESI.†
mmol) was added to water (0.3 mL) in a Schlenk tube, then
Compound 22. Synthesized according to the general proce- anisaldehyde 15 (73 mL, 0.6 mmol) and the distillated DBU (22
dure for Stetter reaction in water. Azolium salt 8 (57 mg, 0.15 mL, 0.15 mmol), then chalcone (104 mg, 0.5 mmol). Reaction
ꢀ
mmol) was added to water (0.3 mL) in a Schlenk tube, then Boc- was stirred 20 hours at 75 C. The crude was puried by ash
L-alaninal 13 (104 mg, 0.6 mmol) and the distillated DBU (22 mL, chromatography over silica-gel (pentane/EtOAc 95/5 to 90/10) to
0.15 mmol), then chalcone (104 mg, 0.5 mmol). Reaction was provide product 24 as a pale yellow oil (49 mg, 30%) and traces
stirred 20 hours at 75 ꢀC. The crude was puried by ash of the corresponding benzoin.
chromatography over silica-gel (CH2Cl2) to provide product 22
Rf: 0.4 (pentane/AcOEt: 90/10). 1H NMR (300 MHz, CDCl3)
as a yellow oil (128 mg, 67%). A mixture of two diaster- d (ppm): 8.12–7.95 (m, 4H), 7.63–7.16 (m, 8H), 6.90 (d, J ¼
eoisomeres d1 and d2 (d.r. ¼ 52 : 48) was obtained which were 8.7 Hz, 2H), 5.31 (dd, J ¼ 3.6 Hz, 9.9 Hz, 1H), 4.22 (dd, J ¼ 9.9 Hz,
not separated.
18 Hz, 1H), 3.83 (s, 3H), 3.29 (dd, J ¼ 3.9 Hz, 18 Hz, 1H). 13C
Rf: 0.20 (EP/AcOEt: 90/10). 1H NMR (300 MHz, CDCl3) NMR (75.46 MHz, CDCl3) d (ppm): 198.3, 197.5, 163.5, 139.3,
d (ppm) 8.01–7.91 (m, 4H, d1 + d2), 7.64–7.51 (m, 2H, d1 + d2), 136.7, 133.3, 131.4, 129.5, 129.3, 128.7, 128.3, 127.4, 113.8, 55.5,
7.50–7.39 (m, 4H, d1 + d2), 7.39–7.22 (m, 10H, d1 + d2), 5.54 (d, J 48.5, 43.9. IR (ATR) n (cmꢁ1): 3063, 2965, 2921, 2842, 1666, 1600,
¼ 7.5 Hz, 1H, d2), 5.26 (d, J ¼ 7.5 Hz, 1H, d1), 4.75–4.55 (m, 3H, 1575, 1494, 1450, 1249, 998, 843, 754, 701. HRMS (ESI) m/z calcd
d1 + d2), 4.52–4.38 (m, 3H, d1 or d2), 4.06 (dd, J ¼ 3 Hz, 10.2 Hz, for C23H21O3 [M + H]+ 345.14852, found 345.14835. NMR
+
1H, d2), 4.01 (dd, J ¼ 3.2 Hz, 10.2 Hz, 1H, d1), 3.32 (dd, J ¼ spectra for compound 24 are reported in the ESI.†
3.6 Hz, 18 Hz, 1H, d2), 3.18 (dd, J ¼ 3.6 Hz, 18.3 Hz, 1H, d1), 1.57
Compound 25. Synthesized according to the general proce-
(d, J ¼ 7.2 Hz, 3H, d2), 1.49 (s, 9H, d1), 1.41 (s, 9H, d2), 1.18 (d, J dure for Stetter reaction in water. Azolium salt 8 (57 mg, 0.15
¼ 6 Hz, 3H, d1) 13C NMR (75.5 MHz, CDCl3) d (ppm) 208.9 d2, mmol) was added to water (0.3 mL) in a Schlenk tube, then
207.7 d1, 198.1 d2, 197.7 d1, 155.2 d2, 154.8 d1, 133.4, 129.4, pyrrolecarboxaldehyde 16 (57 mg, 0.6 mmol), and the distillated
129.1, 128.6, 128.4, 128.4, 128.2, 128.1, 127.9, 127.7, 79.6 d1 or DBU (22 mL, 0.15 mmol), then chalꢀcone (104 mg, 0.5 mmol).
d2, 79.4 d1 or d2, 54.7 d2, 54.0 d1, 49.8 d1, 49.4 d2, 44.1 d1, 42.5 Reaction was stirred 60 hours at 75 C. The crude was puried
d1, 30.3 d2, 29.7 d1, 28.4 d1, 28.4 d2, 18.6 d1, 17.4 d2. IR (ATR) n by ash chromatography over silica-gel (pentane/EtOAc 85/15)
(cmꢁ1) 3423, 2978, 2932, 1705, 1684, 1493, 1449, 1365, 1241, to provide product 25 as a pale yellow oil (105 mg, 69%).
1164, 1004, 753, 690. HRMS (ESI) m/z calcd for C27H28NO4+ [M +
Rf: 0.25 (pentane/AcOEt: 85/15). H NMR (300 MHz, CDCl3)
1
H]+ 382.20128, found 382.20113. NMR spectra for compound 22 d (ppm) 9.48 (bs, 1H), 8.04–7.96 (m, 2H), 7.61–7.21 (m, 8H),
are reported in the ESI.† 7.07–7.02 (m, 1H), 6.97–6.92 (m, 1H), 6.28–6.21 (m, 1H), 5.06
Compound 23. Synthesized according to the general proce- (dd, J ¼ 4.2 Hz, 9.9 Hz, 1H), 4.17 (dd, J ¼ 9.9 Hz, 18 Hz, 1H), 3.32
dure for Stetter reaction in water. Azolium salt 8 (57 mg, 0.15 (dd, J ¼ 4.2 Hz, 18 Hz, 1H). 13C NMR (75.46 MHz, CDCl3) d (ppm)
mmol) was added to water (0.3 mL) in a Schlenk tube, then N- 198.1, 189.0, 139.8, 136.7, 133.3, 131.3, 129.1, 128.7, 128.3,
40716 | RSC Adv., 2020, 10, 40709–40718
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