10.1002/ejoc.202001343
European Journal of Organic Chemistry
FULL PAPER
Thiopyran 10n
n-hexane/MTBE (80:1, v:v) yielded the desired cycloadduct 10q
(22.7 mg, 0.12 mmol, 67 %) as yellow oil. Rf: (n-hexane/Et2O = 2:1,
According to the general procedure a solution of phenacyl sulfide 3f
(R=CH2OAc, 108 mg, 0.45 mmol, 1.0 equiv.) and 2,3-dimethylbuta-
1,3-diene 9e (373 mg, 4.54 mmol, 10.0 equiv.) in 45 ml CH2Cl2 was
pumped through the reaction with a flow rate of 303 µL/min and
residence time of 30:00 min. Purification by flash column
chromatography with n-hexane/Et2O (70:1, v:v) yielded the desired
cycloadduct 10n (14.7 mg, 0.07 mmol, 16 %) as colorless oil.
Rf: (n-hexane/Et2O = 5:2, v:v) = 0.83. 1H-NMR (CDCl3, 400 MHz):
(ppm) = 4.17 (dd, J = 11.0, 6.0 Hz, 2H), 3.19-3.06 (m, 2H), 2.98 (d,
J = 17.0 Hz, 1H), 2.36-2.26 (m, 1H), 2.14-2.11 (m, 1H), 2.09 (s, 3H),
1.71 (q, J = 2.0 Hz, 3H), 1.68 (q, J = 2.0 Hz, 3H). 13C-NMR (CDCl3,
100 MHz) = 171.0, 125.9, 123.4, 66.4, 37.5, 35.0, 30.1, 21.0, 20.5,
19.6. IR ( in cm-1) 2959, 2928, 1740, 1457, 1383, 1635, 1238, 1126,
1073, 1039, 757, 666, 604. UV (CH2Cl2): (nm) = 280, 234. HRMS
(ESI+) [M+Na]+ calcd. for C10H16NaO2S+ 223.0763, found 223.0765.
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v:v) = 0.60. H-NMR (CDCl3, 400 MHz): (ppm) = 6.39 (dd, J = 5.5,
3.0 Hz, 1H), 5.95 (dd, J = 5.50, 3.0 Hz, 1H), 4.21 (q, J = 7.0 Hz, 2H),
4.12 (ddt, J = 3.0, 2.0, 1.0 Hz, 1H), 3.54 (tt, J = 2.5, 1.0 Hz, 1H), 3.30
(d, J = 1.0, 1H), 1.92 (d, J = 10.0 Hz, 1H) 1.68 (dt, J = 10.0, 2.0 Hz,
1H), 1.29 (t, J = 7.0 Hz, 3H). 13C-NMR (CDCl3, 100 MHz) = 173.7,
138.6, 132.7, 61.5, 51.7, 49.8, 49.1, 48.4, 14.3. IR ( in cm-1) 3019,
2926, 1853, 2400, 1728, 1261, 1216, 1181, 1100, 1033, 929, 760, 669.
UV (CH2Cl2): (nm) = 361, 278, 230. HRMS (ESI+) [M+Na]+ calcd. for
C9H12NaO2S+ 207.0450, found 207.0460.
Thiopyran 10r
According to the general procedure a precooled (-10°C) solution of
phenacyl sulfide 3f (R=CH2OAc, 106 mg, 0.44 mmol, 1.0 equiv.) and
cyclopentadiene 9g (294 mg, 4.45 mmol, 10.0 equiv.) in 44 ml CH2Cl2
was pumped through the reaction with a flow rate of 303 µL/min and
residence time of 30:00 min. Crude NMR indicated 90:10 dr.
Purification by flash column chromatography with n-hexane/ CH2Cl2
(2:3, v:v) yielded the desired cycloadduct 10r (72.9 mg, 0.40 mmol,
89 %) as yellow oil. Rf: (n-hexane/CH2Cl2 = 1:5, v:v) = 0.30. 1H-NMR
(CDCl3, 400 MHz): (ppm) = 6.40 (dd, J = 5.5, 3.0 Hz, 1H), 5.79 (dd,
J = 5.5, 3.0 Hz, 1H), 4.03-4.00 (m, 1H), 3.98-3.88 (m, 2H),
3.83-3.75 (m, 1H), 3.49-3.44 (m, 1H), 2.07 (s, 3H), 1.71 (d, J= 9.0 Hz,
1H) 1.60 (d, J = 9.0 Hz, 1H). 13C-NMR (CDCl3, 100 MHz) = 170.8,
138.1, 128.8, 66.3, 51.9, 51.6, 49.1, 46.9, 21.0. IR ( in cm-1) 2969,
2934, 1741, 1384, 1363, 1240, 1224, 1029, 741, 604. UV (CH2Cl2):
Thiopyran 10o
According to the general procedure a solution of phenacyl sulfide 3a
(R=CO2Et, 88.1 mg, 0.37 mmol, 1.0 equiv.) and myrcene 9f (504 mg,
3.70 mmol, 10.0 equiv.) in 37 ml CH2Cl2 was pumped through the
reaction with a flow rate of 303 µL/min and residence time of
30:00 min. The crude NMR indicated 67:33 rr and >95:5 dr.
Purification by flash column chromatography with n-hexane/CH2Cl2
(20:1→10:1, v:v) yielded the desired cycloadduct 10o (92.9 mg,
0.37 mmol, 99 %) as colorless oil. Rf: (n-hexane/CH2Cl2 = 1:1,
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v:v) = 0.81. H-NMR (CDCl3, 400 MHz): = 5.54 (dd, J = 4.5,1.5 Hz,
+
1H), 5.08 (tdp, J = 7.0,4.5, 1.5 Hz, 1H), 4.19 (q, J = 7.0 Hz, 2H), 3.57
(dd, J = 7.0, 5.5 Hz, 1H), 3.11 (p, J = 2.0 Hz, 1H), 2.54 (dd, J = 6.0,
3.5 Hz, 2H), 2.17-1.97 (m, 4H), 1.68 (d, J = 1.5 Hz, 3H), 1.59 (d,
J = 1.5 Hz, 1H), 1.27 (t, J = 7.0, 3H). 13C-NMR (CDCl3, 75 MHz)
= 171.9, 134.6, 132.1, 132.7, 120.5, 117.5, 61.5, 40.2, 38.4, 28.5,
28.0, 26.6, 25.8, 14.3. IR ( in cm-1) =2977, 2915, 1734, 1446, 1369,
1299, 1254, 1175, 1161, 1096, 1031, 782. UV (CH2Cl2): (nm) = 243,
228 nm. HRMS (ESI+) [M+Na]+ calcd. for C14H22NaO2S+ 277.1233,
found 277.1235.
(nm) 282, 230. HRMS (ESI+) [2M+Na]+ calcd. for C18H24NaO4S2
391.1008, found 391.1000.
Thiopyran 10s
According to the general procedure a precooled (-10°C) solution of
phenacyl sulfide 3g (R=Ph, 72.7 mg, 0.30 mmol, 1.0 equiv.) and
cyclopentadiene 9g (198 mg, 3.00 mmol, 10.0 equiv.) in 30 ml CH2Cl2
was pumped through the reaction with a flow rate of 303 µL/min and
residence time of 30:00 min. The crude NMR indicated 75:25 dr.
Purification by flash column chromatography with n-hexane/MTBE
(100:1, v:v) yielded the desired cycloadduct 10s (35.9 mg, 0.19 mmol,
64 %) as colorless oil. Rf: (n-hexane/Et2O = 2:1, v:v) = 0.75. 1H-NMR
(CDCl3, 400 MHz): (ppm) = 7.28-7.14 (m, 5H), 6.52 (dd, J = 5.5, 3.0
Hz, 1H), 5.52 (dd, J = 5.5, 3.0 Hz, 1H), 4.93 (d, J = 4.0 Hz, 1H), 3.0
(dd, J = 3.0, 1.5 Hz, 1H), 3.57 (dd, J = 3.0, 1.5 Hz, 1H), 1.88-1.74 (m,
2H). 13C-NMR (CDCl3, 100 MHz) = 140.5, 137.8, 128.7, 128.1, 54.1,
53.4, 53.0, 52.5. IR ( in cm-1) 2965, 2929, 1682,1599, 1495, 1449,
1338, 1259, 1217, 1075, 1030, 756, 699, 666. UV (CH2Cl2): (nm) =
335, 229. HRMS (EI) [M]˙+ calcd. for C12H11S˙+ 187.0576, found
187.0582.
Thiopyran 10p
According to the general procedure a precooled (-10°C) solution of
phenacyl sulfide 3c (R=CN, 89.0 mg, 0.47 mmol, 1.0 equiv.) and
cyclopentadiene 9g (308 mg, 4.65 mmol, 10.0 equiv.) in 47 ml CH2Cl2
was pumped through the reaction with a flow rate of 303 µL/min and
residence time of 30:00 min. The crude NMR indicated 60:40 dr.
Purification by flash column chromatography with n-hexane/MTBE
(80:1, v:v) yielded the desired cycloadduct 10p (45.9 mg, 0.33 mmol,
72 %) as colorless oil. Rf: (n-hexane/Et2O = 2:1, v:v) = 0.44. 1H-NMR
(CDCl3, 400 MHz): = 6.46 (dd, J = 5.5, 3.0 Hz, 1H), 5.89 (dd, J = 5.5,
3.0 Hz, 1H), 4.28 (d, J = 3.0, 1H), 3.78 (dd, J = 3.0, 1.5 Hz, 1H),, 3.28
(s, 1H), 1.91-1.77 (m, 2H). 13C-NMR (CDCl3, 100 MHz) = 139.4,
130.7, 120.7, 52.8, 51.3, 49.6, 35.1. IR ( in cm-1) = 2941, 2233, 1444,
1336, 1248, 1119, 1017, 912, 856, 779, 741, 699. UV (CH2Cl2): (nm)
Thiopyran 10t
According to the general procedure a precooled (-10°C) solution of
phenacyl sulfide 3e (R=CH2iPr, 101 mg, 0.45 mmol, 1.0 equiv.) and
= 302, 232 nm. HRMS (ESI+) [M+Na]+ calcd. for C7H7NNaS+ 160.0191, cyclopentadiene 9g (301 mg, 4.54 mmol, 10.0 equiv.) in 45 ml CH2Cl2
found 160.0194.
was pumped through the reaction with a flow rate of 303 µL/min and
residence time of 30:00 min. Crude NMR indicated 70:30 dr.
Purification by flash column chromatography with n-Hexane/CH2Cl2
(15:1→10:1, v:v) yielded the desired cycloadduct 10t (62.0 mg,
0.37 mmol, 81 %) as yellow oil. Rf: (n-hexane/CH2Cl2 = 1:1, v:v) =
Thiopyran 10q
According to the general procedure a precooled (-10°C) solution of
phenacyl sulfide 3a (R=CO2Et, 44.0 mg, 185 µmol, 1.0 equiv.) and
cyclopentadiene 9g (122 mg, 1.85 mmol, 10.0 equiv.) in 18.5 ml
CH2Cl2 was pumped through the reaction with a flow rate of
303 µL/min and residence time of 30:00 min. The crude NMR
indicated 67:33 dr. Purification by flash column chromatography with
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0.83. H-NMR (CDCl3, 400 MHz): = 6.39 (dd, J = 5.5, 3.0 Hz, 1H),
5.75 (dd, J = 5.5, 3.0 Hz, 1H), 3.93 (td, J = 2.5, 1.0 Hz, 1H), 3.82 (ddd,
J = 9.5, 6.0, 3.5 Hz, 1H), 3.32 (dd, J = 3.5, 1.0 Hz, 1H), 1.69-1.54 (m,
4H), 1.35 (dddd, J = 13.5, 7.5, 6.0, 1.0 Hz, 1H), 1.14 (ddd, J = 13.5,
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