F
D. S. Ziegler et al.
Special Topic
Synthesis
IR (diamond-ATR, neat): 3072, 1716, 1535, 148, 1398, 1090, 1074,
845, 801 cm–1
1H NMR (400 MHz, acetone-d6): δ = 7.53–7.46 (m, 3 H), 7.40–7.29 (m,
3 H), 6.50 (dt, J = 6.6, 1.0 Hz, 1 H), 6.13–6.09 (m, 1 H), 5.52 (d,
J = 3.8 Hz, 1 H), 5.42 (d, J = 4.4 Hz, 1 H).
13C NMR (101 MHz, acetone-d6): δ = 167.7, 161.8, 144.9, 141.7, 129.2,
128.9, 127.8, 114.4, 101.9, 73.1.
(0.75 mL, 1.00 M in THF, 0.75 mmol, 1.50 equiv) and stirring for 30
min at −40 °C. The zinc reagent underwent a Negishi cross-coupling
reaction in the presence of Pd(dba)2 (11.0 mg, 8 mol%), P(2-furyl)3
(9.00 mg, 15 mol%) and 1-chloro-4-iodobenzene (143 mg, 0.60 mmol,
1.20 equiv) at 25 °C for 12 h. The crude product was purified by flash
column chromatography (silica gel, i-hexane/Et2O, 5:5) furnishing 9d.
.
Yield: 78.0 mg (75%); yellowish solid; mp 100–101 °C.
IR (diamond-ATR, neat): 3072, 1716, 1535, 1488, 1398, 1090, 1074,
845, 801 cm–1.1H NMR (400 MHz, acetone-d6): δ = 7.87–7.83 (m, 2 H),
7.58 (dd, J = 9.3, 6.8, 1 H), 7.53–7.48 (m, 2 H), 6.92 (dd, J = 6.8, 0.8 Hz,
1 H), 6.25 (dd, J = 9.3, 0.8 Hz, 1 H).
MS (EI, 70 eV): m/z (%) = 202 (48), 198 (46), 186 (100), 173 (14), 128
(16), 107 (52), 95 (100).
HRMS (EI): m/z calcd for C12H10O3: 202.0630; found: 202.0622.
13C NMR (101 MHz, acetone-d6): δ = 161.3, 160.2, 144.9, 137.0, 131.3,
130.0, 127.9, 115.0, 102.4.
6-[(4-Chlorophenyl)(hydroxy)methyl]-2H-pyran-2-one (9b)
According to TP1, 2-pyrone (1, 1.00 mL, 0.50 M in THF, 0.50 mmol)
was completely metalated within 15 min at –40 °C, using TMPMgCl·
LiCl (5, 0.54 mL, 1.10 M in THF, 0.60 mmol, 1.20 equiv). 4-Chloro-
benzaldehyde (60.0 μL, 0.60 mmol, 1.20 equiv) was then added drop-
wise at –40 °C. The reaction mixture was warmed to 25 °C and was
stirred until completion of the reaction. The crude product was puri-
fied by flash column chromatography (silica gel, i-hexane/Et2O, 4:6)
furnishing 9b.
MS (EI, 70 eV): m/z (%) = 206 (53), 180 (31), 179 (11), 178 (100), 149
(16), 139 (10), 115 (30), 111 (14).
HRMS (EI): m/z calcd for C11H7ClO2: 206.0135; found: 206.0110.
6-(4-Methoxyphenyl)-2H-pyran-2-one (9e)
According to TP1, 2-pyrone (1, 1.00 mL, 0.5 M in THF, 0.50 mmol) was
completely metalated within 15 min at –40 °C, using TMPMgCl·LiCl
(5, 0.54 mL, 1.10 M in THF, 0.60 mmol, 1.20 equiv). The magnesium
reagent was transmetalated to zinc in the presence of ZnCl2 (0.75 mL,
1.00 M in THF, 0.75 mmol, 1.50 equiv) and stirring for 30 min at
−40 °C. The zinc reagent underwent a Negishi cross-coupling reaction
in the presence of Pd(dba)2 (11.0 mg, 8 mol%), P(2-furyl)3 (9.00 mg,
15 mol%) and 1-iodo-4-methoxybenzene (140 mg, 0.60 mmol,
1.20 equiv) at 25 °C for 12 h. The crude product was purified by flash
column chromatography (silica gel, i-hexane/Et2O, 6:4) furnishing 9e.
Yield: 71.0 mg (60%); yellow oil.
IR (diamond-ATR, neat): 3072, 1716, 1535, 1488, 1398, 1090, 1074,
845, 801 cm–1.1H NMR (400 MHz, acetone-d6): δ = 7.54–7.47 (m, 3 H),
7.43–7.38 (m, 2 H), 6.50 (dt, J = 6.6, 0.9 Hz, 1 H), 6.12 (dd, J = 9.4,
1.2 Hz, 1 H), 5.53 (d, J = 12.5 Hz, 2 H).
13C NMR (101 MHz, acetone-d6): δ = 167.0, 161.6, 144.9, 140.7, 134.2,
129.5, 129.3, 114.7, 102.1, 72.4.
MS (EI, 70 eV): m/z (%) = 236 (20), 234 (10), 220 (11), 143 (34), 142
(10), 138 (100), 113 (25), 111 (45), 97 (56), 96 (28), 77 (79), 75 (33),
51 (19), 50 (15).
Yield: 91.0 mg (90%); yellowish solid; mp 137–139 °C.
IR (diamond-ATR, neat): 3007, 1719, 1606, 1505, 1415, 1235, 1178,
1021, 835, 787 cm–1.1H NMR (400 MHz, acetone-d6): δ = 7.85–7.80
(m, 2 H), 7.55 (dd, J = 9.3, 6.9 Hz, 1 H), 7.08–7.03 (m, 2 H), 6.79 (dd,
J = 6.9, 0.8 Hz, 1 H), 6.16 (dd, J = 9.3, 0.8 Hz, 1 H), 3.87 (s, 3 H).
HRMS (EI): m/z calcd for C12H9ClO3: 236.0240; found: 236.0243.
6-(Methylthio)-2H-pyran-2-one (9c)
13C NMR (101 MHz, acetone-d6): δ = 162.8, 161.8, 161.8, 145.3, 128.0,
According to TP1, 2-pyrone (1, 1.00 mL, 0.50 M in THF, 0.50 mmol)
was completely metalated within 15 min at –40 °C, using TMPMgCl·
LiCl (5, 0.54 mL, 1.10 M in THF, 0.60 mmol, 1.20 equiv). Methyl meth-
anethiosulfonate (60.0 μL, 0.60 mmol, 1.20 equiv) was then added
dropwise at –40 °C. The reaction mixture was warmed to 25 °C and
was stirred until completion of the reaction. The crude product was
purified by flash column chromatography (silica gel, i-hexane/Et2O,
4:6) furnishing 9c.
125.0, 115.3, 113.2, 100.5, 55.9.
MS (EI, 70 eV): m/z (%) = 202 (44), 174 (100), 131 (40), 103 (16).
HRMS (EI): m/z calcd for C12H10O3: 202.0630; found: 202.0622.
6-(Pyridin-3-yl)-2H-pyran-2-one (9f)
According to TP1, 2-pyrone (1, 1.00 mL, 0.50 M in THF, 0.50 mmol)
was completely metalated within 15 min at –40 °C, using TMPMgCl·
LiCl (5, 0.54 mL, 1.10 M in THF, 0.60 mmol, 1.20 equiv). The magne-
sium reagent was transmetalated to zinc in the presence of ZnCl2
(0.75 mL, 1.00 M in THF, 0.75 mmol, 1.50 equiv) and stirring for 30
min at −40 °C. The zinc reagent underwent a Negishi cross-coupling
reaction in the presence of Pd(dba)2 (11.0 mg, 8 mol%), P(2-furyl)3
(9.00 mg, 15 mol%) and 3-iodopyridine (60.0 mg, 0.60 mmol,
1.20 equiv) at 25 °C for 12 h. The crude product was purified by flash
column chromatography (silica gel, i-hexane/Et2O, 4:6) furnishing 9f.
Yield: 67.0 mg (95%); orange oil.
IR (diamond-ATR, neat): 2928, 1724, 1606, 1513, 1435, 1173, 1080,
780 cm–1.1H NMR (400 MHz, acetone-d6): δ = 7.42 (dd, J = 9.3, 7.0 Hz,
1 H), 6.22 (dd, J = 7.0, 0.8 Hz, 1 H), 5.99 (dd, J = 9.3, 0.8 Hz, 1 H), 2.54
(s, 3 H).
13C NMR (101 MHz, acetone-d6): δ = 165.7, 161.7, 145.0, 110.1, 102.4,
13.8.
MS (EI, 70 eV): m/z (%) = 142 (42), 114 (12), 95 (100), 43 (13), 39 (37),
28 (22), 18 (20).
Yield: 83.0 mg (95%); yellowish solid; mp 96–98 °C.
IR (diamond-ATR, neat): 2917, 2849, 1726, 1628, 1540, 1476, 1266,
1108, 1069, 841, 793, 695 cm–1.1H NMR (400 MHz, acetone-d6): δ =
9.07 (d, J = 0.8 Hz, 1 H), 8.68 (dd, J = 4.8, 1.6 Hz, 1 H), 8.22 (ddd, J = 8.1,
2.4, 1.6 Hz, 1 H), 7.65 (dd, J = 9.4, 6.8 Hz, 1 H), 7.55–7.50 (m, 1 H), 7.05
(dd, J = 6.8, 0.8 Hz, 1 H), 6.32 (dd, J = 9.4, 0.8 Hz, 1 H).
13C NMR (101 MHz, acetone-d6): δ = 161.3, 159.2, 152.2, 147.6, 144.9,
133.5, 124.6, 115.6, 103.1.
HRMS (EI): m/z calcd for C6H6O2S: 142.0089; found: 142.0076.
6-(4-Chlorophenyl)-2H-pyran-2-one (9d)
According to TP1, 2-pyrone (1, 1.00 mL, 0.50 M in THF, 0.50 mmol)
was completely metalated within 15 min at –40 °C, using TMPMgCl·
LiCl (5, 0.54 mL, 1.10 M in THF, 0.60 mmol, 1.20 equiv). The magne-
sium reagent was transmetalated to zinc in the presence of ZnCl2
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L