10.1002/ejoc.201800642
European Journal of Organic Chemistry
FULL PAPER
(E)-5-(iodopropylidene)-2-oxo-3-phenyl-3-(pent-2-yn-1-
[α]D20 (c = 1.0, CHCl3) = + 2.7°. IR (film): 2918w, 1794s, 1689m, 1602w,
1510s, 1432w, 1242s, 1218m, 1133s, 1072s, 1030s, 988s, 833s, 639w.
1H-NMR (300 MHz, CDCl3, 300 K): δ = 7.45-7.36 (m, 2H), 7.11-7.01 (m,
2H), 3.44 (dq, J = 16.9, J = 2.2 Hz, 1H), 3.30 (dq, J = 16.9, J = 1.7 Hz,
1H), 2.89 (dq, J = 16.5, J = 2.5 Hz, 1H), 2.70 (dq, J = 16.5, J = 2.5 Hz,
1H), 2.45 (t, J = 1.9 Hz, 3H), 1.77 (t, J = 2.5 Hz, 3H). 13C-NMR (75 MHz,
CDCl3): δ = 176.1, 162.5 (d, 246.8 Hz), 145.7, 134.8 (d, J = 3.5 Hz),
127.9 (d, J = 8.2 Hz), 116.0 (d, J = 21.4 Hz), 80.2, 73.3, 73.0, 52.8, 42.3,
30.1, 24.9, 3.6. 19F-NMR (282 MHz, CDCl3, 300 K): δ = -113.9. HRMS
(ESI) m/z = 406.9915 calcd. for C16H14FIO2Na [M+Na]+, found 406.9915.
HPLC (Chiralpak IA column, eluent: hexane/2-PrOH = 98/2, flow rate: 1
mL/min): retention times: 6.4 min (major), 9.7 min (minor).
yl)tetrahydrofuran (4g) According to the general procedure dialkynoic
acid 3g (80.5 mg, 0.30 mmol, 1.0 equiv.) was cyclized using
(DHQD)2PHAL (23.4 mg, 0.03 mmol) and N-Iodopyrrolidin-2-one (76.0
mg, 0.36 mmol) in CHCl3 (1 mL) and hexane (1 mL). Purification of the
crude product by column chromatography (pentane/Et2O 2:1) provided
the product 4g as a colourless oil (117.1 mg, 0.30 mmol, 99%, 77:23 er).
[α]D (c = 0.5, CHCl3) = -2.8. IR (film): 2975w, 2936w, 2505w, 2202w,
20
1958w, 1798s, 1682m, 1497w, 1450w, 1381w, 1322w, 1266w, 1239m,
1135m, 1093m, 1032m, 988m, 917w, 768w, 697w, 638w, 613w, 568w.
1H-NMR (300 MHz, CDCl3, 300 K): δ = 7.45-7.28 (m, 5H), 3.47 (dt, J =
17.1, J = 1.4 Hz, 1H), 3.31 (dt, J = 17.1, J = 1.1 Hz, 1H), 2.95 (dt, J =
16.4, J = 2.3 Hz, 1H), 2.75 (dt, J = 16.5, J = 2.4 Hz, 1H), 2.63-2.52 (m,
2H), 2.21-2.09 (m, 2H), 1.10 (t, J = 7.4 Hz, 3H), 1.04 (t, J = 7.4 Hz, 3H).
13C-NMR (75 MHz, CDCl3, 300 K): δ = 176.4, 145.2, 139.5, 129.1, 128.1,
126.0, 86.1, 84.1, 73.9, 53.3, 42.7, 30.1, 30.1, 14.5, 14.1, 12.5. HRMS
(ESI) m/z = 417.0322 calcd. for C18H19O2INa [M+Na]+, found 417.0308.
HPLC (Chiralpak OD-H column, eluent: hexane/2-PrOH = 98/2, flow rate:
1 mL/min): retention times: 4.8 min (major), 8.1 min (minor).
(E)-5-(bromomethylene)-2-oxo-3-methyl-3-
phenyltetrahydrofuran (6a-Br) According to the general procedure
alkynoic acid rac-5a (18.8 mg, 0.10 mmol, 1.0 equiv.) was cyclized using
(DHQD)2PHAL (7.8 mg, 0.01 mmol, 10 mol%) and NBS (8.9 mg, 0.05
mmol, 0.5 equiv.) in CHCl3 (1 mL) and hexane (1 mL). Purification of the
crude product by column chromatography (pentane/Et2O 2:1) provided
the bromolactonization product 6a-Br as a yellow oil (10.0 mg, 0.04 mmol,
37%, 64:36 er). [α]D20 (c = 0.5, CHCl3) = -4.6°. IR (film): 3092w, 2929w,
1799m, 1711m, 1672w, 1447w, 1261w, 1166w, 1125w, 1052s, 952w,
(E)-5-(iodo(4-chlorophenyl)methylene)-2-oxo-3-phenyl-3-(3-(4-
chlorophenylprop-2-yn-1-yl)tetrahydrofuran (4h) According to the
general procedure dialkynoic acid 3h (130.0 mg, 0.30 mmol, 1.0 equiv.)
was cyclized using (DHQD)2PHAL (23.4 mg, 0.03 mmol, 10 mol%.) and
NIS (81.0 mg, 0.36 mmol, 1.2 equiv.) in CHCl3 (3 mL) and hexane (3 mL).
Purification of the crude product by column chromatography
(pentane/Et2O 1:1) provided the product 4h as colorless oil (138.0 mg,
0.25 mmol, 82%, 91:9 er). [α]D20 (c = 1.0, CHCl3) = + 5.0°. IR (film): 1798s,
1656m, 1591w, 1487s, 1210w, 1122m, 1089s, 1030m, 992m, 970m,
933m, 870w, 823s, 695m. 1H-NMR (300 MHz, CHCl3, 300 K): δ = 7.56-
7.17 (m, 13H), 3.73 (d, J = 17.6 Hz, 1H), 3.60 (d, J = 17.6 Hz, 1H), 3.22
(d, J = 16.8 Hz, 1H), 3.06 (d, J = 16.8 Hz, 1H). 13C-NMR (75 MHz, CDCl3):
δ = 175.8, 147.1, 138.8, 136.2, 134.7, 134.1, 133.2, 131.2, 129.3, 128.8,
128.5, 128.4, 125.9, 121.1, 84.9, 83.5, 74.9, 53.1, 44.7, 31.1. HRMS
(ESI) m/z = 580.9543 calcd. for C26H17Cl2IO2Na [M+Na]+, found
580.9543. HPLC (Chiralpak OD-H column, eluent: hexane/2-PrOH =
98/2, flow rate: 1 mL/min): retention times: 12.4 min (major), 13.8 min
(minor).
1
904s, 728s, 647m, 585w. H-NMR (600 MHz, CDCl3, 300 K): δ = 7.42-
7.36 (m, 4H), 7.34-7.29 (m, 1H), 6.05 (t, J = 2.3 Hz, 1H), 3.37 (dd, J =
17.2, J = 2.1 Hz, 1H), 3.05 (dd, J = 17.2, J = 2.4 Hz, 1H), 1.74 (s, 3H).
13C-NMR (151 MHz, CDCl3, 300 K): δ = 177.2, 150.2, 140.8, 129.2, 128.0,
125.7, 86.0, 48.0, 41.5, 29.7. HRMS (ESI) m/z = 288.9835 calcd. for
C12H11O2BrNa [M+Na]+, found 288.9839. HPLC (Chiralpak IA column,
eluent: hexane/2-PrOH = 98/2, flow rate: 1 mL/min): retention times: 8.0
min (major), 9.0 min (minor).
(E)-5-(iodomethylene)-2-oxo-3-methyl-3-phenyltetrahydrofuran
(6a) According to the general procedure alkynoic acid rac-5a (56.5 mg,
0.30 mmol, 1.0 equiv.) was cyclized using (DHQD)2PHAL (23.4 mg, 0.03
mmol, 10 mol%) and NIS (33.7 mg, 0.15 mmol, 0.5 equiv.) in CHCl3 (1
mL) and hexane (1 mL). Purification of the crude product by column
chromatography (pentane/Et2O 2:1) provided the iodolactonization
product 6a as a yellow oil (28.3 mg, 0.09 mmol, 30%, 71:29 er). [α]D20 (c
= 0.5, CHCl3) = -4.0°. IR (film): 1800w, 1715w, 1657w, 1447w, 1265w,
1
(E)-5-(1-iodoethylidene)-2-oxo-3-(3-chlorophenyl)-3-(but-2-yn-
1-yl)tetrahydrofuran (4i) According to the general procedure dialkynoic
acid 3i (82.2 mg, 0.30 mmol, 1.0 equiv.) was cyclized using
(DHQD)2PHAL (23.4 mg, 0.03 mmol, 10 mol%) and NIS (81.0 mg, 0.36
mmol, 1.2 equiv.) in CHCl3 (3 mL) and hexane (3 mL). Purification of the
crude product by column chromatography (pentane/Et2O 2:1) provided
the product 4i as colourless oil (114.0 mg, 0.26 mmol, 95%, 87:13 er).
[α]D20 (c = 1.0, CHCl3) = - 1.0°. IR (film): 2917w, 1798s, 1691m, 1596m,
1480w, 1429w, 1216m, 1137s, 1074m, 1035m, 997m, 692w, 631m. 1H-
NMR (300 MHz, CDCl3, 300 K): δ = 7.44-7.40 (m, 1H), 7.34-7.27 (m, 3H),
3.44 (dq, J = 16.9, J = 2.2 Hz, 1H), 3.28 (dq, J = 16.9, J = 1.7 Hz, 1H),
2.88 (dq, J = 16.5, J = 2.5 Hz, 1H), 2.71 (dq, J = 16.5, J = 2.5 Hz, 1H),
2.45 (t, J = 1.9 Hz, 3H), 1.77 (t, J = 2.5 Hz, 3H). 13C-NMR (75 MHz,
CDCl3): δ = 175.6, 145.5, 141.1, 135.1, 130.3, 128.4, 126.5, 124.2, 80.4,
73.1, 73.1, 53.1, 42.2, 30.1, 24.9, 3.6. HRMS (ESI) m/z = 422.9619 calcd.
for C16H14ClIO2Na [M+Na]+, found 422.9609. HPLC (Chiralpak OD-H
column, eluent: hexane/2-PrOH = 98/2, flow rate: 1 mL/min): retention
times: 6.0 min (major), 7.1 min (minor).
1163w, 1106w, 1052m, 905s, 725s, 648m. H-NMR (300 MHz, CDCl3,
300 K): δ = 7.44-7.26 (m, 5H), 5.88 (t, J = 2.2 Hz, 1H), 3.35 (dd, J = 17.1,
J = 2.1 Hz, 1H), 3.02 (dd, J = 17.1, J = 2.3 Hz, 1H), 1.73 (s, 3H). 13C-
NMR (75 MHz, CDCl3, 300 K): δ = 177.7, 152.3, 140.8, 129.2, 128.0,
125.7, 54.0, 48.8, 44.0, 25.9. HRMS (ESI) m/z = 336.9696 calcd. for
C12H11O2INa [M+Na]+, found 336.9693. HPLC (Chiralpak OD-H column,
eluent: hexane/2-PrOH = 98/2, flow rate: 1 mL/min): retention times: 9.1
min (minor), 9.7 min (major).
Methyl (E)-5-(iodomethylene)-2-oxo-3-ethyl-tetrahydrofuran-3-
carboxylate (6b) According to the general procedure alkynoic acid rac-
5b (55.3 mg, 0.30 mmol, 1.0 equiv.) was cyclized using (DHQD)2PHAL
(23.4 mg, 0.03 mmol, 10 mol%) and NIS (33.7 mg, 0.18 mmol, 0.5
equiv.) in CHCl3 (3 mL) and hexane (3 mL). Purification of the crude
product by column chromatography (pentane/Et2O 2:1) provided the
iodolactonization product 6b as a colorless oil (34.6 mg, 0.11 mmol, 37%,
59:41 er). IR (film): 3081w, 2956w, 1799s, 1733s, 1657s, 1435m, 1244m,
1150s, 1071s, 963m, 762m. 1H-NMR (300 MHz, CDCl3, 300 K): δ = 5.87
(t, J = 2.3 Hz, 1H), 3.80 (s, 3H), 3.37 (dd, J = 17.8, J = 2.3 Hz, 1H), 2.82
(dd, J = 17.7, J = 2.3 Hz, 1H), 2.17-1.95 (m, 2H), 0.97 (t, J = 7.4 Hz, 3H).
13C-NMR (75 MHz, CDCl3, 300 K): δ = 172.5, 169.3, 151.8, 56.3, 54.1,
53.6, 37.2, 28.2, 8.9. HRMS (ESI) m/z = 332.9594 calcd. for C9H11O4INa
[M+Na]+, found 332.9591. HPLC (Chiralpak OD-H column, eluent:
hexane/2-PrOH = 98/2, flow rate: 1 mL/min): retention times: 8.0 min
(major), 9.5 min (minor).
(E)-5-(1-iodoethylidene)-2-oxo-3-(4-fuorophenyl)-3-(but-2-yn-1-
yl)tetrahydrofuran (4j) According to the general procedure dialkynoic
acid 3j (77.5 mg, 0.30 mmol, 1.0 equiv.) was cyclized using
(DHQD)2PHAL (23.4 mg, 0.03 mmol, 10 mol%) and NIS (81.0 mg, 0.36
mmol, 1.2 equiv.) in CHCl3 (3 mL) and hexane (3 mL). Purification of the
crude product by column chromatography (pentane/Et2O 2:1) provided
the product 4i as colourless oil (114.5 mg, 0.30 mmol, 99%, 88:12 er).
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