The Journal of Organic Chemistry
Article
(s, 2 H), 4.41 (q, J = 7.1 Hz, 2 H), 3.46 (s, 2 H), 1.38 (t, J = 7.1 Hz, 3
H). 13C NMR (126 MHz, CDCl3): δ 195.5, 181.6, 160.8 (J = 245.6
Hz), 130.6 (J = 4.5 Hz), 127.6 (J = 8.1 Hz), 126.6 (J = 15.9 Hz), 123.8
(J = 3.6 Hz), 115.0 (J = 21.9 Hz), 92.1, 74.9, 65.9, 18.5 (J = 4.2 Hz),
14.7. HRMS (FAB): m/z [M+H]+ calcd for C13H14FO3, 237.0927;
found, 237.0927.
1696, 1603, 725, 699 cm−1. 1H NMR (500 MHz, CDCl3): δ 7.26−7.23
(m, 4 H), 7.18−7.14 (m, 1 H), 5.29−5.26 (m, 1 H), 4.56 (s, 2 H), 3.39
(s, 2 H), 1.89−1.83 (m, 4 H), 1.75−1.69 (m, 2 H), 1.66−1.59 (m, 2
H). 13C NMR (126 MHz, CDCl3): δ 195.4, 181.4, 140.4, 128.4, 128.2,
125.9, 94.3, 83.6, 74.9, 33.2, 25.7, 23.4. HRMS (FAB): m/z [M+H]+
calcd for C16H19O3, 259.1334; found, 259.1334.
5-Ethoxy-4-methyl-3(2H)-furanone (3ah).27 White solid (22.6 mg,
79%). Mp 55.0−55.5 °C. Rf = 0.18 (n-hexane/EtOAc = 1:4). IR
4-Benzyl-5-cyclohexyloxy-3(2H)-furanone (3da). Pale yellow oil
(41.2 mg, 77%). Rf = 0.60 (n-hexane/EtOAc = 1:4). IR (neat): 2938,
1
(KBr): 1695, 1600 cm−1. H NMR (500 MHz, CDCl3): δ 4.55 (s, 2
1
2860, 1696, 1604, 732, 699 cm−1. H NMR (500 MHz, CDCl3): δ
H), 4.44 (q, J = 7.1 Hz, 2 H), 1.61 (s, 3 H), 1.44 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ 196.5, 181.5, 89.3, 74.7, 65.6, 14.8,
3.8. HRMS (FAB): m/z [M+H]+ calcd for C7H11O3, 143.0708; found,
143.0695.
5-Ethoxy-4-ethyl-3(2H)-furanone (3ai). Pale yellow oil (16.5 mg,
53%). Rf = 0.24 (n-hexane/EtOAc = 1:4). IR (neat): 1696, 1604 cm−1.
1H NMR (500 MHz, CDCl3): δ 4.53 (s, 2 H), 4.44 (q, J = 7.1 Hz, 2
H), 2.12 (q, J = 7.5 Hz, 2 H), 1.43 (t, J = 7.1 Hz, 3 H), 1.03 (t, J = 7.5
Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ 196.2, 181.4, 95.4, 74.6,
65.6, 14.8, 12.9, 12.8. HRMS (FAB): m/z [M+H]+ calcd for C8H13O3,
157.0865; found, 157.0853.
7.28−7.23 (m, 4 H), 7.17−7.14 (m, 1 H), 4.87−1.82 (m, 1 H), 4.55
(s, 2 H), 3.41 (s, 2 H), 1.91−1.86 (m, 2 H), 1.75−1.69 (m, 2 H),
1.69−1.57 (m, 2 H), 1.54−1.49 (m, 1 H), 1.41−1.30 (m, 3 H). 13C
NMR (126 MHz, CDCl3): δ 195.4, 181.4, 140.4, 128.4, 128.2, 125.9,
94.1, 79.1, 74.8, 31.9, 25.7, 25.0, 23.1. HRMS (FAB): m/z [M+H]+
calcd for C17H21O3, 273.1491; found, 273.1496.
5-Allyloxy-4-benzyl-3(2H)-furanone (3ea). Pale yellow oil (35.1
mg, 76%). Rf = 0.52 (n-hexane/EtOAc = 1:4). IR (neat): 1696, 1604,
1
725, 700 cm−1. H NMR (500 MHz, CDCl3): δ 7.27−7.23 (m, 4 H),
7.18−7.15 (m, 1 H), 5.95 (ddt, J = 17.1, 10.5, 5.7 Hz, 1 H), 5.38−5.32
(m, 2 H), 4.84 (dt, J = 5.7, 1.4 Hz, 2 H), 4.58 (s, 2 H), 3.43 (s, 2 H).
13C NMR (126 MHz, CDCl3): δ 195.6, 181.3, 140.1, 130.7, 128.34,
128.30, 126.0, 119.8, 94.1, 75.0, 69.8, 25.5. HRMS (FAB): m/z [M
+H]+ calcd for C14H15O3, 231.1021; found, 231.1011.
4-Allyl-5-ethoxy-3(2H)-furanone (3aj).28 Pale yellow oil (23.7 mg,
71%). Rf = 0.28 (n-hexane/EtOAc = 1:4). IR (neat): 1698, 1603 cm−1.
1H NMR (500 MHz, CDCl3): δ 5.83 (ddt, J = 17.0, 10.0, 6.2 Hz, 1 H),
5.04 (dq, J = 17.0, 1.5 Hz, 1 H), 4.97 (dq, J = 10.0, 1.5 Hz, 1 H), 4.57
(s, 2 H), 4.44 (q, J = 7.1 Hz, 2 H), 2.85 (dt, J = 6.2, 1.5 Hz, 2 H), 1.42
(t, J = 7.1 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ 195.7, 181.6,
135.0, 114.8, 91.8, 74.8, 65.8, 23.7, 14.8. HRMS (FAB): m/z [M+H]+
calcd for C9H13O3, 169.0865; found, 169.0856.
4-Benzyl-5-propargyloxy-3(2H)-furanone (3fa). White solid (32.1
mg, 70%). Mp 78.2−78.8 °C. Rf = 0.56 (n-hexane/EtOAc = 1:4). IR
(KBr): 3210, 1693, 1601, 735, 696 cm−1. 1H NMR (500 MHz,
CDCl3): δ 7.28−7.24 (m, 4 H), 7.19−7.16 (m, 1 H), 4.95 (d, J = 2.4
Hz, 2 H), 4.61 (s, 2 H), 3.44 (s, 2 H), 2.62 (t, J = 2.4 Hz, 1 H). 13C
NMR (126 MHz, CDCl3): δ 195.8, 180.5, 139.8, 128.30, 128.28,
126.0, 94.1, 77.1, 76.0, 75.2, 56.7, 25.4. HRMS (FAB): m/z [M+H]+
calcd for C14H13O3, 229.0865; found, 229.0862.
4-Cinnamyl-5-ethoxy-3(2H)-furanone (3ak).21 Pale yellow oil
(37.1 mg, 76%). Rf = 0.28 (n-hexane/EtOAc = 1:4). IR (neat):
1
1735, 1693, 1583, 758, 700 cm−1. H NMR (500 MHz, CDCl3): δ
4-Benzyl-5-phenyloxy-3(2H)-furanone (3ga). Pale yellow oil (20.5
7.34−7.32 (m, 2 H), 7.29−7.25 (m, 2 H), 7.20−7.16 (m, 1 H), 6.41
(d, J = 15.8 Hz, 1 H), 6.21 (dt, J = 15.8, 6.7 Hz, 1 H), 4.58 (s, 2 H),
4.45 (q, J = 7.1 Hz, 2 H), 3.00 (dd, J = 6.7, 1.5 Hz, 2 H), 1.43 (t, J =
7.1 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ 195.6, 181.6, 137.6,
130.2, 128.4, 126.93, 126.91, 126.1, 92.1, 74.9, 65.9, 23.0, 14.8. HRMS
(FAB): m/z [M+H]+ calcd for C15H17O3, 245.1178; found, 245.1174.
5-Ethoxy-4-propargyl-3(2H)-furanone (3al). Orange oil (22.2 mg,
76%). Rf = 0.26 (n-hexane/EtOAc = 1:4). IR (neat): 3245, 1701, 1605
mg, 38%). Rf = 0.74 (n-hexane/EtOAc = 1:4). IR (neat): 1702, 1620,
1
724, 690 cm−1. H NMR (500 MHz, CDCl3): δ 7.41−7.37 (m, 2 H),
7.31−7.25 (m, 5 H), 7.21−7.18 (m, 1 H), 7.12−7.10 (m, 2 H), 4.59
(s, 2 H), 3.53 (s, 2 H). 13C NMR (126 MHz, CDCl3): δ 196.4, 180.0,
151.3, 139.7, 129.7, 128.40, 128.36, 126.5, 126.1, 120.5, 95.9, 75.2,
25.7. HRMS (FAB): m/z [M+H]+ calcd for C17H15O3, 267.1021;
found, 267.1003.
1
cm−1. H NMR (500 MHz, CDCl3): δ 4.59 (s, 2 H), 4.49 (q, J = 7.1
4-Benzyl-5-benzyloxy-3(2H)-furanone (3ha). Pale yellow oil (38.5
mg, 69%). Rf = 0.46 (n-hexane/EtOAc = 1:4). IR (neat): 1699, 1607,
Hz, 2 H), 3.03 (d, J = 2.7 Hz, 2 H), 1.94 (t, J = 2.7 Hz, 1 H), 1.46 (t, J
= 7.1 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ 194.4, 181.1, 89.4,
80.9, 75.0, 67.4, 66.3, 14.8, 9.4. HRMS (FAB): m/z [M+H]+ calcd for
C9H11O3, 167.0708; found, 167.0708.
1
729, 698 cm−1. H NMR (500 MHz, CDCl3): δ 7.39−7.37 (m, 3 H),
7.31−7.29 (m, 2 H), 7.26−7.22 (m, 4 H), 7.19−7.15 (m, 1 H), 5.36
(s, 2 H), 4.59 (s, 2 H), 3.43 (s, 2 H). 13C NMR (126 MHz, CDCl3): δ
195.6, 181.3, 140.1, 134.3, 129.0, 128.8, 128.4, 128.3, 127.9, 126.0,
94.4, 75.1, 71.0, 25.6. HRMS (FAB): m/z [M+H]+ calcd for
C18H17O3, 281.1178; found, 281.1191.
5-Ethoxy-4-ethoxycarbonylmethyl-3(2H)-furanone (3am). Pale
yellow oil (31.3 mg, 73%). Rf = 0.18 (n-hexane/EtOAc = 1:4). IR
1
(neat): 1738, 1701, 1609 cm−1. H NMR (500 MHz, CDCl3): δ 4.63
4-Benzyl-5-(4-bromobenzyloxy)-3(2H)-furanone (3ia). Pale yellow
solid (48.7 mg, 68%). Mp 92.8−93.0 °C. Rf = 0.50 (n-hexane/EtOAc =
1:4). IR (KBr): 1694, 1591, 806, 720, 701 cm−1. 1H NMR (500 MHz,
CDCl3): δ 7.50 (d, J = 8.5 Hz, 2 H), 7.26−7.16 (m, 5 H), 7.13 (d, J =
8.5 Hz, 2 H), 5.29 (s, 2 H), 4.58 (s, 2 H), 3.42 (s, 2 H). 13C NMR
(126 MHz, CDCl3): δ 195.6, 181.1, 140.0, 133.2, 132.0, 129.5, 128.4,
128.3, 126.0, 123.1, 94.5, 75.1, 70.1, 25.5. HRMS (FAB): m/z [M+H]+
calcd for C18H1681BrO3, 361.0262; found, 361.0272; calcd for
C18H1679BrO3, 359.0283; found, 359.0296.
(s, 2 H), 4.46 (q, J = 7.1 Hz, 2 H), 4.14 (q, J = 7.1 Hz, 2 H), 3.12 (s, 2
H), 1.43 (t, J = 7.1 Hz, 3 H), 1.26 (t, J = 7.1 Hz, 3 H). 13C NMR (126
MHz, CDCl3): δ 195.0, 181.9, 170.6, 88.0, 75.2, 66.2, 60.9, 25.2, 14.7,
14.2. HRMS (FAB): m/z [M+H]+ calcd for C10H15O5, 215.0919;
found, 215.0916.
5-Ethoxy-4-(2-thienylmethyl)-3(2H)-furanone (3an). Colorless oil
(32.8 mg, 73%). Rf = 0.32 (n-hexane/EtOAc = 1:4). IR (neat): 1698,
1
1603, 850, 695 cm−1. H NMR (500 MHz, CDCl3): δ 7.08 (dd, J =
5.1, 1.2 Hz, 1 H), 6.88 (dd, J = 5.1, 3.4 Hz, 1 H), 6.86−6.85 (m, 1 H),
4.58 (s, 2 H), 4.46 (q, J = 7.1 Hz, 2 H), 3.62 (d, J = 0.9 Hz, 2 H), 1.43
(t, J = 7.1 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ 195.0, 181.4,
142.9, 126.7, 124.6, 123.3, 93.4, 75.0, 66.1, 19.8, 14.8. HRMS (FAB):
m/z [M+H]+ calcd for C11H13O3S, 225.0585; found, 225.0575.
4-Benzyl-5-isopropyloxy-3(2H)-furanone (3ba). Pale yellow oil
(32.7 mg, 70%). Rf = 0.50 (n-hexane/EtOAc = 1:4). IR (neat): 1696,
1603, 731, 699 cm−1. 1H NMR (500 MHz, CDCl3): δ 7.26−7.23 (m, 4
H), 7.18−7.14 (m, 1 H), 5.08 (sept, J = 6.2 Hz, 1 H), 4.56 (s, 2 H),
3.40 (s, 2 H), 1.37 (d, J = 6.2 Hz, 6 H). 13C NMR (126 MHz, CDCl3):
δ 195.5, 181.4, 140.4, 128.4, 128.2, 125.9, 94.1, 74.8, 74.7, 25.6, 22.4.
HRMS (FAB): m/z [M+H]+ calcd for C14H17O3, 233.1178; found,
233.1181.
Synthesis of Aza-prostaglandin Analogue 10.21 NaOMe
(101.1 mg, 1.87 mmol) was added to a solution of 6-aminohexanoate
hydrochloride (339.8 mg, 1.87 mmol) in dry MeOH (0.5 mL) and
stirred for 30 min at room temperature. After removal of the
precipitate by filtration under an argon atmosphere, to the filtrate was
added 3ak (70.3 mg, 0.288 mmol) in dry MeOH (0.5 mL) via cannula,
and the mixture was stirred for 2 h at room temperature. After the
solvent was concentrated under reduced pressure, the mixture was
treated with 2 M HCl and extracted with diethyl ether. The extract was
dried over anhydrous Na2SO4 and concentrated under reduced
pressure. Purification by flash column chromatography on silica gel
(EtOAc/MeOH = 9:1) gave 10 as a pale yellow liquid (66.3 mg, 67%).
Rf = 0.40 (EtOAc/MeOH = 9:1). IR (neat): 3217, 3024, 1737, 1677,
4-Benzyl-5-cyclopentyloxy-3(2H)-furanone (3ca). Pale yellow oil
(37.6 mg, 73%). Rf = 0.56 (n-hexane/EtOAc = 1:4). IR (neat): 2964,
1
1651, 1573, 1496, 692 cm−1. H NMR (500 MHz, CDCl3): δ 7.33−
F
J. Org. Chem. XXXX, XXX, XXX−XXX