A convenient synthesis of functionalized furans

Article abstract of DOI:10.1055/s-2008-1067183

An efficient synthesis of substituted furans was achieved from ketones by alkylation with 3-iodopropynylphosphonate and cyclization of the resulting 5-oxo-1-ynylphosphonates under mild conditions. The process can also be carried out as a one-pot reaction to give furan derivatives in excellent yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067183

PAPER
2617
A Convenient Synthesis of Functionalized Furans
F
unctionalized
a
Furans bine Mann, Vasiliki Sarli, Athanassios Giannis*
Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany
Fax +49(341)9736599; E-mail: giannis@uni-leipzig.de
Received 8 February 2008; revised 6 May 2008
from propargyl alcohol making use of the procedure of
Poss,13 with a small modification in the last step [conver-
sion of 3-hydroxypropynephosphonate into diethyl 3-io-
dopropynephosphonate (2), see experimental section].
For the alkylation reaction, we applied Negishi’s enoxy-
borate strategy using potassium hexamethyldisilazide
(KHMDS) as a base.14 Compounds 8a, 13a, 15a, and 16a
were selectively formed, indicating that in these cases the
reaction occurred slowly via the kinetic enolates. In addi-
tion, high stereoselectivity was observed in the cases 8a,
11a, 12a, and 14a, whereas 5a and 13a were obtained as
two diastereomers in a 2.3:1 and 1:1 ratio, respectively.
Depending on the structure of the ketone used as starting
material we observed variable yields of the alkylated com-
pounds of type 3 (see Table 1). The alkylation procedure
was not optimized. However, unreacted ketone was re-
covered and could be used again.
Abstract: An efficient synthesis of substituted furans was achieved
from ketones by alkylation with 3-iodopropynylphosphonate and
cyclization of the resulting 5-oxo-1-ynylphosphonates under mild
conditions. The process can also be carried out as a one-pot reaction
to give furan derivatives in excellent yields.
Key words: furans, pent-4-ynones, furylphosphonates, cycloiso-
merizations, Horner–Wadsworth–Emmons
Furan derivatives are found as structural units in many
natural products and pharmacologically active com-
pounds (e.g., zantac, wortmanin).1–5 In addition, they are
reactive heteroaromatic compounds that have been fre-
quently used as versatile building blocks in the synthesis
of natural products and other heterocyclic compounds.6
Despite the variety of the existing synthetic methods, new
approaches to substituted and fused-ring furans are in con-
stant demand. Classical methods involve the cyclization
of dicarbonyl compounds or a substitution reaction at an
existing furan ring.7 A variety of cycloisomerization
methods for the synthesis of substituted furans starting
from alkyne or allene derivatives have been described in
the literature.8 Among them the palladium-mediated (5-
endo-dig) cyclization of alkynones (Fukuda9) as well as
the gold-catalyzed cyclization recently developed by
Hashmi et al.10 are particularly important. Furthermore
the isomerization of a- and b-alkynyl allylic alcohols us-
ing silver, ruthenium, and palladium salts as catalysts has
been described.11,12
Subsequently, the obtained pent-4-ynones were readily
transformed into furans in the presence of a base. In some
cases the cyclization proceeded in excellent yield under
mild conditions in the presence of K2CO3 in EtOH. For
some cyclizations the use of t-BuOK was necessary for
furan formation. In these cases more forcing conditions
(extended reaction time), especially for the examples 10a
and 14a, lead to extensive decomposition. The results are
summarized in Table 1.
We were also able to perform the synthesis of the furans
by a one-pot reaction without the isolation of the interme-
diate pent-4-ynones. In this procedure, after the formation
of pent-4-ynone (TLC control) the temperature was low-
ered to –30 °C, and one more equivalent of KHMDS was
added. The reaction mixture was then allowed to warm to
room temperature. Furans 5b (88%) and 11b (35%) were
prepared in this way.
Herein, we report the synthesis of functionalized furans
under mild conditions from readily available starting ma-
terials through the cyclization of pent-4-ynones of type 3
(Scheme 1). The synthesized derivatives bear a phospho-
nate group, which allows further modifications and may
provide useful intermediates for natural product synthesis.
A probable mechanism for the formation of the furans de-
scribed here may be a 5-exo-dig cyclization of the enolate
(Scheme 2).
The pent-4-ynones of type 3 were synthesized by alkyla-
tion of the corresponding ketones with propargyl iodide 2.
Propargyl iodide 2 was synthesized in three steps starting
O
O
R1
O
O
I
O
O
P
OEt
P
+
P
OEt
R2
OEt
EtO
R1
OEt
R2
OEt
R1
R2
1
2
3
4
Scheme 1
SYNTHESIS 2008, No. 16, pp 2617–2625
x
x.
x
x
.
2
0
0
8
Advanced online publication: 17.07.2008
DOI: 10.1055/s-2008-1067183; Art ID: T02508SS
© Georg Thieme Verlag Stuttgart · New York

2618
S. Mann et al.
PAPER
Table 1 Conversion of Pent-4-ynones into Furans
Pent-4-ynones (Yield, %)
Furans (Yield, %)
PO(OEt)2
O
O
O
PO(OEt)2
O
O
O
5a (89)
5b (99)a
PO(OEt)2
O
O
PO(OEt)2
6a (56, 96b)
6b (93)a
PO(OEt)2
O
O
PO(OEt)2
7a (37, 92b)
7b (97)a
PO(OEt)2
O
O
PO(OEt)2
8a (50, 95b)
8b (96)a
PO(OEt)2
O
O
PO(OEt)2
9a (40, 89b)
9b (100)a
PO(OEt)2
O
O
PO(OEt)2
10a (35, 75b)
10b (26)c
PO(OEt)2
O
O
PO(OEt)2
11a (55, 94b)
11b (36, 66b)c
PO(OEt)2
O
O
PO(OEt)2
O
O
O
O
O
O
O
O
12a (58, 93b)
12b (35, 70b)c
Synthesis 2008, No. 16, 2617–2625 © Thieme Stuttgart · New York

PAPER
Functionalized Furans
2619
Table 1 Conversion of Pent-4-ynones into Furans (continued)
Pent-4-ynones (Yield, %)
Furans (Yield, %)
PO(OEt)2
PO(OEt)2
O
O
13b (20, 30b)c
13a (30, 93b)
PO(OEt)2
O
O
PO(OEt)2
14a (59, 97b)
14b (22)c
PO(OEt)2
O
O
PO(OEt)2
15a (35, 85b)
15b (100)a
(EtO)2OP
PO(OEt)2
O
O
H
H
H
H
H
H
TBSO
TBSO
16a (38, 88b)
16b (98)a
a K2CO3 was used as a base.
b Yield based on recovered starting material (brsm).
c t-BuOK was used as a base.
The utilization of furyl phosphonates as starting materials also be performed as a one-pot reaction is simple and ef-
in Horner–Wadsworth–Emmons (HWE) reactions (well ficient, and enables access to otherwise difficult-to-syn-
known15–18) followed by one- or two-step hydrogenation thesize furan and tetrahydrofuran derivatives.
leads to a multitude of interesting compounds. In fact, we
were also able to obtain alkenes 5c, 6c, and 7c starting
Unless otherwise noted all reagents were used as supplied commer-
from derivatives 5b–7b using this reaction. Subsequent
hydrogenation depending on the reaction conditions af-
forded furans 5d–7d or the tetrahydrofurans 5e and 6e in
excellent yields (Table 2).
cially. All solvents were distilled and dried using standard proce-
dures. All reactions were performed in oven-dried glassware.
Analytical TLC was performed on Merck Silica gel 60 F254 plates.
Flash column chromatography was performed on Acros Silica gel
60 Å. Nuclear magnetic resonance spectra were recorded on a Vari-
an Gemini-200BB, Varian Mercury-300BB, or Varian Mercury-
400BB spectrometer. The chemical shifts are reported in ppm and
In conclusion, a synthetic approach to substituted and/or
fused furans through the cyclization of 5-oxo-1-ynylphos-
phonates has been developed. The generality of the meth- the residual solvent signal is used as an internal standard. IR spectra
were collected on a Genesis Series ATI/Mattson FT-IR spectrome-
od was demonstrated by the variety of the furans that
ter. For high resolution mass spectra a Bruker Daltonics ApexTM II
could be synthesized. This two-step procedure which can
O
O
EtO
R1
O
O
R1
R2
R1
R2
O
O
OEt
base
P
OEt
O
P
P
P
OEt
EtO
O
OEt
OEt
EtO
R2
R2
R1
Scheme 2
Synthesis 2008, No. 16, 2617–2625 © Thieme Stuttgart · New York

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S. Mann et al.
PAPER
Table 2 HWE Reaction of Phosphonates and Hydrogenation of the Products
Phosphonate
HWE reaction
(Yield, %)
Hydrogenation (20 min)
(Yield, %)
Hydrogenation (5 h)
(Yield, %)
PO(OEt)2
O
O
O
O
O
O
O
O
O
5b
O
O
O
5c (86)
5d (89)
5e (69)
PO(OEt)2
O
H
O
O
H
O
H
6b
6c (92)
6d (95)
rac-6e (92)
PO(OEt)2
O
O
O
7b
7c (88)
7d (~100)
(ESI-FT-ICR-MS) was used. Melting points were determined on a
Büchi Melting Point B-540. The optical rotation was measured on a
Schmidt + Haensch Polartronic D polarimeter.
Diethyl 5-Oxopent-1-ynylphosphonates 5a–16a; General Proce-
dure
A solution of KHMDS (6 mL of 0.5 M in toluene, 3 mmol) was
cooled to –78 °C and the respective ketone 3 (for R1 and R2, see
Tables; 13 mmol) in THF (3 mL) was added. The mixture was
stirred for 30 min at the same temperature. After the addition of
Et3B (3.45 mL of 1 M in THF, 3.45 mmol), the mixture was warmed
immediately to –30 °C and stirred for 30 min. Diethyl 3-iodoprop-
ynephosphonate (2; 3 mmol) in THF (3 mL) was added dropwise
and the resultant mixture was stirred for 2 h at r.t. The mixture was
quenched with aq sat. NH4Cl (10 mL) and extracted with EtOAc
(3 × 10 mL). The combined organic extracts were washed with
brine (10 mL) and dried (Na2SO4). After evaporation of the solvent,
the crude product was purified by column chromatography
(Table 1).
Diethyl 3-Iodopropynephosphonate (2)
To a stirred solution of diethyl 3-hydroxypropynephosphonate
(6.00 g, 31.2 mmol) in CH2Cl2 (105 mL) was added imidazole (3.02
g, 44.3 mmol) and Ph3P (12.3 g, 46.8 mmol) at 0 °C. To the resultant
mixture was added I2 (11.3 g, 44.3 mmol) in small portions. The
mixture was stirred for 30 min at 0 °C and overnight at r.t.. After the
addition of 10% aq Na2S2O3 (50 mL), the layers were separated and
the organic layer was extracted with CH2Cl2 (3 × 50 mL). The com-
bined organic layers were washed with brine (50 mL), dried
(Na2SO4), and evaporated. The crude product was purified by col-
umn chromatography (EtOAc–n-hexane, 1:1) to give 2 as a yellow
oil (5.94 g, 63%).
5a
IR (CCl4): 2986, 2201, 1262, 1024 cm–1.
Column chromatography (EtOAc–n-hexane, 3:1) gave compound
5a (1.06 g, 89%) as a pale yellow oil (7:3 mixture of diastereomers).
IR (CCl4): 1027, 1089, 1258, 1713, 2208, 2982 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.32 (s, 3 H), 1.34 (t, 3J = 6.9 Hz,
6 H), 1.60–1.95 (m, 4 H), 2.10–2.13 (m, 1 H), 2.15–2.19 (m, 1 H),
2.37 (ddd, 2J = 18.0 Hz, 3J = 9.0 Hz, 3J = 4.5 Hz, 1 H), 2.54–2.61
(m, 1 H), 2.70–2.81 (m, 2 H), 3.08–3.18 (m, 1 H), 3.88–3.96 (m, 4
H), 4.08–4.18 (m, 4 H), 5.47–5.50 (m, 1 H).
1H NMR (CDCl3, 300 MHz): d = 1.37 (t, 3J = 7.0 Hz, 6 H), 3.71 (d,
2J = 4.7 Hz, 2 H), 4.08–4.21 (m, 4 H).
13C NMR (CDCl3, 50 MHz): d = –22.8 (d, J = 6.1 Hz), 16.2 (d,
3
3J = 6.9 Hz, 2 C), 63.7 (d, 2J = 5.3 Hz, 2 C), 74.6 (d, 1J = 296.8 Hz),
96.9 (d, 2J = 51.9 Hz).
HRMS-ESI: m/z calcd for C7H13IO3P [M + H]+: 302.96415; found:
302.96429.
13C NMR (75.0 MHz, CDCl3): d = 16.2 (d, 3J = 6.1 Hz, 2 C), 19.4
3
(d, J = 4.4 Hz), 23.2, 30.3, 30.5, 32.4, 40.9, 41.0, 47.3, 63.2 (d,
Synthesis 2008, No. 16, 2617–2625 © Thieme Stuttgart · New York

PAPER
Functionalized Furans
2621
2J = 5.6 Hz, 2 C), 64.5, 64.6, 70.0, 74.0 (d, 1J = 301.8 Hz), 100.6,
101.3 (d, 2J = 53.0 Hz), 108.9, 120.3, 139.5, 212.3.
HRMS-ESI: m/z calcd for C20H29O6P + Na [M + Na]+: 419.15940;
10a
Column chromatography (EtOAc–n-hexane, 1:1) gave 10a (284
mg, 75% brsm, 35% 10a) as a pale yellow oil.
IR (CCl4): 1088, 1258, 1427, 1678, 1708, 2207, 2933, 2985 cm–1.
found: 419.15899.
1H NMR (400 MHz, CDCl3): d = 1.32–1.38 (m, 7 H), 1.82–1.88 (m,
1 H), 2.32–2.37 (m, 1 H), 2.42–2.50 (m, 2 H), 2.55–2.60 (m, 1 H),
2.92–2.99 (m, 1 H), 4.09–4.17 (m, 4 H), 6.03 (d, 3J = 10.0 Hz, 1 H),
6.98–7.01 (m, 1 H).
6a
Column chromatography (EtOAc–n-hexane, 2:1) gave compound
6a (538 mg, 96% brsm, 56% 6a) as a pale yellow oil.
IR (CCl4): 1025, 1159, 1222, 1264, 1456, 1601, 1684, 2206, 2936,
2984, 3067 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.26–1.34 (m, 6 H), 1.83–2.05 (m,
1 H), 2.36–2.79 (m, 3 H), 2.97–3.09 (m, 3 H), 4.01–4.17 (m, 4 H),
7.19–7.26 (m, 2 H), 7.43 (dd, 3J = 7.3 Hz, 3J = 7.3 Hz, 1 H), 7.95
(d, 3J = 7.3 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 16.1 (d, 3J = 6.9 Hz, 2 C), 20.3 (d,
3J = 4.6 Hz), 28.5, 29.0, 46.1 (d, 4J = 2.3 Hz), 63.1 (d, 2J = 5.3 Hz,
2 C), 72.1 (d, 1J = 301.4 Hz), 100.8 (d, 2J = 52.6 Hz), 126.8, 127.5,
128.9, 131.9, 133.8, 144.0, 196.9.
13C NMR (100 MHz, CDCl3): d = 16.3 (d, 3J = 7.3 Hz, 2 C), 19.9 (d,
2
3J = 5.1 Hz), 26.0, 28.1, 45.2, 63.1 (d, J = 5.2 Hz, 2 C), 72.2 (d,
1J = 300.8 Hz), 103.1 (d, 2J = 52.3 Hz), 104.9, 129.3, 150.7, 159.3,
198.1.
HRMS-ESI: m/z calcd for C13H19O4P [M + Na]+: 293.09175; found:
293.09164.
11a
Column chromatography (EtOAc–n-hexane, 1:1) gave 11a (539
mg, 94% brsm, 55% 11a) as a pale yellow oil; [a]D23 +45.8 (c 1.18,
EtOH).
IR (CCl4): 1028, 1259, 1682, 2207, 2931, 2982 cm–1.
HRMS-ESI: m/z calcd for C17H21O4P + Na [M + Na]+: 343.10697;
found: 343.10672.
1H NMR (400 MHz, CDCl3): d = 1.08 (d, 3J = 6.3 Hz, 3 H), 1.32 (m,
6 H), 1.43 (m, 1 H), 1.75 (s, 3 H), 1.89 (m, 1 H), 1.90 (s, 3 H), 1.94
(m, 1 H), 2.15 (m, 1 H), 2.24 (m, 1 H), 2.63 (m, 1 H), 2.70 (m, 1 H),
2.79 (m, 1 H), 4.08 (m, 4 H).
7a
Column chromatography (EtOAc–n-hexane, 1:1) gave compound
7a (396 mg, 92% brsm, 37% 7a) as a pale yellow oil.
IR (CCl4): 1027, 1163, 1264, 1444, 1470, 1708, 2207, 2865, 2932
cm–1.
1H NMR (400 MHz, CDCl3): d = 1.01–1.73 (m, 21 H), 1.74–1.88
(m, 2 H), 1.91–2.01 (m, 1 H), 2.19–2.26 (m, 1 H), 2.44–2.51 (m, 1
H), 2.54–2.61 (m, 1 H), 2.86–2.94 (m, 2 H), 4.02–4.16 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 16.2 (d, 3J = 7.4 Hz, 2 C), 18.3 (d,
3J = 4.4 Hz), 20.8, 22.0, 22.8, 28.4, 32.4, 35.5, 56.0 (d, 4J = 1.5 Hz),
63.0 (d, 2J = 5.9 Hz, 2 C), 71.3 (d, 1J = 300.8 Hz), 101.3 (d,
2J = 53.1 Hz), 131.9, 141.9, 202.8.
HRMS-ESI: m/z calcd for C17H27O4P + Na [M + Na]+: 349.15392;
found: 349.15414.
13C NMR (100 MHz, CDCl3): d = 16.2 (d, 3J = 7.4 Hz, 2 C), 16.5,
18.9, 19.7 (d, 3J = 5.9 Hz), 20.9, 21.8, 22.6, 23.0, 23.4, 24.0, 26.0,
4
2
26.1, 28.2, 37.9, 49.5 (d, J = 2.9 Hz), 63.1 (d, J = 4.4 Hz, 2 C),
71.9 (d, 1J = 300.8 Hz), 100.9 (d, 2J = 53.1 Hz), 211.3.
12a
Column chromatography (EtOAc–n-hexane, 1:1) gave 12a (728
mg, 93% brsm, 58% 12a) as a pale yellow oil; [a]D23 –45.2 (c 1.59,
EtOH).
IR (CCl4): 1035, 1112, 1261, 1375, 1679, 2210, 2991 cm–1.
HRMS-ESI: m/z calcd for C19H33NaO4P + Na [M + Na]+:
379.20087; found: 379.20120.
8a
1H NMR (400 MHz, CDCl3): d = 1.29 (s, 3 H), 1.32 (s, 3 H), 1.33
(t, 3J = 7.0 Hz, 3 H), 1.34 (t, 3J = 7.0 Hz, 3 H), 2.65 (m, 1 H), 2.84
(m, 1 H), 2.91 (m, 1 H), 3.21 (s, 3 H), 3.28 (s, 3 H), 4.14 (m,1 H),
4.74 (m, 1 H), 6.00 (d, 3J = 10.2 Hz, 1 H), 6.84 (d, 3J = 10.2 Hz, 1
H).
Column chromatography (EtOAc–n-hexane, 1:1) gave 8a (493 mg,
95% brsm, 50% 8a) as a colorless oil; [a]D23 –15.6 (c 2.05, EtOH).
IR (CCl4): 1089, 1163, 1261, 1456, 1708, 2206, 2872, 2930 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.84 (d, 3J = 6.3 Hz, 3 H), 0.90 (d,
3J = 7.0 Hz, 3 H), 1.09 (d, 3J = 6.3 Hz, 3 H), 1.33 (t, 3J = 7.0 Hz, 6
H), 1.36–1.40 (m, 1 H), 1.45–1.55 (m, 1 H), 1.66–1.77 (m, 1 H),
1.85–1.93 (m, 1 H), 2.05–2.12 (m, 3 H), 2.21–2.26 (m, 1 H), 2.52–
2.58 (m, 1 H), 2.61–2.69 (m, 1 H), 4.06–4.19 (m, 4 H).
3
13C NMR (100 MHz, CDCl3): d = 15.7 (d, J = 4.4 Hz), 16.2 (d,
3J = 7.3 Hz, 2 C), 17.6, 17.7, 47.5 (d, 4J = 2.2 Hz), 48.1, 48.3, 63.2
2
1
(d, J = 3.7 Hz, 2 C), 64.7, 69.3, 72.5 (d, J = 298.5 Hz), 99.0 (d,
2J = 52.3 Hz), 100.2, 100.3, 129.4, 148.5, 198.8.
13C NMR (100 MHz, CDCl3): d = 16.2 (d, 3J = 7.4 Hz, 2 C), 17.1 (d,
HRMS-ESI: m/z calcd for C19H29O8P + Na [M + Na]+: 439.14923;
found: 439.14915.
3J = 4.4 Hz), 18.9, 20.8, 21.4, 26.4, 28.7, 34.4, 40.1, 56.1 (d,
2
1
4J = 2.2 Hz), 56.5, 63.1 (d, J = 5.2 Hz, 2 C), 70.9 (d, J = 300.8
Hz), 101.9 (d, 2J = 53.1 Hz), 210.0.
13a
Column chromatography (EtOAc–n-hexane, 1:1) gave 13a (294
mg, 93% brsm, 30% 13a) as a pale yellow oil (2S:2R = 56:44,
inseparable mixture of diastereomers).
HRMS-ESI: m/z calcd for C17H30O4P [M + H]+: 329.18762; found:
329.18782.
9a
IR (CCl4): 1025, 1082, 1263, 1455, 1740, 2208, 2875, 2964 cm–1.
Column chromatography (EtOAc–n-hexane, 1:1) gave 9a (394 mg,
89% brsm, 40% 9a) as a yellow oil (inseparable mixture of diaste-
reomers).
IR (CCl4): 1029, 1081, 1240, 1442, 1720, 2210, 2870, 2963 cm–1.
HRMS-ESI: m/z calcd for C17H29O4P + Na [M + Na]+: 351.16957;
found: 351.16975.
(2S)-13a
1H NMR (400 MHz, CDCl3): d = –0.15 to –0.12 (m, 1 H), 0.69 (d,
3J = 6.3 Hz, 3 H), 0.78–0.98 (m, 1 H), 1.00 (d, J = 6.3 Hz, 3 H),
3
1.23 (d, 3J = 7.8 Hz, 3 H), 1.33–1.38 (m, 6 H), 1.40–1.43 (m, 1 H),
2.22–2.45 (m, 3 H), 2.61–2.83 (m, 2 H), 4.08–4.18 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 14.9, 16.3 (d, 3J = 7.0 Hz, 2 C),
17.0, 17.5, 20.1 (d, 3J = 4.4 Hz), 21.7, 25.0 (2 C), 31.7, 47.3, 52.2
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S. Mann et al.
PAPER
(d, 4J = 2.2 Hz), 63.2 (d, 2J = 5.1 Hz, 2 C), 71.9 (d, 1J = 300.7 Hz),
100.1 (d, 2J = 51.6 Hz), 222.5.
C), 31.6, 31.9, 32.1, 36.7, 37.4, 39.0, 41.6, 42.8, 44.5, 50.1, 57.0,
62.9, 63.2 (d, 2J = 5.9 Hz, 2 C), 70.8 (d, 1J = 302.2 Hz), 72.6, 102.0,
120.9, 141.6, 208.1.
(2R)-13a
HRMS-ESI: m/z calcd for C34H57O5PSi + Na [M + Na]+: 627.36051;
found: 627.36127.
1H NMR (400 MHz, CDCl3): d = 0.12–0.15 (m, 1 H), 0.78–0.80 (m,
1 H), 0.94 (d, 3J = 7.0 Hz, 3 H), 1.01–1.08 (m, 1 H), 1.10 (d, 3J = 7.0
Hz, 3 H), 1.17 (d, 3J = 7.0 Hz, 3 H), 1.33–1.38 (m, 6 H), 1.74–1.81
(m, 1 H), 2.22–2.45 (m, 2 H), 2.61–2.83 (m, 2 H), 4.08–4.18 (m, 4
H).
Diethyl ([b]Furan-2-yl)methylphosphonates 5b–9b, 15b, and
16b; General Method A
Appropriate diethyl 3-prop-1-ynylphosphonate 5a–9a, 15a, or 16a
(0.2 mmol) was dissolved in EtOH (2 mL), and K2CO3 was added
(82.9 mg, 0.6 mmol). The resultant mixture was stirred at r.t. for 24
h. The solvent was removed under reduced pressure, the residue
was dissolved in H2O (10 mL), and extracted with EtOAc (3 × 10
mL). The combined organic phases were dried (Na2SO4) and evap-
orated. The crude product was purified by column chromatography
to afford the furan (Table 1).
13C NMR (100 MHz, CDCl3): d = 15.7, 16.3 (d, 3J = 7.0 Hz, 2 C),
18.4, 18.4 (d, 3J = 4.4 Hz), 19.2, 20.8, 28.8, 31.0, 33.5, 46.5, 47.1
(d, 4J = 2.2 Hz), 63.2 (d, 2J = 5.1 Hz, 2 C), 72.9 (d, 1J = 299.9 Hz),
101.4 (d, 2J = 53.1 Hz), 218.1.
HRMS-ESI: m/z calcd for C17H27O4P [M + Na]+: 349.15392; found:
349.15421.
14a
5b
Column chromatography (EtOAc–n-hexane, 1:1) gave 14a (574
mg, 97% brsm, 59% 14a) as a pale yellow oil; [a]D23 –42.1 (c 1.81,
EtOH).
Column chromatography (EtOAc–n-hexane, 3:1) gave 5b (78.5 mg,
99%) as a yellow oil; [a]D23 +62.4 (c 2.00, EtOH).
IR (CCl4): 1085, 1441, 1659, 1721, 2982 cm–1.
IR (CCl4): 1027, 1081, 1253, 1455, 1632, 1722, 2205, 2873, 2929,
2963 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.32 (t, 3J = 7.0 Hz, 6 H), 1.72 (s,
3 H), 1.76–1.77 (m, 3 H), 2.29–2.36 (m, 1 H), 2.40–2.56 (m, 3 H),
2.80–2.93 (m, 2 H), 4.04–4.13 (m, 4 H), 4.90–4.93 (m, 2 H), 6.71–
6.74 (m, 1 H).
1H NMR (300 MHz, CDCl3): d = 1.23 (t, 3J = 7.0 Hz, 6 H), 1.38 (s,
3 H), 1.66–1.80 (m, 2 H), 1.89–2.09 (m, 3 H), 2.27–2.30 (m, 1 H),
2.60–2.67 (m, 1 H), 3.06–3.09 (m, 1 H), 3.20 (d, 2J = 20.5 Hz, 2 H),
3.89–4.01 (m, 4 H), 4.01–4.12 (m, 4 H), 5.48–5.51 (m, 1 H), 6.03
(d, 4J = 4.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 16.5 (d, J = 5.6 Hz, 2 C), 22.9,
3
13C NMR (100 MHz, CDCl3): d = 16.1, 16.2 (d, 3J = 7.4 Hz, 2 C),
24.7, 27.0 (d, 1J = 143.7 Hz), 31.2, 34.5, 35.9, 41.1, 62.4 (d, 2J = 6.6
Hz, 2 C), 64.5, 64.5, 108.2 (d, 3J = 7.7 Hz), 109.2, 113.3 (d, 4J = 3.3
Hz), 120.0, 137.8, 143.6 (d, 2J = 10.0 Hz), 155.4 (d, 4J = 3.8 Hz).
17.6 (d, 3J = 4.4 Hz), 18.5, 31.0, 47.4, 47.7 (d, 4J = 2.9 Hz), 63.0 (d,
2J = 5.9 Hz, 2 C), 71.4 (d, 1J = 300.8 Hz), 101.1 (d, J = 53.1 Hz),
2
114.9, 135.1, 144.1, 144.2, 197.7.
HRMS-ESI: m/z calcd for C17H25O4P + Na [M + Na]+: 347.13827;
found 349.13856.
HRMS-ESI: m/z calcd for C20H29O6P + Na [M + Na]+: 419.15940;
found: 419.15920.
6b
15a
Column chromatography (EtOAc–n-hexane, 1:1) gave 6b (59.6 mg,
93%) as a pale yellow oil.
IR (CCl4): 1025, 1087, 1236, 1443, 1716, 2984 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.29–1.39 (m, 6 H), 2.69 (t,
3J = 7.9 Hz, 2 H), 2.94 (t, 3J = 7.9 Hz, 2 H), 3.29 (d, 2J = 21.1 Hz, 2
H), 4.07–4.17 (m, 4 H), 6.22 (d, 4J = 3.5 Hz, 1 H), 7.06–7.22 (m, 3
H), 7.40 (d, 3J = 7.6 Hz, 1 H).
Column chromatography (EtOAc–n-hexane, 1:1) gave 15a (315
mg, 85% brsm, 35% 15a) as a pale yellow oil.
IR (CCl4): 1027, 1078, 1263, 1449, 1709, 2208, 2855, 2931, 2983
cm–1.
1H NMR (200 MHz, CDCl3): d = 1.20–1.34 (m, 11 H), 1.64–1.85
(m, 5 H), 2.26–2.38 (m, 1 H), 2.51–2.61 (m, 2 H), 2.70–2.78 (m, 2
H), 4.04–4.19 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 16.2 (d, J = 7.3 Hz), 16.5 (d,
3
13C NMR (50 MHz, CDCl3): d = 13.7 (d, J = 4.6 Hz), 16.2 (d,
3
3J = 5.9 Hz), 21.0, 27.2 (d, J = 143.0 Hz), 29.1, 62.5 (d, J = 7.4
1
2
3J = 7.4 Hz, 2 C), 25.7 (2 C), 25.9 (2 C), 28.5, 38.1 (d, 4J = 2.3 Hz),
2
3
Hz), 63.0 (d, J = 5.9 Hz), 109.9 (d, J = 7.4 Hz), 118.9, 120.6 (d,
4J = 4.4 Hz), 126.2, 126.7, 128.0, 128.1, 134.4, 145.1 (d, 2J = 10.3
Hz), 149.5 (d, 4J = 2.9 Hz).
HRMS-ESI: m/z calcd for C17H21O4P + Na [M + Na]+: 343.10697;
2
1
50.7, 63.1 (d, J = 5.7 Hz, 2 C), 71.0 (d, J = 304.9 Hz), 101.8 (d,
2J = 53.0 Hz), 210.6.
HRMS-ESI: m/z calcd for C15H25O4P + Na [M + Na]+: 323.13827;
found: 323.13791.
found: 343.10663.
16a
7b
The starting ketone (1.29 g, 3 mmol) was dissolved in a 1:1 mixture
of THF–toluene (3 mL). Column chromatography (EtOAc–n-hex-
ane, 1:1) gave 16a (693 mg, 88% brsm, 38% 16a) as a white solid;
mp 74 °C; [a]D23 +19.8 (c 1.52, EtOH).
Column chromatography (EtOAc–n-hexane, 1:1) gave 7b (69.1 mg,
97%) as a pale yellow oil.
IR (CCl4): 1027, 1252, 1444, 1719, 2868, 2934, 2982 cm–1.
IR (CCl4): 1028 1079, 1254, 1440, 1708, 2209, 2855, 2933 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.19–1.38 (m, 18 H), 1.56–1.62
3
(m, 2 H), 1.67–1.72 (m, 2 H), 2.33 (t, J = 6.8 Hz, 2 H), 2.57 (t,
1H NMR (400 MHz, CDCl3): d = 0.03 (s, 6 H), 0.59 (s, 3 H), 0.88
(s, 9 H), 0.89–0.94 (m, 1 H), 0.97 (s, 3 H), 1.01–1.05 (m, 1 H), 1.08–
1.16 (m, 1 H), 1.18–1.24 (m, 1 H), 1.33 (t, 3J = 7.4 Hz, 6 H), 1.37–
1.71 (m, 7 H), 1.76–1.81 (m, 1 H), 1.95–2.02 (m, 3 H), 2.12–2.23
(m, 3 H), 2.45–2.50 (m, 2 H), 2.54–2.60 (m, 2 H), 2.63–2.68 (m, 2
H), 3.41–3.49 (m, 1 H), 4.05–4.16 (m, 4 H), 5.28–5.29 (m, 1 H).
2
3J = 6.6 Hz, 2 H), 3.17 (d, J = 20.8 Hz, 2 H), 4.03–4.15 (m, 4 H),
6.03 (d, 4J = 4.0 Hz, 1 H).
3
13C NMR (75 MHz, CDCl3): d = 16.2 (d, J = 7.2 Hz), 16.5 (d,
1
3J = 6.1 Hz), 21.6, 22.2, 22.4, 23.7 (d, J = 146.0 Hz), 24.4, 24.6,
24.9, 26.0, 26.2, 27.6, 27.9, 62.4 (d, 2J = 6.6 Hz), 63.0 (d, 2J = 5.5
Hz), 109.7 (d, 3J = 7.8 Hz), 120.9 (d, 4J = 2.8 Hz), 143.0 (d, 2J = 9.9
Hz), 150.7 (d, 4J = 4.4 Hz).
13C NMR (100 MHz, CDCl3): d = –4.5 (2 C), 13.5, 13.7 (d, 3J = 4.4
Hz), 16.2 (d, 3J = 7.4 Hz, 2 C), 18.3, 19.5, 21.1, 23.1, 24.6, 26.0 (3
Synthesis 2008, No. 16, 2617–2625 © Thieme Stuttgart · New York

PAPER
Functionalized Furans
2623
HRMS-ESI: m/z calcd for C19H33O4P + Na [M + Na]+: 379.20087;
found: 379.20120.
13C NMR (100 MHz, CDCl3): d = –4.4 (2 C), 13.1, 16.5 (d, 3J = 5.9
Hz, 2 C), 18.4, 19.6, 21.0, 24.6, 25.5, 26.1 (3 C), 26.9 (d, 1J = 143.8
Hz), 32.1, 32.2, 32.4, 36.8, 37.5, 38.1, 43.0, 44.1, 50.1, 50.5, 56.0,
62.3 (d, 2J = 6.6 Hz), 62.4 (d, 2J = 6.6 Hz), 72.7, 106.6 (d, 4J = 3.0
8b
3
2
Column chromatography (EtOAc–n-hexane, 1:1) gave 8b (63.0 mg,
Hz), 108.5 (d, J = 8.1 Hz), 121.1, 141.8, 143.7 (d, J = 10.3 Hz),
96%) as a colorless oil; [a]D23 –1.3 (c 1.56, EtOH).
156.9 (d, 4J = 3.0 Hz).
IR (CCl4): 1079, 1243, 1445, 1713, 1763, 2874, 2965 cm–1.
HRMS-ESI: m/z calcd for C34H57O5PSi + Na [M + Na]+: 627.36051;
found: 627.36078.
1H NMR (300 MHz, CDCl3): d = 0.83 (d, 3J = 6.4 Hz, 3 H), 0.94 (d,
3J = 7.0 Hz, 3 H), 1.09 (d, 3J = 7.0 Hz, 3 H), 1.29 (t, 3J = 7.0 Hz, 6
H), 1.33–1.38 (m, 1 H), 1.41–1.50 (m, 1 H), 1.60–1.94 (m, 2 H),
1.98–2.16 (m, 1 H), 2.49–2.57 (m, 1 H), 2.58–2.67 (m, 1 H), 3.18
Diethyl ([b]Furan-2-yl)methylphosphonates 10b–14b; General
Method B
The appropriate diethyl 3-prop-1-ynylphosphonate 10a–14a (0.2
mmol) was dissolved in THF–t-BuOH (1:1, 2 mL) and t-BuOK was
added (22.4 mg, 0.2 mmol). The resultant mixture was stirred at r.t.
for 15 min. The solvent was removed under reduced pressure, the
residue dissolved in H2O (10 mL), and extracted with EtOAc
(3 × 10 mL). The combined organic phases were dried Na2SO4) and
evaporated. The crude product was purified by column chromatog-
raphy to afford the furan (Table 1).
4
(d, 2J = 20.5 Hz, 2 H), 4.02–4.11 (m, 4 H), 6.08 (d, J = 4.1 Hz, 1
H).
3
13C NMR (100 MHz, CDCl3): d = 16.6 (d, J = 7.4Hz, 2 C), 18.7,
19.8, 21.0, 24.3, 27.0 (d, 1J = 143.0 Hz), 28.6, 30.0, 32.5, 40.7, 62.4
(d, 2J = 3.0 Hz), 62.5 (d, 3J = 3.0 Hz), 107.7 (d, 3J = 7.3 Hz), 124.9
(d, 4J = 3.0 Hz), 143.1 (d, 2J = 9.6 Hz), 152.6 (d, 4J = 3.7 Hz).
HRMS-ESI: m/z calcd for C17H30O4P [M + H]+: 329.18762; found:
329.18766.
10b
Column chromatography (EtOAc–n-hexane, 1:1) gave 10b (14.1
mg, 26%) as a colorless oil.
IR (CCl4): 1081, 1442, 1672, 1721, 2930 cm–1.
9b
Column chromatography (EtOAc–n-hexane, 1:1) gave 9b (65.1 mg,
quant) as a pale yellow oil.
IR (CCl4): 1027, 1078, 1245, 1443, 1721, 2214, 2871, 2964 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.90 (s, 9 H), 1.29 (t, 3J = 7.0 Hz,
3 H), 1.29 (t, 3J = 7.0 Hz, 3 H), 1.33–1.42 (m, 1 H), 1.81–1.92 (m,
1 H), 1.97–2.19 (m, 1 H), 2.38–2.74 (m, 4 H), 3.16 (d, 2J = 21.1 Hz,
2 H), 4.01–4.17 (m, 4 H), 6.02 (d, 4J = 4.1 Hz, 1 H).
3
1H NMR (400 MHz, CDCl3): d = 1.30 (t, J = 7.0 Hz, 6 H), 2.32–
2.38 (m, 2 H), 2.59 (t, 3J = 9.4 Hz, 2 H), 3.20 (d, 2J = 21.1 Hz, 2 H),
4.04–4.14 (m, 4 H), 5.66–5.70 (m, 1 H), 6.11 (d, 4J = 3.1 Hz, 1 H),
6.29 (d, 3J = 9.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 16.6 (d, 3J = 5.9 Hz, 2 C), 20.8,
1
2
13C NMR (100 MHz, CDCl3): d = 16.2 (d, J = 7.3 Hz), 16.5 (d,
3
24.1, 27.1 (d, J = 144.5 Hz), 62.5 (d, J = 7.4 Hz, 2 C), 109.7 (d,
3J = 7.4 Hz), 117.9 (d, 4J = 2.9 Hz), 118.0, 124.7, 143.5 (d,
2J = 10.3 Hz), 150.3.
3J = 5.8 Hz), 23.5, 23.9, 24.0, 25.5 (d, J = 151.8 Hz), 27.6 (3 C),
1
2
2
32.6, 45.4, 62.4 (d, J = 6.6 Hz), 63.1 (d, J = 5.8 Hz), 99.0 (d,
4J = 3.0 Hz), 109.5 (d, 3J = 8.1 Hz), 143.2 (d, 2J = 9.6 Hz), 150.3.
HRMS-ESI: m/z calcd for C13H19O4P + Na [M + Na]+: 293.09175;
found: 293.09167.
HRMS-ESI: m/z calcd for C17H29O4P +Na [M + Na]+: 351.16957;
found: 351.16998.
11b
Column chromatography (EtOAc–n-hexane, 1:1) gave 11b (23.5
mg, 66% brsm, 36% 11b) as a pale yellow oil; [a]D23 +2.4 (c 1.64,
EtOH).
15b
Column chromatography (EtOAc–n-hexane, 1:1) gave 15b (60.1
mg, quant) as a pale yellow oil.
IR (CCl4): 1067, 1241, 1392, 1444, 1620, 1675, 1716, 2932, 2980
cm–1.
IR (CCl4): 1028, 1078, 1252, 1449, 1714, 2212, 2855, 2930, 2981
cm–1.
1H NMR (400 MHz, CDCl3): d = 1.14 (d, 3J = 7.0 Hz, 3 H), 1.29 (t,
3J = 7.0 Hz, 6 H), 1.78 (s, 3 H), 1.81–1.94 (m, 2 H), 2.11 (s, 3 H),
2.16–2.24 (m, 1 H), 2.56–2.62 (m, 1 H), 2.66–2.71 (m, 1 H), 3.22
3
1H NMR (200 MHz, CDCl3): d = 1.27 (t, J = 7.1 Hz, 6 H), 1.32–
1.38 (m, 2 H), 1.55–1.82 (m, 4 H), 1.89–2.07 (m, 4 H), 2.48–2.77
(m, 1 H), 3.17 (d, 2J = 20.5 Hz, 2 H), 3.98–4.20 (m, 4 H), 5.85 (d,
3J = 3.4 Hz, 1 H), 6.10 (d, 3J = 3.4 Hz, 1 H).
4
(d, 2J = 21.1 Hz, 2 H), 4.05–4.12 (m, 4 H), 6.15 (d, J = 3.9 Hz, 1
H).
13C NMR (50 MHz, CDCl3): d = 16.48 (d, 3J = 5.7 Hz, 2 C), 26.0 (2
13C NMR (100 MHz, CDCl3): d = 16.5 (d, 3J = 5.9 Hz, 2 C), 20.8,
21.7, 22.2, 27.2, 27.2 (d, 1J = 143.0 Hz), 28.9, 32.8, 62.4 (d, 2J = 7.4
Hz, 2 C), 108.5 (d, 3J = 8.8 Hz), 120.1 (d, 4J = 2.2 Hz), 123.7, 126.7,
143.3 (d, 2J = 10.3 Hz), 150.3 (d, 4J = 3.6 Hz).
HRMS-ESI: m/z calcd for C17H27O4P [M + Na]+: 349.15392; found:
349.15391.
C), 26.2, 26.8 (d, 1J = 143.4 Hz), 31.6 (2 C), 37.3, 62.3 (d, 2J = 6.5
4
3
Hz, 2 C), 103.9 (d, J = 3.1 Hz), 108.6 (d, J = 7.6 Hz), 143.2 (d,
2J = 9.6 Hz), 160.5 (d, 4J = 3.1 Hz).
HRMS-ESI: m/z calcd for C15H25O4P + Na [M + Na]+: 323.13827;
found: 323.13825.
16b
12b
Column chromatography (EtOAc–n-hexane, 1:1) gave 16b (118.6
mg, 98%) as a white solid; mp 69 °C; [a]D23 –23.2 (c 0.69, EtOH).
Column chromatography (EtOAc–n-hexane, 1:1) gave 12b (29.1
mg, 70% brsm, 35% 12b) as a pale yellow oil; [a]D23 –102.4 (c 3.24,
EtOH).
IR (CCl4): 1029 1088, 1252, 1471, 2856, 2903, 2932 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.05 (s, 6 H), 0.50 (s, 3 H), 0.89
(s, 9 H), 0.85–0.97 (m, 1 H), 0.99 (s, 3 H), 1.05–1.16 (m, 2 H), 1.24–
1.30 (m, 2 H), 1.29 (t, 3J = 7.0 Hz, 6 H), 1.38–1.68 (m, 5 H), 1.70–
1.84 (m, 3 H), 1.89–2.25 (m, 4 H), 2.15–2.20 (m, 1 H), 2.59–2.64
(m, 1 H), 3.19 (d, 2J = 20.8 Hz, 2 H), 3.45–3.52 (m, 1 H), 4.03–4.11
(m, 4 H), 5.31–5.33 (m, 1 H), 5.93 (d, 3J = 3.2 Hz, 1 H), 6.12 (dd,
3J = 3.2 Hz, 4J = 4.0 Hz, 1 H).
IR (CCl4): 1034, 1115, 1214, 1377, 1444, 1632, 1681, 2835, 2950,
2991 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.28–1.37 (m, 12 H), 3.20 (d,
2J = 21.1 Hz, 2 H), 3.24 (s, 3 H), 3.27 (s, 3 H), 4.04–4.15 (m, 4 H),
3
3
4.73 (d, J = 14.7 Hz, 1 H), 4.98 (d, J = 14.7 Hz, 1 H), 5.80 (d,
Synthesis 2008, No. 16, 2617–2625 © Thieme Stuttgart · New York

2624
S. Mann et al.
PAPER
3
3J = 10.0 Hz, 1 H), 6.27 (dd, J = 2.9 Hz, 3J = 10.0 Hz, 1 H), 6.37
2.33 (m, 1 H), 2.64–2.71 (m, 1 H), 3.11–3.15 (m, 2 H), 3.91–4.01
(m, 4 H), 5.52–5.55 (m, 1 H), 6.16 (s, 1 H), 6.84 (d, 3J = 16.1 Hz, 1
H), 6.95 (d, 3J = 16.1 Hz, 1 H), 7.18–7.24 (m, 1 H), 7.30–7.35 (m,
2 H), 7.44–7.47 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 23.0, 24.7, 31.2, 34.5, 36.2, 41.2,
64.5, 64.6, 108.9, 109.2, 114.3, 117.2, 119.8, 125.6, 126.3 (2 C),
127.3, 128.8 (2 C), 137.5, 137.9, 151.7, 156.3.
(d, 4J = 3.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 16.5 (d, 3J = 5.9 Hz, 2 C), 18.0,
18.0, 27.1 (d, 1J = 143.7 Hz), 48.1, 48.1, 62.5 (d, 2J = 7.4 Hz, 2 C),
3
70.3, 72.1, 100.0, 100.5, 107.3 (d, J = 7.4 Hz), 117.8, 120.7 (d,
4J = 2.9 Hz), 126.8, 145.7 (d, 2J = 10.3 Hz), 149.3.
HRMS-ESI: m/z calcd for C19H30O8P [M + H]+: 417.16728; found:
417.16730.
HRMS-ESI: m/z calcd for C23H24O3 +Na [M + Na]+: 371.16231;
found: 371.16207.
13b
Column chromatography (EtOAc–n-hexane, 1:1) gave 13b (13.1
mg, 30% brsm, 20% 13b) as a pale yellow oil; [a]D23 +27.1 (c 0.96,
EtOH).
6c
Column chromatography (EtOAc–n-hexane, 1:100) gave 6c (300
mg, 92%) as a yellow oil.
IR (CCl4): 1027, 1081, 1253, 1368, 1392, 1455, 1632, 1722, 2873,
2929, 2963 cm–1.
IR (CCl4): 1083, 1098, 1123, 1257, 2873, 2930, 2959, 2970 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.74 (t, 3J = 8.0 Hz, 2 H), 2.98 (t,
3J = 7.8 Hz, 2 H), 6.32 (s, 1 H), 6.90 (d, 3J = 16.2 Hz, 2 H), 7.09–
7.38 (m, 6 H), 7.48–7.58 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 21.1, 29.1, 110.5, 116.7, 119.5,
121.7, 126.4 (2 C), 126.7, 126.9, 127.6, 128.0, 128.1, 128.6, 128.9
(2 C), 135.0, 137.4, 150.0, 152.9.
1H NMR (400 MHz, CDCl3): d = 0.27–0.29 (m, 1 H), 0.87–0.90 (m,
1 H), 0.96 (d, 3J = 6.3 Hz, 3 H), 1.10 (d, 3J = 7.0 Hz, 3 H), 1.19 (d,
3J = 7.0 Hz, 3 H), 1.25–1.29 (m, 6 H), 1.31–1.35 (m, 1 H), 1.41–
1.48 (m, 1 H), 2.85–2.91 (m, 1 H), 3.17 (d, 2J = 21.1 Hz, 2 H), 4.01–
4.10 (m, 4 H), 6.16 (d, 4J = 3.9 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 16.5 (d, 3J = 5.9 Hz, 2 C), 20.9,
21.1, 22.9, 27.7 (d, 1J = 144.5 Hz), 29.8, 30.9, 31.5, 32.3, 35.9, 62.5
(d, 2J = 5.9 Hz, 2 C), 106.8 (d, 3J = 8.8 Hz), 129.1 (d, 4J = 2.9 Hz),
147.0 (d, 2J = 10.3 Hz), 161.4 (d, 4J = 3.6 Hz).
HRMS-ESI: m/z calcd for C20H16O + Na [M + Na]+: 295.10934;
found: 295.10964.
7c
HRMS-ESI: m/z calcd for C17H28O4P [M + H]+: 327.17197; found:
Column chromatography (EtOAc–n-hexane, 1:100) gave 7c (271
327.17321.
mg, 88%) as a colorless oil.
IR (CCl4): 1087, 1239, 1446, 1466, 1740, 2857, 2929 cm–1.
14b
1H NMR (400 MHz, CDCl3): d = 1.22–1.31 (m, 4 H), 1.32–1.40 (m,
8 H), 1.62–1.68 (m, 2 H), 1.78–1.84 (m, 2 H), 2.39 (t, 3J = 6.6 Hz,
2 H), 2.67 (t, 3J = 6.6 Hz, 2 H), 6.19 (s, 1 H), 6.83 (d, 3J = 16.4 Hz,
1 H), 6.95 (d, 3J = 16.4 Hz, 1 H), 7.23 (t, 3J = 7.8 Hz, 1 H), 7.33 (t,
3J = 7.8 Hz, 2 H), 7.45 (d, 3J = 7.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 21.6, 22.3, 22.5, 23.1, 24.5, 24.6,
24.9, 24.9, 26.4, 27.8, 110.7, 117.0, 122.2, 125.3, 126.2 (2 C),
127.2, 128.7 (2 C), 137.6, 151.2, 151.8.
Column chromatography (EtOAc–n-hexane, 1:1) gave 14b (14.3
mg, 22% 14b and 20% aromatized product) as a pale yellow oil;
[a]D23 –10.8 (c 0.37, EtOH).
IR (CCl4): 1081, 1392, 1444, 1645, 2980 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.30 (t, 3J = 7.0 Hz, 6 H), 1.72 (s,
4
3 H), 1.93 (d, J = 1.8 Hz, 3 H), 2.33–2.42 (m, 2 H), 3.22 (d,
2J = 20.5 Hz, 2 H), 3.41–3.47 (m, 1 H), 4.04–4.14 (m, 4 H), 4.76 (s,
2 H), 5.34–5.37 (m, 1 H), 6.09 (d, 4J = 3.5 Hz, 1 H).
HRMS-ESI: m/z calcd for C22H28NaO + Na [M + Na]+: 331.20324;
found: 331.20346.
13C NMR (75 MHz, CDCl3): d = 15.9, 16.5 (d, J = 5.5 Hz, 2 C),
3
20.0, 27.1 (d, 1J = 143.2 Hz), 30.1, 41.2, 62.5 (d, 2J = 5.0 Hz, 2 C),
109.5 (d, 3J = 7.7 Hz), 111.3, 119.5, 120.1 (d, J = 3.9 Hz), 125.7,
4
2-Phenethyl[b]furans 5d–7d; General Procedure
143.5 (d, 2J = 10.5 Hz), 147.2, 151.7.
The appropriate 2-styryl[b]furans 5c, 6c, or 7c (0.2 mmol) was dis-
solved in THF (2 mL) and Pd/C 5% (4 mg) was added. After hydro-
genation at ambient pressure for 20 min, the catalyst was removed
by filtration using Celite. Removal of the solvent and column
chromatography of the residue on silica gel afforded 2-phen-
ethyl[b]furans (Table 2).
HRMS-ESI: m/z calcd for C34H50O8P2 + Na [2 M + Na]+:
671.28731; found: 671.28802.
2-Styryl[b]furans 5c–7c; General Procedure
The appropriate diethyl ([b]furan-2-yl)methylphosphonates 5b, 6b,
or 7b (1 mmol) was dissolved in THF (5 mL) at 0 °C. A suspension
of NaH (115 mg, 3 mmol, 60% in mineral oil) in THF (5 mL) was
added and the resulting mixture was stirred at 0 °C for 30 min.
Freshly distilled benzaldehyde (152 mL, 159 mg, 1.5 mmol) in THF
(5 mL) was added and the mixture was stirred overnight at r.t. After
quenching with aq sat. NH4Cl (15 mL), the aqueous phase was ex-
tracted with EtOAc (3 × 15 mL). The combined organic phases
were washed with brine (15 mL), dried (Na2SO4), evaporated, and
the residue was purified by column chromatography on silica gel
(Table 2).
5d
Column chromatography (EtOAc–n-hexane, 1:10) gave 5d (62.4
mg, 89%) as a colorless oil; [a]D23 +100.0 (c 0.34, EtOH).
IR (CCl4): 1023, 1097, 1117, 1178, 1259, 1359, 1427, 1454, 1663,
2886, 2950 cm–1.
1H NMR (400 MHz, C6D6): d = 1.40 (s, 3 H), 1.69–1.74 (m, 1 H),
1.89–1.97 (m, 1 H), 2.03–2.17 (m, 1 H), 2.31–2.35 (m, 1 H), 2.69–
2.74 (m, 2 H), 2.75–2.84 (m, 4 H), 2.93–2.95 (m, 2 H), 3.39–3.53
(m, 4 H), 5.40–5.42 (m, 1 H), 5.63 (s, 1 H), 6.95–7.01 (m, 3 H),
7.05–7.10 (m, 2 H).
5c
Column chromatography (EtOAc–n-hexane, 1:10) gave 5c (300
mg, 86%) as a pale yellow solid; mp 138–140 °C; [a]D23 +259.2 (c
0.71, EtOH).
IR (KBr): 1086, 1289, 1384, 1445, 1519, 1593, 1633, 2934 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.47 (s, 3 H), 1.75–1.80 (m, 1 H),
1.82–1.85 (m, 1 H), 1.92–1.98 (m, 1 H), 2.15–2.21 (m, 1 H), 2.28–
13C NMR (100 MHz, CDCl3): d = 23.1, 25.1, 30.5, 31.9, 34.9, 35.1,
36.4, 41.7, 64.3, 64.4, 105.6, 109.4, 112.8, 120.2, 126.3 (2 C),
128.6, 128.7 (2 C), 128.3, 141.7, 153.8, 154.9.
HRMS-ESI: m/z calcd for C23H27O3 [M + H]+: 351.15947; found:
351.15917.
Synthesis 2008, No. 16, 2617–2625 © Thieme Stuttgart · New York

PAPER
Functionalized Furans
2625
6d
rac-6e
Column chromatography (EtOAc–n-hexane, 1:100) gave 6d (52.2
Column chromatography (EtOAc–n-hexane, 1:100) gave rac-6e
mg, 95%) as a colorless oil.
(51.2 mg, 92%) as a colorless oil.
IR (CCl4): 1084, 1426, 1453, 1495, 1548, 1597, 2843, 2932, 3026,
3060 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.69 (t, 3J = 7.8 Hz, 2 H), 2.96 (t,
3J = 7.8 Hz, 2 H), 3.00–3.04 (m, 4 H), 5.96 (s, 1 H), 7.06–7.46 (m,
9 H).
IR (CCl4): 1081, 1454, 1494, 2857, 3024, 3061 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.31–1.40 (m, 1 H), 1.51–1.64 (m,
1 H), 1.76–1.88 (m, 2 H), 1.96–2.08 (m, 1 H), 2.32–2.52 (m, 2 H),
2.58–2.82 (m, 4 H), 3.89–3.98 (m, 1 H), 4.67 (d, 3J = 6.6 Hz, 1 H),
7.11–7.30 (m, 8 H), 7.44–7.47 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 21.2, 29.3, 30.4, 34.6, 107.1,
118.8, 120.2, 125.9, 126.2 (2 C), 126.8, 128.0, 128.5, 128.5 (2 C),
128.6, 134.3, 141.4, 148.6, 155.3.
13C NMR (75 MHz, CDCl3): d = 28.1, 29.0, 32.8, 32.9, 37.8, 38.9,
77.6, 78.3, 126.0, 126.5, 127.7, 128.5, 128.6 (2 C), 128.7 (2 C),
130.5, 135.5, 138.4, 142.4.
HRMS-ESI: m/z calcd for C20H18NaO + Na [M + Na]+: 297.12499;
HRMS-ESI: m/z calcd for C20H22O + Na [M + Na]+: 301.15629;
found: 297.12507.
found: 301.15617.
7d
Acknowledgment
Product 7d (62.1 mg, quant) was obtained as a colorless oil and did
not require further purification.
We thank the DFG (GI 204/6-1) for financial support. We also
thank Prof. Peter Welzel for helpful discussions and for reading the
manuscript.
IR (CCl4): 1087, 1214, 1454, 1466, 1496, 1575, 2856, 2927, 3027,
3062 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.16–1.26 (m, 4 H), 1.31–1.37 (m,
8 H), 1.53–1.61 (m, 2 H), 1.68–1.76 (m, 2 H), 2.32 (t, 3J = 6.7 Hz,
2 H), 2.58 (t, 3J = 6.4 Hz, 2 H), 2.82–2.96 (m, 4 H), 5.74 (s, 1 H),
7.15–7.30 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = 21.7, 22.3, 22.5, 22.8, 24.5, 24.6,
24.8, 25.0, 26.3, 27.7, 30.3, 34.7, 106.6, 120.1, 126.0, 128.4 (2 C),
128.6 (2 C), 141.7, 149.5, 153.1.
References
(1) Pudhom, K.; Vilaivan, T.; Ngamrojanavanich, N.;
Dechangvipart, S.; Sommit, D.; Petsom, A.; Roengsumran,
S. J. Nat. Prod. 2007, 70, 659.
(2) Bock, I.; Bornowski, H.; Ranft, A.; Theis, H. Tetrahedron
1990, 46, 1199.
(3) Holtzapfel, C. W.; Marais, W.; Wessels, L. P.; Van Wyk,
B.-E. Phytochemistry 2002, 59, 405.
HRMS-ESI: m/z calcd for C22H31O [M + H]+: 311.23694; found:
311.23711.
(4) Mortensen, D. S.; Rodriguez, A. L.; Carlson, K. E.; Sun, J.;
Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J. Med.
Chem. 2001, 44, 3838.
(5) Piggot, M. J. Tetrahedron 2005, 61, 9929.
(6) Lipshutz, B. H. Chem. Rev. 1986, 86, 795.
(7) Hou, X. L.; Cheung, H. Y.; Hon, T. Y.; Kwan, P. L.; Lo, T.
H.; Tong, S. Y.; Wong, H. N. C. Tetrahedron 1998, 54,
1955.
(8) Review: Brown, R. C. D. Angew. Chem. Int. Ed. 2005, 44,
850; Angew. Chem. 2005, 117, 872.
(9) Fukuda, Y.; Shiragami, H.; Utimoto, K.; Nozaki, H.
J. Org. Chem. 1991, 56, 5816.
(10) Hashmi, A. S. K. Angew. Chem. Int. Ed. 2000, 39, 2285;
Angew. Chem. 2000, 112, 2382.
(11) Marshall, J. A.; Sehon, C. A. J. Org. Chem. 1995, 60, 5966.
(12) Seiller, B.; Bruneau, Ch.; Dixneuf, P. H. Tetrahedron 1995,
51, 13089.
(13) Poss, A. J.; Belter, R. K. J. Org. Chem. 1987, 52, 4810.
(14) Negishi, E.; Chatterjee, S. Tetrahedron Lett. 1983, 24, 1341.
(15) Lazo J, S.; Nunes, R.; Skoko, J. J.; Queiroz de Oliveira P,
E.; Vogt, A.; Wipf, P. Bioorg. Med. Chem. 2006, 14, 5643.
(16) Muthiah, C.; Praveen Kumar, K.; Aruna Mani, C.;
Kumara Swamy, K. C. J. Org. Chem. 2000, 65, 3733.
(17) Castagnino, E. Tetrahedron Lett. 1985, 26, 6399.
(18) Rivalle, C.; Andre-Luisfert, I.; Bisogni, E. Tetrahedron
1976, 32, 829.
Tetrahydro-2-phenethyl[b]furans 5e, 6e; General Procedure
2-Styryl[b]furans 5c or 6c (0.2 mmol) was dissolved in THF (2 mL)
and Pd/C 5% (4 mg) was added. After hydrogenation at ambient
pressure for 5 h, the catalyst was removed by filtration using Celite.
Removal of the solvent and column chromatography of the residue
afforded tetrahydro-2-phenethyl[b]furans (Table 2).
5e
Column chromatography (EtOAc–n-hexane, 1:10) gave 5e (48.9
mg, 69%) as a colorless oil (inseparable mixture of diastereomers).
IR (CCl4): 1016, 1064, 1098, 1117, 1205, 1258, 1291, 1365, 1454,
1496, 2929, 3026 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.24 (s, 3 H), 1.26–1.37 (m, 1 H),
1.42–1.47 (m, 1 H), 1.50–1.61 (m, 1 H), 1.64–1.70 (m, 1 H), 1.73–
1.81 (m, 1 H), 1.86–2.07 (m, 3 H), 2.12–2.45 (m, 3 H), 2.60–2.79
(m, 2 H), 2.82–2.95 (m, 4 H), 3.87–3.98 (m, 4 H), 5.73 (s, 1 H),
7.17–7.30 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = 19.1, 21.0, 24.7, 30.3, 31.8, 32.9,
34.7, 35.5, 38.7, 40.1, 64.2, 64.4, 79.1, 106.0, 109.6, 115.6, 126.1,
128.4 (2 C), 128.5 (2 C), 141.7, 153.4.
HRMS-ESI: m/z calcd for C23H30O3 + Na [M + Na]+: 377.20872;
found: 377.20906.
Synthesis 2008, No. 16, 2617–2625 © Thieme Stuttgart · New York