Regioselective synthesis of functionalized furans by cyclization of 1,3-bis-silyl enol ethers with 1-chloro-2,2-dimethoxyethane

FULL PAPER

Regioselective Synthesis of Functionalized Furans by Cyclization of 1,3-Bis-

Silyl Enol Ethers with 1-Chloro-2,2-dimethoxyethane

Esen Bellur^[a]and Helmar Görls,^[b]Peter Langer*^[a,c]

Keywords: Cyclization / Chemoselectivity / Silyl enol ethers / Regioselectivity / Tetrahydrofurans

Cyclization of 1,3-bis-silyl enol ethers with 1-chloro-2,2-di-

larly, 2,3,3a,4,5,6-hexahydro-2,3-benzofurans were prepared

methoxyethane allowed an efficient, regio- and diastereo- and transformed into 4,5,6,7-tetrahydro-2,3-benzofurans by

selective synthesis of a variety of 2-alkylidene-4-methoxy-

tetrahydrofurans. The TFA-mediated elimination of meth-

anol resulted in the formation of functionalized furans. Simi-

treatment with TFA.

Germany, 2005)

zations of 1,3-bis-silyl enol ethers with 1-chloro-2,2-di-

methoxyethane.^[18]Here we wish to report studies related to

the preparative scope of this reaction. With regard to our

earlier publication, we have significantly extended its scope

and have also studied its stereoselectivity in detail. In ad-

dition, the synthesis of furans through elimination reactions

of 2-alkylidenetetrahydrofurans is reported. Our methodol-

ogy allows a convenient synthesis of a great variety of func-

tionalized mono- and bicyclic furans.

Introduction

Functionalized furans are of considerable pharmacologi-

cal relevance and occur in a variety of natural products,

such as terpenes. They include, for instance, the calicogorg-

ins, furan fatty acids, cytotoxic furanocembranes, gersol-

anes, pseudopteranes, rosefuran, agassizin, furodysin, mi-

kanifuran, and α-clausenan.^[1,2]A number of synthetic ap-

proaches to furans have been reported.^[2–8]Lewis-acid medi-

ated condensation of silyl enol ethers—masked enolates—

with aldehydes and acetals plays an important role in or-

ganic synthesis,^[9,10]and a number of cyclization reactions

have been reported in this context. As one example, the

TiCl₄-mediated reaction of silyl enol ethers with α-bro-

moacetals has been reported to give β-alkoxy-γ-bromo-

ketones that could be transformed into substituted fu-

rans.^[11]

The reaction of 1,3-bis-silyl enol ethers—masked 1,3-di-

carbonyl dianions^[12]—with aldehydes and acetals is also of

great synthetic importance.^[13]Reactions between 1,3-bis-si-

lyl enol ethers and enantiomerically pure α-substituted alde-

hydes often proceed with very good diastereoselectivity,^[14]

and the enantioselective condensation of a 1,3-bis-silyl enol

ether with α-benzyloxyacetic aldehyde has recently been re-

ported.^[15]A number of cyclizations of 1,3-bis-silyl enol

ethers and of 1-methoxy-3-trimethylsilyloxy-1,3-butadiene

with functionalized aldehydes are known.^[16]We have re-

cently developed a new approach to 2-alkylidenetetrahydro-

furans based on pioneering work by Chan,^[17]through cycli-

Results and Discussion

The Me₃SiOTf-catalysed reaction between 1,3-bis-silyl

enol ether 1a, prepared from methyl acetoacetate in two

steps,^[12b]and 1-chloro-2,2-dimethoxyethane (2) afforded

the open-chained condensation product 3a in 72% yield

(Scheme 1, Table 1). Treatment of 3a with DBU, by our re-

cently published procedure,^[18]resulted in regioselective cy-

[a] Institut für Chemie und Biochemie, Universität Greifswald,

Soldmannstr. 16, 17487 Greifswald, Germany

[b] Institut für Anorganische und Analytische Chemie, Universität

Jena,

August-Bebel-Str. 2, 07740 Jena, Germany

[c] New address: Institut für Chemie, Universität Rostock,

Albert-Einstein-Str. 3a, 18051 Rostock, Germany

Fax: +49-381-498-6412

Scheme 1. Synthesis of monocyclic furans. a) 0.5 equiv. Me₃SiOTf,

CH₂Cl₂, –78 Ǟ 20 °C, b) 2.0 equiv. DBU, THF, 20 °C, c) TFA,

CH₂Cl₂, 20 °C.

E-mail: Peter.Langer@uni-rostock.de

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DOI: 10.1002/ejoc.200400805

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Regioselective Synthesis of Functionalized Furans

Table 1. Products and yields.

FULL PAPER

3,4,5

R¹

R²

% (3)^[a]

% (4)^[a]

% (5)^[a]

δ [ppm]^[b]

δ [ppm]^[c]

E/Z^[d]

a

b

c

d

e

f

g

h

i

OMe

OEt

OiPr

O(CH₂)₂OMe

OBn

Ph

OMe

OEt

OMe

OEt

H

Me

Et

OMe

Allyl

nPr

nBu

nHex

nOct

nNon

nDec

(CH₂)₆Cl

72

66

70

67

51

63

83

64

86

74

80

68

94

–

90

99

49

33

80

79

73

76

97

87

70

93

80

100

61

100

70

84

79

–

98

100

76

5.38

5.37

5.35

5.43

5.44

–

5.33

5.54

5.05

5.35

5.32

5.31

5.32

168.4

168.5

–

167.9

168.3

–

168.2

167.9

167.8

165.5

167.8

167.6

168.0

167.8

167.7

167.8

Ͼ 98:2

–

Ͼ 98:2

Ͻ 2:98

Ͼ 98:2

i

j

57

87

85

88

53

79

86

78

k

l

m

n

o

p

q

[a] Yields of isolated products. For all compounds 4g–q: trans/cis Ͼ 98:2. Compounds 3 were obtained as mixtures of keto/enol tautomers.

In some cases a small amount of starting material (1,3-dicarbonyl compound derived from hydrolysis of 1,3-bis-silyl enol ether) could

not be separated. [b] Chemical shift (¹H NMR, CDCl₃) of the hydrogen atom of the exocyclic double bond of 4. [c] Chemical shift (¹³C

NMR, CDCl₃) of the carbonyl group of 4. [d] E/Z ratio of the exocyclic double bond of 4.

clization and formation of the 2-alkylidene-4-methoxytetra- ization to give E/Z mixtures of 4i and small amounts of

hydrofuran 4a in 86% yield. The regioselectivity can be ex- decomposition products. However, elimination of methanol

plained by stereoelectronic considerations.^[19]The thermo- and clean formation of methoxy-substituted furan 5i could

dynamically favoured isomer, containing an E-configured be achieved by heating of a CH₂Cl₂solution of (Z)-4i at

exocyclic double bond, was formed with very good selectiv- reflux. The corresponding reaction of (E)-4i has not been

ity. Treatment of 4a with TFA afforded the furan 5a by carried out. Treatment of methyl (3-methoxydihydrofuran-

elimination of methanol.

2-ylidene)acetate^[20]with TFA was not successful and re-

Cyclizations of 2 with 1,3-bis-silyl enol ethers 1b–e af- sulted in the formation of complex mixtures rather than

forded 3b–e, which were transformed into the known 2-al- furan 5a (Scheme 2). This result and the formation of 5i

kylidenetetrahydrofurans 4b–e (Scheme 1, Table 1).^[18]The from (Z)-4i indicate that the presence of a methoxy group

latter were treated with TFA to give the furans 5b–e in good at C-4 is mandatory for a clean elimination and formation

yields. Treatment of 2 with 1,3-bis-silyl enol ether 1f, pre- of a furan.

pared from benzoylacetone, gave 3f, and treatment of this

with DBU directly afforded furan 5f. The reactions between

2 and 1g–q gave the corresponding open-chain products 3g–

q with very good diastereoselectivity, while treatment of 3g–

q with DBU afforded the 2-alkylidenetetrahydrofurans 4g–

q. The exocyclic double bond was formed with very good

E diastereoselectivity (except in the case of 4i), despite the

presence of the substituent at C-3. The synthesis of 4g, 4h

and 4l has been reported by us previously.^[18]Treatment of

4g–h and 4j–q with TFA afforded the substituted furans 5g–

h and 5j–q in good yields. The furans 4q and 5q, prepared

from the novel chloro-substituted 1,3-bis-silyl enol ether 1q,

are of special interest, due to their functionalized side-

chain. For some derivatives of 3, a small amount of 1,3-

Scheme 2.

dicarbonyl compound (derived from hydrolysis of the 1,3-

The configurations of the exocyclic double bonds of 2-

bis-silyl enol ether) could not be separated, but this impu- alkylidenetetrahydrofurans 4 were established by NOESY

rity could be separated during the synthesis of 4. Very good experiments and by comparison of the chemical shifts of

diastereoselectivities were observed for 3g–q and 4g–q. With the hydrogen atoms of the exocyclic double bonds with

regard to our initial procedure,^[18]the employment of 0.5 those of related 2-alkylidenetetrahydrofurans (Table 1).^[21,22]

rather than 1.0 equiv. of TMSOTf and the use of a higher As would be expected, characteristic chemical shifts in the δ

concentration of the reactants proved preferable in terms of = 5.31–5.54 range were observed for all E-configured ester-

diastereoselectivity.

derived 2-alkylidenetetrahydrofurans. In contrast, a reso-

Treatment of the methoxy-substituted 2-alkylidenetetra- nance at δ = 5.05 was observed for the Z-configured isomer

hydrofurans (E)-4i and (Z)-4i with TFA resulted in isomer- of 4i. The E-configured 2-alkylidenetetrahydrofurans gen-

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E. Bellur, H. Görls, P. Langer

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erally showed a characteristic carbonyl ¹³C NMR reso-

nance in the δ = 167.6–168.5 range (for ester derivatives).

In contrast, a resonance of δ = 165.6 was observed for the

Z-configured isomer of 4i.

Independent and unambiguous confirmation of the con-

figuration was established by crystal structure analysis of

4g (Figure 1). The crystal structure of 4g revealed a trans

(erythro) configuration of the C(2)–C(3) bond. Analysis of

the coupling constants (Karplus) indicated that all the

tetrahydrofurans 4g–q, containing a substituent at C-3, pos-

sess trans configurations. However, the attribution of the

relative stereochemistry in five-membered rings through J

values has to be treated with great care and is not entirely

unambiguous, due to the small differences between the di-

hedral angles of the cis and trans configurations. The excel-

lent 1,2-diastereoselectivity can be explained by known ster-

eoelectronic considerations (comparison of acyclic extended

transition states with minimized electrostatic repul-

sion).^[10,18]The transition state leading to the trans isomer

Scheme 3. Synthesis of 4r and 5r. a) 1.0 equiv. Me₃SiOTf,

CH₂Cl₂, –78 Ǟ 20 °C, 49%, b) 2.0 equiv. DBU, THF, 20 °C,

77%, c) TFA, CH₂Cl₂, 20 °C, 76%.

is sterically favoured over that leading to the cis product. novel bicyclic furan 5t. A very good trans diastereoselectiv-

The configuration of the terminal double bond of the 1,3- ity was observed for the synthesis of 5,8-bicyclic tetra-

bis-silyl enol ether is irrelevant to the stereoselection.

hydrofuran 4u, which was prepared from 1u. Treatment of

4u with TFA afforded the furan 5u. The reaction between

2 and 1v afforded 3v with very good diastereoselectivity,

treatment of 3v with DBU afforded the trans-configured

5,12-bicyclic tetrahydrofuran 4v as a separable mixture of

E/Z isomers. The reaction of 4v with TFA gave the furan

5v. The reaction of 2 with 1w, prepared from ethyl 4-methyl-

2-oxocyclohexan-1-carboxylate, afforded 3w. Three ste-

reogenic centres were formed with very good double 1,2-

diastereoselectivity. The diastereomerically pure, cis-config-

ured 3-methoxyhexahydro-2,3-benzofuran 4w was prepared

from 3w, treatment of 4w with TFA affording furan 5w. The

reaction of 2 with 1x, prepared from methyl 2-oxo-3-phen-

ylcyclohexan-1-carboxylate, afforded 3x, treatment of 3x

with DBU affording the Z-configured 3-methoxyhexahy-

dro-2,3-benzofuran 4x as a separable mixture of dia-

stereomers. Heating of 4x at reflux in dichloromethane af-

forded furan 5x as an inseparable mixture of two dia-

stereomers.

Figure 1. ORTEP plot of 4g. Thermal ellipsoids of 50% probability

are shown for the non-hydrogen atoms. Selected bond lengths (Å)

and angles (°): O(1)–C(4) 1.3580(17), O(1)–C(1) 1.4548(19), O(3)–

C(6) 1.2119(18), C(1)–C(2) 1.516(2), C(2)–C(3) 1.530(2), C(3)–C(4)

1.505(2), C(4)–C(5) 1.341(2), C(5)–C(6) 1.452(2); C(4)–O(1)–C(1)

109.57(11), O(1)–C(1)–C(2) 104.94(11), C(1)–C(2)–C(3) 102.00(12),

C(4)–C(3)–C(8) 111.58(12), C(5)–C(4)–O(1) 119.17(13).

The structure of the 5,6-bicyclic 2-alkylidenetetrahydro-

The reactions of cyclic 1,3-bis-silyl enol ethers^[23]with 1- furan 4r was studied by crystal structure analysis (Figure 2).

chloro-2,2-dimethoxyethane (2) were studied next A cis configuration was observed for the C(2)–C(3) bond

(Scheme 3, Table 2). The reaction of 2 with 1r, prepared of 4r, in contrast to the monocyclic derivatives 4g–q. Three

from ethyl 2-oxocyclohexan-1-carboxylate, afforded the stereogenic centres are present in the 5,6-bicyclic products

condensation product 3r with very good 1,2-diastereoselec- 4w and 4x. The relative configuration of 4w was established

tivity. Treatment of the latter with DBU afforded the cis- by analysis of the coupling constants (Karplus) and by

configured 3-methoxy-2,3,3a,4,5,6-hexahydro-2,3-benzofu- comparison with 4r and related 5,6-bicyclic 2-alkylidenete-

ran 4r, and treatment of 4r with TFA resulted in formation trahydrofurans.^[24]Analysis of the coupling constants

of the bicyclic furan 5r.^[24]The reaction between 2 and 1s, (Karplus) also suggested that the 5,5- and 5,7-bicyclic het-

prepared from ethyl 2-oxocyclopentan-1-carboxylate, af- erocycles 4s–t possess cis configurations. In contrast, a trans

forded 3s with very good diastereoselectivity. Treatment of configuration is present in the case of the medium-sized 5,8-

3s with DBU afforded the diastereomerically pure cis-con- bicyclic product 4u. However, attribution of the relative

figured bicyclo[3.3.0]octene 4s. All attempts to transform 4s configuration through the J values is once again not entirely

into furan 5s resulted in decomposition. The 5,7-bicyclic unambiguous, due to the small differences between the di-

tetrahydrofuran 4t was prepared from the corresponding hedral angles of the cis and trans configurations. This prob-

cyclic 1,3-bis-silyl enol ethers 1t, again with very good cis lem is particularly apparent for 4t and 4u, since no clear

diastereoselectivity. Treatment of 4t with TFA afforded the trend in the diastereoselectivity was observed. The crystal

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Regioselective Synthesis of Functionalized Furans

Table 2. Products and yields

FULL PAPER

[a] Yields of isolated products. For all products 4 (except for 4x): dr Ͼ 98:2 in favour of the diastereomer drawn. The assignment of the

relative configuration is not entirely unambiguous (except for 4r and 4v).

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E. Bellur, H. Görls, P. Langer

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structure of the 5,12-bicyclic tetrahydrofuran 4v (Figure 3) idenetetrahydrofurans 4. In contrast, the opposite stereo-

clearly showed the presence of a trans-configured C(3)–C(4) chemistry (cis) was observed for 4r–t and 4w.

bond, which is also in agreement with the solution structure

The reaction between 1,3-bis-silyl enol ether 1y, prepared

examined by NMR spectroscopy. The isomer studied by from 2-acetyl-γ-butyrolactone, and 1-chloro-2,2-dimethoxy-

crystal structure analysis exhibited a Z-configured double ethane (2) afforded the condensation product 3y

bond. In summary, the reactions of medium-sized cyclic (Scheme 4). Treatment of the latter with DBU afforded the

1,3-bis-silyl enol ethers (1v, 1u) and of open-chained 1,3- 2-alkylidenetetrahydrofuran 4y. Heating of a dichlorometh-

bis-silyl enol ethers (1g–q) lead to trans-configured 2-alkyl- ane solution of 4y at reflux gave the furan 5y in very good

yield.

Scheme 4. Synthesis of 4y and 5y. a) 0.5 equiv. Me₃SiOTf,

CH₂Cl₂, –78 Ǟ 20 °C, 97%. b) 2.0 equiv. DBU, THF, 20 °C, 92%.

c) reflux in CH₂Cl₂, 98%.

Figure 2. ORTEP plot of 4r. Thermal ellipsoids of 50% probability

are shown for the non-hydrogen atoms. Selected bond lengths (Å)

and angles (°): O(1A)–C(8A) 1.356(2), O(1A)–C(1A) 1.460(2),

The reaction between 2,4-bis(trimethylsilyloxy)penta-1,3-

diene (1z), prepared from acetylacetone, and 1-chloro-2,2-

dimethoxyethane (2) was studied next (Scheme 5). The reac-

tion between 2 and 1z afforded the open-chained products

3z and 6, the latter formed by reaction of 1z with two equiv-

C(1A)–C(2A) 1.521(3), C(2A)–C(3A) 1.522(3), C(3A)–C(8A)

1.507(2), C(6A)–C(7A) 1.516(3), C(7A)–C(8A) 1.343(3); C(8A)–

O(1A)–C(1A) 108.72(14), C(1A)–C(2A)–C(3A) 100.19(15), C(8A)–

C(3A)–C(4A) 112.06(15), C(8A)–C(3A)–C(2A) 101.37(14), C(4A)–

C(5A)–C(6A) 111.73(15), C(8A)–C(7A)–C(9A) 121.74(17).

Figure 3. ORTEP plot of 4v. Thermal ellipsoids of 50% probability

are shown for the non-hydrogen atoms. Selected bond lengths (Å)

and angles (°): O(1)–C(14) 1.363(3), O(1)–C(1) 1.459(4), C(1)–C(2)

1.504(5), C(2)–C(3) 1.536(4), C(3)–C(14) 1.506(4), C(3)–C(4)

1.541(4), C(13)–C(14) 1.349(4), C(13)–C(15) 1.474(4); C(14)–O(1)–

C(1) 109.5(2), O(4)–C(2)–C(1) 108.2(2), C(14)–C(3)–C(2) 102.1(2),

C(5)–C(4)–C(3) 112.7(3), C(5)–C(6)–C(7), 113.6(3), C(14)–C(13)–

C(15) 120.4(3), C(15)–C(13)–C(12) 119.0(2), C(13)–C(14)–O(1)

122.4(3).

Scheme 5. Synthesis of 3z and 6. a) 0.5 equiv. Me₃SiOTf, CH₂Cl₂,

–78 Ǟ 20 °C, b) 2.0 equiv. DBU, THF, 20 °C.

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(1.70 g, 67%). ¹H NMR (CDCl₃, 600 MHz, 5% enol form): δ =

2.83 (d, J = 6.0 Hz, 2 H, CH₂), 3.39 (s, 3 H, OCH₂CH₂OCH₃),

3.41 (s, 3 H, OCH₃), 3.54 (s, 2 H, CH₂), 3.59–3.65 (m, 4 H, OCH_2-

CH₂OCH₃, CH₂Cl), 3.95 (m, 1 H, CH), 4.32 (t, J = 6.0 Hz, 2 H,

OCH₂CH₂OCH₃), 5.18 (s, 1 H, CH=C from enol form) ppm.

alents of 2. The reaction of 3z and 6 with DBU resulted in

decomposition rather than cyclization.

In summary, the cyclization of 1,3-bis-silyl enol ethers

with 1-chloro-2,2-dimethoxyethane allowed an efficient

synthesis of a variety of novel 2-alkylidene-4-methoxytetra-

hydrofurans. The reactions proceeded with very good Compound 3e: This compound was produced from 2 (1.14 mL,

10.0 mmol), 1e (3.366 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3e being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 10:1) as a yellow oil

(1.45 g, 51%). ¹H NMR (CDCl₃, 300 MHz, 5% enol form): δ =

2.85 (d, J = 7.2 Hz, 2 H, CH₂), 3.37 (s, 3 H, OCH₃), 3.55 (s, 2 H,

CH₂), 3.58 (dd, J = 4.5, 3.9 Hz, 2 H, CH₂Cl), 3.91 (m, 1 H, CH),

5.18 (s, 2 H, OCH₂Ph), 5.15 (s, 1 H, CH=C from enol form), 7.33–

7.39 (m, 5 H, 5×CH from Ph), 12.20 (s, 1 H, OH from enol

form) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 44.69 (CH₂), 45.17

(CH₂Cl), 49.85 (CH₂), 57.58 (OCH₃), 67.08 (OCH₂Ph), 75.84

(CH), 128.20, 128,37, 128.51 (CH from Ph), 135.11 (C from Ph),

chemo-, regio- and 1,2-diastereoselectivity. In addition, a

new approach to functionalized furans based on elimi-

nation reactions of 2-alkylidenetetrahydrofurans was devel-

oped.

Experimental Section

General Procedure for Reactions between 1,3-Bis-silyl Enol Ethers

and 1-Chloro-2,2-dimethoxyethane: Me₃SiOTf (0.5 equiv.) was

added at –78 °C to a CH₂Cl₂solution (4 mL mmol^–1) of 1 (1 equiv.)

and 2 (1 equiv.), and the mixture was stirred for 2 h at –78 °C. The

temperature of the reaction mixture was allowed to rise to 20 °C

over 14 h, and the system was then stirred for 3 h at 20 °C. A satu-

rated aqueous solution of NaHCO₃was added to this solution, the

organic layer was separated, and the aqueous layer was repeatedly

extracted with dichloromethane. The combined organic extracts

were dried over Na₂SO₄and filtered, and the solvent of the filtrate

was removed in vacuo. The residue was purified by column

chromatography (silica gel, n-hexane/EtOAc) to give 3. Some prod-

ucts 3 contain a small amount of unknown impurity which was

separated during the synthesis of 4.

166.54 (O–C=O), 200.21 (C=O) ppm. IR (neat; cm^–1): ν = 2957

˜

(w), 2936 (m, C–H), 1744 (s, O–C=O), 1717 (s, C=O), 1651 (w),

1498 (w), 1456 (m), 1429 (w), 1409 (w), 1378 (m), 1322 (m), 1299

(w), 1264 (m), 1251 (m), 1231 (m), 1181 (m), 1151 (m), 1099 (s),

1028 (w), 996 (w), 750 (m), 699 (m) cm^–1. MS (EI, 70 eV): m/z (%)

= 284 [M]⁺(48), 248 (19), 217 (23), 177 (100). C₁₄H₁₇O₄Cl

(284.739): C 59.06, H 6.02; found C 59.01, H 6.22.

Compound 3f: This compound was produced from 2 (1.14 mL,

10.0 mmol), 1f (3.066 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3f being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a brown solid

(1.29 g, 51%). ¹H NMR (CDCl₃, 300 MHz, 95% enol form, analy-

sis for enol): δ = 2.76 (d, J = 7.2 Hz, 2 H, CH₂), 3.45 (s, 3 H,

OCH₃), 3.63 (dd, J = 10.8, 4.5 Hz, 1 H, CH₂Cl), 3.71 (dd, J = 10.8,

4.5 Hz, 1 H, CH₂Cl), 3.98 (m, 1 H, CH), 6.24 (s, 1 H, CH from

enol), 7.43–7.56 (m, 3 H, 3×H from Ph), 7.90 (d, J = 6.0 Hz, 2 H,

2×H from Ph), 16.07 (broad s, 1 H, OH from enol) ppm. ¹³C NMR

(CDCl₃, 75 MHz): δ_C= 41.83 (CH₂), 45.16 (CH₂Cl), 57.54 (OCH₃),

77.06 (CH), 97.21 (CH=C), 126.90, 128.49, 132.34 (CH from Ph),

134.30 (C from Ph), 182.83 (HO–C=CH), 193.34 (O=C–Ph) ppm.

Compound 3a: This compound was produced from 2 (2.86 mL,

25.0 mmol), 1a (6.512 g, 25.0 mmol) and Me₃SiOTf (2.778 g,

12.5 mmol) in CH₂Cl₂(100 mL), 3a being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil

(3.76 g, 72%). ¹H NMR (CDCl₃, 300 MHz, 5% enol form): δ =

2.88 (d, J = 6.0 Hz, 2 H, CH₂), 3.41 (s, 3 H, OCH₃), 3.51 (s, 2 H,

CH₂), 3.62 (dd, J = 3.9, 3.3 Hz, 2 H, CH₂Cl), 3.75 (s, 3 H, OCH₃),

3.95 (m, 1 H, CH), 5.10 (s, 1 H, CH=C from enol form), 12.10 (s,

1 H, OH from enol form) ppm.

IR (KBr (cm^–1)): ν = 2925 (w), 2919 (w, C–H), 1610 (s, C=C from

˜

Compound 3b: This compound was produced from 2 (1.14 mL,

10.0 mmol), 1b (2.745 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3b being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil

(1.47 g, 66%). ¹H NMR (CDCl₃, 300 MHz, 5% enol form): δ =

1.29 (t, J = 7.2 Hz, 3 H, OCH₂CH₃), 2.88 (d, J = 6.0 Hz, 2 H,

CH₂), 3.41 (s, 3 H, OCH₃), 3.49 (s, 2 H, CH₂), 3.62 (dd, J = 4.5,

3.3 Hz, 2 H, CH₂Cl), 3.94 (m, 1 H, CH), 4.20 (q, J = 7.2 Hz, 2 H,

OCH₂CH₃), 5.09 (s, 1 H, CH=C from enol form), 12.15 (s, 1 H,

OH from enol form) ppm.

enol from), 1575 (s), 1495 (m), 1458 (m), 129 (m), 1411 (w), 1371

(m), 1332 (w), 1303 (w), 1284 (w), 1263 (w), 1214 (w), 1188 (w),

1147 (m), 1094 (s), 1069 (m), 1002 (w), 947 (w), 830 (w), 765 (s),

702 (m), 690 (m) cm^–1. MS (EI, 70 eV): m/z (%) = 254 [M]⁺(37),

218 (48), 205 (59), 187 (100). C₁₃H₁₅O₃Cl (254.713): C 61.39, H

5.94; found C 61.42, H 6.71. The exact molecular mass m/z =

254.0710 2 ppm [M]⁺for C₁₃H₁₅O₃Cl was confirmed by HRMS

(EI, 70 eV).

Compound 3g: This compound was produced from 2 (1.37 mL,

12.0 mmol), 1g (2.745 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3g being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a colourless oil

(1.40 g, 63%). ¹H NMR (CDCl₃, 300 MHz, 5% enol form, con-

tains a small amount of starting material): δ = 1.08 (d, J = 6.9 Hz,

3 H, CH₃), 3.11 (m, 1 H, CH), 3.35 (s, 3 H, OCH₃), 3.40–3.61 (m,

4 H, CH₂, CH₂Cl), 3.74 (s, 3 H, OCH₃), 3.84 (m, 1 H, CH), 5.11

(s, 1 H, CH=C from enol form), 12.12 (s, 1 H, OH from enol

form) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 13.43 (CH₃), 42.80

(CH₂), 47.30 (CH), 49.68 (CH₂Cl), 51.81, 57.40 (OCH₃), 81.71

Compound 3c: This compound was produced from 2 (1.14 mL,

10.0 mmol), 1c (2.885 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol in CH₂Cl₂(100 mL), 3c being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil

(1.66 g, 70%). ¹H NMR (CDCl₃, 300 MHz, 5% enol form): δ =

1.27 (d, J = 6.3 Hz, 6 H, OCH(CH₃)₂), 2.88 (d, J = 6.3 Hz, 2 H,

CH₂), 3.41 (s, 3 H, OCH₃), 3.45 (s, 2 H, CH₂), 3.64 (dd, J = 4.5,

3.3 Hz, 2 H, CH₂Cl), 3.93 (m, 1 H, CH), 5.08 (sept, J = 6.3 Hz, 1

H, OCH(CH₃)₂), 5.11 (s, 1 H, CH=C from enol form), 12.22 (s, 1

H, OH from enol form) ppm.

(CH), 167.14 (O–C=O), 204.98 (C=O) ppm. IR (neat; cm^–1): ν =

˜

Compound 3d: This compound was produced from 2 (1.14 mL,

10.0 mmol), 1d (3.085 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3d being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil

2980 (m), 2954 (s), 2942 (s), 2833 (w, C–H), 1749 (s, O=C–O), 1716

(s, C=O), 1656 (w), 1632 (w, C=C from enol form), 1455 (s), 1438

(s), 1405 (m), 1378 (m), 1327 (s), 1263 (s), 1248 (s), 1208 (s), 1180

(m), 1152 (s), 1127 (m), 1099 (s), 1047 (w), 1011 (m), 1004 (m) cm^–1.

Eur. J. Org. Chem. 2005, 2074–2090

www.eurjoc.org

2079

E. Bellur, H. Görls, P. Langer

FULL PAPER

MS (EI, 70 eV): m/z (%) = 222 [M]⁺(5), 191 (15), 186 (12), 173

(100), 155 (29), 141 (31).

OCH₂CH₃), 1.23–1.35 (m, 2 H, CH₂), 1.58–1.66 (m, 2 H, CH₂),

3.08 (m, 1 H, CH), 3.34 (s, 3 H, OCH₃), 3.43 (s, 2 H, CH₂), 3.53–

3.60 (m, 2 H, CH₂Cl), 3.81 (m, 1 H, CH), 4.20 (q, J = 7.2 Hz, 2

H, OCH₂), 5.09 (s, 1 H, CH=C from enol form), 12.20 (s, 1 H, OH

from enol form) ppm. ¹³C NMR (CDCl₃, 150 MHz): δ_C= 14.15

(CH₃), 20.25, 30.38 (CH₂), 43.40 (CH₂Cl), 51.83 (CH₂), 53.27

(CH), 57.93 (OCH₃), 61.11 (OCH₂), 81.84 (CH), 166.82 (O=C–O),

Compound 3h: This compound was produced from 2 (1.37 mL,

12.0 mmol), 1h (3.026 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3h being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil

1

(2.07 g, 83%). H NMR (CDCl₃, 300 MHz, 11% enol form): δ =

205.25 (C=O) ppm. IR (neat; cm^–1): ν = 2962 (s), 2935 (s), 2874

˜

0.91 (t, J = 7.2 Hz, 3 H, CH₃), 1.28 (t, J = 7.2 Hz, 3 H, OCH₂CH₃),

1.49–1.72 (m, 2 H, CH₂), 2.99–3.04 (m, 1 H, CH), 3.34 (s, 3 H,

OCH₃), 3.43–3.59 (m, 4 H, CH₂, CH₂Cl), 3.82 (m, 1 H, CH), 4.20

(q, J = 7.2 Hz, 2 H, OCH₂CH₃), 5.09 (s, 1 H, CH=C from enol

form), 12.19 (s, 1 H, OH from enol form) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ_C= 11.12, 13.86 (CH₃), 21.04, 43.16 (CH₂), 51.62

(CH₂Cl), 54.55 (CH), 57.69 (OCH₃), 60.87 (OCH₂CH₃), 81.30

(m), 2832 (w, C–H), 1746 (s, O=C–O), 1715 (s, C=O), 1647 (m),

1463 (m), 1410 (w), 1369 (m), 1306 (s), 1234 (s), 1210 (m), 1179

(m), 1115 (s), 1099 (s), 1034 (s) cm^–1. MS (EI, 70 eV): m/z (%) =

264 [M]⁺(11), 249 (19), 215 (100). C₁₂H₂₁O₄Cl (264.749): C 54.44,

H 8.00; found C 55.35, H 8.43.

Compound 3l: This compound was produced from 2 (1.37 mL,

12.0 mmol), 1l (3.306 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3l being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a dark yellow

(CH), 166.57 (O=C–O), 205.13 (C=O) ppm. IR (neat; cm^–1): ν =

˜

2971 (s), 2937 (m), 2880 (w, C–H), 1746 (s, O–C=O), 1715 (s, C=O),

1649 (m, C=C from enol form), 1462 (m), 1448 (w), 1432 (w), 1409

(w),1387 (w), 1368 (m), 1306 (s), 1239 (s), 1205 (m), 1179 (m), 1154

(s), 1099 (s), 1062 (w), 1032 (s) cm^–1. MS (EI, 70 eV): m/z (%) =

251 (100) [M]⁺, 205 (62). C₁₁H₁₉O₄Cl (250.722): C 52.70, H 7.64;

found C 52.45, H 8.11.

1

oil (2.38 g, 85%). H NMR (CDCl₃, 300 MHz, 24% enol form): δ

= 0.88 (t, J = 6.9 Hz, 3 H, CH₃), 1.28 (t, J = 7.2 Hz, 3 H,

OCH₂CH₃), 1.22–1.35 (m, 2 H, CH₂), 1.37–1.41 (m, 2 H, CH₂),

1.58–1.69 (m, 2 H, CH₂), 3.02–3.10 (m, 1 H, CH), 3.34 (s, 3 H,

OCH₃), 3.43 (s, 2 H, CH₂), 3.52–3.57 (m, 2 H, CH₂Cl), 3.81 (m, 1

H, CH), 4.20 (q, J = 7.2 Hz, 2 H, OCH₂), 5.08 (s, 1 H, CH=C

from enol form), 12.20 (s, 1 H, OH from enol form) ppm. ¹³C

NMR (CDCl₃, 150 MHz): δ_C= 14.15, 14.77 (CH₃), 22.35, 27.90,

29.26 (CH₂), 43.91 (CH₂Cl), 51.79 (CH₂), 53.38 (CH), 57.88

(OCH₃), 61.27 (OCH₂), 81.81 (CH), 166.80 (O=C–O), 205.18

Compound 3i: This compound was produced from 2 (1.37 mL,

12.0 mmol), 1i (2.905 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3i being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil

1

(1.53 g, 64%). H NMR (CDCl₃, 300 MHz, 25% enol form, con-

tains ca. 40% of starting material): δ = 3.39 (s, 3 H, OCH₃), 3.44

(s, 3 H, OCH₃), 3.45 (s, 3 H, OCH₃), 3.53 (s, 2 H, CH₂), 3.62–3.73

(m, 2 H, CH₂Cl), 3.75 (d, J = 3.0 Hz, 1 H, CH), 3.98 (m, 1 H,

CH), 5.31/5.40 (ds, 1 H, CH=C from enol forms of both isomers),

11.93/12.00 (ds, 1 H, OH from enol forms of both isomers) ppm.

¹³C NMR (CDCl₃, 75 MHz): δ_C= 41.54 (CH₂), 46.09 (CH₂Cl),

51.97, 58.13, 60.35 (OCH₃), 82.21, 84.92 (CH), 167.36 (O=C–O),

(C=O) ppm. IR (neat; cm^–1): ν = 2959 (s), 2933 (s), 2869 (w, C–H),

˜

1745 (s, O=C–O), 1716 (s, C=O), 1648 (w), 1631 (w), 1463 (w),

1412 (w), 1369 (w), 1308 (m), 1241 (m), 1209 (m), 1178 (w), 1155

(m), 1099 (s), 1033 (m) cm^–1. MS (EI, 70 eV): m/z (%) = 278 [M]⁺

(92), 265 (100), 229 (32).

Compound 3m: This compound was produced from 2 (1.37 mL,

12.0 mmol), 1m (3.587 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3m being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a dark yellow

205.12 (C=O) ppm. IR (neat; cm^–1): ν = 2992 (w), 2954 (s), 2941

˜

(s), 2909 (w), 2809 (w), 2835 (m, C–H), 1751 (s, O–C=O), 1722 (s,

C=O), 1660 (m), 1635 (w, C=C from enol form), 1439 (s), 1401

(w), 1323 (s), 1262 (s), 1228 (s), 1211 (s), 1122 (s), 1094 (s), 1022

(m) cm^–1. MS (EI, 70 eV): m/z (%) = 238 [M]⁺(58), 207 (4), 146

(100). C₉H₁₅O₅Cl (238.668): C 45.29, H 6.34; found C 45.31, H

6.39.

1

oil (2.70 g, 88%). H NMR (CDCl₃, 300 MHz, 11% enol form): δ

= 0.87 (t, J = 6.9 Hz, 3 H, CH₃), 1.28 (t, J = 7.2 Hz, 3 H,

OCH₂CH₃), 1.25–1.32 (m, 6 H, 3×H₂), 1.33–1.48 (m, 2 H,CH₂),

1.55–1.68 (m, 2 H, CH₂), 3.02–3.10 (m, 1 H, CH), 3.34 (s, 3 H,

OCH₃), 3.43 (s, 2 H, CH₂), 3.49–3.56 (m, 2 H, CH₂Cl), 3.81 (m, 1

H, CH), 4.20 (q, J = 7.2 Hz, 2 H, OCH₂), 5.08 (s, 1 H, CH=C

from enol form), 12.20 (s, 1 H, OH from enol form) ppm. ¹³C

NMR (CDCl₃, 150 MHz): δ_C= 14.26, 14.30 (CH₃), 22.60, 27.00,

28.36, 29.24, 31.69 (CH₂), 43.50 (CH₂Cl), 51.97 (CH₂), 53.54 (CH),

58.77 (OCH₃), 61.22 (OCH₂), 81.93 (CH), 166.91 (O=C–O), 205.27

Compound 3j: This compound was produced from 2 (1.37 mL,

12.0 mmol), 1j (3.146 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3j being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil

1

(1.49 g, 57%). H NMR (CDCl₃, 300 MHz, 12% enol form): δ =

1.28 (t, J = 7.2 Hz, 3 H, CH₃), 2.20–2.41(m, 2 H, CH₂), 3.12 –3.20

(m, 1 H, CH), 3.35 (s, 3 H, OCH₃), 3.52 (s, 2 H, CH₂), 3.55–3.63

(m, 2 H, CH₂Cl), 3.79–3.84 (m, 1 H, CH), 4.19 (q, J = 7.2 Hz, 2

H, OCH₂), 5.00–5.22 (m, 2 H, CH₂=CH), 5.65–5.79 (m, 1 H,

CH=CH₂), 12.22 (s, 1 H, OH from enol form) ppm. IR (neat;

(C=O) ppm. IR (neat; cm^–1): ν = 2956 (s), 2929 (s), 2857 (s, C–H),

˜

1749 (s, O=C–O), 1715 (S, C=O), 1649 (m), 1463 (s), 1411 (m),

1306 (s), 1236 (s), 1178 (s), 1153 (s), 1099 (s), 1033 (s), 845 (w), 696

(w) cm^–1. MS (EI, 70 eV): m/z (%) = 306 [M]⁺(3), 274 (6), 257

(100), 139 (33).

cm^–1): ν = 2983 (m), 2937 (m), 2832 (w, C–H), 1746 (s, O=C–O),

˜

1715 (s, C=O), 1643 (m, C=C from enol), 1463 (m), 1445 (m), 1417

(w), 1386 (w), 1369 (m), 1318 (m), 1305 (m), 1248 (m), 1205 (m),

1181 (m), 1153 (m), 1099 (s), 1032 (m), 999 (w), 845 (w) cm^–1. MS

(EI, 70 eV): m/z (%) = 262 [M]⁺(2), 230 (13), 217 (11), 213 (63),

181 (15), 169 (100).

Compound 3n: This compound was produced from 2 (1.37 mL,

12.0 mmol), 1n (3.867 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol), in CH₂Cl₂(100 mL), 3n being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a brown oil

1

(1.77 g, 53%). H NMR (CDCl₃, 300 MHz, 25% enol form): δ =

Compound 3k: This compound was produced from 2 (1.37 mL,

12.0 mmol), 1k (3.166 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3k being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a dark yellow

0.88 (t, J = 6.8 Hz, 3 H, CH₃), 1.25–1.32 (m, 17 H, 7×H₂, CH₃),

3.05 (m, 1 H, CH), 3.34 (s, 3 H, OCH₃), 3.49–3.58 (m, 4 H, CH₂,

CH₂Cl), 3.76–3.84 (m, 1 H, CH), 4.20 (q, J = 7.2 Hz, 2 H, OCH₂),

5.08 (s, 1 H, CH=C from enol form), 12.20 (s, 1 H, OH from enol

1

oil (2.30 g, 87%). H NMR (CDCl₃, 300 MHz, 24% enol form): δ

form) ppm. IR (neat; cm^–1): ν = 2955 (m), 2928 (s), 2856 (m, C–

˜

= 0.91 (t, J = 7.2 Hz, 3 H, CH₃), 1.27 (t, J = 7.2 Hz, 3 H,

H), 1746 (s, O=C–O), 1716 (s, C=O), 1647 (m, C=C from enol),

2080

www.eurjoc.org

Eur. J. Org. Chem. 2005, 2074–2090

Regioselective Synthesis of Functionalized Furans

FULL PAPER

1463 (m), 1370 (w), 1307 (m), 1234 (m), 1179 (w), 1153 (m), 1100

(s), 1033 (m) cm^–1. MS (EI, 70 eV): m/z (%) = 334 [M]⁺(3), 289

(15), 285 (100), 224 (36).

5.0 mmol) in CH₂Cl₂(100 mL), 3r being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 40:1) as a yellow oil

(1.29 g, 49%). H NMR (CDCl₃, 300 MHz, 55% enol form): δ =

1

1.25–1.33 (m, 3 H, OCH₂CH₃), 1.38–1.58 (m, 2 H, CH₂), 1.62–1.85

(m, 2 H, CH₂), 1.97–2.39 (m, 2 H, CH₂), 2.69–3.09 (m, 1 H, CH),

3.40/3.50 (ds, 3 H, OCH₃), 3.43–3.48 (m, 1 H, CH), 3.59–3.70 (m,

2 H, CH₂Cl), 3.72–3.92 (m, 1 H, CH), 4.22 (q, J = 7.1 Hz, 2 H,

OCH₂CH₃), 12.53/12.61 (ds, 1 H, OH from two possible enol

forms) cm^–1. MS (EI, 70 eV): m/z (%) = 262 (100) [M]⁺, 230 (59),

226 (66), 217 (70).

Compound 3o: This compound was produced from 2 (1.37 mL,

12.0 mmol), 1o (4.01 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3o being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a dark yellow

1

oil (2.75 g, 79%). H NMR (CDCl₃, 300 MHz, 15% enol form): δ

= 0.88 (t, J = 6.9 Hz, 3 H, CH₃), 1.20–1.34 (m, 15 H, 6×CH₂,

CH₃), 1.37–1.48 (m, 2 H, CH₂), 1.59–1.68 (m, 2 H, CH₂), 3.01–

3.10 (m, 1 H, CH), 3.33 (s, 3 H, OCH₃), 3.42 (s, 2 H, CH₂), 3.47–

3.56 (m, 2 H, CH₂Cl), 3.81 (m, 1 H, CH), 4.20 (q, J = 7.2 Hz, 2

H, OCH₂), 5.07 (s, 1 H, CH=C from enol form), 12.23 (s, 1 H, OH

from enol form) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 13.77,

13.89 (CH₃), 22.36, 26.67, 27.95, 28.97, 29.02, 29.18, 29.42, 31.55

(CH₂), 43.11 (CH₂Cl), 51.49 (CH₂), 53.15 (CH), 57.61 (OCH₃),

60.77 (OCH₂), 81.57 (CH), 166.48 (O=C–O), 205.13 (C=O) ppm.

Compound 3s: This compound was produced from 2 (1.14 mL,

10.0 mmol), 1s (3.00 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol), in CH₂Cl₂(100 mL), 3s being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil

(1.03 g, 42%). ¹H NMR (CDCl₃, 300MHz): δ = 1.24–1.32 (m, 3 H,

CH₃), 1.59–1.66 (m, 1 H, CH₂), 1.98–2.08 (m, 1 H, CH₂), 2.18–

2.45 (m, 2 H, CH₂), 3.45 (s, 3 H, OCH₃), 3.49 (m, 1 H, CH), 3.66

(m, 1 H, CH), 3.75–3.85 (m, 2 H, CH₂Cl), 4.12–4.23 (m, 2 H,

OCH₂), 4.58–4.61 (m, 1 H, CH) ppm. MS (EI, 70 eV): m/z (%) =

213 [M – Cl]⁺(33), 198 (24), 153 (100).

IR (neat; cm^–1): ν = 2927 (s), 2855 (s, C–H), 1746 (s, O=C–O),

˜

1716 (s, C=O), 1649 (m), 1630 (m), 1463 (m), 1369 (m), 1307 (m),

1233 (s), 1154 (m), 1100 (s), 1033 (m) cm^–1. MS (EI, 70 eV): m/z

(%) = 348 [M]⁺(6), 316 (13), 299 (100), 281 (34). C₁₈H₃₃O₄Cl

(348.909): C 61.96, H 9.53; found C 62.71, H 8.85.

Compound 3t: This compound was produced from 2 (0.3 mL,

2.4 mmol), 1t (0.66 g, 2.0 mmol) and Me₃SiOTf (0.222 g, 1.0 mmol)

in CH₂Cl₂(30 mL), 3t being isolated after chromatography (silica

gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil (0.50 g, 90%).

¹H NMR (CDCl₃, 300 MHz): δ = 1.26 (t, J = 7.2 Hz, 3 H, CH₃),

1.31–1.40 (m, 2 H, CH₂), 1.73–1.87 (m, 2 H, CH₂), 1.88–2.03 (m,

4 H, 2×H₂), 2.11–2.26 (m, 1 H, CH₂), 2.94–3.01 (m, 1 H, CH),

3.45 (s, 3 H, OCH₃), 3,52–3.63 (m, 2 H, CH₂Cl), 3.71–3.77 (m, 1

H, CH), 4.18 (q, J = 7.2 Hz, 2 H, OCH₂) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ = 13.86 (CH₃), 26.26, 27.27, 27.41, 28.40 (CH₂), 43.36

(CH₂Cl), 53.54 (OCH₃), 58.05, 59.31 (CH), 61 12 (OCH₂), 80.89

Compound 3p: This compound was produced from 2 (1.37 mL,

12.0 mmol), 1p (4.148 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3p being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a dark yellow

oil (3.12 g, 86%). ¹H NMR (CDCl₃, 300 MHz, 16% of enol form):

δ = 0.89 (t, J = 6.9 Hz, 3 H, CH₃), 1.20–1.38 (m, 19 H, 8×CH₂,

CH₃), 1.58–1.65 (m, 2 H, CH₂), 3.02–3.09 (m, 1 H, CH), 3.33 (s, 3

H, OCH₃), 3.42 (s, 2 H, CH₂), 3.43–3.59 (m, 2 H, CH₂Cl), 3.81

(m, 1 H, CH), 4.20 (q, J = 7.2 Hz, 2 H, OCH₂), 5.07 (s, 1 H, CH=C

from enol form), 12.23 (s, 1 H, OH from enol form) ppm. ¹³C

NMR (CDCl₃, 75 MHz): δ_C= 13.87, 13.90 (CH₃), 22.46, 26.75,

27.52, 28.05, 29.09, 29.32, 29.34, 29.51, 31.67 (CH₂), 43.18

(CH₂Cl), 51.64 (CH₂), 53.24 (CH), 57.72 (OCH₃), 60.89 (OCH₂),

81.65 (CH), 166.58 (O=C–O), 205.29 (C=O) ppm. IR (neat; cm^–1):

(CH), 169.73 (O=C–O), 209.47 (C=O) ppm. IR (neat; cm^–1): ν =

˜

2981 (s), 2934 (s), 2859 (s), 2832 (m, C–H), 1747 (s, O=C–O), 1704

(s, C=O), 1637 (w), 1451 (s), 1372 (s), 1352 (m), 1305 (s), 1241 (s),

1186 (s), 1142 (s), 1100 (s), 1027 (s), 943 (m), 863 (w), 751 (w) cm^–1.

MS (EI, 70 eV): m/z (%) = 276 [M]⁺(3), 240 (39), 231 (17), 227

(100). C₁₃H₂₁O₄Cl (276.60): C 56.42, H 7.65; found C 56.28, H

7.89.

ν = 2927 (s), 2855 (s, C–H), 1745 (s, O=C–O), 1716 (s, C=O), 1649

˜

(m), 1631 (m), 1463 (m), 1369 (m), 1306 (m), 1234 (s), 1155 (m),

1100 (s), 1034 (m) cm^–1. MS (EI, 70 eV): m/z (%) = 362 [M]⁺(7),

330 (10), 313 (100), 295 (29).

Compound 3u: This compound was produced from 2 (0.75 mL,

0.6 mmol), 1u (1.71 g, 5.0 mmol) and Me₃SiOTf (0.556 g,

2.5 mmol) in CH₂Cl₂(50 mL), 3u being isolated as a yellow oil

Compound 3q: This compound was produced from 2 (0.14 mL,

1.2 mmol), 1q (0.391 g, 1.0 mmol) and Me₃SiOTf (0.111 g,

0.5 mmol) in CH₂Cl₂(30 mL), 3q being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil

1

(0.95 g, 65%). H NMR (CDCl₃, 300 MHz, 19% enol form): δ =

1.20–1.34 (m, 7 H, 2×H₂, CH₃), 1.53–1.65 (m, 2 H, CH₂), 1.66–

1.83 (m, 2 H, CH₂), 2.01–2.35 (m, 2 H, CH₂), 2.41–2.55 (m, 1 H,

CH), 2.61–2.71 (m, 1 H, CH), 3.48 (s, 3 H, OCH₃), 3.52–3.78 (m,

2 H, CH₂Cl), 3.85–4.05 (m, 1 H, CH), 4.13–4.24 (m, 2 H, OCH₂),

1

(0.267 g, 78%). H NMR (CDCl₃, 300 MHz, 15% enol form): δ =

1.29 (t, J = 7.2 Hz, 3 H, CH₃) 1.26–1.33 (m, 2 H, CH₂), 1.35–1.45

(m, 4 H, 2×CH₂), 1.58–1.69 (m, 2 H, CH₂), 1.70–1.76 (m, 2 H,

CH₂), 3.01–3.11 (m, 1 H, CH), 3.34 (s, 3 H, OCH₃), 3.43 (s, 2 H,

CH₂), 3.49–3.59 (m, 4 H, 2×CH₂–Cl), 3.82 (dd, J = 13.2, 4.2 Hz,

1 H, CH), 4.20 (q, J = 7.2 Hz, 2 H, OCH₂), 5.08 (s, 1 H, CH=C

from enol form), 12.21 (s, 1 H, OH from enol form) ppm. ¹³C

NMR (CDCl₃, 75 MHz): δ_C= 14.09 (CH₃), 26.37, 26.66, 27.95,

28.79, 32.28 (CH₂), 43.23, 44.81 (CH₂–Cl), 51.74 (CH₂), 53.21

(CH), 57.82 (OCH₃), 61.03 (OCH₂), 81.69 (CH), 91.77 (CH=C

from enol form), 166.67 (O=C–O), 172.45 (O=C–O from enol

form), 176.83 (HO–C=CH from enol form), 205.35 (C=O) ppm.

12.80 (s, 1 H, OH from enol form) ppm. IR (neat; cm^–1): ν = 2933

˜

(s), 2859 (m, C–H), 1745 (s, O=C–O), 1706 (s, C=O), 1644 (s), 1617

(m), 1463 (m), 1449 (m), 1399 (w), 1374 (m), 1328 (m), 1306 (m),

1299 (m), 1247 (s), 1201 (m), 1184 (m), 1011 (s), 847 (s), 792

(w) cm^–1. MS (EI, 70 eV): m/z (%) = 290 [M]⁺(13), 275 (26), 241

(100).

Compound 3v: This compound was produced from 2 (1.37 mL,

12.0 mmol), 1v (3.97 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

5.0 mmol) in CH₂Cl₂(100 mL), 3v being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil

(2.62 g, 76%). ¹H NMR (CDCl₃, 300 MHz, 9% enol form, 30%

minor diastereomer, spectra analysis for the main isomer): δ =

1.22–1.43 (m, 17 H, 7×H₂, CH₃), 1.55–1.70 (m, 2 H, CH₂), 1.73–

2.01 (m, 2 H, CH₂), 2.25–2.38 (m, 1 H, CH), 3.31/3.44 (ds, 3 H,

OCH₃), 3.47–3.57 (m, 2 H, CH₂Cl), 3.80–3.88 (m, 1 H, CH), 3.96–

4.06 (m, 1 H, CH), 4.16 (q, J = 7.2 Hz, 2 H, OCH₂CH₃), 13.00 (s,

IR (neat; cm^–1): ν = 2954 (s), 2860 (m, C–H), 1745 (s, O=C–O),

˜

1715 (s, C=O), 1646 (m), 1460 (m), 1408 (w), 1368 (w), 1307 (m),

1236 (s), 1153 (m), 1100 (s), 1033 (m) cm^–1. MS (EI, 70 eV): m/z

(%) = 324 [M – Me]⁺(26), 273 (13), 259 (9), 225 (63), 220 (4), 199

(3), 185 (9), 161 (37), 153 (10), 130 (24), 116 (79), 93 (13), 55 (100).

Compound 3r: This compound was produced from 2 (1.14 mL,

10.0 mmol), 1r (3.15 g, 10.0 mmol) and Me₃SiOTf (1.111 g,

Eur. J. Org. Chem. 2005, 2074–2090

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2081

E. Bellur, H. Görls, P. Langer

FULL PAPER

1 H, OH from enol form) ppm. ¹³C NMR (CDCl₃, 50 MHz): δ_C

=

being isolated after chromatography (silica gel, n-hexane/EtOAc,

14.01 (CH₃), 19.94, 22.03, 23.06, 23.26, 23.92, 24.14, 24.36, 26.15, 100:1 to 1:1) as yellow oils.

26.79 (CH₂), 44.07 (CH₂Cl), 52.72, 54.33 (CH), 57.47 (OCH₃),

1

Compound 3z: (75% of enol form) H NMR (CDCl₃, 300 MHz): δ

= 2.07 (s, 3 H, CH₃), 2.61 (m, 2 H, CH₂), 3.42 (s, 3 H, OCH₃),

3.56–3.69 (m, 2 H, CH₂Cl), 3.90 (m, 1 H, CH), 5.56 (s, 1 H, CH

from enol), 15.58 (broad s, 1 H, OH from enol) ppm. ¹³C NMR

(CDCl₃, 75 MHz): δ_C= 24.51 (CH₃), 40.95 (CH₂), 45.08 (CH₂Cl),

57.52 (OCH₃), 76.99 (CH), 101.02 (CH from enol), 190.78, 190.85

61.79 (OCH₂CH₃), 79.33 (CH), 169.36 (O=C–O), 205.96

(C=O) ppm. IR (neat; cm^–1): ν = 2932 (s), 2867 (m, C–H), 1743 (s,

˜

O=C–O), 1711 (s, C=O), 1469 (m), 1444 (w), 1369 (w), 1291 (w),

1263 (m), 1248 (m), 1203 (m), 1178 (s), 1155 (m), 1102 (s), 1028

(m) cm^–1. MS (EI, 70 eV): m/z (%) = 347 [M]⁺(27), 315 (56), 280

(100).

(C=O and C=C–OH) ppm. IR (neat; cm^–1): ν = 3408 (broad, O–

˜

Compound 3w: This compound was produced from 2 (0.7 mL,

H from enol), 2960 (w), 2932 (w, C–H), 1765 (w), 1722 (m), 1704

6.0 mmol), 1w (1.643 g, 5.0 mmol) and Me₃SiOTf (0.56 g, (m), 1663 (s), 1612 (s, C=C from enol), 1431 (m), 1401 (m), 1365

2.5 mmol) in CH₂Cl₂(50 mL), 3w being isolated after chromatog-

(m), 1339 (m), 1299 (w), 1247 (m), 1208 (w), 1167 (w), 1100 (s),

raphy (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil

1052 (w), 1027 (w), 968 (w) cm^–1. MS (EI, 70 eV): m/z (%) = 177

1

(1.19 g, 86%). H NMR (CDCl₃, 300 MHz, 48% enol form): δ = [M – CH₃]⁺(100), 161 (62), 143 (29).

1.04 (dd, J = 12, 6.6 Hz, 3 H, CH₃), 1.26–1.34 (m, 3 H, OCH₂CH₃),

1

Compound 6: (75% of enol form) H NMR (CDCl₃, 300 MHz): δ

1.59–2.01 (m, 2 H, CH₂), 2.06–2.35 (m, 2 H, CH₂), 2.45–2.54 (m,

1 H, CH), 3.45 (s, 3 H, OCH₃), 3.52 (m, 1 H, CH), 3.59 (m, 1 H,

CH), 3.68–3.85 (m, 2 H, CH₂Cl), 4.15–4.21 (m, 1 H, CH), 4.22–

4.29 (m, 2 H, OCH₂CH₃), 12.20/12.45 (ds, 1 H, OH from two pos-

= 2.63 (m, 4 H, 2×H₂), 3.40 (s, 2 H, CH₂from keto form), 3.42

(s, 6 H, 2×OCH₃), 3.64 (m, 4 H, 2×H₂–Cl), 3.87–3.93 (m, 2 H,

2×H), 5.63 (s, 1 H, CH=C from enol), 15.30 (broad s, 1 H, OH

from enol) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 40.77 (2×H₂),

44.96 (2×H₂–Cl), 57.47 (2×OCH₃), 76.91 (2×H), 101.63 (CH=C),

sible enol forms) ppm. IR (neat; cm^–1): ν = 2957 (s), 2932 (s), 2873

˜

(s, C–H), 1741 (s, O=C–O), 1715 (s, C=O), 1652 (s), 1617 (s), 1458

(s), 1428 (m), 1402 (s), 1374 (s), 1304 (s), 1276 (s), 1216 (s), 1159

(s), 1096 (s), 1029 (s), 975 (w), 827 (m) cm^–1. MS (EI, 70 eV): m/z

(%) = 276 [M]⁺(29), 244 (41), 227 (62), 213 (100).

190.40 (O–C=CH) ppm. IR (neat; cm^–1): ν = 3404 (w, O–H), 2935

˜

(m), 2831 (w, C–H), 1726 (w), 1706 (m, C=O), 1613 (s, C=C–O),

1458 (m), 1447 (m), 1431 (m), 1352 (m), 1313 (m), 1236 (m), 1202

(m), 1185 (m), 1153 (w), 1101 (s), 1019 (w) cm^–1. MS (EI, 70 eV):

m/z (%) = 285 [M]⁺(4), 249 (4), 217 (17), 203 (55), 192 (30), 187

(7), 177 (100), 160 (10), 145 (35), 141 (19), 127 (8). The exact mol-

ecular mass m/z = 284.0582 2 ppm [M]⁺for C₁₁H₁₈O₄Cl₂was

confirmed by HRMS (EI, 70 eV).

Compound 3x: This compound was produced from 2 (1.37 mL,

12 mmol), 1x (3.777 g, 10 mmol), and Me₃SiOTf (1.111 g, 5 mmol),

in CH₂Cl₂(100 mL), 3x being isolated after chromatography (silica

gel, n-hexane/EtOAc, 100:1 to 1:1) as a yellow oil (2.890 g, 89%).

¹H NMR (CDCl₃, 300 MHz, 70% enol form, analysis for enol

form): δ = 1.80–2.15 (m, 2 H, CH₂), 2.23–2.42 (m, 2 H, CH₂), 2.62–

2.70 (m, 1 H, CH), 2.87–3.15 (m, 1 H, CH), 3.45–3.46, 3.49 (ts, 3

H, OCH₃), 3.41–3.61 (m, 1 H, CH₂–Cl), 3.68–3.81 (m, 5 H, CH₂–

Cl, OCH₃, CH), 7.19–7.31 (m, 5 H, 5×H from Ph), 12.18, 12.43,

General Procedure for the Preparation of (E)-2-Alkylidene-4-meth-

oxytetrahydrofurans (4): DBU (2 equiv.) was added to a THF solu-

tion (3 mL mmol^–1) of 3 (1 equiv.), and the mixture was stirred for

12 h at 20 °C. The solvent was removed in vacuo and the residue

was purified by chromatography (silica gel, n-hexane/EtOAc, 50:1

to 1:1) to give 4.

12.44 (ts, 1 H, OH) ppm. IR (neat; cm^–1): ν = 3085 (w), 3061 (w),

˜

3028 (m), 2998 (m), 2951 (s), 2935 (s), 2858 (m), 2833 (m, C–H),

1745 (m, O=C–O), 1716 (m, C=O), 1659 (s), 1618 (s), 1495 (m),

1443 (s), 1361 (s), 1333 (s), 1286 (s), 1260 (s), 1247 (s), 1225 (s),

1205 (s), 1094 (s), 1035 (m), 1011 (m), 958 (w), 906 (w), 844 (s),

761 (s), 702 (s), 527 (w), 435 (w) cm^–1. MS (EI, 70 eV): m/z (%) =

324 [M]⁺(30), 294 (5), 292 (21), 275 (3), 232 (97), 219 (17), 200

(11), 171 (26), 157 (5), 104 (59), 95 (35), 93 (100), 91 (42), 77 (12).

C₁₇H₂₁O₄Cl (324.804): C 62.87, H 6.52; found C 63.20, H 7.02.

Compound 4i: This compound was produced from 3i (1.40 g,

5.9 mmol) and DBU (1.75 mL, 11.7 mmol) in THF (10 mL); (E)-

4i (0.583 g, 49%) and (Z)-4i (0.40 g, 33%) were isolated after

chromatography (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as yellow

oils.

1

Compound (E)-4i: H NMR (CDCl₃, 300 MHz): δ = 3.36 (s, 3 H,

OCH₃), 3.51 (s, 3 H, OCH₃), 3.70 (s, 3 H, OCH₃), 3.89 (d, J =

3.2 Hz, 1 H, CH), 4.24 (d, J = 10 Hz, 1 H, OCH₂), 4.33 (dd, J =

10, 3.2 Hz, 1 H, OCH₂), 5.08 (s, 1 H, CH), 5.54 (s, 1 H,

CH=C) ppm. ¹³C NMR (CDCl₃, 50 MHz): δ_C= 50.88, 56.81, 57.77

(OCH₃), 74.44 (C–5), 79.05, 81.41 (CH), 94.57 (CH=C), 167.75

Compound 3y: This compound was produced from 2 (2.74 mL,

24 mmol), 1y (5.450 g, 20 mmol) and Me₃SiOTf (0.222 g, 10 mmol)

in CH₂CL₂(200 mL), 3y being isolated after chromatography (sil-

ica gel, n-hexane/EtOAc, 50:1 to 1:1) as a yellow oil (4.260 g, 97%).

¹H NMR (CDCl₃, 300 MHz): δ = 2.24–2.39 (m, 2 H, CH₂), 3.42

(s, 3 H, OCH₃), 3.60–3.66 (m, 2 H, CH₂–Cl), 3.71–3.77 (m, 1 H,

(O=C–O), 171.42 (O–C=CH) ppm. IR (neat; cm^–1): ν = 2992 (w),

˜

2952 (m), 2831 (w, C–H), 1713 (s, C=C–O), 1658 (s, C=C–C=O),

1641 (m), 1437 (m), 1385 (m), 1356 (m), 1318 (w), 1296 (w), 1254

(w), 1234 (w), 1192 (m), 1186 (m), 1127 (s), 1110 (s), 1050 (m),

1032 (w), 980 (m), 952 (w), 848 (w) cm^–1. MS (EI, 70 eV): m/z (%)

= 202 (100) [M]⁺, 171 (74), 155 (5). The exact molecular mass m/z

= 202.0841 2 ppm [M]⁺for C₉H₁₄O₅was confirmed by HRMS

(EI, 70 eV).

CH), 3.93–3.99 (m, 1 H, CH), 4.28–4.43 (m, 2 H, OCH₂) ppm. ¹³

C

NMR (CDCl₃, 150 MHz): δ_c= (23.85, 44.16 (CH₂), 45.10 (CH₂–

Cl), 53.06 (CH), 57.63 (OCH₃), 67.45 (OCH₃), 76.09 (CH), 172.77

(O=C–O), 200.58 (C=O) ppm. IR (neat; cm^–1): ν = 3519 (w, OH

˜

from enol form), 2988 (s), 2922 (s), 2832 (m, C–H), 1770 (s, O=C–

O), 1721 (s, C=O), 1655 (m, C=C from enol form), 1482 (m), 1457

(s), 1430 (m), 1379 (s), 1307 (m), 1218 (m), 1174 (s), 1161 (s), 1127

(m), 1097 (s), 1025 (s), 969 (w), 946 (m), 883 (w), 863 (w) 844 (w),

790 (w), 748 (m), 695 (m), 683 (m), 591 (w), 531 (w), 468 (w) cm^–1.

MS (EI, 70 eV): m/z (%) = 220 [M]⁺(1), 184 (2), 171 (87), 155 (2),

139 (6), 135 (11), 128 (17), 112 (22), 95 (28), 93 (84), 85 (100).

1

Compound (Z)-4i: H NMR (CDCl₃, 600 MHz): δ = 3.35 (s, 3 H,

OCH₃), 3.39 (s, 3 H, OCH₃), 3.68 (s, 3 H, OCH₃), 3.88 (d, J =

3.2 Hz, 1 H, CH), 4.05 (s, 1 H, CH), 4.38 (d, J = 10 Hz, 1 H,

OCH₂), 4.47 (dd, J = 10, 3.2 Hz, 1 H, OCH₂), 5.05 (s, 1 H,

CH=C) ppm. ¹³C NMR (CDCl₃, 50 MHz): δ_C= 50.93, 56.78, 57.02

(OCH₃), 75.66 (C–5), 81.06, 84.22 (CH), 92.71 (CH=C), 165.59

Compound 3z: This compound was produced from 2 (1.37 mL,

12 mmol), 1z (2.445 g, 10 mmol) and Me₃SiOTf (1.111 g, 5 mmol)

in CH₂Cl₂(100 mL), with 3z (0.466 g, 24%) and 6 (0.536 g, 19%)

(O=C–O), 166.74 (O–C=CH) ppm. IR (neat; cm^–1): ν = 2993 (w),

2951 (m), 2831 (w, C–H), 1716 (s, C=C–O), 1663 (s, C=C–C=O),

˜

2082

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Eur. J. Org. Chem. 2005, 2074–2090

Regioselective Synthesis of Functionalized Furans

FULL PAPER

1461 (m), 1438 (m), 1400 (w), 1357 (w), 1315 (w), 1276 (m), 1247

(w), 1197 (s), 1139 (m), 1113 (s), 1094 (m), 1049 (m), 996 (m), 849

(w) cm^–1. MS (EI, 70 eV): m/z (%) = 202 [M]⁺(94), 171 (100), 156

(50), 125 (35). C₉H₁₄O₅(202.207): C 53.46, H 6.98; found C 52.97,

H 6.97.

ing isolated after chromatography (silica gel, n-hexane/EtOAc,

100:1 to 1:1) as a colourless oil (0.30 g, 97%). H NMR (CDCl₃,

1

300 MHz): δ = 0.88 (t, J = 6.9 Hz, 3 H, CH₃), 1.22–1.29 (m, 13 H,

5×H₂, CH₃), 1.33–1.51 (m, 3 H, CH₂), 1.68–1.79 (m, 1 H, CH₂),

3.32 (s, 3 H, OCH₃), 3.68 (dd, J = 10.8, 3.3 Hz, 1 H, CH), 3.82 (d,

J = 3.3 Hz, 1 H, CH), 4.13 (dq, J = 7.2, 3.3 Hz, 2 H, OCH₂CH₃),

4.22–4.32 (m, 2 H, OCH₂), 5.31 (s, 1 H, CH=C) ppm. ¹³C NMR

(CDCl₃, 75 MHz): δ_C= 14.08, 14.42 (CH₃), 22.63, 27.17, 29.20,

29.32, 29.37, 31.79, 32.03 (CH₂), 50.30 (CH), 56.43 (OCH₃), 59.31

(OCH₂), 75.99 (C–5), 82.36 (CH), 89.65 (CH=C), 165.84 (O=C–

Compound 4j: This compound was produced from 3j (0.25 g,

0.9 mmol) and DBU (0.28 mL, 1.9 mmol) in THF (10 mL), 4j be-

ing isolated after chromatography (silica gel, n-hexane/EtOAc,

100:1 to 1:1) as a yellow oil (0.17 g, 80%). ¹H NMR (CDCl₃,

300 MHz): δ = 1.27 (t, J = 7.2 Hz, 3 H, CH₃), 2.03–2.11 (m, 1 H,

CH₂), 2.54–2.61 (m, 1 H, CH₂), 3.30 (s, 3 H, OCH₃), 3.80 (dd, J =

10.5, 3.3 Hz, 1 H, CH), 3.83 (d, J = 3.3 Hz, 1 H, CH), 4.14 (dq, J

= 7.2, 4.2 Hz, 2 H, OCH₂CH₃), 4.22–4.32 (m, 2 H, OCH₂), 5.10

(s, 1 H, CH₂=CH), 5.16 (dd, J = 4.5, 1.5 Hz, 1 H, CH₂=CH), 5.35

(s, 1 H, CH=C), 5.80–5.88 (m, 1 H, CH=CH₂) ppm. ¹³C NMR

(CDCl₃, 75 MHz): δ_C= 14.34 (CH₃), 34.66 (CH₂), 46.90 (CH),

56.04 (OCH₃), 59.24 (OCH₂), 74.34 (C–5), 82.23 (CH), 90.76

(CH=C), 117.44 (CH₂=CH), 135.20 (CH=CH₂), 167.80 (O=C–

O), 174.23 (O–C=CH) ppm. IR (neat; cm^–1): ν = 2954 (m), 2928

˜

(s), 2856 (m, C–H), 1713 (s, O=C–O); 1697 (s, C=C–O), 1650 (s,

C=C–C=O), 1464 (m), 1371 (w), 1318 (w), 1267 (m), 1189 (s), 1137

(m), 1102 (m), 1048 (m), 1022 (m) cm^–1. MS (EI, 70 eV): m/z (%)

= 298 [M]⁺(3), 267 (100), 253 (77). The exact molecular mass m/z

= 298.2144 2 ppm [M]⁺for C₁₇H₃₀O₄was confirmed by HRMS

(EI, 70 eV).

Compound 4o: This compound was produced from 3o (0.85 g,

2.44 mmol) and DBU (0.73 mL, 4.9 mmol) in THF (20 mL), 4o

being isolated after chromatography (silica gel, n-hexane/EtOAc,

100:1 to 1:1) as a yellow oil (0.66 g, 87%). ¹H NMR (CDCl₃,

300 MHz): δ = 0.88 (t, J = 6.9 Hz, 3 H, CH₃), 1.26 (t, J = 7.2 Hz,

3 H, OCH₂CH₃), 1.19–1.29 (m, 12 H, 6×CH₂), 1.30–1.41 (m, 1 H,

CH₂), 1.43–1.50 (m, 2 H, CH₂), 1.66–1.73 (m, 1 H, CH₂), 3.32 (s,

3 H, OCH₃), 3.68 (dd, J = 10.8, 3.3 Hz, 1 H, CH), 3.82 (d, J =

3.3 Hz, 1 H, CH), 4.14 (dq, J = 7.2, 3.3 Hz, 2 H, OCH₂CH₃), 4.22–

4.32 (m, 2 H, OCH₂), 5.31 (s, 1 H, CH=C) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ_C= 14.00, 14.36 (CH₃), 22.57, 28.16, 29.21, 29.38, 29.44

(2C), 30.60, 31.78 (CH₂), 47.59 (CH), 56.01 (OCH₃), 59.10 (OCH₂),

74.28 (C–5),82.63 (CH), 90.45 (CH=C–O), 167.77 (O=C–O),

O),178.04 (O–C=CH) ppm. IR (neat; cm^–1): ν = 2983 (m), 2934

˜

(m), 2907 (m, C–H), 1701 (s, C=C–O), 1644 (s, C=C–C=O), 1464

(m), 1444 (m), 1376 (m), 1343 (m), 1319 (w), 1288 (m), 1247 (m),

1224 (m), 1169 (m), 1124 (s), 1099 (s), 1050 (s), 1008 (m), 971 (w),

923 (m), 830 (m) cm^–1. MS (EI, 70 eV): m/z (%) = 226 [M]⁺(6), 195

(100), 181 (51), 165 (20). The exact molecular mass m/z = 226.1205

2 ppm [M]⁺for C₁₂H₁₈O₄was confirmed by HRMS (EI, 70 eV).

Compound 4k: This compound was produced from 3k (0.70 g,

2.6 mmol) and DBU (0.79 mL, 5.3 mmol) in THF (20 mL), 4k be-

ing isolated after chromatography (silica gel, n-hexane/EtOAc,

100:1 to 1:1) as a yellow oil (0.48 g, 79%). ¹H NMR (CDCl₃,

300 MHz): δ = 0.99 (t, J = 6.9 Hz, 3 H, CH₃), 1.27 (t, J = 7.2 Hz,

3 H, OCH₂CH₃), 1.21–1.31 (m, 1 H, CH₂), 1.55 (sextet, J = 7.2 Hz,

2 H, CH₂), 1.65–1.71 (m, 1 H, CH₂), 3.32 (s, 3 H, OCH₃), 3.69

(dd, J = 10.8, 3.3 Hz, 1 H, CH), 3.82 (d, J = 3.3 Hz, 1 H, CH),

4.09–4.18 (m, 2 H, OCH₂CH₃), 4.22–4.32 (m, 2 H, OCH₂), 5.32 (s,

1 H, CH=C) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 13.64, 14.16

(CH₃), 21.07, 32.41 (CH₂), 47.20 (CH), 55.80 (OCH₃), 58.88

(OCH₂), 74.09 (C–5), 82.43 (CH), 90.17 (CH=C–O), 167.55 (O=C–

179.05 (O–C=CH) ppm. IR (neat; cm^–1): ν = 2927 (s), 2856 (m, C–

˜

H), 1704 (s, C=C–O), 1644 (s, C=C–C=O), 1463 (w), 1376 (w),

1168 (w), 1121 (s), 1098 (s), 1050 (m), 1019 (w) cm^–1. MS (EI,

70 eV): m/z (%): 312 [M]⁺(11), 281 (91), 267 (100). Anal. calcd. for

C₁₈H₃₂O₄(312.448): C 69.20, H 10.32; found C 69.18, H 10.49.

Compound 4p: This compound was produced from 3p (0.83 g,

2.3 mmol), and DBU (0.68 mL, 4.6 mmol) in THF (20 mL), 4p be-

ing isolated after chromatography (silica gel, n-hexane/EtOAc,

100:1 to 1:1) as a yellow oil (0.53 g, 70%). ¹H NMR (CDCl₃,

300 MHz): δ = 0.88 (t, J = 6.9 Hz, 3 H, CH₃), 1.26 (t, J = 7.2 Hz,

3 H, OCH₂CH₃), 1.19–1.29 (m, 14 H, 7×CH₂), 1.30–1.40 (m, 1 H,

CH₂), 1.41–1.49 (m, 2 H, CH₂), 1.66–1.74 (m, 1 H, CH₂), 3.32 (s,

3 H, OCH₃), 3.68 (dd, J = 10.8, 3.3 Hz, 1 H, CH), 3.82 (d, J =

3.3 Hz, 1 H, CH), 4.14 (dq, J = 7.2, 3.3 Hz, 2 H, OCH₂CH₃), 4.22–

4.32 (m, 2 H, OCH₂), 5.31 (s, 1 H, CH=C) ppm. ¹³C NMR (CDCl₃,

150 MHz): δ_C= 13.93, 14.29 (CH₃), 22.52, 28.10, 29.16, 29.37,

29.39, 29.43, 30.52, 31.74, 31.79 (CH₂), 47.56 (CH), 55.95 (OCH₃),

59.04 (OCH₂), 74.23 (C-5), 82.60 (CH), 90.35 (CH=C), 167.71

O), 178.96 (O–C=CH) ppm. IR (neat; cm^–1): ν = 2962 (w), 2934

˜

(w, C–H), 1702 (s, C=C–O), 1644 (s, C=C–C=O), 1463 (w), 1385

(w), 1339 (w), 1170 (w), 1123 (s), 1094(s), 1048 (m), 1019 (m) cm^–1.

MS (EI, 70 eV): m/z (%) = 228 [M]⁺(7), 197 (18), 183 (39), 155

(100). C₁₂H₂₀O₄(228.288): C 63.14, H 8.83; found C 62.69, H 8.39.

Compound 4m: This compound was produced from 3m (0.50 g,

1.6 mmol) and DBU (0.49 mL, 3.3 mmol) in THF (20 mL), 4m be-

ing isolated after chromatography (silica gel, n-hexane/EtOAc,

100:1 to 1:1) as a yellow oil (0.33 g, 76%). ¹H NMR (CDCl₃,

300 MHz): δ = 0.89 (t, J = 6.9 Hz, 3 H, CH₃), 1.26 (t, J = 7.2 Hz,

3 H, OCH₂CH₃), 1.22–1.35 (m, 6 H, 3×CH₂), 1.36–1.40 (m, 1 H,

CH₂), 1.43–1.49 (m, 2 H, CH₂), 1.68–1.78 (m, 1 H, CH₂), 3.32 (s,

3 H, OCH₃), 3.67 (dd, J = 10.8, 3.3 Hz, 1 H, CH), 3.82 (d, J =

3.3 Hz, 1 H, CH), 4.15 (dq, J = 7.2, 3.3 Hz, 2 H, OCH₂CH₃), 4.22–

4.32 (m, 2 H, OCH₂), 5.31 (s, 1 H, CH=C) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ_C= 13.86, 14.25 (CH₃), 22.39, 28.02, 29.02, 30.50, 31.54

(CH₂), 47.52 (CH), 55.88 (OCH₃), 58.98 (OCH₂), 74.17 (C–5),

82.54 (CH), 90.29 (CH=C–O), 167.64 (O=C–O), 179.01 (O–

(O=C–O), 179.03 (O–C=CH) ppm. IR (neat; cm^–1): ν = 2927 (s),

˜

2855 (m, C–H), 1704 (s, C=C–O), 1644 (s, C=C–C=O), 1464 (m),

1377 (m), 1339 (w), 1288 (w), 1246 (w), 1223 (w), 1168 (w), 1123

(s), 1099 (s), 1050 (m), 1019 (w), 937 (w), 828 (w), 723 (w) cm^–1. MS

(EI, 70 eV): m/z (%) = 326 [M]⁺(3), 295 (100), 281 (48). C₁₉H₃₄O₄

(326.475): C 69.90, H 10.50; found C 69.80, H 10.74.

C=CH) ppm. IR (neat; cm^–1): ν = 2956 (m), 2929 (s), 2858 (w, C–

˜

Compound 4q: This compound was produced from 3q (0.154 g,

0.45 mmol) and DBU (0.13 mL, 0.90 mmol) in THF (5 mL), 4q

being isolated after chromatography (silica gel, n-hexane/EtOAc,

100:1 to 1:1) as a slightly yellow oil (0.128 g, 93%). ¹H NMR

(CDCl₃, 300 MHz): δ = 1.29 (t, J = 7.2 Hz, 3 H, CH₃), 1.32–1.39

(m, 6 H, 3×CH₂), 1.65–1.84 (m, 4 H, 2×CH₂), 3.32 (s, 3 H,

OCH₃), 3.54 (t, J = 6.6 Hz, 2 H, CH₂–Cl), 3.68 (dd, J = 10.8,

3.3 Hz, 1 H, CH), 3.82 (d, J = 3.3 Hz, 1 H, CH), 4.15 (dq, J = 7.2,

H), 1703 (s, C=C–O), 1644 (s, C=C–C=O), 1464 (m), 1417 (m),

1384 (m), 1338 (w), 1169 (w), 1122 (s), 1097 (s), 1051 (m), 1014

(w) cm^–1. MS (EI, 70 eV): m/z (%) = 270 [M]⁺(11), 241 (15), 240

(100), 239 (89), 226 (61). C₁₅H₂₆O₄(270.368): C 66.64, H 9.69;

found C 67.04, H 10.12.

Compound 4n: This compound was produced from 3n (0.35 g,

1.0 mmol) and DBU (0.31 mL, 2.1 mmol) in THF (20 mL), 4n be-

Eur. J. Org. Chem. 2005, 2074–2090

www.eurjoc.org

2083

E. Bellur, H. Görls, P. Langer

3.3 Hz, 2 H, OCH₂CH₃), 4.29–4.33 (m, 2 H, OCH₂), 5.32 (s, 1 H, C=O), 1447 (m), 1388 (m), 1370 (m), 1328 (w), 1301 (m), 1278 (m),

FULL PAPER

CH=C) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 14.39 (CH₃),

1250 (m), 1222 (m), 1178 (s), 1150 (s), 1122 (m), 1102 (s), 1050 (s),

26.64, 27.95, 28.65, 30.44, 32.43 (CH₂), 44.98 (CH₂–Cl), 47.51 998 (m), 962 (m), 939 (w), 876 (w), 856 (w), 831 (w), 783 (m) cm^–1.

(CH), 56.08 (OCH₃), 59.18 (OCH₂), 74.27 (C–5), 82.62 (CH), 90.52 MS (EI, 70 eV): m/z (%) = 240 [M]⁺(100), 211 (32), 195 (90).

(CH=C–O), 167.81 (O=C–O), 178.92 (O–C=CH) ppm. IR (neat;

C₁₃H₂₀O₄(240.299): C 64.98, H 8.39; found C 64.75, H 8.97.

cm^–1): ν = 2981 (m), 2933 (s), 2860 (m), 2828 (w, C–H), 1701 (s,

˜

Compound 4u: This compound was produced from 3u (0.50 g,

1.7 mmol) and DBU (0.51 mL, 3.4 mmol) in THF (10 mL), 4u be-

ing isolated after chromatography (silica gel, n-hexane/EtOAc,

100:1 to 1:1) as a yellow oil (0.35 g, 80%). ¹H NMR (CDCl₃,

300 MHz): δ = 1.27 (t, J = 7.2 Hz, 3 H, CH₃), 1.31–1.42 (m, 2 H,

CH₂), 1.54–1.72 (m, 4 H, 2×CH₂), 1.77–1.92 (m, 2 H, CH₂), 2.01–

2.12 (m, 1 H, CH₂), 2.75 (dt, J = 14.3, 3.7 Hz, 1 H, CH₂), 3.08

(dd, J = 12.3, 3.3 Hz, 1 H, CH), 3.32 (s, 3 H, OCH₃), 3.63 (d, J =

3.3 Hz, 1 H, CH), 4.17 (dq, J = 7.2, 1.5 Hz, 2 H, OCH₂CH₃), 4.36

(dd, J = 10.5, 3.3 Hz, 1 H, OCH₂), 4.50 (d, J = 10.8 Hz, 1 H,

OCH₂) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 14.24 (CH₃),

24.98, 25.99, 26.51, 28.98, 33.33 (CH₂), 49.47 (CH), 56.01 (OCH₃),

59.25 (OCH₂), 74.47 (C–5), 84.29 (CH), 99.73 (C=C–O), 166.38

C=C–O), 1641 (s, C=C–C=O), 1377 (m), 1338 (m), 1290 (m), 1225

(m), 1168 (m), 1121 (s), 1099 (s), 1050 (s), 1020 (m), 936 (w), 828

(m), 725 (w), 650 (w) cm^–1. MS (EI, 70 eV): m/z (%) = 304 [M]⁺

(2), 273 (32), 259 (17), 245 (2), 237 (8), 213 (2), 199 (11), 195 (3),

186 (16), 181 (5), 167 (6), 155 (100). C₁₅H₂₅O₄Cl (304.813): C 59.11,

H 8.27; found C 59.84, H 8.25.

Compound 4r: This compound was produced from 3r (0.80 g,

3.0 mmol) and DBU (0.91 mL, 6.1 mmol) in THF (10 mL), 4r be-

ing isolated after chromatography (silica gel, n-hexane/EtOAc, 50:1

to 1:1) as a white solid (0.53 g, 77%). ¹H NMR (CDCl₃, 300 MHz):

δ = 1.27 (t, J = 7.2 Hz, 3 H, OCH₂CH₃), 1.41–1.56 (m, 1 H, CH₂),

1.61–1.75 (m, 1 H, CH₂), 1.88–2.02 (m, 2 H, CH₂), 2.26–2.39 (m,

2 H, CH₂), 2.64–2.73 (m, 1 H, CH), 3.35 (s, 3 H, OCH₃), 3.92 (m,

1 H, CH), 4.15 (m, 1 H, OCH₂), 4.17 (q, J = 7.2 Hz, 2 H,

OCH₂CH₃), 4.49 (d, J = 10.5 Hz, 1 H, OCH₂) ppm. ¹³C NMR

(CDCl₃, 75 MHz): δ_C= 14.13 (CH₃), 21.17, 21.89, 23.61 (CH₂),

45.46 (CH), 56.77 (OCH₃), 59.14 (OCH₂CH₃), 74.13 (C-5), 78.88

(CH), 97.66 (C=C), 166.29 (O–C=O), 166.45 (O–C=C) ppm. IR

(O=C–O), 169.31 (O–C=C) ppm. IR (neat; cm^–1): ν = 2979 (s),

˜

2926 (s), 2855 (s), 2827 (m, C–H), 1708 (s, O=C–O), 1676 (s, C=C–

O), 1639 (s, C=C–C=O), 1457 (s), 1386 (s), 1367 (s), 1329 (m), 1305

(s), 1261 (m), 1243 (m), 1226 (w), 1173 (s), 1138 (s), 1104 (s), 1022

(m), 1047 (s), 988 (m), 952 (m), 226 (w), 884 (w), 849 (m), 818 (w),

791 (m), 751 (m), 731 (w) cm^–1. MS (EI, 70 eV): m/z (%) = 254

(100) [M]⁺, 223 (31), 209 (94). C₁₄H₂₂O₄(254.325): C 66.12, H 8.72;

found C 65.62, H 8.44.

(KBr (cm^–1)): ν = 2948 (w, C–H), 1708 (s, C=C–O), 16.84 (w), 1642

˜

(s, C=C–C=O), 1293 (w), 1270 (m), 1240 (m) 1201 (s), 1147 (m),

1122 (m), 1102 (s), 1074 (w), 1063 (m) cm^–1. MS (EI, 70 eV): m/z

(%) = 226 [M]⁺(71), 197 (27), 181 (100). The exact molecular mass

m/z = 226.1205 2 ppm [M]⁺for C₁₂H₁₈O₄was confirmed by

HRMS (EI, 70 eV).

Compound 4v: This compound was produced from 3v (2.40 g,

6.9 mmol) and DBU (2.07 mL, 13.8 mmol) in THF (10 mL), with

(E)-4v (0.77 g, 60%) and (Z)-4v (0.50 g, 38%) being isolated after

chromatography (silica gel, n-hexane/EtOAc, 100:1 to 1:1) as yellow

oils.

Compound 4s: This compound was produced from 3s (0.20 g,

0.8 mmol) and DBU (0.24 mL, 1.6 mmol) in THF (10 mL), 4s be-

ing isolated after chromatography (silica gel, n-hexane/EtOAc,

Compound (E)-4v: ¹H NMR (CDCl₃, 300 MHz): δ = 1.14–1.39 (m,

12 H, 6×CH₂), 1.28 (t, J = 7.2 Hz, 3 H, CH₃), 1.49–1.62 (m, 2 H,

CH₂), 2.00–2.12 (m, 2 H, CH₂), 2.28–2.38 (m, 2 H, CH₂), 2.49–

2.61 (m, 1 H, CH₂), 3.31 (s, 3 H, OCH₃), 3.82 (t, J = 3.9 Hz, 1 H,

CH), 3.95 (dd, J = 5.7, 3.9 Hz, 1 H, CH), 4.11–4.24 (m, 2 H,

OCH₂CH₃), 4.31 (d, J = 3.9 Hz, 2 H, OCH₂) ppm. ¹³C NMR

(CDCl₃, 50 MHz): δ_C= 14.35 (CH₃), 21.62, 22.39, 23.60, 24.15,

24.25, 25.40, 25.83, 26.31, 29.07 (CH₂), 47.55 (CH), 56.10 (OCH₃),

59.34 (OCH₂), 75.38 (C–5), 83.95 (CH), 104.62 (C=C–O), 168.79

1

100:1 to 1:1) as a colourless oil (0.15 g, 91%). H NMR (CDCl₃,

300 MHz): δ = 1.29 (t, J = 7.2 Hz, 3 H, CH₃), 1.83–1.89 (m, 1 H,

CH₂), 2.26–2.35 (m, 2 H, CH₂), 2.81–2.85 (m, 1 H, CH₂), 3.15 (t,

J = 9.0 Hz, 1 H, CH), 3.37 (s, 3 H, OCH₃), 3.77 (dd, J = 5.1,

3.0 Hz, 1 H, CH), 4.18 (q, J = 7.2 Hz, 2 H, OCH₂CH₃), 4.63 (dd,

J = 10.8, 3.0 Hz, 1 H, OCH₂), 4.84 (d, J = 10.8 Hz, 1 H,

OCH₂) ppm. ¹³C NMR (CDCl₃, 150 MHz): δ_C= 14.36 (CH₃),

21.16, 27.59 (CH₂), 54.18 (CH), 57.47 (OCH₃), 59.80 (OCH₂),

77.04 (CH), 84.32 (C–5), 96.45 (C=C–O), 164.78 (O=C–O), 169.64

(O=C–O), 173.25 (O–C=C) ppm. IR (neat; cm^–1): ν = 2931 (s),

˜

2861 (m, C–H), 1741 (w), 1693 (s, C=C–O), 1622 (s, C=C–C=O),

1465 (m), 1446 (m), 1383 (w), 1366 (w), 1302 (m), 1283 (m), 1238

(m), 1218 (w), 1196 (m), 1176 (m), 1150 (m), 1097 (s), 1049 (s),

1020 (m) cm^–1. MS (EI, 70 eV): m/z (%) = 310 [M]⁺(29), 279 (100),

265 (11). The exact molecular mass m/z = 310.2144 2 ppm [M]⁺

for C₁₈H₃₀O₄was confirmed by HRMS (EI, 70 eV).

(O–C=C) ppm. IR (neat; cm^–1): ν = 2962 (m), 2938 (m), 2836 (w,

˜

C–H), 1755 (s, O=C–O), 1725 (s, C=C–O), 1461 (m), 1449 (m),

1365 (w), 1257 (m), 1237 (m), 1192 (m), 1153 (m), 1114 (s) cm^–1.

MS (EI, 70 eV): m/z (%) = 313 [M]⁺(68), 199 (36), 181 (19), 167

(100), 152 (31). The exact molecular mass m/z = 212.1049 2 ppm

[M]⁺for C₁₁H₁₆O₄was confirmed by HRMS (EI, 70 eV).

Compound (Z)-4v: M.p. 77.5 °C. ¹H NMR (CDCl₃, 600 MHz): δ =

1.10 (t, J = 7.2 Hz, 3 H, CH₃), 1.18–1.22 (m, 10 H, 5×H₂), 1.24–

1.41 (m, 2 H, CH₂), 1.47–1.53 (m, 2 H, CH₂), 1.54–1.60 (m, 1 H,

CH₂), 1.62–1.69 (m, 1 H, CH₂), 1.97 (m, 1 H, CH₂), 2.13–2.19 (m,

1 H, CH₂), 2.97 (dd, J = 11, 5.5 Hz, 1 H, CH), 3.14 (s, 3 H, OCH₃),

3.48 (d, J = 5.5 Hz, 1 H, CH), 3.95–4.02 (m, 1 H, OCH₂CH₃),

Compound 4t: This compound was produced from 3t (0.27 g,

0.98 mmol) and DBU (0.29 mL, 2.0 mmol) in THF (15 mL), 4t be-

ing isolated after chromatography (silica gel, n-hexane/EtOAc,

100:1 to 1:1) as a yellow oil (0.21 g, 90%). ¹H NMR (CDCl₃,

300 MHz): δ = 1.28 (t, J = 7.2 Hz, 3 H, CH₃), 1.47–1.50 (m, 2 H,

CH₂), 1.59–1.69 (m, 1 H, CH₂), 1.75–1.87 (m, 2 H, CH₂), 1.98– 4.03–4.08 (m, 1 H, OCH₂CH₃), 4.21 (dd, J = 11, 5.5 Hz, 1 H,

2.13 (m, 2 H, CH₂), 2.86 (dd, J = 15.3, 6.9 Hz, 1 H, CH₂), 3.08 OCH₂), 4.29 (d, J = 11 Hz, 1 H, OCH₂) ppm. ¹³C NMR (CDCl₃,

(dt, J = 12.3, 2.1 Hz, 1 H, CH), 3.34 (s, 3 H, OCH₃), 3.65–3.68 (m,

1 H, CH), 4.19 (q, J = 7.2 Hz, 2 H, OCH₂CH₃), 4.38 (d, J = 3.6 Hz,

2 H, OCH₂) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 14.20 (CH₃),

50 MHz): δ_C= 14.37 (CH₃), 21.52, 23.15, 25.40, 25.87, 26.75, 27.16,

27.36, 27.53, 29.84 (CH₂), 46.81 (CH), 56.11 (OCH₃), 59.47

(OCH₂), 74.64 (C–5), 82.88 (CH), 102.96 (C=C–O), 167.19 (O=C–

26.81, 26.87, 29.30, 31.13 (CH₂), 51.21 (CH), 56.38 (OCH₃), 59.56 O), 169.13 (O–C=C) ppm. IR (neat; cm^–1): ν = 2975 (m), 2930 (s),

˜

(OCH₂), 75.02 (C-5), 84.71 (CH), 103.00 (C=C–O), 167.04 (O=C–

28.62 (m), 28.28 (w, C–H), 1708 (s, C=C–O), 1680 (s, C=C–C=O),

1630 (s), 1469 (m), 1446 (m), 1382 (w), 1367 (m), 1353 (w), 1339

O), 172.03 (O–C=C) ppm. IR (neat; cm^–1): ν = 2981 (m), 2926 (s),

˜

2953 (m, C–H), 1705 (s, O=C–O), 1677 (s, C=C–O), 1640 (s, C=C– (w), 1322 (m), 1295 (m), 1281 (m), 1232 (m), 1170 (s), 1145 (s),

Eur. J. Org. Chem. 2005, 2074–2090

Regioselective Synthesis of Functionalized Furans

FULL PAPER

1105 (s), 1095 (s), 1047 (m), 1032 (m), 1012 (w), 959 (w), 735

(m) cm^–1. MS (EI, 70 eV): m/z (%) = 310 [M]⁺(30), 279 (100), 265

(26). The exact molecular mass m/z = 310.2144 2 ppm [M]⁺for

C₁₈H₃₀O₄was confirmed by HRMS (EI, 70 eV).

91 (12). The exact molecular mass m/z = 288.1362 2 ppm [M]⁺

for C₁₇H₂₀O₄was confirmed by HRMS (EI, 70 eV).

1

Compound 4x (3): M.p. 155 °C. H NMR (CDCl₃, 300 MHz): δ =

2.02–2.17 (m, 2 H, CH₂), 2.34–2.45 (m, 1 H, CH), 2.63–2.71 (m, 1

H, CH), 2.84–2.98 (m, 2 H, CH₂), 3.37 (s, 3 H, OCH₃), 3.71 (s, 3

H, OCH₃), 3.95 (dd, J = 4.8, 3.0 Hz, 1 H, CH), 4.24 (dd, J = 10.5,

3.0 Hz, 1 H, OCH₂), 4.58 (d, J = 10.5 Hz, 1 H, OCH₂), 7.19–7.35

Compound 4w: This compound was produced from 3w (0.24 g,

0.87 mmol) and DBU (0.26 mL, 1.7 mmol) in THF (10 mL), 4w

being isolated after chromatography (silica gel, n-hexane/EtOAc,

1

100:1 to 1:1) as a yellow solid (0.14 g, 68%). M.p. 59 °C H NMR (m, 5 H, 5×CH from Ph) ppm. ¹³C NMR (CDCl₃, 150 MHz): δ_C

(CDCl₃, 300 MHz): δ = 1.13 (d, J = 6.6 Hz, 3 H, CH₃), 1.28 (t, J = 28.27, 33.24 (CH₂), 40.80, 46.95 (CH), 51.20, 57.30 (OCH₃),

= 7.2 Hz, 3 H, OCH₂CH₃), 1.21–1.31 (m, 1 H, CH₂), 1.49–1.61 (m, 75.16 (C–5), 79.29 (CH), 97.88 (C=C–O), 126.59, 127.02 (2 C),

1 H, CH₂), 1.75–1.87 (m, 1 H, CH), 2.28–2.38 (m, 3 H, CH₂, CH), 128.64 (2 C) (CH from Ph), 145.57 (C from Ph), 166.37 (O=C–O),

3.39 (s, 3 H, OCH₃), 3.81 (dt, J = 6.6, 9.0 Hz, 1 H, CH), 3.94 (t, J

= 8.4 Hz, 1 H, OCH₂), 4.18 (q, J = 7.2 Hz, 2 H, OCH₂CH₃), 4.55

(dd, J = 6.6, 8.4 Hz, 1 H, OCH₂) ppm. ¹³C NMR (CDCl₃,

166.98 (O–C=C) ppm. IR (KBr (cm^–1)): ν = 2948 (w), 2933 (w),

˜

2901 (w), 2845 (w, C–H), 1714 (s, O=C–O), 1683 (w), 1650 (s,

C=C–O), 1495 (w), 1459 (w), 1432 (w), 1389 (w), 1358 (w), 1291

150 MHz): δ_C= 14.62, 19.66 (CH₃), 24.41, 31.63 (CH₂), 33.95, (w), 1255 (s), 1195 (s), 1146 (s), 1126 (m), 1091 (s), 1056 (m), 1015

51.70 (CH), 58.53 (OCH₃), 59.84 (OCH₂), 73.68 (C–5), 82.56 (CH), (m), 966 (w), 940 (m), 856 (w), 839 (w), 768 (m), 707 (m) cm^–1. MS

98.89 (C=C–O), 165.95 (O=C–O), 166.83 (O(O–C=C) ppm. IR (EI, 70 eV): m/z (%) = 288 [M]⁺(41), 257 (11), 230 (5), 213 (13),

(KBr (cm^–1)): ν = 2979 (w), 2954 (m), 2929 (m), 2894 (w, C–H), 197 (4), 184 (27), 169 (8), 152 (100), 121 (17), 93 (24), 91 (21), 77

˜

1708 (s, O=C–O), 1685 (s, C=C–O), 1652 (s, C=C–C=O), 1371 (w),

(10). C₁₇H₂₀O₄(288.343): C 70.81, H 6.99; found C 70.17, H 6.96.

1295 (m), 1276 (m), 1228 (m), 1200 (m), 1155 (m), 1131 (s), 1096 The exact molecular mass m/z = 288.1362 2 ppm [M]⁺for

(m), 1047 (s) cm^–1. MS (EI, 70 eV): m/z (%) = 240 [M]⁺(38), 211

(16), 195 (47), 167 (100). The exact molecular mass m/z =

240.1362 2 ppm [M]⁺for C₁₃H₂₀O₄was confirmed by HRMS (EI,

70 eV).

C₁₇H₂₀O₄was confirmed by HRMS (EI, 70 eV).

Compound 4y: This compound was produced from 3y (0.500 g,

2.27 mmol) and DBU (0.68 mL, 4.53 mmol) in THF (20 mL), 4y

being isolated after chromatography (silica gel, n-hexane/EtOAc,

30:1 to 1:1) as a yellow oil (0.384 g, 92%). ¹H NMR (CDCl₃,

150 MHz): δ = 2.87–2.96 (m, 3 H, 2×CH₂), 3.34 (s, 3 H, OCH₃),

Compound 4x: This compound was produced from 3x (0.300 g,

0.92 mmol) and DBU (0.28 mL, 1.85 mmol) in THF (10 mL), with

4x (1) (0.079 g, 30%), 4x (2) (0.047 g, 18%) and 4x (3) (0.124 g, 3.55–3.62 (dm, J = 18.3, 1.4 Hz, 1 H, CH₂), 4.16–4.42 (m, 5 H,

47%) being isolated after chromatography (silica gel, n-hexane/

2×OCH₂, CH) ppm. ¹³C NMR (CDCl₃, 150 MHz): δ_C= 24.68,

EtOAc, 50:1 to 1:1) as a slightly yellow solid, an oil and a solid, 34.80 (CH₂), 56.17 (OCH₃), 65.03 (OCH₂), 76.13 (C–5), 77.92

respectively.

(CH), 94.06 (C=C–O), 167.27 (O=C–O), 172.65 (O–C=C) ppm. IR

(neat; cm^–1): ν = 2986 (m), 2925 (s), 2916 (s), 2830 (w, C–H), 1738

˜

1

Compound 4x (1): H NMR (CDCl₃, 300 MHz): δ = 1.69 (q, J =

12.0 Hz, 1 H, CH₂), 2.29–2.43 (m, 2 H, CH₂, CH), 2.65–2.73 (m,

1 H, CH), 2.81–2.97 (m, 2 H, CH₂), 3.44 (s, 3 H, OCH₃), 3.72 (s,

3 H, OCH₃), 3.85–3.90 (m, 1 H, CH), 4.01 (dd, J = 8.7, 8.7 Hz, 1

H, OCH₂), 4.58 (dd, J = 8.7, 6.9 Hz, 1 H, OCH₂), 7.20–7.35 (m, 5

(s, O=C–O), 1679 (s, C=C–O), 1462 (m), 1414 (w), 1372 (s), 1307

(m), 1263 (s), 1241 (s), 1213 (s), 1160 (m), 1100 (s), 1039 (s), 1002

(s), 948 (m), 927 (w), 841 (w), 801 (w), 772 (w), 753 (m), 695

(w) cm^–1. MS (EI, 70 eV): m/z (%) = 184 [M]⁺(17), 152 (100), 126

(11), 116 (1), 95 (27), 84 (5), 68 (9). Anal.: calcd. for C₉H₁₂O₄

(184.191): C 58.69, H 6.57; found C 58.52, H 6.42.

H, 5×CH from Ph) ppm. ¹³C NMR (CDCl₃, 150 MHz): δ_C

=

32.79, 33.28 (CH₂), 40.38, 47.47 (CH), 51.28, 58.85 (OCH₃), 73.93

(C–5), 82.32 (CH), 98.65 (C=C–O), 126.67, 126.91 (2 C), 128.86 (2

C) (CH from Ph), 145.20 (C from Ph), 166.12 (O=C–O), 166.84

General Procedure for the Synthesis of Furans 5: TFA (0.88 mL,

11.5 mmol) was added to a CH₂Cl₂solution (10 mL) of 4

(O–C=C) ppm. IR (KBr (cm^–1)): ν = 2946 (w, C–H), 1711 (s, O=C– (0.9 mmol). After the mixture had been stirred for 4 h at room tem-

˜

O), 1683 (m), 1655 (s, C=C–O), 1454 (w), 1438 (w), 1392 (w), 1302

(w), 1258 (s), 1198 (s), 1134 (s), 110 (s), 1080 (s), 1010 (w), 978 (w),

769 (m), 704 (m).) cm^–1. MS (EI, 70 eV): m/z (%) = 288 [M]⁺(43),

257 (12), 230 (6), 213 (5), 197 (3), 184 (27), 169 (9), 152 (100),

121 (12), 93 (27), 91 (16), 77 (7). The exact molecular mass m/z =

288.1362 2 ppm [M]⁺for C₁₇H₂₀O₄was confirmed by HRMS (EI,

70 eV).

perature, a saturated aqueous solution of Na₂CO₃was added. The

organic layer was separated, and the aqueous layer was repeatedly

extracted with diethyl ether. The combined organic extracts were

dried (Na₂SO₄) and filtered, and the filtrate was concentrated in

vacuo. The residue was purified by chromatography (silica gel, n-

hexane/EtOAc, 100:1 to 1:1) to give 5. These furan derivatives are

not UV-active (neither short nor long wavelength). To make the

product visible on TLC, the following mixture was used as a dying

agent: MeOH/AcOH/anisaldehyde, 85:14:1. Alternatively, pro-

duction of furans from 2-alkylidene-4-methoxy tetrahydrofurans by

elimination of methanol was achieved successfully by heating at

reflux in CH₂Cl₂, and for some of them in 1,4-dioxane, with very

good yields.

1

Compound 4x (2): H NMR (CDCl₃, 300 MHz): δ = 1.98–2.21 (m,

2 H, CH₂), 2.35–2.41 (m, 1 H, CH), 2.65–2.73 (m, 2 H, CH₂), 3.33

(s, 3 H, OCH₃), 3.37–3.44 (m, 1 H, CH), 3.78 (s, 3 H, OCH₃), 3.98–

4.10 (m, 1 H, CH), 4.08 (dd, J = 10.5, 2.6 Hz, 1 H, OCH₂), 4.49

(d, J = 10.5 Hz, 1 H, OCH₂), 7.19–7.32 (m, 5 H, 5×CH from

Ph) ppm. ¹³C NMR (CDCl₃, 150 MHz): δ_C= 28.22, 28.44 (CH₂),

36.56, 41.09 (CH), 51.41, 57.31 (OCH₃), 74.71 (C–5), 79.71 (CH),

Compound 5a: This compound was produced from 4a (0.30 g,

97.31 (C=C–O), 126.37, 127.23 (2 C), 128.51 (2 C), (CH from Ph), 1.7 mmol) and TFA (1.75 mL, 22.7 mmol) in CH₂Cl₂(20 mL), 5a

145.26 (C from Ph), 166.81 (O=C–O), 167.13 (O–C=C) ppm. IR being isolated without further purification as a yellow oil (0.20 g,

1

(neat; cm^–1): ν = 3027 (w), 2975 (w), 2935 (m), 2900 (m), 2867 (w,

C–H), 1711 (s, O=C–O), 1686 (s), 1656 (s, C=C–O), 1494 (w), 1439

80%). H NMR (CDCl₃, 300 MHz): δ = 3.68 (s, 2 H, CH₂), 3.73

(s, 3 H, OCH₃), 6.22 (dt, J = 3.3, 0.9 Hz, 1 H, CH), 6.34 (dd, J =

˜

(m), 1388 (m), 1365 (w), 1332 (w), 1299 (w), 1268 (m), 1245 (m), 3.3, 1.2 Hz, 1 H, CH), 7.36 (dd, J = 1.2, 0.9 Hz, 1 H, CH) ppm.

1201 (m), 1148 (m), 1109 (s), 1080 (m), 1059 (w), 1017 (w), 989 ¹³C NMR (CDCl₃, 75 MHz): δ_C= 33.79 (CH₂), 52.15 (OCH₃),

(w), 939 (w), 917 (w), 761 (w), 703 (m) cm^–1. MS (EI, 70 eV): m/z 107.96, 110.44, 142.02 (CH), 147.52 (C), 169.78 (O=C–O) ppm. IR

(%) = 288 [M]⁺(20), 184 (17), 152 (100), 121 (2), 98 (26), 93 (7),

(neat; cm^–1): ν = 2962 (s), 2923 (s), 2852 (w, C–H), 1738 (s, O=C–

˜

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2085

E. Bellur, H. Görls, P. Langer

FULL PAPER

O), 1719 (s), 1647 (w), 1439 (m), 1414 (w), 1342 (w), 1308 (m),

1079 (m), 1014 (s), 800 (m), 740 (m), 699 (m) cm^–1. MS (EI, 70 eV):

1261 (s), 1197 (s), 1096 (s), 1020 (s), 866 (m), 800 (s) cm^–1. MS (EI, m/z (%) = 216 [M]⁺(15), 91 (100), 81 (77). The exact molecular

70 eV): m/z (%) = 140 [M]⁺(31), 81 (100). The exact molecular

mass m/z = 140.0473 2 ppm [M]⁺for C₇H₈O₃was confirmed by

HRMS (EI, 70 eV).

mass m/z = 216.0786 2 ppm [M]⁺for C₁₃H₁₂O₃was confirmed by

HRMS (EI, 70 eV).

Compound 5f: This compound was produced from 3f (0.550 g,

2.2 mmol) and DBU (0.65 mL, 4.3 mmol) in THF (10 mL), 5f be-

Compound 5b: This compound was produced from 4b (0.10 g,

0.54 mmol) and TFA (0.54 mL, 7.0 mmol) in CH₂Cl₂(5 mL), 5b ing isolated after chromatography (silica gel, n-hexane/EtOAc,

being isolated without further purification as a yellow oil (0.08 g,

100:1 to 1:1) as a black oil (0.29 g, 72%). ¹H NMR (CDCl₃,

600 MHz): δ = 4.29 (s, 2 H, CH₂), 6.22 (dd, J = 3.3, 0.9 Hz, 1 H,

100%). ¹H NMR (CDCl₃, 300 MHz): δ = 1.27 (t, J = 7.2 Hz, 3 H,

CH₃), 3.68 (s, 2 H, CH₂), 4.19 (q, J = 7.2 Hz, 2 H, OCH₂CH₃), CH), 6.32 (dt, J = 3.3, 1.2 Hz, 1 H, CH), 7.35 (d, J = 1.2, 0.9 Hz,

6.22 (dt, J = 3.3, 0.9 Hz, 1 H, CH), 6.33 (dd, J = 3.3, 1.8 Hz, 1 H,

CH), 7.36 (dd, J = 1.8, 0.9 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ_C= 14.15 (CH₃), 34.15 (CH₂), 61.19 (OCH₂), 107.98,

110.52, 142.06 (CH), 147.79 (C), 169.47 (O=C–O) ppm. IR (neat;

1 H, CH), 7.45 (t, J = 6.0 Hz, 2 H, 2×CH from Ph), 7.55 (t, J =

6.0 Hz, 1 H, CH from Ph), 7.99 (d, J = 6.0 Hz, 2 H, 2×CH from

Ph) ppm. ¹³C NMR (CDCl₃, 50 MHz): δ = 38.30 (CH₂), 108.25,

110.58 (CH), 128.35, 128.49, 128.57 (CH from Ph), 136.04 (C from

cm^–1): ν = 2964 (m, C–H), 1638 (m, O=C–O), 1261 (s), 1222 (w), Ph), 141.98 (CH), 148.14 (C), 171.25 (O=C–O) ppm. IR (neat,

˜

1180 (m), 1095 (s), 1022 (s), 866 (w), 800 (s) cm^–1. MS (EI, 70 eV):

m/z (%) = 154 [M]⁺(74), 125 (33), 93 (87), 81 (100). The exact

molecular mass m/z = 154.0630 2 ppm [M]⁺for C₈H₁₀O₃was con-

firmed by HRMS (EI, 70 eV).

cm^–1): ν = 2955 (w, C–H), 1719 (w), 1691 (s, O=C–O), 1598 (m),

˜

1582 (w), 1568 (w), 1505 (w), 1449 (m), 1385 (w), 1337 (w), 1319

(w), 1279 (m), 1226 (m), 1208 (m), 1181 (w), 1152 (w), 1074 (w),

1014 (m), 996 (w), 737 (m), 715 (w), 689 (m) cm^–1. MS (EI, 70 eV):

m/z (%) = 186 (100) [M]. The exact molecular mass m/z =

186.0681 2 ppm [M]⁺for C₁₂H₁₀O₂was confirmed by HRMS (EI,

70 eV).

Compound 5c: This compound was produced from 4c (0.25 g,

1.3 mmol) and TFA (1.3 mL, 16.2 mmol) in CH₂Cl₂(10 mL), 5c

being isolated after chromatography (silica gel, n-hexane/EtOAc,

100:1 to 1:1) as a yellow oil (0.13 g, 61%). ¹H NMR (CDCl₃,

300 MHz): δ = 1.25 (d, J = 6.3 Hz, 6 H, 2×CH₃), 3.64 (s, 2 H,

CH₂), 5.04 (sept, J = 6.3 Hz, 1 H, OCH), 6.22 (dt, J = 3.3, 0.9 Hz,

1 H, CH), 6.33 (dd, J = 3.3, 1.8 Hz, 1 H, CH), 7.35 (dd, J = 1.8,

0.9 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 21.74

Compound 5g: This compound was produced from 4g (0.08 g,

0.4 mmol) and TFA (0.40 mL, 5.2 mmol) in CH₂Cl₂(5 mL), 5g be-

ing isolated after chromatography (silica gel, n-hexane/EtOAc,

1

100:1 to 1:1) as a colourless oil (0.05 g, 84%). H NMR (CDCl₃,

300 MHz): δ = 1.99 (s, 3 H, CH₃), 3.62 (s, 2 H, CH₂), 3.71 (s, 3 H,

(2CH₃), 34.46 (CH₂), 68.63 (OCH), 107.84, 110.49, 141.97 (CH), OCH₃), 6.21 (d, J = 1.8 Hz, 1 H, CH), 7.27 (d, J = 1.8 Hz, 1 H,

148.02 (C), 168.98 (O=C–O) ppm. IR (neat; cm^–1): ν = 2963 (m),

CH) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 9.77 (CH₃), 32.03

˜

2927 (w, C–H), 1739 (w, O=C–O), 1261 (s), 1178 (w), 1100 (s), 1020

(s), 800 (s) cm^–1. MS (EI, 70 eV): m/z (%) = 168 [M]⁺(31), 125 (93),

108 (100). The exact molecular mass m/z = 168.0786 2 ppm [M]⁺

for C₉H₁₂O₃was confirmed by HRMS (EI, 70eV).

(CH₂), 52.20 (OCH₃), 113.01 (CH), 116.95 (C), 141.10 (CH),

143.09 (C), 170.08 (O=C–O) ppm. IR (neat; cm^–1): ν = 2960 (m),

˜

2925 (s), 2855 (w, C–H), 1727 (m, O=C–O), 1675 (w), 1458 (m),

1442 (m), 1406 (w), 1386 (w), 1319 (w), 1261 (s), 1200 (m), 1175

(m), 1161 (m), 1120 (m), 1118 (m), 1095 (s), 1022 (s), 800 (s) cm^–1.

MS (EI, 70 eV): m/z (%) = 154 (100) [M]⁺, 139 (18), 123 (19), 95

(60). The exact molecular mass m/z = 154.0630 2 ppm [M]⁺for

C₈H₁₀O₃was confirmed by HRMS (EI, 70 eV).

Compound 5d: This compound was produced from 4d (0.15 g,

0.69 mmol) and TFA (0.7 mL, 9.0 mmol) in CH₂Cl₂(5 mL), 5d be-

ing isolated without further purification as a yellow oil (0.13 g,

100%). ¹H NMR (CDCl₃, 300 MHz): δ = 3.38 (s, 3 H, OCH₃), 3.61

(t, J = 4.8 Hz, 2 H, OCH₂CH₂OCH₃), 3.73 (s, 2 H, CH₂), 4.28 (t, Compound 5h: This compound was produced from 4h (0.15 g,

J = 4.8 Hz, 2 H, OCH₂CH₂OCH₃), 6.23 (dt, J = 3.3, 0.9 Hz, 1 H, 0.7 mmol) and TFA (0.70 mL, 9.1 mmol) in CH₂Cl₂(15 mL), 5h

CH), 6.33 (dd, J = 3.3, 1.8 Hz, 1 H, CH), 7.36 (dd, J = 1.8, 0.9 Hz, being isolated after chromatography (silica gel, n-hexane/EtOAc,

1 H, CH) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 33.71 (CH₂), 100:1 to 1:1) as a yellow oil (0.10 g, 79%). ¹H NMR (CDCl₃,

58.76 (OCH₃), 63.98 (OCH₂CH₂OCH₃), 70.09 (OCH₂CH₂OCH₃), 300 MHz): δ = 1.15 (t, J = 7.5 Hz, 3 H, CH₃), 1.26 (t, J = 7.2 Hz,

107.92, 110.34, 141.88 (CH), 147.40 (C), 169.23 (O=C–O) ppm. IR 3 H, OCH₂CH₃), 2.93 (q, J = 7.5 Hz, 2 H, CH₂), 3.61 (s, 2 H,

(neat; cm^–1): ν = 2977 (s), 2931 (s), 2880 (s), 2823 (w, C–H), 1792 CH₂), 4.16 (q, J = 7.2 Hz, 2 H, OCH₂CH₃), 6.26 (d, J = 1.8 Hz, 1

˜

(w), 1745 (s), 1741 (s, O=C–O), 1646 (m), 1604 (w), 1506 (w), 1453 H, CH), 7.28 (d, J = 1.8 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃,

(m), 1405 (m), 1384 (m), 1374 (m), 1338 (m), 1261 (m), 1227 (m), 150 MHz): δ_C= 14.05, 14.69 (CH₃), 17.84, 22.61 (CH₂), 60.89

1198 (s), 1180 (s), 1149 (s), 1128 (s), 1077 (m), 1037 (s), 1015 (m),

950 (w), 940 (w), 843 (w), 817 (w), 740 (w) cm^–1. MS (EI, 70 eV):

m/z (%) = 184 (100) [M]⁺, 139 (2), 125 (8), 109 (2). The exact mol-

ecular mass m/z = 184.0736 2 ppm [M]⁺for C₉H₁₂O₄was con-

firmed by HRMS (EI, 70 eV).

(OCH₂), 111.19 (CH), 123.51 (C), 141.19 (CH), 142.55 (C), 169.70

(O=C–O) ppm. IR (neat; cm^–1): ν = 2965 (m), 2928 (m), 2879 (w),

˜

2857 (w, C–H), 1742 (s, O=C–O), 1648 (w), 1600 (w), 1463 (m),

1446 (w), 1433 (w), 1400 (w), 1369 (w), 1332 (w), 1300 (w), 1264

(m), 1246 (w), 1214 (m), 1180 (m), 1162 (m), 1095 (m), 1069 (w),

1032 (m), 893 (w), 737 (w) cm^–1. MS (EI, 70 eV): m/z (%) = 182

[M]⁺(94), 153 (32), 152 (27), 137 (100), 109 (49), 107 (90), 93 (12).

The exact molecular mass m/z = 182.0943 2 ppm [M]⁺for

C₁₀H₁₄O₃was confirmed by HRMS (EI, 70 eV).

Compound 5e: This compound was produced from 4e (0.08 g,

0.30 mmol) and TFA (0.3 mL, 0.39 mmol) in CH₂Cl₂(5 mL), 5e

being isolated without further purification as a yellow oil (0.07 g,

1

100%). H NMR (CDCl₃, 300 MHz): δ = 3.73 (s, 2 H, CH₂), 5.16

(s, 2 H, OCH₂), 6.23 (dd, J = 3.3, 0.6 Hz, 1 H, CH), 6.33 (t, J =

Compound 5i: The reaction was carried out by heating of a CH₂Cl₂

solution (5 mL) of 4i (0.100 g, 0.495 mmol) under reflux for 24 h.

3.3 Hz, 1 H, CH), 7.31–7.38 (m, 6 H, CH, 5×CH from Ph) ppm.

¹³C NMR (CDCl₃, 75 MHz): δ_C= 34.09 (CH₂), 66.87 (OCH₂), The solvent was removed in vacuo and the residue was purified by

108.14, 110.55 (CH), 128.18, 128.31, 128.57 (CH from Ph), 135.61

(C from Ph), 142.11 (CH), 147.53 (C), 169.26 (O=C–O) ppm. IR

chromatography (silica gel, n-hexane/EtOAc, 100:1 to 50:1) to give

5i as a slight yellow oil (0.082 g, 98%). ¹H NMR (CDCl₃,

(neat; cm^–1): ν = 2962 (w, C–H), 1741 (s, O=C–O), 1455 (w), 1382 300 MHz): δ = 3.64 (s, 2 H, CH₂), 3.71 (s, 3 H, OCH₃), 3.75 (s, 3

˜

(w), 1338 (w), 1262 (s), 1224 (m), 1206 (m), 1180 (m), 1153 (s),

H, OCH₃), 6.31 (d, J = 2.1 Hz, 1 H, CH), 7.19 (d, J = 2.1 Hz, 1

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Regioselective Synthesis of Functionalized Furans

FULL PAPER

H, CH) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 30.76 (CH₂), (0.11 g, 100%). ¹H NMR (CDCl₃, 300 MHz): δ = 0.88 (t, J =

52.07, 59.12 (OCH₃), 102.77 (CH), 131.43 (C), 140.38 (CH), 145.19 7.2 Hz, 3 H, CH₃), 1.25 (t, J = 7.2 Hz, 3 H, OCH₂CH₃), 1.26–1.35

(C), 170.06 (O=C–O) ppm. IR (neat; cm^–1): ν = 3004 (w), 2953 (m),

2846 (w, C–H), 1742 (m, O=C–O), 1665 (m), 1642 (m), 1508 (w),

(m, 6 H, 3×CH₂), 1.51 (quint, J = 7.2 Hz, 2 H, CH₂), 2.34 (t, J =

7.2 Hz, 2 H, CH₂), 3.60 (s, 2 H, CH₂), 4.16 (q, J = 7.2 Hz, 2 H,

˜

1458 (m), 1441 (m), 1413 (m), 1340 (m), 1284 (s), 1239 (s), 1196 OCH₂), 6.23 (d, J = 1.8 Hz, 1 H, CH), 7.28 (d, J = 1.8 Hz, 1 H,

(s), 1173 (s), 1101 (s), 1011 (s), 890 (w), 786 (w), 736 (m) cm^–1. MS

CH) ppm. ¹³C NMR (CDCl₃, 150 MHz): δ_C= 13.99, 14.07 (CH₃),

22.54, 24.59, 28.85, 30.14, 31.61, 32.29 (CH₂), 60.96 (OCH₂),

111.59 (CH), 122.01 (C), 141.07 (CH), 142.92(C), 169.60 (O=C–

(EI, 70 eV): m/z (%) = 170 [M]⁺(19), 110 (100).

Compound 5j: This compound was produced from 4j (0.10 g,

0.4 mmol) and TFA (0.44 mL, 5.7 mmol) in CH₂Cl₂(10 mL), 5j

being isolated without further purification as a colourless oil

(0.09 g, 100%). ¹H NMR (CDCl₃, 300 MHz): δ = 1.25 (t, J =

7.2 Hz, 3 H, CH₃), 3.14 (dt, J = 6.3, 1.5 Hz, 2 H, CH₂), 3.61 (s, 2

H, CH₂), 4.16 (q, J = 7.2 Hz, 2 H, OCH₂), 5.01–5.09 (m, 2 H,

CH₂=CH), 5.82–5.95 (m, 1 H, CH=CH₂), 6.23 (d, J = 1.8 Hz, 1

H, CH), 7.30 (d, J = 1.8 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ_C= 14.11 (CH₃), 29.12, 32.37 (CH₂), 61.06 (OCH₂),

112.07 (CH), 115.46 (CH₂=CH), 119.41 (C), 136.21 (CH=CH₂),

O) ppm. IR (neat; cm^–1): ν = 2958 (m), 2930 (s), 2857 (m, C–H),

˜

1742 (s, O=C–O), 1463 (m), 1401 (w), 1370 (w), 1333 (w), 1264

(m), 1226 (m), 1211 (m), 1179 (m), 1160 (s), 1119 (w), 1099 (m),

1030 (m), 733 (w) cm^–1. MS (EI, 70 eV): m/z (%) = 238 [M]⁺(94),

210 (23), 194 (11), 165 (100). The exact molecular mass m/z =

238.1569 2 ppm [M]⁺for C₁₄H₂₂O₃was confirmed by HRMS (EI,

70 eV).

Compound 5n: This compound was produced from 4n (0.10 g,

0.3 mmol) and TFA (0.34 mL, 4.4 mmol) in CH₂Cl₂(10 mL), 5n

being isolated without further purification as a yellow oil (0.09 g,

100%). ¹H NMR (CDCl₃, 300 MHz): δ = 0.88 (t, J = 7.2 Hz, 3 H,

CH₃), 1.19–1.28 (m, 13 H, 5×H₂, OCH₂CH₃), 1.45 (t, J = 7.2 Hz,

2 H, CH₂), 2.34 (t, J = 7.2 Hz, 2 H, CH₂), 3.60 (s, 2 H, CH₂), 4.16

(q, J = 7.2 Hz, 2 H, OCH₂CH₃), 6.23 (d, J = 1.8 Hz, 1 H, CH),

7.28 (d, J = 1.8 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃, 75 MHz):

δ_C= 14.05, 14.11 (CH₃), 22.63, 24.63, 29.22, 29.24, 29.41, 30.21,

31.84, 32.34 (CH₂), 61.00 (OCH₂), 111.63 (CH), 122.06 (C), 141.11

141.25 (CH), 143.56 (C), 169.48 (O=C–O) ppm. IR (neat; cm^–1): ν

˜

= 2982 (m), 2932 (w, C–H), 1741 (s, O=C–O), 1641 (m), 1512 (w),

1440 (m), 1417 (m), 1369 (w), 1334 (m), 1302 (m), 1264 (m), 1235

(m), 1180 (s), 1160 (s), 1100 (m), 1060 (m), 1030 (s), 997 (w), 918

(m), 894 (w), 737 (m) cm^–1. MS (EI, 70 eV): m/z (%) = 194 [M]⁺

(48), 165 (5), 121 (100). The exact molecular mass m/z =

194.0943 2 ppm [M]⁺for C₁₁H₁₄O₃was confirmed by HRMS (EI,

70 eV).

(CH), 142.93 (C), 169.64 (O=C–O) ppm. IR (neat; cm^–1): ν = 2957

˜

Compound 5k: This compound was produced from 4k (0.13 g,

0.6 mmol) and TFA (0.57 mL, 7.4 mmol), in CH₂Cl₂(10 mL), 5k

being isolated without further purification as a colourless oil

(0.11 g, 100%). ¹H NMR (CDCl₃, 300 MHz): δ = 0.92 (t, J =

7.2 Hz, 3 H, CH₃), 1.25 (t, J = 7.2 Hz, 3 H, OCH₂CH₃), 1.55 (sex-

tet, J = 7.2 Hz, 2 H, CH₂), 2.33 (t, J = 7.2 Hz, 2 H, CH₂), 3.60 (s,

2 H, CH₂), 4.16 (q, J = 7.2 Hz, 2 H, OCH₂), 6.23 (d, J = 1.8 Hz,

1 H, CH), 7.28 (d, J = 1.8 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃,

150 MHz): δ_C= 13.58, 13.98 (CH₃), 23.25, 26.55, 32.21 (CH₂),

60.88 (OCH₂), 111.54 (CH), 121.71 (C), 141.01 (CH), 143.02 (C),

(w), 2928 (s), 2856 (m, C–H), 1743 (s, O=C–O), 1463 (w), 1266 (w),

1215 (w), 1177 (m), 1159 (m), 1101 (w), 1032 (w) cm^–1. MS (EI,

70 eV): m/z (%) = 266 (100) [M]⁺, 193 (86). The exact molecular

mass m/z = 266.1882 2 ppm [M]⁺for C₁₆H₂₆O₃was confirmed by

HRMS (EI, 70 eV).

Compound 5o: This compound was produced from 4o (0.12 g,

0.4 mmol) and TFA (0.38 mL, 5.0 mmol) in CH₂Cl₂(10 mL), 5o

being isolated without further purification as a yellow oil (0.11 g,

100%). ¹H NMR (CDCl₃, 300 MHz): δ = 0.88 (t, J = 7.2 Hz, 3 H,

CH₃), 1.23–1.32 (m, 15 H, 6×CH₂, CH₃), 1.51 (quint, J = 7.2 Hz,

2 H, CH₂), 2.34 (t, J = 7.2 Hz, 2 H, CH₂), 3.60 (s, 2 H, CH₂), 4.16

(q, J = 7.2 Hz, 2 H, OCH₂), 6.23 (d, J = 1.8 Hz, 1 H, CH), 7.28

(d, J = 1.8 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃, 150 MHz): δ_C

= 14.02, 14.07 (CH₃), 22.60, 24.59, 29.20, 29.26, 29.42, 29.50, 30.23,

31.83, 32.29 (CH₂), 60.95 (OCH₂), 111.59 (CH), 122.01 (C), 141.07

169. 52 (O=C–O) ppm. IR (neat; cm^–1): ν = 2962 (m), 2932 (m),

˜

2872 (w, C–H), 1741 (s, O=C–O), 1510 (w), 1462 (m), 1415 (w),

1402 (w), 1370 (w), 1333 (w), 1302 (w), 1263 (m), 1239 (m), 1208

(m), 1163 (s), 1097 (m), 1031 (s), 801 (w), 735 (w) cm^–1. MS (EI,

70 eV): m/z (%) = 196 [M]⁺(24), 166 (96), 123 (100). The exact

molecular mass m/z = 196.1099 2 ppm [M]⁺for C₁₁H₁₆O₃was

confirmed by HRMS (EI, 70 eV).

(CH), 142.92 (C), 169.58 (O=C–O) ppm. IR (neat; cm^–1): ν = 2960

˜

(m), 2927 (s), 2856 (m, C–H), 1744 (s, O=C–O), 1463 (m), 1262

(m), 1210 (w), 1175 (m), 1158 (m), 1100 (m), 1078 (m), 1031 (s),

799 (w) cm^–1. MS (EI, 70 eV): m/z (%) = 280 (100) [M]⁺, 207 (79).

The exact molecular mass m/z = 280.2038 2 ppm [M]⁺for

C₁₇H₂₈O₃was confirmed by HRMS (EI, 70 eV).

Compound 5l: This compound was produced from 4l (0.10 g,

0.4 mmol) and TFA (0.41 mL, 5.4 mmol) in CH₂Cl₂(10 mL), 5l

being isolated without further purification as a colourless oil

(0.09 g, 100%). ¹H NMR (CDCl₃, 300 MHz): δ = 0.91 (t, J =

7.2 Hz, 3 H, CH₃), 1.25 (t, J = 7.2 Hz, 3 H, OCH₂CH₃), 1.33 (sex-

tet, J = 7.2 Hz, 2 H, CH₂), 1.50 (quint, J = 7.2 Hz, 2 H, CH₂),

2.35 (t, J = 7.2 Hz, 2 H, CH₂), 3.60 (s, 2 H, CH₂), 4.16 (q, J =

7.2 Hz, 2 H, OCH₂), 6.23 (d, J = 1.8 Hz, 1 H, CH), 7.28 (d, J =

1.8 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃, 150 MHz): δ_C= 13.82,

14.07 (CH₃), 22.22, 24.28, 32.30, 32.32 (CH₂), 60.98 (OCH₂),

111.61 (CH), 121.98 (C), 141.08 (CH), 142.94 (C), 169.63 (O=C–

Compound 5p: This compound was produced from 4p (0.15 g,

0.5 mmol) and TFA (0.5 mL, 6.0 mmol) in CH₂Cl₂(15 mL), 5p be-

ing isolated without further purification as a yellow oil (0.14 g,

100%). ¹H NMR (CDCl₃, 300 MHz): δ = 0.88 (t, J = 7.2 Hz, 3 H,

CH₃), 1.19–1.28 (m, 17 H, 7×CH₂, CH₃), 1.51 (quint, J = 7.2 Hz,

2 H, CH₂), 2.34 (t, J = 7.2 Hz, 2 H, CH₂), 3.60 (s, 2 H, CH₂), 4.16

(q, J = 7.2 Hz, 2 H, OCH₂), 6.23 (d, J = 1.8 Hz, 1 H, CH), 7.28

O) ppm. IR (neat; cm^–1): ν = 2962 (w), 2931 (w), 2860 (w, C–H),

˜

(d, J = 1.8 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C

=

1743 (s, O=C–O), 1462 (w), 1261 (s), 1230 (m), 1097 (s), 1026 (s),

14.04, 14.09 (CH₃), 22.63, 24.61, 29.22, 29.29, 29.41, 29.43, 29.57,

30.20, 31.85, 32.31 (CH₂), 60.96 (OCH₂), 111.60 (CH), 122.01 (C),

800 (s) cm^–1. MS (EI, 70 eV): m/z (%) = 210 (100) [M]⁺, 181 (10),

166 (99), 137 (86). The exact molecular mass m/z

=

141.06 (CH), 142.93 (C), 169.58 (O=C–O) ppm. IR (neat; cm^–1): ν

˜

210.1256 2 ppm [M]⁺for C₁₂H₁₈O₃was confirmed by HRMS (EI,

= 2959 (m), 2927 (s), 2955 (m, C–H), 1744 (s, O=C–O), 1463 (w),

1262 (m), 1226 (w), 1210 (w), 1159 (m), 1100 (m), 1031 (m), 800

(w) cm^–1. MS (EI, 70 eV): m/z (%) = 294 (100) [M]⁺, 221 (68). The

exact molecular mass m/z = 294.2195 2 ppm [M]⁺for C₁₈H₃₀O₃

was confirmed by HRMS (EI, 70 eV).

70 eV).

Compound 5m: This compound was produced from 4m (0.13 g,

0.5 mmol) and TFA (0.46 mL, 6.0 mmol) in CH₂Cl₂(10 mL), 5m

being isolated without further purification as a colourless oil

Eur. J. Org. Chem. 2005, 2074–2090

www.eurjoc.org

2087

E. Bellur, H. Görls, P. Langer

FULL PAPER

Compound 5q: This compound was produced from 4q (0.100 g,

0.293 mmol) in CH₂Cl₂(10 mL), 5q being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 10:1) as a slight yellow

O) ppm. IR (neat; cm^–1): ν = 2928 (s), 2856 (w, C–H), 1739 (s,

O=C–O), 1449 (m), 1370 (w), 1302 (m), 1265 (m), 1229 (m), 1176

(s), 1159 (m), 1097 (m), 1029 (m) cm^–1. MS (EI, 70 eV): m/z (%) =

222 [M]⁺(9), 207 (54), 193 (8), 148 (100).

˜

1

oil (0.061 g, 76%). H NMR (CDCl₃, 300 MHz): δ = 1.19 (t, J =

7.2 Hz, 3 H, CH₃), 1.23–1.51 (m, 6 H, 3×CH₂), 1.70 (quint, J =

6.9 Hz, 2 H, CH₂), 2.29 (t, J = 7.5 Hz, 2 H, CH₂), 3.46 (t, J =

6.6 Hz, 2 H, CH₂–Cl), 3.60 (s, 2 H, CH₂), 4.10 (q, J = 7.2 Hz, 2

H, OCH₂), 6.16 (d, J = 1.8 Hz, 1 H, CH), 7.22 (d, J = 1.8 Hz, 1

H, CH) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 14.15 (CH₃),

24.50, 26.65, 28.39, 29.98, 32.35, 32.50 (CH₂), 45.06 (CH₂–Cl),

61.07 (OCH₂), 111.59 (CH), 121.80 (C), 141.23 (CH), 143.06 (C),

Compound 5v: This compound was produced from (E)-4v (0.40 g,

1.3 mmol) and TFA (1.3 mL, 17.0 mmol) in CH₂Cl₂(5 mL), 5v be-

ing isolated without further purification as an orange oil (0.36 g,

100%). ¹H NMR (CDCl₃, 300 MHz): δ = 0.98–1.13 (m, 2 H, CH₂),

1.21 (t, J = 7.2 Hz, 3 H, CH₃), 1.15–1.29 (m, 6 H, 3×H₂), 1.31–

1.46 (m, 4 H, 2×H₂), 1.57–1.66 (m, 2 H, CH₂), 1.92–2.03 (m, 1 H,

CH₂), 2.06–2.15 (m, 1 H, CH₂), 2.38–2.53 (m, 2 H, CH₂), 3.84 (dd,

J = 9.4, 5.9 Hz, 1 H, CH), 4.07–4.17 (dq, J = 7.2, 3.6 Hz, 2 H,

OCH₂), 6.21 (d, J = 1.8 Hz, 1 H, CH), 7.32 (d, J = 1.8 Hz, 1 H,

169.64 (O=C–O) ppm. IR (neat; cm^–1): ν = 2983 (w), 2934 (s), 2859

˜

(m, C–H), 1742 (s, O=C–O), 1510 (w), 1461 (m), 1444 (m), 1400

(w), 1369 (w), 1335 (w), 1303 (w), 1269 (m), 1204 (m), 1164 (s),

1118 (m), 1092 (m), 1031 (m), 894 (w), 736 (m) cm^–1. MS (EI,

70 eV): m/z (%) = 272 [M]⁺(17), 258 (4), 199 (25), 184 (4), 168

(14), 148 (10), 121 (5), 107 (9), 95 (100).

13

CH) ppm. C NMR (CDCl₃, 75 MHz): δ_C= 13.99 (CH₃), 21.11,

22.07, 22.13, 23.67, 23.84, 23.91, 24.87, 27.12, 28,49 (CH₂), 40.03

(CH), 60.62 (OCH₂), 110.62 (CH), 121.28 (C), 141.42 (CH), 146.99

(C), 172.15 (O=C–O) ppm. IR (neat; cm^–1): ν = 2934 (s), 2860 (s,

˜

C–H), 1740 (s, O=C–O), 1512 (w), 1465 (s), 1445 (s), 1391 (w),

1369 (m), 1346 (w), 1260 (s), 1241 (s), 1221 (s), 1172 (s), 1151 (s),

1098 (s), 1030 (s), 891 (w), 804 (s), 738 (m) cm^–1. MS (EI, 70 eV):

m/z (%) = 278 [M]⁺(40), 205 (100). The exact molecular mass m/z

= 278.1882 2 ppm [M]⁺for C₁₇H₂₆O₃was confirmed by HRMS

(EI, 70 eV).

Compound 5r: This compound was produced from 4r (0.20 g,

0.88 mmol) and TFA (0.9 mL, 11.5 mmol) in CH₂Cl₂(10 mL), 5r

being isolated after chromatography (silica gel, n-hexane/EtOAc,

100:1 to 1:1) as a yellow oil (0.13 g, 76%). ¹H NMR (CDCl₃,

300 MHz): δ = 1.27 (t, J = 7.2 Hz, 3 H, CH₃), 1.68–1.79 (m, 1 H,

CH₂), 1.81–1.94 (m, 1 H, CH₂), 1.97–2.08 (m, 1 H, CH₂), 2.09–

2.18 (m, 1 H, CH₂), 2.37–2.55 (m, 2 H, CH₂), 3.69 (t, J = 7.2 Hz,

1 H, CH), 4.19 (q, J = 7.2 Hz, 2 H, OCH₂CH₃), 6.22 (d, J = 1.8 Hz,

1 H, CH), 7.30 (d, J = 1.8 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ_C= 14.24 (CH₃), 21.12, 21.90, 27.16 (CH₂), 40.261

(CH), 60.98 (OCH₂), 110.35 (CH), 119.13 (C), 141.53 (CH), 146.54

Compound 5w: This compound was produced from 4w (0.08 g,

0.31 mmol) and TFA (0.31 mL, 4.1 mmol) in CH₂Cl₂(5 mL), 5w

being isolated without further purification as a yellow oil (0.07 g,

100%). ¹H NMR (CDCl₃, 300 MHz): δ = 1.15 (d, J = 6.9 Hz, 3 H,

CH₃), 1.28 (t, J = 7.2 Hz, 3 H, OCH₂CH₃), 1.29–1.38 (m, 1 H,

CH₂), 1.94–2.05 (m, 2 H, CH₂), 2.15–2.20 (m, 1 H, CH₂), 2.73

(sextet, J = 7.2 Hz, 1 H, CH), 3.68 (t, J = 6.3 Hz, 1 H, CH), 4.19

(q, J = 7.2 Hz, 2 H, OCH₂CH₃), 6.27 (d, J = 1.8 Hz, 1 H, CH),

7.29 (dd, J = 1.8, 0.9 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ_C= 14.24, 20.67 (CH₃), 25.87 (CH₂), 27.65 (CH), 30.41

(CH₂), 40.84 (CH), 60.98 (OCH₂), 109.10 (CH), 124.55 (C), 141.64

(C), 172.74 (O=C–O) ppm. IR (neat; cm^–1): ν = 2963 (s), 2931 (m),

˜

2909 (m), 2856 (w, C–H), 1740 (m, O=C–O), 1446 (w), 1413 (w),

1261 (s), 1224 (w), 1176 (m), 1151 (m), 1096 (s), 1054 (s), 1024 (s),

865 (m), 798 (s), 703 (w) cm^–1. MS (EI, 70 eV): m/z (%) = 194

[M]⁺(16), 121(100).

Compound 5t: This compound was produced from 4t (0.10 g,

0.4 mmol) and TFA (0.42 mL, 5.4 mmol) in CH₂Cl₂(10 mL), 5t

being isolated without further purification as a colourless oil

(0.09 g, 100%). ¹H NMR (CDCl₃, 300 MHz): δ = 1.25 (t, J =

7.2 Hz, 3 H, CH₃), 1.53–1.59 (m, 2 H, CH₂), 1.71–1.80 (m, 1 H,

CH₂), 1.84–1.89 (m, 2 H, CH₂), 2.22–2.27 (m, 1 H, CH₂), 2.50–

2.53 (m, 2 H, CH₂), 3.90 (t, J = 4.2 Hz, 1 H, CH), 4.19 (dq, J =

7.2, 2.9 Hz, 2 H, OCH₂), 6.16 (d, J = 1.5 Hz, 1 H, CH), 7.18 (d, J

= 1.5 Hz, 1 H, CH) ppm. ¹³C NMR (CDCl₃, 75 Hz): δ_C= 14.24

(CH₃), 25.58, 26.91, 28.22, 29.57 (CH₂), 45.29 (CH), 60.86 (OCH₂),

113.27 (CH), 122.75 (C), 139,74 (CH), 148.89 (C), 172.31 (O=C–

(CH), 146.03 (C), 172.82 (O=C–O) ppm. IR (neat; cm^–1): ν = 2959

˜

(m), 2930 (s), 2856 (w, C–H), 1737 (s, O=C–O), 1453 (m), 1372 (w),

1310 (w), 1286 (w), 1260 (m), 1228 (w), 1179 (s), 1142 (m), 1122

(w), 1097 (m), 1032 (m), 736 (w) cm^–1. MS (EI, 70 eV): m/z (%) =

208 [M]⁺(12), 125 (100). The exact molecular mass m/z =

208.1099 2 ppm [M]⁺for C₁₂H₁₆O₃was confirmed by HRMS (EI,

70 eV).

Compound 5x: This compound was produced from 4x (0.100 g,

0.35 mmol) in CH₂Cl₂(10 mL), 5x being isolated after chromatog-

raphy (silica gel, n-hexane/EtOAc, 100:1 to 50:1) as a yellow oil

1

(0.087 g, 98%). H NMR (CDCl₃, 300 MHz): δ = 2.15–2.48 (m, 2

O) ppm. IR (neat; cm^–1): ν = 2931 (m), 2857 (w, C–H), 1736 (s,

˜

H, CH₂), 2.54–2.82 (m, 2 H, CH₂), 2.94–3.04, 3.17–3.27 (dm, 1 H,

CH–Ph), 3.74, 3.75 (ds, 3 H, OCH₃), 3.80–4.02 (dm, 1 H, CH),

6.24–6.27 (dd, J = 6.0, 1.8 Hz, 1 H, CH), 7.21–7.36 (m, 6 H, CH,

5×CH from Ph) ppm. ¹³C NMR (CDCl₃, 150 MHz): δ_C= 29.90,

30.32 (1×CH), 33.71, 34.81 (1×CH₂), 38.07, 39.66 (1×CH–Ph),

40.96, 42.02 (1×H), 51.53, 52.43 (1×OCH₃), 110.43 (CH), 119.42,

119.61 (1×C), 126.64, 126.78 (1×CH from Ph), 127.04, 127.12

(2×CH from Ph), 128.68, 128.74 (2×CH from Ph), 142.21, 142.29

(1×CH), 144.97, 145.22 (1×C), 146.04, 146.28 (1×C), 172.83,

O=C–O), 1707 (m), 1449 (m), 1371 (w), 1307 (w), 1259 (m), 1239

(m), 1222 (m), 1191 (m), 1157 (m), 1104 (m), 1080 (m), 1026

(m) cm^–1. MS (EI, 70 eV): m/z (%) = 208 [M]⁺(13), 194 (12), 162

(8), 135 (100). The exact molecular mass m/z = 208.1099 2 ppm

[M]⁺for C₁₂H₁₆O₃was confirmed by HRMS (EI, 70 eV).

Compound 5u: This compound was produced from 4u (0.15 g,

0.6 mmol) and TFA (0.59 mL, 7.7 mmol) in CH₂Cl₂(5 mL), 5u be-

ing isolated after chromatography (silica gel, n-hexane/EtOAc,

1

100:1 to 20:1) as a colourless oil (0.11 g, 84%). H NMR (CDCl₃,

172.88 (1×O=C–O) ppm. IR (neat; cm^–1): ν = 3062 (w), 3029 (w),

˜

300 MHz): δ = 1.26 (t, J = 7.2 Hz, 3 H, CH₃), 1.30–1.49 (m, 2 H,

3002 (w), 2952 (m), 2927 (m), 2853 (w, C–H), 1740 (s, O=C–O),

CH₂), 1.52–1.71 (m, 4 H, 2×CH₂), 1.93–2.03 (m, 1 H, CH₂), 2.12– 1685 (w), 1608 (w), 1499 (m), 1448 (m), 1439 (m), 1354 (w), 1313

2.21 (m, 1 H, CH₂), 2.47–2.56 (m, 1 H, CH₂), 2.65–2.74 (m, 1 H, (w), 1282 (m), 1252 (s), 1230 (s), 1200 (s), 1169 (s), 1103 (w), 1975

CH₂), 3.87 (dd, J = 11.1, 3.9 Hz, 1 H, CH), 4.21 (q, J = 7.2 Hz, 2 (w), 1038 (m), 1016 (m), 844 (s), 762 (m), 738 (m), 701 (m) cm^–1.

H, OCH₂), 6.14 (d, J = 1.8 Hz, 1 H, CH), 7.25 (d, J = 1.8 Hz, 1

MS (EI, 70 eV): m/z (%) = 256 [M]⁺(66), 197 (1009, 179 (8), 170

H, CH) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ_C= 14.19 (CH₃), (7), 165 (6), 151 (29), 119 (9), 104 (27), 91 (43), 81 (17), 59 (11).

23.85, 24.85, 25.26, 28.90, 29.60 (CH₂), 43.80 (CH), 60.87 (OCH₂),

The exact molecular mass m/z = 256.1099 2 ppm [M]⁺for

112.67 (CH), 120.04 (C), 140.41 (CH), 147.38 (C), 172.57 (O=C– C₁₆H₁₆O₃was confirmed by HRMS (EI, 70 eV).

2088

www.eurjoc.org

Eur. J. Org. Chem. 2005, 2074–2090

Regioselective Synthesis of Functionalized Furans

FULL PAPER

Compound 5y: A solution of 4y (0.130 g, 0.71 mmol) in CH₂Cl₂

(100 mL) was heated at for 5 h and the solvent was removed in

vacuo. The residue was purified by column chromatography (silica

gel, n-hexane/EtOAc, 20:1 to 5:1) to give 5y as a yellow oil (0.105 g,

be determined by Mo-radiation), largest difference peak and hole:

0.331/–0.396 eÅ^–3.

1

98%). H NMR (CDCl₃, 300 MHz): δ = 2.54–2.71 (m, 2 H, CH₂),

Acknowledgments:

3.91 (t, J = 9.2 Hz, 1 H, CH), 4.32–4.40 (m, 1 H, OCH₂), 4.46–

4.52 (m, 1 H, OCH₂), 6.31–6.33 (m, 1 H, CH), 6.36 (dd, J = 3.3,

1.8 Hz, 1 H, CH), 7.39 (dd, J = 1.8, 0.9 Hz, 1 H, CH) ppm. ¹³C

Financial support from the DAAD (scholarship for E. B.) and from

NMR (CDCl₃, 150 MHz): δ_C= 28.69 (CH₂), 39.66 (CH), 67.08 the Deutsche Forschungsgemeinschaft is gratefully acknowledged.

(OCH₂), 107.80, 110.66, 142.64 (CH), 149.36 (C), 175.18 (O=C– We thank Dr. Ilia Freifeld for an experimental contribution.

O) ppm. IR (neat; cm^–1): ν = 2917 (w, C–H), 1771 (s, O=C–O),

˜

1506 (w), 1483 (w), 1455 (w), 1376 (m), 1262 (w), 1241 (w), 1203

[1] Römpp Lexikon Naturstoffe (Eds.: W. Steglich, B. Fugmann, S.

(m), 1154 (s), 1097 (w), 1072 (w), 1023 (m), 951 (m), 885 (w), 742

Lang-Fugmann), Thieme, Stuttgart, 1997.

(m), 689 (w) cm^–1. MS (EI, 70 eV): m/z (%) = 152 [M]⁺(29), 108

(73), 94 (21), 80 (100), 67 (17). The exact molecular mass m/z =

152.0473 2 ppm [M]⁺for C₈H₈O₃was confirmed by HRMS (EI,

70 eV).

[2] For furan natural products, see references 1–11 cited in: T.

Bach, L. Krüger, Eur. J. Org. Chem. 1999, 2045.

[3] For reviews of furan syntheses, see: a) W. Friedrichsen, in Com-

prehensive Heterocyclic Chemistry (A. R. Katritzky, C. W. Rees,

E. F. V. Scriven, Eds.), vol. 2, Elsevier: 1996, pp. 359–363, and

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3450; b) J. A. Marshall, X. Wang, J. Org. Chem. 1991, 56,

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d) J. A. Marshall, W. J. DuBay, J. Org. Chem. 1993, 58, 3602;

e) J. A. Marshall, G. S. Bartley, J. Org. Chem. 1994, 59, 7169;

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Brownbridge, Synthesis 1983, 85.

Crystal Structure Determination: The intensity data for the com-

pounds were collected on a Nonius Kappa CCD diffractometer,

using graphite-monochromated Mo-K_αradiation. Data were cor-

rected for Lorentz and polarization effects, but not for absorption

effects.^[25,26]The structures were solved by direct methods

(SHELXS)^[27]and refined by full-matrix least-squares techniques

against Fo²(SHELXL-97).^[28]For the C3 group of both symmetry-

independent molecules of 4r the hydrogen atoms were located by

difference Fourier synthesis and refined isotropically. All other hy-

drogen atoms were included at calculated positions with fixed ther-

mal parameters. All non-hydrogen atoms were refined

anisotropically. XP (SIEMENS Analytical X-ray Instruments, Inc.)

was used for structure representations.

Crystal Data for 4g:^[29]C₉H₁₄O₄, Mr = 186.20 gmol^–1, colourless

prism, size 0.03×0.03×0.03 mm, orthorhombic, space group Pbca,

a = 13.4002(2), b = 8.0370(4), c = 17.9872(6) Å, V = 1937.1(1) Å³,

T = –90 °C, Z = 8, ρ_calcd.= 1.277 g cm^–3, μ(Mo-K_α) = 1.0 cm^–1,

F(000) = 800, 3998 reflections in h(–17/17), k(–10/10), l(–23/23),

[10] For the use of Me₃SiOTf in the reaction of simple silyl enol

ethers with monofunctional acetals, see: a) S. Murata, M. Su-

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ata, M. Suzuki, R. Noyori, J. Am. Chem. Soc. 1980, 102, 3248.

[11] T. Mukaiyama, H. Ishihara, K. Inomata, Chem. Lett. 1975,

527.

measured in the range 3.96° Յ Θ Յ 27.45°, completeness Θ_max

=

99.4%, 2197 independent reflections, R_int= 0.021, 1696 reflections

with F_oϾ 4σ(F_o), 118 parameters, 0 restraints, R1_obs= 0.044,

wR²

= 0.113, R1_all= 0.061, wR²= 0.124, GOOF = 1.033,

obs

all

largest difference peak and hole: 0.231/–0.184 eÅ^–3.

[12] a) T.-H. Chan, P. Brownbridge, J. Am. Chem. Soc. 1980, 102,

3534b) G. A. Molander, K. O. Cameron, J. Am. Chem. Soc.

1993, 115, 830.

[13] For a review of 1,3-bis-silyl enol ethers, see: P. Langer, Synthe-

sis 2002, 441.

[14] D. Enders, F. Burkamp, J. Runsink, Chem. Commun. 1996, 609.

a) T.-H. Chan, P. Brownbridge, J. Chem. Soc., Chem. Commun.

1979, 578; b) S. J. Danishefsky, D. F. Harvey, G. Quallich, B. J.

Uang, J. Org. Chem. 1984, 49, 393.

[15] a) D. A. Evans, J. A. Murry, M. C. Kozlowski, J. Am. Chem.

Soc. 1996, 118, 5814; b) D. A. Evans, M. C. Kozlowski, J. A.

Murry, C. S. Burgey, K. R. Campos, B. T. Connell, R. J. Sta-

ples, J. Am. Chem. Soc. 1999, 121, 669. For related reactions,

see: c) J. Krüger, E. M. Carreira, J. Am. Chem. Soc. 1998, 120,

837, and references cited therein.

[16] a) S. J. Danishefsky, D. F. Harvey, G. Quallich, B. J. Uang, J.

Org. Chem. 1984, 49, 393; b) reviews: K. A. Jorgensen, Angew.

Chem. 2000, 112, 3702; Angew. Chem. Int. Ed. Engl. 2000, 39,

3558; c) S. J. Danishefsky, M. T. Bilodeau, Angew. Chem. 1996,

108, 1482; Angew. Chem. Int. Ed. Engl. 1996, 35, 1380; d) M. D.

Bednarski, J. P. Lyssikatos, Comprehensive Organic Synthesis:

Selectivity, Strategy and Efficiency in Modern Organic Chemis-

try (Ed.: B. M. Trost), 1991, 2, 661.

Crystal Data for 4r:^[29]C₁₂H₁₈O₄, Mr = 226.26 gmol^–1, colourless

prism, size 0.03×0.03×0.02 mm, triclinic, space group P1, a =

¯

8.8743(2), b = 10.1470(3), c = 13.5326(4) Å, α = 101.701(1), β =

95.436(1), γ = 91.924(1)°, V = 1186.14(6) Å³, T = –90 °C, Z = 4,

ρ_calcd.= 1.267 g cm^–3, μ(Mo-K_α) = 0.94 cm^–1, F(000) = 488, 8710

reflections in h(–11/11), k(–13/12), l(–17/16), measured in the range

2.05° Յ Θ Յ 27.46°, completeness Θ_max= 99.2%, 5390 indepen-

dent reflections, R_int= 0.020, 3883 reflections with F_oϾ 4σ(F_o),

297 parameters, 0 restraints, R1_obs= 0.056, wR²= 0.138, R1_all

obs

= 0.083, wR²= 0.155, GOOF = 1.027, largest difference peak

all

and hole: 0.523/–0.304 eÅ^–3.

Crystal Data for 4v:^[29]C₁₈H₂₈O₄·1/6C₆H₁₄, Mr = 322.41 gmol^–1,

colourless prism, size 0.03×0.03×0.02 mm, hexagonal, space

group P6(5), a = 21.1201(4), b = 21.1201(4), c = 6.7753(2) Å, V =

2617.3(1) Å³, T = –90 °C, Z = 6, ρ_calcd.= 1.220 g cm^–3, μ(Mo-K_α)

= 0.84 cm^–1, F(000) = 1044, 6661 reflections in h(–27/27), k(–23/

21), l(–6/8), measured in the range 1.93° Յ Θ Յ 27.46°, complete-

ness Θ_max= 99.9%, 3574 independent reflections, R_int= 0.036,

2704 reflections with F_oϾ 4σ(F_o), 208 parameters, 1 restraints,

R1_obs= 0.056, wR²_obs= 0.140, R1_all= 0.082, wR²_all= 0.155, GOOF

= 1.054, Flack parameter 0.2(15) (the absolute structures could not

[17] P. Brownbridge, T.-H. Chan, M. A. Brook, G. J. Kang, Can. J.

Chem. 1983, 61, 688.

Eur. J. Org. Chem. 2005, 2074–2090

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E. Bellur, H. Görls, P. Langer

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[25] COLLECT, Data Collection Software; B. V. Nonius, Nether-

lands, 1998.

[26] Z. Otwinowski, W. Minor, “Processing of X-ray Diffraction

Data Collected in Oscillation Mode”, in Methods in Enzy-

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(Eds.: C. W. Carter, R. M. Sweet), pp. 307–326, Academic

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[27] G. M. Sheldrick, Acta Crystallogr. Sect. A 1990, 46, 467.

[28] G. M. Sheldrick, SHELXL-97 (Release 97–2), University of

Göttingen, Germany, 1997.

[29] CCDC-230692 (for 4g), -230693 (for 4q), and -230694 (for 4u)

contain the supplementary crystallographic data for this paper.

These data can be obtained free of charge from The Cambridge

Crystallographic Data Centre via www.ccdc.cam.ac.uk/

data_request/cif.

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4-methoxy-2-alkylidenetetrahydrofurans by palladium-cata-

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[24] For the synthesis of 2-vinyl-2,3,3a,4,5,6-hexahydro-2,3-benzo-

furans by cyclization of dianions with 1,4-dibromo-2-butene,

Received: November 10, 2004

2090

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Eur. J. Org. Chem. 2005, 2074–2090

Article Doi

Regioselective synthesis of functionalized furans by cyclization of 1,3-bis-silyl enol ethers with 1-chloro-2,2-dimethoxyethane

DOI: 10.1002/ejoc.200400805

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