Synthesis of dihydropyrans and dihydrofurans via radical cyclization of unsaturated alcohols and 1,3-dicarbonyl compounds

Article abstract of DOI:10.1002/hlca.201300229

The oxidative cyclization reactions of 1,3-dicarbonyl compounds 1a-1c and α,β-unsaturated alcohols 2a-2f with Mn(OAc)₃ were performed, leading to dihydrofurans. Treatment of 1a and 1b with 2-methylbut-3-en-2-ol (2a) gave dihydrofurans 3aa and 3ba, and dihydropyrans 4aa and 4ba, as unexpected products. While the reaction of 2-methylbut-3-yn-2-ol (2b) with acetylacetone (1b) yielded a bifuran, ethyl acetoacetate (1a) led to a mixture of furan, bifuran, and salicylate derivatives. Besides, surprisingly, styryl-substituted dihydrofurans were obtained from the reactions of 1,3-dicarbonyl compounds and (3E)-2,4-diphenylbut-3-en-2-ol. The reaction mechanisms were proposed for the formation of the different products, considering intermediates in these reaction mixtures. Copyright

Full text of DOI:10.1002/hlca.201300229

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Helvetica Chimica Acta – Vol. 97 (2014)
Synthesis of Dihydropyrans and Dihydrofurans via Radical Cyclization of
Unsaturated Alcohols and 1,3-Dicarbonyl Compounds
by Hakan Aslan*a), Deniz E. Akpınara), Atilla ꢀktemera), Mehtap Yakuta), and Og˘uzhan Alagçzb)
a) Department of Chemistry, Faculty of Science, Ankara University, TR-06100 Tandogan, Ankara
(phone: þ 90-312-2126720; fax: þ 90-312-2232395; e-mail: hakaslan@gmail.com)
b) Department of Chemical Engineering, Faculty of Engineering, Afyon Kocatepe University,
TR-03200 Afyonkarahisar
The oxidative cyclization reactions of 1,3-dicarbonyl compounds 1a – 1c and a,b-unsaturated
alcohols 2a – 2f with Mn(OAc)3 were performed, leading to dihydrofurans. Treatment of 1a and 1b with
2-methylbut-3-en-2-ol (2a) gave dihydrofurans 3aa and 3ba, and dihydropyrans 4aa and 4ba, as
unexpected products. While the reaction of 2-methylbut-3-yn-2-ol (2b) with acetylacetone (1b) yielded a
bifuran, ethyl acetoacetate (1a) led to a mixture of furan, bifuran, and salicylate derivatives. Besides,
surprisingly, styryl-substituted dihydrofurans were obtained from the reactions of 1,3-dicarbonyl
compounds and (3E)-2,4-diphenylbut-3-en-2-ol. The reaction mechanisms were proposed for the
formation of the different products, considering intermediates in these reaction mixtures.
Introduction. – Dihydrofurans form the basic structure of many natural compounds,
and they possess a wide range of biological activities [1]. These compounds are
synthesized easily by cyclization of a 1,3-dicarbonyl compound with an unsaturated
system mediated by transition metal salts (Mn3þ, Ce4þ, Agþ, etc.). Among these metal
salts, Mn(OAc)3 [2] and [(NH4)2Ce(NO3)6][3] are widely used in organic synthesis for
the formation of CꢀC bonds.
Radical cyclizations of unsaturated alcohols and 1,3-dicarbonyl compounds in
Mn(OAc)3- and [(NH4)2Ce(NO3)6]-mediated reactions were rarely studied, mainly
based on natural product synthesis [4]. The aim of this study on radical cyclizations of
unsaturated alcohols and 1,3-dicarbonyl compounds was the synthesis of dihydrofurans
which commonly have biological activity. Further, dihydropyrans, bifuran, styryl ((E)-
2-phenylethenyl)-substituted dihydrofurans, and salicylate derivatives were obtained
from the same reactions.
Dihydropyrans also widely occur in natural products with various biological
activities [5], and, therefore, numerous methods have been reported for the synthesis of
functionalized pyran ring systems [6]. Frequently used methods are hetero DielsꢀAlder
cycloadditions [7], ring-expansion reactions [8], intramolecular ring-opening reactions
[9], dioxanone Claisen rearrangements [10], and SN2 reactions [11]. In this study, we
synthesized dihydropyrans via cyclization of unsaturated alcohols and 1,3-dicarbonyl
compounds by treatment with Mn(OAc)3 as a new approach to these molecules.
Results and Discussion. – Reaction of 2-Methylbut-3-en-2-ol (2a) with 1a and 1b in
the Presence of Mn(OAc)3, Synthesis of Dihydrofurans and Dihydropyrans. We initially
ꢀ 2014 Verlag Helvetica Chimica Acta AG, Zꢁrich

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examined the reactions of ethyl acetoacetate (1a) and acetylacetone (1b) with 2-
methylbut-3-en-2-ol (2a), which furnished 2,3-dihydrofurans, 3aa and 3ba, and
dihydropyrans, 4aa and 4ba (Table 1). The reaction mechanism for the formation of
these compounds are proposed in Scheme 1. The interaction of the MnIIIꢀenolate
complex and 2a affords the C-radical A, which is subsequently oxidized with Mn(OAc)3
to give the corresponding carbocation B, as usually observed in similar reactions of 1,3-
dicarbonyl compounds or 3-oxopropanenitriles with alkenes [12]. Cyclization of B
gives dihydrofuran 3 via pathway i or affords oxirane cation C via pathway ii. Similarly,
3 can be produced via pathway iii. Via pathway iv, ring opening of the oxirane leads to
the more stable carbocation D, and dihydropyran 4 forms after the cyclization.
1
Compounds 3 and 4 were distinguished by H- and 13C-NMR spectroscopy [13].
The CH2(4) and HꢀC(5) of dihydrofuran resonated at lower field than those of
Table 1. Radical Cyclization of 1a and 1b with 2a
a
Entry
1
1,3-Dicarbonyl compounds
X
1/2a/Mn(OAc)3
)
Products
Yield [%]
1a
EtO
2 : 2 : 4.4
3aab)
4aa
3ba
35
20
26
14
2
1b
Me
2.5 : 2 : 5.5
4ba
a) Molar ratio. b) 3aa was synthesized by another method [14].
Scheme 1. Proposed Mechanism for the Formation of Dihydrofurans and Dihydropyrans

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dihydropyran in the 1H-NMR spectra. Similarly, the C(5) of dihydrofuran resonated at
lower field than C(6) of dihydropyran in the 13C-NMR spectra.
Of the compounds obtained, CH2(4) of 4aa and 3aa resonate at 2.35 – 2.59 and
2.76 – 2.84 ppm, respectively. Apart from that, HꢀC(5) of 4aa and 3aa resonates at 3.64
and 4.44 ppm, respectively. In the 13C-NMR spectrum, the signal of C(6) of 4aa appears
at 78.2 ppm, and C(5) of 3aa resonates at 88.5 ppm.
Reaction of 2-Methylbut-3-yn-2-ol (2b) with 1a and 1b in the Presence of Mn(OAc)3,
Synthesis of Furan, Bifurans, and Salicylate Derivatives. The Mn(OAc)3-mediated
reaction of 2b with 1a and 1b gave bifurans 6ab and 6bb, respectively, in low yields
(Table 2). The mechanism proposed for the formation of compounds 6 (Path i) is
outlined in Scheme 2. First, the C-radical E is formed from 2b and the MnIIIꢀenolate
complex. Oxidation of E may generate carbocation F, and furan G is formed by
subsequent cyclization of F. The dehydration of G leads to an alkene intermediate of
type 5, which, in the case of 5ab, was isolated from the reaction mixture of 1a and 2b by
terminating the reaction at the half of the reaction time. Finally, bifuran 6 is formed by
the reaction of the 1,3-dicarbonyl compound and 5 with 2 equiv. of Mn(OAc)3.
The reaction of 2-methylbut-1-en-3-yne, the dehydrated product of 2b, with 1a and
Mn(OAc)3/Cu(OAc)2 gave ethyl 5-ethynyl-2,5-dimethyl-4,5-dihydrofuran-3-carboxyl-
ate (11; 51%) and bifuran-dicarboxylate 6ab (6%) reported by Melikyan et al. in 1982
(Scheme 3) [15]. In our study, inability to obtain 11 from the performed reactions
established that dehydration step occurs after the first intramolecular cyclization. In
addition, the isolation of the intermediate product 5ab from the reaction of 1a and 2b
with Mn(OAc)3 supported our proposed mechanism.
The Mn(OAc)3-mediated reaction of 1a with 2-methylbut-3-yn-2-ol (2b) gave also
small amounts of salicylate derivatives 7ab and 8ab (Table 2). The mechanism
proposed for the formation of salicylate derivatives (Path ii) is depicted in Scheme 2.
Table 2. Radical Cyclization of 1a and 1b with 2b
Entry
1
1,3-Dicarbonyl compounds
X
Intermediates
Products
Yield [%]
1a
EtO
5ab
7ab
–
6ab
8ab
6bb
13
3
16
2
1b
Me

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Scheme 3. Reaction of 2-Methylbut-1-en-3-yne, Dehydrated Form of 2b, with 1a
The interaction of E and acetic acidꢀenolateꢀMnIII complex affords acid intermediate
product H, which may be decarboxylated with Mn(OAc)3 to give C-radical I.
Cyclization of J, which is another enol form of I, gives cyclic C-radical K, followed by
aromatization of K in the presence of Mn(OAc)3 leading to product L. Dehydration of
L gives the alkene intermediate 7ab, which was isolated from the reaction mixture by
terminating the reaction at the half of the reaction time. Then, 8ab is formed by radical
cyclization of 7ab and 1a mediated by Mn(OAc)3. Decarboxylation [16] and
aromatization [17] steps via reaction with Mn(OAc)3 are known.
In the NMR spectra of 7ab and 8ab, the signals in the range of 6.9 – 7.8 ppm
(1H-NMR) and 112 – 161 ppm (13C-NMR) establish the presence of an aromatic
structure.
Reaction of 2c – 2e with 1a – 1c in the Presence of Mn(OAc)3, Synthesis of
Dihydrofurans. From the reactions of 1,3-dicarbonyl compounds with allylic alcohols
mediated by Mn(OAc)3, dihydrofurans were obtained in moderate yields (Table 3).
The value of the coupling constant 3J(4,5) in tetrasubstituted 4,5-dihydrofurans
obtained from the reactions of 1,2-disubstituted alkene is in the range of 4.0 – 6.8.
Therefore, these compounds are cis-isomers [18].
Table 3. Radical Cyclization of 1a – 1c with 2c – 2e
a
Entry
1
R1
R2
2
R3
R4
R5
1/2/Mn(OAc)3
)
Products
Yield [%]
1
2
3
1a
1b
1c
Me
Me
Me
EtO
Me
Ph
2c
2c
2c
Me
Me
Me
Me
Me
Me
H
H
H
2.5 : 3 : 5
2 : 4 : 5
2 : 2 : 4.4
3ac
3bc
3cc
9cc
3ad
3bd
3cd
9cd
3ae
3be
42
20
14
7
35
38
18
16
25
25
4
5
6
1a
1b
1c
Me
Me
Me
EtO
Me
Ph
2d
2d
2d
Ph
Ph
Ph
H
H
H
H
H
H
2 : 1 : 3
2 : 1 : 3
3 : 1 : 3
7
8
1a
1b
Me
Me
EtO
Me
2e
2e
Ph
Ph
H
H
Me
Me
2.5 : 5 : 5
3 : 1 : 3
a) Molar ratio.

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The 1H-NMR spectrum of 3be in CDCl3 was examined; it was observed that Hb and
Hc (cf. Fig.) did not couple. It is assumed that this results from a rigid structure as a
consequence of the C¼O and OH groups forming a H-bond, and positioning Hb and Hc
1
at nearly 908 angle. In (D6)acetone or in CDCl3, the H-NMR spectra revealed that
these H-atoms were coupled or not (see also the COSY spectrum of 3be in
(D6)acetone and CDCl3 in the Figure).
Figure. Structure and COSY Spectra of 3be in (D6)acetone and CDCl3
Reaction of (3E)-2,4-Diphenylbut-3-en-2-ol (2f) with 1a – 1c in the Presence of
Mn(OAc)3, Synthesis of Styryl-Substituted Dihydrofurans. Unexpectedly, the reaction
of 2f with 1a – 1c did not give any HOCH2-substituted dihydrofurans, but styryl-
substituted dihydrofurans were obtained as the sole products (Table 4). A plausible
mechanism for the formation of these products is proposed in Scheme 4. According to
this mechanism, a diene is formed in situ from 2f, and it reacts with the MnIIIꢀenolate
complex to produce C-radical M, which is then oxidized to the carbocation N by
Mn(OAc)3, and intramolecular cyclization of N affords 10.
In 1H-NMR spectra of 10af and 10bf, the diastereotopic H-atoms at C(4), resonated
at 3.30 – 3.44 ppm (2J(H,H) ¼ 14.4 – 14.8). Besides, the Me at C(2) gave rise to a triplet
(5J(H,H) ¼ 1.6) through coupling with CH2(4).
Conclusions. – In this study, the free-radical cyclizations of 1,3-dicarbonyl
compounds and unsaturated alcohols mediated by Mn(OAc)3 were investigated.

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Table 4. Radical Cyclization of 1a – 1c with 2f
a
Entry
1,3-Dicarbonyl compounds
R1
R2
1/2/Mn(OAc)3
)
Products
Yield [%]
1
2
3
1a
1b
1c
Me
Me
Ph
EtO
Me
Me
1 : 1.25 : 2.5
1.25 : 1 : 2.5
2 : 1 : 2.5
10af
10bf
10cf
61
57
35
a) Molar ratio.
Scheme 4. Proposed Mechanism for the Formation of Styryl-Substituted Dihydrofurans
It is well-known that dihydrofurans and furans can be synthesized via the
Mn(OAc)3-mediated reactions of 1,3-dicarbonyl compounds, and alkenes and alkynes.
Using of unsaturated alcohols instead of alkenes/alkynes in these reactions led to the
formation of dihydropyrans, bifurans, and salicylate derivatives in low yields besides
dihydrofurans and furans. The cyclization of some unsaturated alcohols and 1,3-
dicarbonyl compounds with Mn(OAc)3 offers a new aproach for the dihydropyran
formation.
The mechanism for the formation of salicylate derivatives include oxidative
addition, formation of AcOHꢀenolateꢀMnIII complex, radical coupling, decarboxyla-
tion, cyclization, and aromatization steps. This is the first example including almost all
reaction types of Mn(OAc)3-mediated reactions.
Finally, synthesized dihydrofuran and dihydropyran derivatives were evaluated for
their antimicrobial activities against Gram-positive (e.g., Bacillus megaterium M22)
and Gram negative bacteria (e.g., Escherichia coli ATCC 25922). The antibacterial
activities were determined by the disc-diffusion method and minimum inhibition
concentration (MIC) against Gram-positive and Gram-negative bacteria. All the

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bacteria were studied against to antibiotics such as ampicillin and penicillin to compare
with our productsꢂ zone diameters. Antibiogram test of our new compounds showed
better results than some known antibiotics.
˘
˘
We are grateful to Prof. Elif Logoglu, Laboratory of Biochemistry, Faculty of Science, Gazi
University, Turkey, for antimicrobial activity test.
Experimental Part
General. 1,3-Dicarbonyl compounds 1a – 1c and unsaturated alcohols 2a – 2d are commercially
available, and they were used in highest purity. (3E)-4-Phenylbut-3-en-2-ol (2e) was prepared by the
reduction of benzylideneacetone with NaBH4 as described in [19]. (3E)-2,4-Diphenylbut-3-en-2-ol (2f)
was prepared by the reaction of PhMgBr and benzylideneacetone in E2O as described in [20]. TLC:
Merck Al-packed silica gel (SiO2) plates. Prep. TLC: SiO2 PF254 – 366 nm (Merck). Column chromatography
(CC): SiO2 (Merck 60, 40 – 60 mm). M.p.: Electrothermal cap. melting-point apparatus. IR Spectra:
PerkinElmer Spectrum 100 FT-IR in the 400 – 4000-cmꢀ1 range with 4-cmꢀ1 resolution; in KBr or CHCl3;
.
˜n in cmꢀ1 1H- and 13C-NMR spectra: Varian Mercury-400 high performance digital FT-NMR
spectrophotometer; d in ppm rel. to Me4Si as internal standard, J in Hz. MS: Waters 2695 Alliance
Micromass ZQ LC/ESI-MS spectrometer and Agilent Technologies 6890 N Network GC/MS System; in
m/z (rel. %). Elemental analyses: Leco CHNS-932 instrument; in %.
Synthesis of 2e [19]. In a round-bottomed 250-ml flask equipped with a condenser and magnetic
stirrer, benzylideneacetone (5.00 g, 34.25 mmol) was dissolved in EtOH (80 ml). Then, NaBH4 (1.30 g;
34.25 mmol) was added. The mixture was stirred at r.t. for 5 min, and the reaction progress was
monitored by TLC. After completion of the reaction, the mixture was filtered through a pad of Celite, and
the filtrate was concentrated under reduced pressure. The product was purified by CC (hexane/AcOEt
3 :1): 4.28 g (84%) of 2e; m.p. 318 ([19]: 30 – 318).
Synthesis of 2f [20]. A soln. of benzylideneacetone 2.92 g, (20 mmol) in Et2O (10 ml) was added
dropwise to a soln. of PhMgBr at 08 in dried Et2O (20 ml). The mixture was heated at reflux for 2 h and
then hydrolyzed with sat. aq. NH4Cl soln. in an ice-salt bath, and the soln. was extracted with Et2O (3 ꢁ
20 ml). The combined org. layers were washed with H2O and brine, and dried (Na2SO4). The product was
purified by CC (hexane/AcOEt 3 :1): 2.33 g (52%) of 2f; m.p. 56 – 588 ([20]: 588).
General Procedure for the Reactions of 1,3-Dicarbonyl Compounds with Unsaturated Alcohols. A
soln. of Mn(OAc)3 · H2O in glacial AcOH was heated under N2 at 808 until it dissolved. Then, a soln. of
1,3-dicarbonyl compound and unsaturated alcohol in glacial AcOH (5 ml) was added to the mixture. The
reaction was complete when the dark brown color of the soln. disappeared. H2O was added to the
mixture, which was extracted with CHCl3 (3 ꢁ 20 ml). The combined org. layers were neutralized with
sat. aq. NaHCO3 soln., washed with H2O, dried (Na2SO4), and evaporated to give an oil. Products were
purified by CC (SiO2) or prep. TLC (SiO2), eluating with hexane/AcOEt mixtures.
Ethyl 4,5-Dihydro-5-(1-hydroxy-1-methylethyl)-2-methylfuran-3-carboxylate (3aa). Colorless oil. IR
1
(KBr): 3473 (OH), 2982 – 2940 (CH), 1732 (C¼O), 1648 (C¼C). H-NMR (400 MHz, CDCl3): 1.18 (s,
3 H); 1.25 (s, 3 H); 1.28 (t, J ¼ 7.2, 3 H); 2.20 (t, J ¼ 1.6, 3 H); 2.76 (ddq, J ¼ 14.4, 9.6, 1.6, H); 2.84 (ddd,
J ¼ 14.4, 10.8, 1.6, H); 4.16 (q, J ¼ 7.2, 2 H); 4.44 (dd, J ¼ 10.4, 9.2, 1 H). 13C-NMR (100 MHz, CDCl3):
14.2; 14.6; 23.8; 25.6; 31.0; 59.8; 72.0; 88.5; 102.8; 166.3 (C¼O); 167.8 (C(2)). MS: 214 (60, Mþ), 181 (88,
[M ꢀ Me ꢀ H2O]þ), 169 (53, [M ꢀ C2H5O]þ), 156 (100, [M ꢀ C3H6O]þ), 127 (9, [M ꢀ C5H11O]þ), 59 (77,
C3H7Oþ), 43 (88, C2H3Oþ), 29 (23, C2H5þ).
Ethyl 3,4-Dihydro-3-hydroxy-2,2,6-trimethyl-2H-pyran-5-carboxylate (4aa). White solid. M.p. 618.
IR (KBr): 3464 (OH), 2977 – 2941 (CH), 1684 (C¼O), 1610 (C¼C). 1H-NMR (400 MHz, CDCl3): 1.25 (s,
3 H); 1.28 (s, 3 H); 1.28 (t, J ¼ 7.2, 1 H); 1.80 (s, 1 H); 2.24 (d, J ¼ 1.6, 3 H); 2.35 (ddd, J ¼ 17.2, 5.6, 1.2,
1 H); 2.59 (ddd, J ¼ 17.2, 5.2, 1.6, 1 H); 3.62 – 3.67 (m, 1 H); 4.15 (q, J ¼ 7.2, 2 H). 13C-NMR (100 MHz,
CDCl3): 14.6; 20.6; 22.0; 24.9; 28.8; 60.0; 69.2; 78.2; 97.7; 163.4 (C(2)); 168.5 (C¼O). MS: 214 (34, Mþ),
169 (25, [M ꢀ C2H5O]þ), 143 (100, [M ꢀ C4H7O]þ), 97 (100, C6H9Oþ), 72 (42, C4H8Oþ), 43 (50,
C2H3Oþ), 29 (9, C2H5þ ). Anal. calc. for C11H18O4 (214.2582): C 61.66, H 8.47; found: C 61.48, H 8.25.

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1-[4,5-Dihydro-5-(1-hydroxy-1-methylethyl)-2-methylfuran-3-yl]ethanone (3ba). Colorless oil. IR
1
(KBr): 3418 (OH), 2981 – 2939 (CH), 1738 (C¼O), 1606 (C¼C). H-NMR (400 MHz, CDCl3): 1.19 (s,
3 H); 1.27 (s, 3 H); 2.0 (s, 1 H); 2.22 (s, 3 H); 2.24 (t, J ¼ 1.2, 3 H); 2.81 – 2.93 (m, 2 H); 4.46 (dd, J ¼ 9.2,
8.8, 1 H). 13C-NMR (100 MHz, CDCl3): 15.2; 24.0; 25.7; 29.7; 31. 71.9; 88.6; 113.1; 167.7 (C(2)); 194.8
(C¼O). MS: 184 (8, Mþ), 151 (13, [M ꢀ Me ꢀ H2O]þ), 111 (66, [M ꢀ C4H9O]þ), 59 (37, C3H7Oþ), 43
(100, C2H3Oþ). Anal. calc. for C10H16O3 (184.2322): C 65.19, H 8.75; found: C 64.95, H 8.58.
1-(3,4-Dihydro-3-hydroxy-2,2,6-trimethyl-2H-pyran-5-yl)ethanone (4ba). White solid. M.p. 92 – 938.
IR (KBr): 3348 (OH), 2992 – 2932 (CH), 1660 (C¼O), 1558 (C¼C). 1H-NMR (400 MHz, CDCl3): 1.27 (s,
3 H); 1.29 (s, 3 H); 1.84 (d, J ¼ 6.8, 1 H); 2.22 (t, J ¼ 1.6, 3 H); 2.23 (s, 3 H); 2.39 (ddd, J ¼ 16.4, 6.0, 1.2,
1 H); 2.64 (ddd, J ¼ 16.0, 5.2, 1.2, 1 H); 3.7 (q, J ¼ 6.0, 1 H). 13C-NMR (100 MHz, CDCl3): 21.5; 21.8; 25.0;
29.9; 30.0; 69.3; 78.1; 106.5; 163.2 (C(2)); 198.9 (C¼O). MS: 184 (14, Mþ), 151 (7, [M ꢀ Me ꢀ H2O]þ),
113 (44, [M ꢀ C4H7O]þ), 72 (37, C4H8Oþ), 43 (100, C2H3Oþ). Anal. calc. for C10H16O3 (184.2322): C
65.19, H 8.75; found: C 64.98, H 8.62.
Ethyl 2-Methyl-5-(1-methylethenyl)furan-3-carboxylate (5ab). Colorless oil. 1H-NMR (400 MHz,
CDCl3): 1.35 (t, J ¼ 7.2, 3 H); 2.00 (s, 3 H); 2.59 (s, 3 H); 4.29 (q, J ¼ 7.2, 2 H); 4.96 (s, 1 H); 5.47 (s, 1 H);
6.50 (s, 1 H).
Diethyl 2,3-Dihydro-2,5,5’-trimethyl-2,2’-bifuran-4,4’-dicarboxylate (6ab). Colorless oil. IR (KBr):
2981 – 2936 (CH), 1704 (C¼O), 1651 (C¼C). 1H-NMR (400 MHz, CDCl3): 1.29 (t, J ¼ 7.2, 3 H); 1.34 (t,
J ¼ 7.2, 3 H); 1.69 (s, 3 H); 2.20 (d, J ¼ 1.6, 3 H); 2.58 (s, 3 H); 2.83 (dd, J ¼ 14.8, 1.6, 1 H); 3.30 (dd, J ¼
14.4, 1.6, 1 H); 4.14 – 4.31 (m, 4 H); 6.58 (s, 1 H). 13C-NMR (100 MHz, CDCl3): 14.1; 14.5; 14.7; 14.9;
21.0; 40.9; 59.8; 60.4; 78.3; 101.5; 107.5; 114.3; 153.7; 164.1; 166.3; 167.6; 172.5. MS: 322 (28, Mþ), 276
(100, [M ꢀ C2H6O]þ), 231 (18, [M ꢀ C7H7]þ), 202 (41, [M ꢀ C9H12]þ), 43 (30, C3Hþ7 ).
1,1’-(2,3-Dihydro-2,5,5’-Trimethyl-2,2’-bifuran-4,4’-diyl)bis[ethanone] (6bb). Pale-yellow oil. IR
(KBr): 2989 – 2938 (CH), 1768 – 1714 (C¼O), 1681 – 1600 (C¼C). 1H-NMR (400 MHz, CDCl3): 1.72
(s, 3 H); 2.24 (t, J ¼ 1.2, 3 H); 2.25 (s, 3 H); 2.41 (s, 3 H); 2.60 (s, 3 H); 2.91 (dd, J ¼ 14.4, 1.6, 1 H); 3.37
(dd, J ¼ 14.0, 1.2, 1 H); 6.6 (s, 1 H). 13C-NMR (100 MHz, CDCl3): 14.8; 15.5; 25.8; 29.4; 29.7; 41.6; 83.4;
107.3; 112.0; 122.2; 153.5 (C(2’)); 159.1 (C(5)); 166.3 (C(5’)); 194.3 (C¼O); 194.9 (C¼O). MS: 262 (100,
Mþ), 219 (22, [M ꢀ MeCO]þ), 177 (33, [M ꢀ C5H9O]þ), 43 (83, MeCOþ). Anal. calc. for C15H18O4
(262.301): C 68.68, H 6.92; found: C 68.91, H 7.05.
Ethyl 2-Hydroxy-5-(1-methylethenyl)benzoate (7ab). Colorless oil. 1H-NMR (400 MHz, CDCl3):
1.43 (t, J ¼ 7.2, 3 H); 2.14 (d, J ¼ 0.8, 3 H); 4.43 (q, J ¼ 7.2, 2 H); 5.04 (t, J ¼ 1.2, 1 H); 5.30 (s, 1 H); 6.95 (d,
J ¼ 8.4, 1 H); 7.61 (dd, J ¼ 8.4, 2.4, 1 H); 7.92 (d, J ¼ 2.4, 1 H); 10.85 (s, 1 H). 13C-NMR (100 MHz,
CDCl3): 14.7; 22.1; 61.7; 111.6; 112.3; 117.6; 126.8; 132.6; 133.0; 142.0; 161.3; 170.5. LC/MS: 207 (100,
[M þ H]þ).
Ethyl 5-[3-(Ethoxycarbonyl)-4-hydroxyphenyl]-4,5-dihydro-2,5-dimethylfuran-3-carboxylate (8ab).
Colorless oil. 1H-NMR (400 MHz, CDCl3): 1.27 (t, J ¼ 7.2, 3 H); 1.44 (t, J ¼ 7.2, 3 H); 1.67 (s, 3 H); 2.29 (t,
J ¼ 1.6, 3 H); 3.03 (dd, J ¼ 14.4, 1.2, 1 H); 3.09 (dd, J ¼ 14.4, 1.6, 1 H); 4.16 (q, J ¼ 7.2, 2 H); 4.43 (q, J ¼ 7.2,
2 H); 6.98 (d, J ¼ 8.4, 1 H); 7.47 (dd, J ¼ 8.8, 2.4, 1 H); 7.81 (d, J ¼ 2.4, 1 H); 10.84 (s, 1 H). 13C-NMR
(100 MHz, CDCl3): 14.5; 14.6; 14.7; 29. 6; 44.5; 59.8; 61.8; 88.1; 101.6; 112.3; 118.0; 125.6; 132.3; 137.3;
161.1; 166.4; 166.6; 170.3. MS: 334 (7, Mþ), 288 (14, [M ꢀ C2H6O]þ), 242 (100, [M ꢀ C4H12O2]þ), 214 (18,
[M ꢀ C5H12O3]þ), 172 (20, [M ꢀ C6H12O4]þ), 43 (22, MeCOþ).
Ethyl 4,5-Dihydro-4-(hydroxymethyl)-2,5,5-trimethylfuran-3-carboxylate (3ac). Colorless oil. IR
1
(KBr): 3491 (OH), 2982 – 2939 (CH), 1739 (C¼O), 1635 (C¼C). H-NMR (400 MHz, CDCl3): 1.31 (t,
J ¼ 7.2, 3 H); 1.37 (s, 3 H); 1.39 (s, 3 H); 2.18 (d, J ¼ 1.6, 3 H); 2.96 (t, J ¼ 4.8, 1 H); 3.64 (s, 1 H); 3.73 (d,
J ¼ 5.6, 2 H); 4.21 (q, J ¼ 7.2, 2 H). 13C-NMR (100 MHz, CDCl3): 14.6; 15.5; 22.0; 29.3; 53.6; 60.2; 62.7;
88.3; 104.0; 168.0 (C¼O); 169.1 (C(2)). MS: 214 (5, Mþ), 183 (100, [M ꢀ MeO]þ), 110 (53, [M ꢀ
C4H8O3]þ), 43 (53, C3H7þ). Anal. calc. for C11H18O4 (214.2582): C 61.66, H 8.47; found: C 61.78, H 8.61.
1-[4,5-Dihydro-4-(hydroxymethyl)-2,5,5-trimethylfuran-3-yl]ethanone (3bc). Colorless oil. IR
1
(KBr): 3472 (OH), 2977 – 2936 (CH), 1741 (C¼O), 1602 (C¼C). H-NMR (400 MHz, CDCl3): 1.34 (s,
3 H); 1.38 (s, 3 H); 2.25 (d, J ¼ 0.8, 3 H); 2.36 (s, 3 H); 3.02 (ddd, J ¼ 8.0, 3.6, 0.8, 1 H); 3.62 (dd, J ¼ 10.4,
8.0, 1 H); 3.69 (d, J ¼ 10.4, 1 H); 4.57 (s, 1 H). 13C-NMR (100 MHz, CDCl3): 16.9; 22.1; 29.0; 29.7; 54.3;
63.3; 88.4; 117.9; 169.3 (C(2)); 196.6 (C¼O). MS: 184 (4, Mþ), 151 (4, [M ꢀ Me ꢀ H2O]þ), 111 (54, [M ꢀ
C4H9O]þ), (100, MeCOþ). Anal. calc. for C10H16O3 (184.2322): C 65.19, H 8.75; found: C 65.32, H 8.82.

Helvetica Chimica Acta – Vol. 97 (2014)
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[4,5-Dihydro-4-(hydroxymethyl)-2,5,5-trimethylfuran-3-yl](phenyl)methanone (3cc). Pale-yellow
oil. IR (KBr): 3464 (OH), 3062 (arom. H), 2981 – 2939 (CH), 1721 (C¼O), 1600 (C¼C). 1H-NMR
(400 MHz, CDCl3): 1.40 (s, 3 H); 1.49 (s, 3 H); 1.61 (s, 3 H); 3.18 (dd, J ¼ 8.0, 4.0, 1 H); 3.73 (dd, J ¼ 10.4,
8.0, 1 H); 3.80 (dd, J ¼ 10.4, 3.2, 1 H); 4.72 (s, 1 H); 7.57 – 7.35 (m, 5 H). 13C-NMR (100 MHz, CDCl3):
16.8; 22.1; 28.9; 55.2; 63.5; 88.6; 116.8; 128.4; 128.7; 131.8; 141.1; 170.9 (C(2)); 196.4 (C¼O). MS: 246 (3,
Mþ), 216 (17, [M – CH2O]þ), 215 (17, [M – MeO]þ), 105 (100, C6H5COþ), 77 (26, C6H5þ), 28 (37, COþ).
Anal. calc. for C15H18O3 (246.3016): C 73.15, H 7.37; found: C 73.25, H 7.42.
1-[4,5-Dihydro-4-(hydroxymethyl)-5,5-dimethyl-2-phenylfuran-3-yl]ethanone (9cc). Pale-yellow oil.
1
IR (KBr): 3427 (OH), 3062 (arom. H), 2978 – 2934 (CH), 1718 (C¼O), 1614 – 1587 (C¼C). H-NMR
(400 MHz, CDCl3): 1.43 (s, 3 H); 1.51 (s, 3 H); 1.93 (s, 3 H); 3.18 (dd, J ¼ 8.4, 4.0, 1 H); 3.75 (dd, J ¼ 10.8,
8.4, 1 H); 3.82 (d, J ¼ 9.6, 1 H); 4.70 (s, 1 H); 7.53 – 7.46 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 22.0;
28.7; 29.0; 55.3; 63.7; 89.1; 119.0; 128.8; 129.4; 131.3; 131.4; 169.4 (C(2)); 198.5 (C¼O). MS: 246 (4, Mþ),
216 (33, [M ꢀ CH2O]þ), 215 (73, [M ꢀ MeO]þ), 173 (38, [M ꢀ C4H9O]þ), 105 (54, C6H5COþ), 77 (33,
C6H5þ), 43 (100, MeCOþ), 27 (57, C2Hþ3 ). Anal. calc. for C15H18O3 (246.3016): C 73.15, H 7.37; found: C
73.32, H 7.48.
Ethyl 4,5-Dihydro-4-(hydroxymethyl)-2-methyl-5-phenylfuran-3-carboxylate (3ad). Colorless oil. IR
(KBr): 3455 (OH), 3065 – 3034 (arom. H), 2982 – 2939 (CH), 1738 (C¼O), 1695 – 1645 (C¼C). 1H-NMR
(400 MHz, CDCl3): 1.30 (t, J ¼ 7.2, 3 H); 2.32 (d, J ¼ 1.2, 3 H); 3.11 (s, 1 H); 3.35 (q, J ¼ 5.6, 1 H); 3.79 (dd,
J ¼ 10.0, 4.4, 1 H); 3.85 (dd, J ¼ 10.8, 5.6, 1 H); 4.16 – 4.24 (m, 2 H); 5.32 (d, J ¼ 6.4, 1 H); 7.39 – 7.30 (m,
5 H). 13C-NMR (100 MHz, CDCl3): 14.6; 15.0; 54.1; 60.3; 65.3; 86.4; 103.2; 125.7; 128.5; 129.0; 141.1;
167.0 (C(2)); 170.2 (C¼O). MS: 262 (4, Mþ), 231 (100, [M ꢀ MeO]þ), 158 (43, [M ꢀ C4H8O3]þ), 77 (12,
C6Hþ5 ), 43 (49, C3H7þ). Anal. calc. for C15H18O4 (262.301): C 68.68, H 6.92; found: C 68.55, H 6.78.
1-[4,5-Dihydro-4-(hydroxymethyl)-2-methyl-5-phenylfuran-3-yl]ethanone (3bd). Colorless oil. IR
(KBr): 3413 (OH), 3064 – 3032 (arom. H), 2983 – 2939 (CH), 1741 (C¼O), 1617 (C¼C). 1H-NMR
(400 MHz, CDCl3): 2.36 (s, 3 H); 2.37 (d, J ¼ 1.2, 3 H); 3.41 (q, J ¼ 5.6, 1 H); 3.74 (dd, J ¼ 10.4, 4.8, 1 H);
3.80 (dd, J ¼ 10.4, 6.8, 1 H); 5.24 (d, J ¼ 6.8, 1 H); 7.39 – 7.28 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 16.3;
29.7; 54.6; 65.7; 86.3; 116.2; 125.7; 128.7; 129.0; 140.6; 167.0 (C(2)); 195.7 (C¼O). MS: 232 (8, Mþ), 202
(38, [M ꢀ CH2O]þ), 201 (100, [M ꢀ MeO]þ), 141 (21, [M ꢀ C7H7]þ), 77 (11, C6Hþ5 ), 43 (100, MeCOþ).
Anal. calc. for C14H16O3 (232.275): C 72.39, H 6.94; found: C 72.27, H 6.78.
[4,5-Dihydro-4-(hydroxymethyl)-2-methyl-5-phenylfuran-3-yl](phenyl)methanone (3cd). Pale-yel-
low oil. IR (KBr): 3423 (OH), 3063 – 3033 (arom. H), 2926 – 2881 (CH), 1721 (C¼O), 1604 – 1571
1
(C¼C). H-NMR (400 MHz, CDCl3): 1.78 (d, J ¼ 1.2, 3 H); 3.59 (q, J ¼ 6.0, 1 H); 3.85 (d, J ¼ 6.4, 2 H);
3.97 (s, 1 H); 5.33 (d, J ¼ 6.0, 1 H); 7.59 – 7.34 (m, 10 H). 13C-NMR (100 MHz, CDCl3): 16.3; 55.2; 65.6;
86.4; 115.1; 125.8; 128.4; 128.7; 129.1; 131.9; 140.5; 140.7; 170.6 (C(2)); 195.3 (C¼O). LC/MS: 295 (100,
[M þ H]þ). Anal. calc. for C19H18O3 (294.3444): C 77.53, H 6.16; found: C 77.44, H 5.97.
1-[4,5-Dihydro-4-(hydroxymethyl)-2,5-diphenylfuran-3-yl]ethanone (9cd). Pale-yellow oil. IR
(KBr): 3421 (OH), 3063 – 3033 (arom. H), 2931 – 2878 (CH), 1740 (C¼O), 1622 – 1590 (C¼C).
1H-NMR (400 MHz, CDCl3): 1.97 (s, 3 H); 3.59 (td, J ¼ 6.8, 4.4, 1 H); 3.87 (dd, J ¼ 10.4, 4.4, 1 H); 3.95
(dd, J ¼ 10.4, 7.6, 1 H); 5.34 (d, J ¼ 6.8, 1 H); 7.59 – 7.36 (m, 10 H). 13C-NMR (100 MHz, CDCl3): 29.2;
55.3; 66.5; 86.4; 117.6; 125.7; 128.8; 128.9; 129.1; 129.5; 130.9; 131.4; 140.5; 169.7 (C(2)); 197.4 (C¼O).
LC/MS: 295 (100, [M þ H]þ). Anal. calc. for C19H18O3 (294.3444): C 77.53, H 6.16; found: C 77.47, H 6.02.
Ethyl 4,5-Dihydro-4-(1-hydroxyethyl)-2-methyl-5-phenylfuran-3-carboxylate (3ae). Colorless oil. IR
(KBr): 3450 (OH), 3033 (arom. H), 2977 – 2932 (CH), 1695 (C¼O), 1652 (C¼C). 1H-NMR (400 MHz,
CDCl3): 1.21 (d, J ¼ 6.8, 3 H); 1.30 (t, J ¼ 7.2, 3 H); 2.34 (d, J ¼ 1.2, 3 H); 3.14 (s, 1 H); 3.34 (m, 1 H); 4.12
(qd, J ¼ 5.6, 2.0, 1 H); 4.16 – 4.24 (m, 2 H); 5.37 (d, J ¼ 5.2, 1 H); 7.38 – 7.27 (m, 5 H). 13C-NMR
(100 MHz, CDCl3): 14.6; 15.0; 19.6; 58.1; 60.3; 68.0; 84.8; 102.1; 125.7; 128.5; 129.0; 141.7; 167.0 (C(2));
170.4 (C¼O). MS: 276 (5, Mþ), 261 (4, [M ꢀ Me]þ), 232 (100, [M ꢀ C3H7]þ), 231 (100, [M ꢀ C3H8]þ), 77
(12, C6Hþ5 ), 43 (62, MeCOþ). Anal. calc. for C16H20O4 (276.3276): C 69.54, H 7.30; found: C 69.39, H 7.49.
1-[4,5-Dihydro-4-(1-hydroxyethyl)-2-methyl-5-phenylfuran-3-yl]ethanone (3be). Colorless oil.
1H-NMR (400 MHz, CDCl3): 1.16 (d, J ¼ 6.0, 3 H); 2.39 (s, 3 H); 2.40 (s, 3 H); 3.47 (d, J ¼ 5.6, 1 H);
1
4.01 (td, J ¼ 6.4, 1.2, 1 H); 4.07 (d, J ¼ 7.2, OH); 5.25 (d, J ¼ 5.6, 1 H); 7.39 – 7.26 (m, 5 H). H-NMR
(400 MHz, CDCl3 þ D2O): 1.15 (d, J ¼ 6.8, 3 H); 2.39 (s, 3 H); 2.40 (s, 3 H); 3.47 (dq, J ¼ 6.0, 1.2, 1 H);
4.00 (qd, J ¼ 6.0, 2.0, 1 H); 5.25 (d, J ¼ 5.6, 1 H); 7.39 – 7.25 (m, 5 H). 1H-NMR (400 MHz, (D6)acetone):

662
Helvetica Chimica Acta – Vol. 97 (2014)
1.14 (d, J ¼ 6.4, 3 H); 2.28 (s, 3 H); 2.36 (d, J ¼ 1.2, 3 H); 3.19 – 3.21 (m, 1 H); 4.07 – 4.11 (m, 1 H); 4.15 (d,
J ¼ 5.2, 1 H); 5.51 (d, J ¼ 4.8, 1 H); 7.40 – 7.29 (m, 5 H). 13C-NMR (100 MHz, CDCl3): 16.3; 19.2; 29.7;
58.6; 68.5; 85.5; 114.7; 125.6; 128.7; 129.1; 141.1; 170.4; 195.7. LC/MS: 247.3 (100, [M þ H]þ). Anal. calc.
for C15H18O3 (246.3016): C 73.15, H 7.37; found: C 72.87, H 7.53.
Ethyl 4,5-Dihydro-2-methyl-5-phenyl-5-[(E)-2-phenylethenyl]furan-3-carboxylate (10af). Yellow
oil. IR (KBr): 3084 (C¼CꢀH), 3059 – 3028 (arom. H), 2938 – 2905 (CH), 1697 (C¼O), 1654 (C¼C).
1H-NMR (400 MHz, CDCl3): 1.27 (t, J ¼ 7.2, 3 H); 2.35 (t, J ¼ 1.6, 3 H); 3.30 (dd, J ¼ 14.4, 1.6, 1 H); 3.39
(dd, J ¼ 14.8, 1.6, 1 H); 4.16 (q, J ¼ 7.2, 2 H); 6.45 (d, J ¼ 16.0, 1 H); 6.51 (d, J ¼ 16.0, 1 H); 7.45 – 7.21 (m,
10 H). 13C-NMR (100 MHz, CDCl3): 14.5; 14.7; 43.2; 59.8; 90.3; 101.8; 125.5; 127.0; 127.8; 128.2; 128.7;
128.8; 129.2; 132.6; 136.4; 144.2; 166.2; 166.6. MS: 334 (7, Mþ), 291 (46, [M ꢀ C3H7]þ), 261 (40, [M ꢀ
C3H5O2]þ), 218 (100, [M ꢀ C9H8]þ), 91 (12, C7H7þ ), 43 (28, C3Hþ7 ). Anal. calc. for C22H22O3
(334.4083): C 79.02, H 6.63; found: C 78.87, H 6.71.
1-{4,5-Dihydro-2-methyl-5-phenyl-5-[(E)-2-phenylethenyl]furan-3-yl}ethanone (10bf). Yellow oil.
IR (KBr): 3083 (C¼CꢀH), 3059 – 3027 (arom. H), 2922 (CH), 1714 (C¼O), 1600 (C¼C). 1H-NMR
(400 MHz, CDCl3): 2.20 (s, 3 H); 2.37 (t, J ¼ 1.6, 3 H); 3.35 (dq, J ¼ 14.4, 1.6, 1 H); 3.44 (dq, J ¼ 14.8, 1.6,
1 H); 6.45 (d, J ¼ 16.0, 1 H); 6.50 (d, J ¼ 16.0, 1 H); 7.19 – 7.44 (m, 10 H). 13C-NMR (100 MHz, CDCl3):
15.5; 29.7; 43.9; 90.4; 112.2; 125.5; 127.0; 128.0; 128.3; 128.8; 128.9; 129.4; 132.5; 136.3; 144.0; 166.3
(C(2)); 194.6 (C¼O). LC/MS: 305 (50, [M þ H]þ), 287 (100). Anal. calc. for C21H20O2 (304.3823): C
82.86, H 6.62; found: C 82.75, H 6.68.
1-{4,5-Dihydro-2,5-diphenyl-5-[(E)-2-phenylethenyl]furan-3-yl}ethanone (10cf). Yellow oil. IR
(KBr): 3083 (C¼CꢀH), 3060 – 3029 (arom. H), 2975 – 2927 (CH), 1717 (C¼O), 1634 – 1627 (C¼C).
1H-NMR (400 MHz, CDCl3): 1.95 (s, 3 H); 3.57 (d, J ¼ 15.6, 1 H); 3.66 (d, J ¼ 15.2, 1 H); 6.53 (d, J ¼ 16.0,
1 H); 6.59 (d, J ¼ 16.0, 1 H); 7.22 – 7.53 (m, 13 H); 7.64 – 7.66 (m, 2 H). 13C-NMR (100 MHz, CDCl3): 29.1;
44.3; 90.6; 114.7; 125.6; 127.1; 128.0; 128.3; 128.7; 128.85; 128.88; 129.6; 131.0; 131.2; 132.5; 136.4; 144.0;
165.0 (C(2)); 194.8 (C¼O). LC/MS: 367 (100, [M þ H]þ). Anal. calc. for C26H22O2 (366.4517): C 85.22, H
6.05; found: C 84.99, H 5.91.
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Received June 5, 2013