Synthesis of halogenated α,β-unsaturated γ-butyrolactone derivatives by triphenylphosphine-catalyzed cyclization of α-halogeno ketones with dialkyl acetylenedicarboxylates (=dialkyl but-2-ynedioates)

Article abstract of DOI:10.1002/hlca.201100376

A Ph₃P-catalyzed cyclization of α-halogeno ketones 2 with dialkyl acetylenedicarboxylates (=dialkyl but-2-ynedioates) 3 produced halogenated α,β-unsaturated γ-butyrolactone derivatives 4 in good yields (Scheme 1, Table). The presence of electro

Full text of DOI:10.1002/hlca.201100376

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Helvetica Chimica Acta – Vol. 95 (2012)
Synthesis of Halogenated a,b-Unsaturated g-Butyrolactone Derivatives by
Triphenylphosphine-Catalyzed Cyclization of a-Halogeno Ketones with
Dialkyl Acetylenedicarboxylates (¼ Dialkyl But-2-ynedioates)
by Sakineh Asghari* and Ahmad Khabbazi Habibi
Department of Chemistry, University of Mazandaran, Babolsar, Iran
(phone: þ 98-112-5342350; fax: þ 98-112-5246000; e-mail: s.asghari@umz.ac.ir)
A Ph3P-catalyzed cyclization of a-halogeno ketones 2 with dialkyl acetylenedicarboxylates
(¼dialkyl but-2-ynedioates) 3 produced halogenated a,b-unsaturated g-butyrolactone derivatives 4 in
good yields (Scheme 1, Table). The presence of electron-withdrawing groups such as halogen atoms at
the a-position of the ketones was necessary in this reaction. Cyclization of a-chloro ketones resulted in
higher yields than that of the corresponding a-bromo ketones. Dihalogeno ketones similarly afforded the
expected g-butyrolactone derivatives in high yields.
Introduction. – Several methods have been reported for the synthesis of a,b-
unsaturated g-butyrolactones [1 – 10]. In 1996, Nozaki and co-workers described a
Ph3P-catalyzed lactone formation from a-keto esters, a-ketonitriles, or a,a,a-trifluoro-
acetophenone and dialkyl acetylenedicarboxylate (¼dialkyl but-2-ynedioate) in
moderate to good yields [10]. a-Keto esters, a-ketonitriles, and a,a,a-trifluoroaceto-
phenone contain electron-withdrawing groups directly bound to their ketonic C¼O
group. The strong electrophilic nature of these ketonic groups is expected to facilitate
nucleophilic additions of zwitterion intermediates derived from Ph3P and dialkyl
acetylenedicarboxylates [11]. We were interested in the use of a-halogeno ketones as
trapping reagents for the zwitterionic intermediate. We reported the reaction of 1,1-
dichloroacetone (¼1,1-dichloropropan-2-one) and phenacyl chloride (¼2-chloro-1-
phenylethanone) as electron-deficient ketones with acetylenic esters in the presence of
Ph3P [12]. In that report, based on spectral data (1H- and 13C-NMR) and lack of X-ray
quality crystal, we suggested the halogenated 2H-oxete-3,4-dicarboxylates 1 as the
product of these reactions.
However, our complementary studies which, in part, are reported here show that
compound 4 as illustrated in Scheme 1, is the sole product of this reaction. In fact, by
NMR spectroscopy, structures 4 and 5 can hardly be distinguished. Thus, stronger
ꢀ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 95 (2012)
811
Scheme 1
evidence was required to confirm the definite structure of the product. In this regard,
we were motivated to use a variety of a-halogeno ketones as trapping reagents for the
zwitterionic intermediate. The spectral data (1H- and 13C-NMR) of the products,
together with a single-crystal X-ray analysis of compound 4d (Fig.), as will be discussed
below, established the formation of the halogenated a,b-unsaturated g-butyrolactone
derivatives 4a – 4r without formation of any 2H-oxete derivatives 5 (Scheme 1). In
addition, to further confirm the formation of a five-membered cyclic compound 4, the
resultant product was refluxed in toluene and xylene for 10 h. The analysis (monitored
by TLC) did not show any change in the product identity. Whereas, if a four-membered
cyclic compound 5 would have been formed, an electrocyclic ring opening should
readily take place under reflux conditions [13 – 17].
Figure. ORTEP Diagram of 4d. Arbitrary atom numbering.
Results and Discussion. – Initially, the reaction of chloroacetone (¼1-chloropro-
pan-2-one; 2a) and dimethyl acetylenedicarboxylate (3, R ¼ Me) with Ph3P was

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Helvetica Chimica Acta – Vol. 95 (2012)
examined at room temperature leading to 4a as the sole product in good yield after 2 h
(Table). To investigate the scope and limitations of this reaction further, we extended
our study to various a-halogeno ketones (Table). All the reactions ran well affording
the desired a,b-unsaturated g-butyrolactone derivatives 4a – 4r in good yields. The a-
chloro ketones were more reactive than the a-bromo ketones (cf. 4f vs. 4k in the Table).
The a,a-dichloro ketones reacted faster than a-chloro ketones and afforded the
expected products in higher yields (cf. 4c vs. 4a in the Table). These results imply that
the electron-withdrawing halogen atoms at the a-position with respect to the C¼O
group play an important role in the reaction. Moreover, the presence of this substituent
was essential for the reaction to proceed. a-Halogeno ketones with electron-donating
groups at the a-position gave lower yields of the expected g-butyrolactone darivative
(Table, 4i and 4j). In the case of a-bromo p-substituted-aryl ketones, the strong
electron-withdrawing NO2 group at the p-position of the aryl moiety resulted in high
yields of the product (Table, 4q and 4r). An interesting feature of this reaction is the
fact that all reactions afforded chemoselectively the desired a,b-unsaturated lactone
derivatives, and no phosphorus ylides were obtained. It is also of interest to note that
triphenyl or trimethyl phosphite in place of Ph3P gave complex mixtures without
formation of any a,b-unsaturated g-lactone derivative.
Table. Ph3P-Catalyzed Synthesis of g-Butyrolactones Derivatives 4 from a-Halogeno Ketones 2 and
Dialkyl Acetylenedicarboxylates 3 (alkyl ¼ R)
2 and 4
Z
X
Y
R
Yield [%]a)
Time [h]
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
Me
Me
Me
CH2Cl
CH2Cl
Ph
Ph
Ph
Me
Me
Ph
Ph
4-BrꢀC6H4
4-BrꢀC6H4
4-ClꢀC6H4
4-ClꢀC6H4
4-NO2ꢀC6H4
4-NO2ꢀC6H4
H
H
Cl
H
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
Br
Br
Me
Et
Me
Me
Et
Me
Me
Et
Me
Et
Me
Et
Me
Et
Me
Et
Me
Et
60
62
70b)
85
82
80b)
87
85
30
trace
50
52
62
60
56
55
80
78
2
2
1
1
1
2
1
1
3
3
2
3
2
2
2
2
H
Cl
Cl
Me
Me
H
H
H
H
H
H
H
H
1.5
1.5
a) Yield of isolated product 4. b) Reported previously [12].
A possible mechanism for the presented reaction is shown in Scheme 2. On the basis
of the well established chemistry of trivalent phosphorus nucleophiles [17 – 25], it is
reasonable to assume that the zwitterionic intermediate 6 results from an initial
addition of Ph3P to the dialkyl acetylenedicarboxylate. Then, intermediate 6 attacks the

Helvetica Chimica Acta – Vol. 95 (2012)
813
Scheme 2
C¼O group of the a-halogeno ketone which leads to the dipolar species 7. Intermediate
7 can either undergo attack at the C¼O group of the ester moiety to form the five-
membered cyclic dipolar species 8, followed by anionic 1,2-alkoxy migration and loss of
Ph3P to give 4 (Route a in Scheme 2), or undergo attack at the C¼C bond to form the
four-membered cyclic dipolar intermediate 9, followed by loss of Ph3P to afford 2H-
oxete derivatives 5 (Route b in Scheme 2).
The structures of 4a – 4q were deduced from their 1H- and 13C-NMR and IR spectra
as well as elemental analyses. The mass spectra of the a,b-unsaturated g-lactone
derivatives displayed molecular-ion peaks for the mono- and dihalogenated forms with
the appropriate m/z values for Mþ and [M þ 2]þ, and for Mþ, [M þ 2]þ, and [M þ 4]þ,
respectively. The 1H-NMR spectrum of 4a in CDCl3 exhibited a s at d(H) 1.67 for the
Me group, two s at d(H) 3.86 and 4.28 for the two MeO groups, and two d at d(H) 3.85
and 4.04 (2J ¼ 11.6 Hz) for the CH2Cl group. The 13C-NMR spectrum of 4a displayed

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Helvetica Chimica Acta – Vol. 95 (2012)
nine sharp lines in agreement with the proposed structure. The partial assignment of
these resonances is given in the Exper. Part. The mass spectrum of 4a exhibited the
molecular-ion peaks at m/z 234 (9, Mþ) and 236 (3, [M þ 2]þ) due to the presence of the
1
isotopes of Cl-atom (35Cl and 37Cl). The H- and 13C-NMR spectra of 4b – 4q were
similar to those of 4a, except for the data of the substituents at positions 2, 3, and 4,
which showed characteristic resonances in the expected spectral regions. Finally, the
structure of product 4d was confirmed unambiguously by a single-crystal X-ray analysis
(Fig.).
Conclusions. – In summary, we developed a highly efficient procedure for the
synthesis of fully substituted a,b-unsaturated g-butyrolactone derivatives involving
halogen atoms from various a-halogeno ketones and dialkyl acetylenedicarboxylate in
the presence of Ph3P. The present work provides new extentions of Ph3P-catalyzed
organic syntheses. Scope and limitation of the reaction are described. The simplicity of
the present procedure also makes it an interesting alternative to other approaches.
Experimental Part
General. Dialkyl acetylenedicarboxylates, Ph3P, chloroacetone (¼1-chloropropan-2-one), 1,1-
dichloroacetone (¼1,1-dichloropropan-2-one), 1,3-dichloroacetone (¼1,3-dichloropropan-2-one), 3-
chlorobutan-2-one, 2-chloroacetophenone (¼2-chloro-1-phenylethanone), 2,2-dichloroacetophenone
(¼2,2-dichloro-1-phenylethanone), 2-bromoacetophenone (¼2-bromo-1-phenylethanone), 2-bromo-4-
nitroacetophenone (¼2-bromo-1-(4-nitrophenyl)ethanone), 2-bromo-4-chloroacetophenone (¼2-bro-
mo-1-(4-chlorophenyl)ethanone) and 2,4-dibromoacetophenone (¼2-bromo-1-(4-bromophenyl)etha-
none) were purchased from Fluka and Merck and used without further purification. M.p.: Electro-
thermal-9100 apparatus. IR Spectra: Bruker-Vector-22 FT-IR spectrometer; n in cmꢀ1. 1H- and 13C-NMR
spectra: Bruker-DRX-400-Avance instrument; at 400.1 (1H) and 100.6 MHz (13C) in CDCl3; d in ppm rel.
to Me4Si as internal standard, J in Hz. MS: Finnigan-Mat-8430 mass spectrometer; ionization potential
70 eV; in m/z (rel. %). Elemental analyses: Heraeus-CHN-O-Rapid analyzer.
Compounds 4: General Procedure. Methyl 2-(Chloromethyl)-2,5-dihydro-4-methoxy-2-methyl-5-
oxofuran-3-carboxylate (4a). Typical procedure: To a magnetically stirred soln. of chloroacetone
(0.16 ml, 2 mmol) and dimethyl acetylenedicarboxylate (0.25 ml, 2 mmol) in CH2Cl2/Et2O 1:4 (10 ml)
was added Ph3P (0.26 g, 1 mmol) at r.t. over 10 min. The mixture was stirred for 2 h. The solvent was
evaporated and the residue purified by column chromatography (silica gel (SiO2 60, 70 – 230 mesh;
Merck), hexane/AcOEt 9 :1): 4a (0.33 g; 70%). White powder. M.p. 65 – 678. Rf (AcOEt/hexane 1:4) 0.6.
1
IR: 1772 and 1701 (C¼O), 1651 (C¼C). H-NMR: 1.67 (s, Me); 3.85 (d, 2J ¼ 11.6, CH); 3.86 (s, MeO);
4.04 (d, 2J ¼ 11.6, CH); 4.28 (s, MeO). 13C-NMR: 23.0 (Me); 48.6 (CH2Cl); 52.5, 60.1 (2 MeO); 83.4 (s,
C(Me)CH2Cl); 123.3 (OꢀC¼C); 150.1 (OꢀC¼C); 162.0, 165.2 (2 C¼O). MS: 236 (3, [M þ 2]þ), 234 (9,
Mþ ), 221 (3), 219 (100), 205 (5), 203 (14), 185 (100), 153 (91), 125 (14), 115 (80), 83 (32), 59 (17), 43
(38). Anal. calc. for C9H11ClO5 (234.49): C 46.07, H 4.73; found: C 45.85, H 4.66.
Ethyl 2-(Chloromethyl)-4-ethoxy-2,5-dihydro-2-methyl-5-oxofuran-3-carboxylate (4b): Yield 0.36 g
(68%). White powder. M.p. 53 – 558. Rf (AcOEt/hexane 1:4) 0.6. IR: 1774, 1703 (C¼O), 1652 (C¼C).
1H-NMR: 1.34 (t, 3J ¼ 7.2, Me); 1.38 (t, 3J ¼ 7.2, Me); 1.66 (s, Me); 3.85 (d, 2J ¼ 11.7, CH); 4.04 (d, 2J ¼ 11.7,
CH); 4.30 (q, 3J ¼ 7.2, CH2); 4.61 – 4.71 (m, CH2O). 13C-NMR: 13.4, 15.8, 23.0 (3 Me); 48.7 (CH2Cl); 61.6,
68.8 (2 CH2O); 83.6 (s, C(Me)CH2Cl); 127.4 (OꢀC¼C); 149.7 (OꢀC¼C); 161.6, 165.6 (2 C¼O). MS: 264
(11, [M þ 2]þ), 262 (34, Mþ), 218 (2), 216 (7), 203 (3), 201 (10), 183 (9), 139 (23), 130 (44), 111 (28), 97
(38), 83 (48), 77 (17), 69 (55), 57 (100), 43 (90). Anal. calc. for C11H15ClO5 (262.51): C 50.29, H 5.76;
found: C 50.15, H 5.69.
Methyl 2,2-Bis(chloromethyl)-2,5-dihydro-4-methoxy-5-oxofuran-3-carboxylate (4d): Yield 0.46 g
(85%). White powder. M.p. 114 – 1168. Rf (AcOEt/hexane 1:4) 0.5. IR: 1774 and 1730 (C¼O), 1652

Helvetica Chimica Acta – Vol. 95 (2012)
815
1
2
(C¼C). H-NMR: 3.87 (s, MeO); 4.00, 4.02 (AB d, J ¼ 11.6, 2 CH2Cl); 4.32 (s, MeO). 13C-NMR: 45.5
(CH2Cl); 52.5, 60.1 (2 MeO); 84.3 (s, C(CH2Cl)2); 119.0 (OꢀC¼C); 151.0 (OꢀC¼C); 161.4, 164.2 (2
C¼O). MS: 273 (9, [M þ 5]þ), 271 (43, [M þ 1 þ 2]þ), 269 (75, [M þ 1]þ), 235 (8), 233 (24), 221 (31), 219
(92), 189 (36), 187 (10), 161 (3), 159 (10), 143 (3), 141 (8), 114 (62), 103 (6), 101 (16), 83 (23), 59 (18),
51 (18), 49 (26). Anal. calc. for C9H10Cl2O5 (268.94): C 40.17, H 3.75; found: C 40.8, H 3.70.
Ethyl 2,2-Bis(chloromethyl)-4-ethoxy-2,5-dihydro-5-oxofuran-3-carboxylate (4e): Yield 0.49 g
(82%). White powder. M.p. 58 – 608. Rf (AcOEt/hexane 1:4) 0.5. IR: 1775 and 1701 (C¼O), 1649
(C¼C). 1H-NMR: 1.32 (t, 3J ¼ 7.2, Me); 1.37 (t, 3J ¼ 7.2, Me); 3.98, 4.00 (AB d, 2J ¼ 12.0, 2 CH2Cl); 4.28 (q,
3J ¼ 7.2, CH2O); 4.68 (q, 3J ¼ 7.2, CH2O). 13C-NMR: 14.0, 15.4 (2 Me); 46.0 (2 CH2Cl); 61.6, 68.8 (2
CH2O); 84.3 (s, C(CH2Cl)2); 120.1 (OꢀC¼C); 150.7 (OꢀC¼C); 161.0, 164.5 (2 C¼O). MS: 301 (2, [M þ
5]þ), 299 (12, [M þ 1 þ 2]þ), 297 (17, [M þ 1]þ), 265 (35), 263 (100), 226 (11), 213 (52), 191 (9), 189 (27),
157 (89), 129 (23), 111 (10), 97 (7), 73 (6). Anal. calc. for C11H14Cl2O5 (296.96): C 44.46, H 4.75; found: C
44.35, H 4.71.
Methyl 2-(Dichloromethyl)-2,5-dihydro-4-methoxy-5-oxo-2-phenylfuran-3-carboxylate (4g): Yield
0.51 g (77%). White powder. M.p. 92 – 948. Rf (AcOEt/hexane 1:4) 0.6. IR: 1782 and 1696 (C¼O), 1643
(C¼C). 1H-NMR: 3.85 (s, MeO); 4.31 (s, MeO); 7.01 (s, CHCl2); 7.38 – 7.44 (m, 3 arom. H); 7.50 – 7.54 (m,
2 arom. H). 13C-NMR: 52.6, 60.0 (2 MeO); 74.0 (CHCl2); 87.8 (s, C(CHCl2); 125.5 (OꢀC¼C); 125.6,
128.9, 129.3, 135.2 (arom. C); 148.7 (OꢀC¼C); 161.9, 164.9 (2 C¼O). MS: 334 (2, [M þ 4]þ), 332 (10,
[M þ 2]þ), 330 (19, Mþ), 319 (1), 317 (6), 315 (8), 303 (3), 301 (13), 299 (26), 287 (4), 285 (24), 283 (36),
279 (33), 277 (100), 264 (12), 262 (36), 247 (62), 299 (38), 219 (12), 217 (36), 201 (57), 183 (48), 173
(36), 153 (30), 115 (22), 105 (90), 83 (40), 77 (88). Anal. calc. for C14H12Cl2O5 (330.99): C 50.78, H 3.65;
found: C 50.67, H 3.60.
Ethyl 2-(Dichloromethyl)-4-ethoxy-2,5-dihydro-5-oxo-2-phenylfuran-3-carboxylate (4h): Yield
0.50 g (70%). White powder. M.p. 67 – 698. Rf (AcOEt/hexane 1:4) 0.6. IR: 1782 and 1696 (C¼O),
1643 (C¼C). 1H-NMR: 1.33 (t, 3J ¼ 7.2, Me); 1.41 (t, 3J ¼ 7.2, Me); 4.25 – 4.37 (m, CH2O); 4.60 – 4.80 (m,
CH2O); 7.01 (s, CHCl2); 7.38 – 7.42 (m, 3 arom. H); 7.52 – 7.54 (m, 2 arom. H). 13C-NMR: 14.0, 15.5 (2
Me); 61.9, 68.6 (2 CH2O); 74.1 (CHCl2); 87.1 (s, C(Ph)CHCl2); 125.5 (OꢀC¼C); 125.6, 128.8, 129.2, 135.3
(arom. C); 147.8 (OꢀC¼C); 161.6, 165.2 (2 C¼O). MS: 362 (1, [M þ 4]þ), 360 (6, [M þ 2]þ), 358 (9, Mþ),
317 (1), 317 (6), 315 (6), 313 (9), 275 (100), 219 (43), 201 (9), 187 (2), 173 (2), 129 (5), 105 (87), 77 (13).
Anal. calc. for C16H16Cl2O5 (359.01): C 53.50, H 4.49; found: C 53.41, H 4.45.
Methyl 2-(1-Chloroethyl)-2,5-dihydro-4-methoxy-2-methyl-5-oxofuran-3-carboxylate (4i): Yield
0.15 g (30%). White powder. M.p. 90 – 938. Rf (AcOEt/hexane 1:4) 0.5. IR: 1776 and 1693 (C¼O),
1644 and 1461 (C¼C). 1H-NMR: 1.38 (d, 3J ¼ 6.8, Me); 1.80 (s, Me); 3.88, 4.28 (2s, 2 MeO); 4.57 (q, 3J ¼
6.8, CH). 13C-NMR: 19.3, 23.4 (2 Me); 52.4 (CHCl); 59.7, 60.0 (2 MeO); 85.7 (s, C(Me)CH(Cl)Me);
124.7, 148.3 (OꢀC¼C); 161.9, 165.2 (2 C¼O). MS: 250 (8, [M þ 2]þ), 248 (22, Mþ), 235 (2), 233 (6), 218
(7), 216 (20), 203 (1), 201 (4), 185 (100), 168 (6), 153 (100), 115 (100), 83 (40). Anal. calc. for C10H13ClO5
(248.50): C 48.30, H 5.27; found: C 48.4, H 5.17.
Methyl 2-(Bromomethyl)-2,5-dihydro-4-methoxy-5-oxo-2-phenylfuran-3-carboxylate (4k): Yield
0.35 g (52%). White powder. M.p. 90 – 928. Rf (AcOEt/hexane 1:4) 0.6. IR: 1778 and 1697 (C¼O),
1646 and 1467 (C¼C). 1H-NMR: 3.85 (s, MeO); 4.19 (d, 2J ¼ 10.8, CH); 7.38 – 7.46 (m, 5 arom. H).
13C-NMR: 37.3 (CH2Br); 52.4, 60.0 (2 MeO); 84.8 (s, C(Ph)CH2Br); 123.8 (OꢀC¼C); 125.9, 128.9, 129.4,
136.1 (arom. C); 149.5 (OꢀC¼C); 161.9, 165.0 (2 C¼O). MS: 343 (3, [M þ 3]þ), 341 (3, [M þ 1]þ), 327
(2), 325 (2), 313 (5), 311 (5), 283 (3), 281 (3), 247 (100), 229 (10), 219 (34), 129 (49), 115 (100), 105
(94), 77 (97), 59 (83). Anal. calc. for C14H13BrO5 (340.99): C 49.29, H 3.84; found: C 49.21, H 3.79.
Ethyl 2-(Bromomethyl)-4-ethoxy-2,5-dihydro-5-oxo-2-phenylfuran-3-carboxylate (4l): Yield 0.37 g
(50%). White powder. M.p. 45 – 478. Rf (AcOEt/hexane 1:4) 0.62. IR: 1772 and 1693 (C¼O), 1644 and
1430 (C¼C). 1H-NMR: 1.31 (t, 3J ¼ 7.2, Me); 1.44 (t, 3J ¼ 7.2, Me); 4.19 (d, 2J ¼ 10.8, CH); 4.23 – 4.34 (m,
CH2O); 4.63 – 4.80 (m, CH2O); 4.59 (d, 2J ¼ 10.8, CH); 7.37 ꢀ 7.46 (m, Ph). 13C-NMR: 14.0, 15.5 (2 Me);
37.4 (CH2Br); 61.5, 68.6 (2 CH2O); 86.9 (s, C(Ph)CH2Br); 124.9 (OꢀC¼C); 125.9, 128.8, 129.3, 136.2
(arom. C); 149.2 (OꢀC¼C); 161.5, 165.3 (2 C¼O). MS: 370 (2, [M þ 2]þ), 368 (2, Mþ), 325 (3), 323 (3),
275 (100), 247 (9), 219 (40), 201 (6), 171 (3), 163 (3), 161 (3), 115 (30), 105 (94), 77 (30). Anal. calc. for
C16H17BrO5 (369.01): C 52.05, H 4.64; found: C 51.93, H 4.59.

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Helvetica Chimica Acta – Vol. 95 (2012)
Methyl 2-(Bromomethyl)-2-(4-bromophenyl)-2,5-dihydro-4-methoxy-5-oxofuran-3-carboxylate
(4m): Yield 0.52 g (62%). White powder. M.p. 83 – 858. Rf (AcOEt/hexane 1:4) 0.6. IR: 1765 and 1702
(C¼O), 1639 and 1461 (C¼C). 1H-NMR: 3.84 (s, MeO); 4.14 (d, 2J ¼ 10.8, CH); 4.33 (s, MeO); 4.52 (d,
2J ¼ 10.8, CH); 7.34 (d, 3J ¼ 8.8, 2 arom. H); 7.52 (d, 3J ¼ 8.8, 2 arom. H). 13C-NMR: 36.8 (CH2Br); 52.5,
60.1 (2 MeO); 84.3 (s, C(Ar)CH2Br); 123.4 (OꢀC¼C); 123.7, 127.5, 132.0, 135.2 (arom. C); 149.5
(OꢀC¼C); 161.8, 164.7 (2 C¼O). MS: 422 (2, [M þ 4]þ), 420 (4, [M þ 2]þ), 418 (2, Mþ), 391 (2), 389 (4),
387 (2), 363 (1), 361 (2), 359 (1), 327 (100), 325 (100), 209 (8), 207 (8), 195 (9), 193 (9), 185 (92), 183
(92), 157 (23), 155 (23), 114 (23), 83 (33), 75 (25), 59 (30). Anal. calc. for C14H12Br2O5 (419.89): C 40.03,
H 2.88; found: C 39.2, H 2.82.
Ethyl 2-(Bromomethyl)-2-(4-bromophenyl)-4-ethoxy-2,5-dihydro-5-oxofuran-3-carboxylate (4n):
Yield 0.54 g (60%). White powder. M.p. 71 – 738. Rf (AcOEt/hexane 1:4) 0.6. IR: 1766 and 1704
1
3
3
2
(C¼O), 1641 and 1488 (C¼C). H-NMR: 1.32 (t, J ¼ 7.2, Me); 1.43 (t, J ¼ 7.2, Me); 4.14 (d, J ¼ 11.2,
CH); 4.26 – 4.34 (m, CH2O); 4.52 (d, 2J ¼ 11.2, CH); 4.63 – 4.80 (m, CH2O); 7.34 (d, 3J ¼ 8.8, 2 arom. H);
7.52 (d, J ¼ 8.8, 2 arom. H). 13C-NMR: 14.0, 15.5 (2 Me); 37.0 (CH2Br); 61.6, 68.7 (2 CH2O); 84.4 (s,
3
C(Ar)CH2Br); 123.6 (OꢀC¼C); 124.4, 127.7, 132.0, 135.4 (arom. C); 149.2 (OꢀC¼C); 161.4, 165.0 (2
C¼O). MS: 450 (1, [M þ 4]þ), 448 (2, [M þ 2]þ), 446 (1, Mþ), 405 (1), 403 (2), 401 (1), 355 (57), 353 (57),
299 (19), 297 (19), 207 (5), 185 (100), 183 (100), 157 (13), 155 (13), 142 (3), 102 (12), 69 (14). Anal. calc.
for C16H16Br2O5 (447.91): C 42.89, H 3.60; found: C 42.78, H 3.55.
Methyl 2-(Bromomethyl)-2-(4-chlorophenyl)-2,5-dihydro-4-methoxy-5-oxofuran-3-carboxylate (4o):
Yield 0.42 g (56%). White powder. M.p. 77 – 798. Rf (AcOEt/hexane 1:4) 0.5. IR: 1772 and 1702 (C¼O),
1461 and 1488 (C¼C). 1H-NMR: 3.84 (s, MeO); 4.14 (d, 2J ¼ 11.2, CH); 4.33 (s, MeO); 4.52 (d, 2J ¼ 11.2,
3
3
CH); 7.36 (d, J ¼ 8.8, 2 arom. H); 7.40 (d, J ¼ 8.8, 2 arom. H). 13C-NMR: 36.9 (CH2Br); 52.5, 60.1 (2
MeO); 84.3 (s, C(Ar)CH2Br); 123.5 (OꢀC¼C); 127.4, 129.1, 134.6, 135.5 (arom. C); 149.5 (OꢀC¼C);
161.8, 164.7 (2 C¼O). MS: 378 (1, [M þ 4]þ), 376 (4, [M þ 2]þ), 374 (3, Mþ), 347 (2), 345 (8), 343 (6), 319
(1), 317 (4), 315 (3), 283 (35), 281 (100), 165 (3), 163 (9), 151 (6), 149 (15), 141 (33), 139 (97), 113 (9),
111 (25), 83 (1.6), 59 (1.6). Anal. calc. for C14H12BrClO5 (375.44): C 44.77, H 3.22; found: C 44.68, H 3.18.
Ethyl 2-(Bromomethyl)-2-(4-chlorophenyl)-4-ethoxy-2,5-dihydro-5-oxofuran-3-carboxylate (4p):
Yield 0.44 g (55%). White powder. M.p. 79 – 818. Rf (AcOEt/hexane 1:4) 0.5. IR: 1785 and 1687
1
3
3
2
(C¼O), 1637 and 1494 (C¼C). H-NMR: 1.32 (t, J ¼ 7.2, Me); 1.43 (t, J ¼ 7.2, Me); 4.14 (d, J ¼ 11.2,
CH); 4.23 – 4.34 (m, CH2O); 4.52 (d, 2J ¼ 11.2, CH); 7.36 (d, 3J ¼ 8.4, 2 arom. H); 7.41 (d, 3J ¼ 8.4, 2 arom.
H). 13C-NMR: 14.0, 15.5 (2 Me); 37.1 (CH2Br); 61.6, 68.7 (2 CH2O); 84.4 (s, C(Ar)CH2Br); 124.5
(OꢀC¼C); 124.7, 129.0, 134.8, 135.4 (arom. C); 149.2 (OꢀC¼C); 161.4, 165.0 (2 C¼O). MS: 406 (1, [M þ
4]þ), 404 (4, [M þ 2]þ), 402 (3, Mþ), 361 (2), 359 (8), 357 (6), 333 (1), 331 (4), 329 (3), 311 (32), 309
(96), 283 (2), 281 (6), 255 (10), 253 (31), 237 (3), 235 (9), 141 (35), 139 (100), 113 (6), 111 (16), 69 (9).
Anal. calc. for C16H16BrClO5 (403.46): C 47.61, H 4.0; found: C 47.54, H 3.95.
Methyl 2-(Bromomethyl)-2,5-dihydro-4-methoxy-2-(4-nitrophenyl)-5-oxofuran-3-carboxylate (4q):
Yield 0.54 g (80%). White powder. M.p. 97 – 998. Rf (AcOEt/hexane 1:4) 0.5. IR: 1779 and 1697 (C¼O),
1644 and 1471(C¼C). 1H-NMR: 3.86 (s, MeO); 4.18 (d, 2J ¼ 11.2, CH); 4.36 (s, MeO); 4.54 (d, 2J ¼ 11.2,
3
3
CH); 7.70 (d, J ¼ 8.8, 2 arom. H), 8.25 (d, J ¼ 8.8, 2 arom. H). 13C-NMR: 36.4 (CH2Br); 52.6, 60.1 (2
MeO); 84.0 (s, C(Ar)CH2Br); 123.1 (OꢀC¼C); 124.0, 127.2, 143.0, 148.2 (arom. C); 149.6 (OꢀC¼C);
161.7, 164.3 (2 C¼O). MS: 387 (2, [M þ 2]þ), 385 (2, Mþ), 311 (42), 309 (42), 292 (43), 277 (43), 262 (5),
229 (9), 178 (15), 150 (37), 139 (94), 122 (13), 97 (25), 83 (32), 69 (89), 57 (73), Anal. calc. for
C14H12BrNO7 (385.97): C 43.55, H, 3.13; found: C 42.95, H 3.80.
Ethyl 2-(Bromomethyl)-4-ethoxy-2,5-dihydro-2-(4-nitrophenyl)-5-oxofuran-3-carboxylate (4r):
Yield 0.56 g (78%). White powder. M.p. 86 – 888. Rf (AcOEt/hexane 1:4) 0.5. IR: 1793 and 1706
1
3
3
2
(C¼O), 1645 and 1430 (C¼C). H-NMR 1.33 (t, J ¼ 7.2, Me); 1.44 (t, J ¼ 7.2, Me); 4.18 (d, J ¼ 11.2,
CH); 4.23 – 4.36 (m, CH2O); 4.53 (d, 2J ¼ 11.2, CH); 4.67 – 4.82 (m, CH2O); 7.70 (d, 3J ¼ 9.2, 2 arom. CH);
8.24 (d, 3J ¼ 9.2, 2 arom. CH). 13C-NMR: 14.0, 15.5 (2 Me); 36.5 (CH2Br); 61.8, 68.9 (2 CH2O); 84.1 (s,
C(Ar)CH2Br); 123.5 (OꢀC¼C); 123.4, 127.2, 143.2, 148.2 (arom. C); 149.3 (OꢀC¼C); 161.3, 164.6 (2
C¼O). MS: 415 (1, [M þ 2]þ), 413 (1, Mþ), 386 (2), 384 (2), 370 (5), 368 (5), 334 (8), 320 (77), 264 (43),
216 (5), 150 (100), 122 (6), 104 (20), 69 (15). Anal. calc. for C16H16BrNO7 (413.99): C 46.40, H 3.89;
found: C 46.31, H 3.84.

Helvetica Chimica Acta – Vol. 95 (2012)
817
X-Ray Crystal Structure of 4d1). C9H10Cl2O5, Mr 269.07, crystal size 0.50 ꢁ 0.49 ꢁ 0.25 mm,
monoclinic; a ¼ 9.7761(11) ꢂ, b ¼ 17.195(2) ꢂ, c ¼ 7.1364(8) ꢂ, a ¼ 908, b ¼ 109.435(8)8, g ¼ 908, space
group C 2/c; Z ¼ 4, V¼ 1131.3(2) ꢂ3, Dcalc. ¼ 1.580 g cmꢀ3; R ¼ 0.0724, Rw ¼ 0.1233; ꢀ13 ꢂ h ꢂ 13, ꢀ23 ꢂ
k ꢂ 20; ꢀ9 ꢂ l ꢂ 8; MoKa radiation (l 0.71073 ꢂ), T 298(2)8.
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Received September 28, 2011
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)
CCDC-823855 contains supplementary crystellographic data for this article. These data can be
obtained free of charge via http://www.cdc.cam.ac.uk.data_request/cif.