Chemistry of acylals, part IV: BF3-catalyzed formation of substituted α,α′-bis(arylmethylidene)cycloalkanones from acylals and 1-cycloalkenyl trimethylsilyl ethers

Article abstract of DOI:10.1055/s-2007-990881

When mixtures of an aromatic aldehyde acylal and a I-cycloalkenyl trimethylsilyl ether in dichloromethane were treated with boron trifluoride at room temperature, the corresponding α,α′-bis(arylmethylidene) cycloalkanones were formed. The yield was sensitive to both the acetal/ether ratio and the structure of the acylal. The best results, up to 97% yield, were obtained when acylals containing a diacetoxy moiety were reacted with 1-cyclohexenyl trimethylsilyl ether with an acetal-to-ether ratio of 2:1. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-990881

3692
PAPER
Chemistry of Acylals, Part IV: BF3-Catalyzed Formation of Substituted
a,a¢-Bis(arylmethylidene)cycloalkanones from Acylals and 1-Cycloalkenyl
Trimethylsilyl Ethers
C
hemistry of
A
e
a
Department of Chemistry, University of Bergen, Allégt. 41, 5007 Bergen, Norway
Fax +4755589490; E-mail: leiv.sydnes@kj.uib.no
Synthetica AS, Forskningsparken, Gaustadalléen 21, 0349 Oslo, Norway
b
Received 22 May 2007; revised 5 September 2007
that the transformation was rather general and our studies,
reported here, proved that this was certainly the case.
Abstract: When mixtures of an aromatic aldehyde acylal and a 1-
cycloalkenyl trimethylsilyl ether in dichloromethane were treated
with boron trifluoride at room temperature, the corresponding a,a¢-
bis(arylmethylidene)cycloalkanones were formed. The yield was
sensitive to both the acetal/ether ratio and the structure of the acylal.
The best results, up to 97% yield, were obtained when acylals con-
taining a diacetoxy moiety were reacted with 1-cyclohexenyl tri-
methylsilyl ether with an acetal-to-ether ratio of 2:1.
Screening reactions with several acylals showed that the
reaction was sensitive to the nature of the acylal, the re-
agent molar ratio, the catalyst and the temperature. Only
acylals from aromatic aldehydes appeared to give conden-
sation product(s); when aliphatic aldehydes were reacted,
condensation did not occur at all. Furthermore, when the
acylal-to-ether ratio was lowered from 2.5 to 0.5, the yield
of the corresponding 2,6-bis(arylidene)cyclohexanone (3)
dropped considerably; below a ratio of approximately 0.8,
formation of 3 barely took place. The best yields were ob-
tained with a molar ratio of 2.0–2.2, which was therefore
applied to a range of reactions on a preparative scale. As
for the Lewis acid catalyst, boron trifluoride gave consis-
tently the best results for a range of acids screened under
various conditions; the second best, aluminum chloride,
was significantly less efficient. Finally, cooling of the re-
action mixture to 0 °C or below at the beginning of the re-
action, generally improved the yield, but when the ratio of
1 to ether was 2.0–2.2, there was no significant difference
between 0 °C and –78 °C. Based on these results, studies
of reactions on a preparative scale were carried out with
acylals from aromatic aldehydes, with an acylal-to-ether
ratio of 2.2–2.0 and with the temperature kept at 0 °C dur-
ing and for a while after the addition of boron trifluoride.
Key words: acylals, bis(benzylidene)cycloalkanones, condensa-
tion, 1,1-diacyloxymethanes
Acylals (1) are compounds containing at least one gem-
bis(acyloxy) group,1 and they therefore possess a C–O–
C–O–C moiety, with the central carbon atom in the alde-
hyde or ketone state of oxidation and the other two in the
carboxylic acid oxidation state. The compounds are easy
to prepare even in large quantities by a large number of
methods2,3 and their chemistry appears to be rich and in-
teresting.2 This is particularly the case with the aldehyde
acylals, which react either as aldehydes or carboxylic ac-
ids depending on the reagent and the reaction conditions.2
An example of aldehyde reactivity was revealed when
some benzylidene diacetates were reacted with 1-cyclo-
hexenyl trimethylsilyl ether (2a) in the presence of boron
trifluoride and afforded, as the only isolated product, 2,6-
bis(benzylidene)cyclohexanone (3a) (Scheme 1),2 which
belongs to an interesting group of compounds that exhib-
its significant biological activity in vitro.4,5
The acylals employed were synthesized from selected ar-
omatic aldehydes (in quantities up to 50 g) following a
procedure derived from a literature description.6 The
products were easy to purify and, as the results compiled
in Table 1 show, the yield was in most cases good to very
good (provided longer stirring at room temperature was
allowed when anhydrides from the larger carboxylic acids
were used; see experimental). This shows that acylal for-
mation is only moderately influenced by the steric bulk of
the acyloxy moieties (for instance, compare entries 4, 13
and 16 in Table 1). However, the structure of the acyloxy
groups does appear to influence the fragmentation pattern
when the acylals are subjected to electron-impact ioniza-
tion – a phenomenon that is currently under investigation.
Products resulting from monocondensation were not ob-
served in any reaction, not even when a significant excess
of the ether was used. Exploratory experiments indicated
PhCH(OAc)2
O
1a
BF3
+
Ph
Ph
OTMS
3a
2a
Scheme 1
Ar
BF3
(RCO)2O
+
SYNTHESIS 2007, No. 23, pp 3692–3696
x
x.
x
x
.
2
0
0
7
ArCHO
RCO2
O2CR
Advanced online publication: 13.11.2007
1
DOI: 10.1055/s-2007-990881; Art ID: P06407SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 2

PAPER
Chemistry of Acylals
3693
Table 1 Acylals (1) Prepared by Treating Aryl Aldehydes with Carboxylic Anhydrides in the Presence of Boron Trifluoride
Entry
1
R
Ar
Acylal
1a
1b
1c
Mp (°C) or bp (°C/torr) Mp (°C) reported Isolated yield (%)
Me
Ph
44–46
45.87
77
52
58
68
54
74
77
60
84
82
86
77
67
61
40
60
2
Me
4-MeOC6H4
4-MeC6H4
4-ClC6H4
4-AcOC6H4
4-O2NC6H4
3-O2NC6H4
3-ClC6H4
1-naphthyl
4-MeC6H4
Ph
63–64
64–658
81–827
80–818
89–908
3
Me
81–82
4
Me
1d
1e
79–80
5
Me
88–90
6
Me
1f
125–126
65–67
1259
7
Me
1g
1h
1i
63–648
65–668
8
Me
63–65
9
Me
106–107
138–140/0.5
120–122/0.2
130–132/0.2
139–141/0.2
100–101
127–128
92–93
105–1068
10
11
12
13
14
15
16
Me(CH2)4
(E)-MeCH=CH
(E)-MeCH=CH
(E)-MeCH=CH
(E)-PhCH=CH
(E)-PhCH=CH
(E)-PhCH=CH
1j
1k
1l
45–4710
4-MeC6H4
4-ClC6H4
Ph
1m
1n
1o
1p
4-MeC6H4
4-ClC6H4
With acylals available in abundance, 1-cyclohexenyl tri- deed observed. Thus, when a para substituent is intro-
methylsilyl ether (2a) as well as the corresponding cyclo- duced and changed from nitro to acetoxy via chloro,
pentenyl ether (2b), were reacted under the conditions methyl and methoxy, the yield increases from 0% to 97%.
outlined above. In each reaction, the only isolable product Thirdly, the cyclohexenyl ether 2a appears to be more re-
was that corresponding a,a¢-bis(arylmethylidene)cyclo- active under our reaction conditions than the correspond-
alkanone (3), which always exhibited E,E configuration ing cyclopentene analogue 2b. When acylals 1a, 1b and
(Scheme 3).
1c were reacted with both ethers, the yields were consis-
tently higher for cyclohexanones 3a, 3b and 3c than the
corresponding cyclopentanones 4a, 4b and 4c (compare
Table 2 entries 1, 4 and 5 with entries 17, 18 and 19, re-
spectively).
TMSO
O
1
Ar
Ar
(CH2)n
BF3
(CH2)n
When the best yields of the a,a¢-bis(arylmethylidene)cy-
2
3: n = 2; 4: n = 1
cloalkanones obtained by the method reported here are
compared with those achieved using other methods,11–19
a
Scheme 3
mixed picture emerges. The cyclopentanone adducts are
formed in far better yields simply by treating mixtures of
cyclopentanone and benzaldehyde derivatives with either
sodium or potassium hydroxide (see Table 2, entries 17–
19).12–14 With cyclohexanone, however, several of the di-
acetate acylals react better than the corresponding alde-
hydes (Table 2, entries 4 and 5). It is also quite
noteworthy that acylal condensation was very successful
with 4-acetyloxybenzylidene diacetate (1e), which con-
tains a hydroxide-sensitive acyloxy group (Table 2, entry
12); the resulting bis(arylmethylidene)cyclohexanone
(3e), isolated in 97% yield, has not been reported to be
formed under sodium or potassium hydroxide catalysis.
The results, which are compiled in Table 2, show several
interesting trends: firstly, the yield is influenced by the
steric bulk of the acylal acyloxy groups – the more steri-
cally demanding the groups, the lower the yield of the
condensation product. Thus, the yield decreases when the
aryl moiety is kept unchanged but the acyloxy group is
changed from acetate to crotonate to cinnamate (for in-
stance, see Table 2, entries 1–3 and 9–11). Secondly, the
yield of 3 increases if the aryl moiety of the acylal is able
to stabilize a positive charge. This is in accordance with
the fact that the condensation is catalyzed by boron triflu-
oride, a Lewis acid, which generates a transient positive
charge at the gem-bis(acyloxy) moiety during the reac-
tion. Electron-donating substituents in the para position
should therefore facilitate the formation of 3, which is in-
In conclusion, we have developed a simple and quite effi-
cient synthesis of a,a¢-bis(arylmethylidene)cyclohex-
Synthesis 2007, No. 23, 3692–3696 © Thieme Stuttgart · New York

3694
L. K. Sydnes et al.
PAPER
Table 2 Synthesis of a,a¢-Bis(arylidene)cycloalkanones (3 and 4) from Acylals (1) and 1-Cycloalkenyl Trimethylsilyl Ether (2)
Entry Acylal 1-Cycloalkenyl ether Product
Mp (°C)
116–117
Mp (°C) reported
11814
Isolated yield (%) Yield reported (%)a
1
2
1a
1k
1n
1b
1c
1j
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
3a
3a
3a
3b
3c
3c
3c
3c
3d
3d
3d
3e
3f
46
49
21
87
78
56
49
39
49
30
20
97
0
9014
3
4
159–160
168–169
160,14 16113
169–17014
8014
6314
5
6
7
1l
8
1o
1d
1m
1p
1e
1f
9
141–142
183–184
14714
8014
10
11
12
13
14
15
16
17
18
19
18613
not reported
not reported
not reported
8115
1g
1h
1i
3g
3h
3i
157–160b
103–104
207–208
188–189
217–219
238–240
18611
32c
24
88
38
69
51
10614
21214
5215
1a
1b
1c
4a
4b
4c
19014
9015
219–220,17 208–210.512
245–246,15 236–238.512
9412
8812
a By direct reaction of cycloalkanone with aldehyde under basic conditions (NaOH or KOH).
b Not pure (reflected by the melting-point deviation).
c Estimated from analysis of impure isolated product.
Preparation of Acylals (1); Typical Procedure
anones. The starting materials are stable and the
condensation products are isolated in yields that are some-
times considerably better than those obtained from alde-
hydes and cyclohexanone with other catalysts.12,14,16,18,19
All the acylals were synthesized from aldehydes and carboxylic an-
hydrides using a procedure published by Sydnes and Sandberg.6
The syntheses are illustrated by a representative preparation of ben-
zylidene diacetate (1a).
Ac2O (7.15 g, 70 mmol) and BF3·OEt2 (10 drops) were added to a
round-bottom flask equipped with a dropping funnel, a magnetic
stirring bar and a thermometer, and immersed in a salt-ice slush
(–10 °C). Benzaldehyde (3.71 g, 35 mmol) was added slowly with
stirring and when the addition was complete, the resulting mixture
was stirred at –10 °C for 30 min and then at r.t. for 2.5 h. The prod-
uct mixture was poured into aq NaOAc (10%, 100 mL) and stirred
rapidly at r.t. for 30 min. An oily layer was formed. The product was
extracted with Et2O (3 × 100 mL), the extracts were combined and
the combined extracts were washed with aq NaHCO3 (10%, 100
mL) and H2O (2 × 100 mL). After drying (MgSO4), the product was
concentrated under vacuum and the crude product was purified by
recrystallization from EtOH to give 1a [Yield: 5.64 g (77%); mp
44–46 °C (Lit.7 45.8 °C)]. Spectroscopic and MS data were in ac-
cordance with those published in the literature.6,8
IR spectra were recorded on a Nicolet Impact 410 infrared spectro-
photometer. NMR spectra were run on a Bruker Spectrospin AC
200 F. Chemical shifts (d) are reported downfield from TMS and
coupling constants (J) are given in Hz. GC analyses were performed
on a HP 5890 Gas Chromatograph with a flame ionization detector
and a HP Ultra 1 column (100% dimethyl-polysiloxane, 25 m, 0.2
mm i.d., 0.33 mm). Flash chromatography was carried out with Sil-
ica gel (230–400 mesh) as the stationary phase and mixtures of hex-
ane–EtOAc as the mobile phase. The eluent composition is given in
each case. TLC analyses of the reaction mixtures were performed
with Silica gel (60 F254) on aluminum sheets with mixtures of hex-
ane–EtOAc as the mobile phase. Mass spectra were obtained on a
VG 7070 Micromass spectrometer or an Autospec Ultima mass
spectrometer (a three-sector instrument with EBE geometry from
Micromass Ltd Manchester), both operated in the EI mode at 70 eV.
Boiling and melting points are uncorrected.
When dihexanoate 1j, dicrotonates 1k–m and dicinnamates 1n–p
were prepared, Ac2O was replaced by hexanoic anhydride, crotonic
anhydride and cinnamic anhydride, respectively, and the reaction
time at r.t., after addition of the aldehyde, was increased from 2.5 h
Synthesis 2007, No. 23, 3692–3696 © Thieme Stuttgart · New York

PAPER
Chemistry of Acylals
3695
to 9.5 h, 15 h and 6 h, respectively. Compounds 1j–m were isolated
by distillation instead of crystallization.
Benzylidene Dicinnamate (1n)
Colorless solid; mp 100–101 °C.
The melting points and the spectroscopic data for diacetates 1b–i
and dicrotonate 1k were in accordance with data published in the lit-
erature.6–10
IR (KBr): 3065, 3031, 1714, 1637, 1451, 1314, 1249, 1170, 1052,
966, 867, 769, 700 cm–1.
1H NMR (200 MHz, CDCl3): d = 6.49 (d, J = 16.1 Hz, 2 H), 7.32–
7.75 (m, 15 H), 7.79 (d, J = 16.1 Hz, 2 H), 8.02 (s, 1 H).
13C NMR (50 MHz, CDCl3): d = 89.8, 116.7, 126.6, 128.1, 128.5,
128.7, 129.6, 130.5, 133.9, 135.6, 146.5, 164.5.
MS (EI): m/z (%) = 384 (0.1) [M+], 278 (2), 250 (7), 205 (1), 132
(10), 131 (100), 106 (5), 105 (9), 103 (21), 77 (20).
HRMS (EI): m/z [M+] calcd for C25H20O4: 384.1362; found:
384.1374.
4-Methylbenzylidene Dihexanoate (1j)
Colorless liquid; bp 138–140 °C/0.5 mmHg.
IR (film): 3089, 3027, 2956, 2930, 2860, 1763, 1496, 1460, 1436,
1375, 1247, 1209, 1122, 1100, 1046, 1010, 965, 731, 696 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.88 (t, J = 6.5 Hz, 6 H), 1.25–
1.33 (m, 8 H), 1.60–1.66 (m, 3 H), 2.32–2.40 (m, 8 H), 7.21 (d,
J = 8.0 Hz, 2 H), 7.40 (d, J = 8.0 Hz, 2 H), 7.68 (s, 1 H).
13C NMR (50 MHz, CDCl3): d = 13.7, 21.1, 22.1, 24.1, 30.9, 33.9,
89.4, 126.4, 120.0, 132.7, 139.4, 171.5.
Anal. Calcd for C25H20O4: C, 78.11; H, 5.24. Found: C, 78.37; H,
4.97.
MS (EI): m/z (%) = 314 (0.1) [M+], 235 (3), 219 (7), 121 (9) 120
(17), 119 (100), 99 (99), 91 (15), 71 (27), 60 (12).
HRMS (EI): m/z [M+ – CH3(CH2)4CO] calcd for C14H19O3:
235.1334; found: 235.1327.
4-Methylbenzylidene Dicinnamate (1o)
Colorless solid; mp 127–128 °C.
IR (KBr): 3080, 3022, 1709, 1636, 1580, 1450, 1339, 1309, 1244,
1202, 1166, 1052, 955, 871, 818, 769, 711, 693 cm–1.
Anal. Calcd for C20H30O4: C, 71.82; H, 9.04. Found: C, 71.65; H,
9.12.
1H NMR (200 MHz, CDCl3): d = 3.37 (s, 3 H), 6.48 (d, J = 16.1 Hz,
2 H), 7.18–7.65 (m, 14 H), 7.77 (d, J = 16.1 Hz, 2 H), 7.99 (s, 1 H).
13C NMR (50 MHz, CDCl3): d = 88.5, 116.1, 121.8, 124.4, 128.2,
128.8, 129.6, 130.7, 132.9, 133.7, 137.8, 147.2, 148.2, 164.3.
4-Methylbenzylidene Dicrotonate (1l)
Colorless liquid; bp 130–132 °C/0.2 mmHg.
MS (EI): m/z (%) = 398 (0.05) [M+], 279 (0.4), 278 (1.5), 267 (4),
250 (10), 233 (0.4), 222 (1.2), 206 (1.3), 205 (2), 147 (3), 132 (14),
131 (100), 120 (11), 119 (19), 103 (26), 91 (12), 77 (14).
HRMS (EI): m/z [M+ – PhCH=CHCO] calcd for C17H15O3:
267.1021; found: 267.1024.
IR (film): 3063, 3038, 2977, 2945, 2917, 1743, 1655, 1443, 1374,
1305, 1293, 1244, 1207, 1163, 1101, 1051, 1005, 970, 918, 793,
766, 699 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.84 (dd, J = 1.7, 6.9 Hz, 6 H),
2.32 (s, 3 H), 5.86 (dd, J = 1.6, 15.5 Hz, 2 H), 7.05 (dq, J = 6.9, 15.5
Hz, 2 H), 7.10–7.25 (m, 2 H), 7.35–7.48 (m, 2 H), 7.83 (s, 1 H).
13C NMR (50 MHz, CDCl3): d = 17.8, 20.8, 89.2, 121.4, 126.1,
128.6, 132.7, 139.1, 146.3, 163.6.
MS (EI): m/z (%) = 274 (1) [M+], 231 (2), 207 (2), 206 (8), 205 (46),
190 (6), 189 (30), 188 (13), 155 (2), 139 (4), 138 (30), 122 (2), 121
(12), 120 (73), 119 (97), 105 (3), 93 (5), 92 (11), 91 (76), 90 (6), 89
(7), 86 (3), 77 (7), 70 (25), 69 (100).
Anal. Calcd for C26H22O4: C, 78.37; H, 5.57. Found: C, 78.41; H,
5.26.
4-Chlorobenzylidene Dicinnamate (1p)
Colorless solid; mp 92–93 °C.
IR (KBr): 3075, 3020, 1743, 1638, 1475, 1425, 1182, 1128, 1057,
973, 944, 767 cm–1.
1H NMR (200 MHz, CDCl3): d = 6.48 (m, J = 15.7 Hz, 2 H), 7.38–
7.61 (m, 14 H), 7.79 (d, J = 15.7 Hz, 2 H), 7.96 (s, 1 H).
13C NMR (50 MHz, CDCl3): d = 88.2, 116.5, 128.1, 128.2, 128.77,
128.82, 130.6, 133.7, 134.2, 135.5, 146.7, 164.5.
HRMS (EI): m/z [M+ – CH3CH=CHCO] calcd for C12H13O3:
205.0865; found: 205.0865.
Anal. Calcd for C16H18O4: C, 70.06; H, 6.61. Found: C, 70.04; H,
6.55.
MS (EI): m/z (%) = 293 (0.3), 289 (0.3), 287 (1.5), 279 (0.6), 278
(1.6), 250 (7), 150 (2), 149 (10), 148 (4), 147 (5), 142 (3), 141 (5),
140 (6), 139 (11), 132 (10), 131 (100), 119 (4), 111 (6), 103 (23), 91
(3), 77 (12).
HRMS (EI): m/z [M+ – PhCH=CHCO] calcd for C16H12O3Cl:
287.0475; found: 287.0475.
4-Chlorobenzylidene Dicrotonate (1m)
Colorless liquid; bp 139–141 °C/0.2 mmHg.
IR (film): 3058, 2975, 2944, 2916, 1741, 1655, 1601, 1493, 1443,
1375, 1294, 1249, 1231, 1211, 1161, 1091, 1057, 1004, 968, 911,
867, 824, 754, 686 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.89 (dd, J = 1.6, 6.9 Hz, 6 H),
5.88 (dd, J = 1.6, 15.6 Hz, 2 H), 7.08 (dq, J = 6.9, 15.6 Hz, 2 H),
7.30–7.52 (m, 4 H), 7.80 (s, 1 H).
Anal. Calcd for C25H19ClO4: C, 71.69; H, 4.57. Found: C, 71.82; H,
4.40.
13C NMR (50 MHz, CDCl3): d = 17.7, 88.5, 121.2, 127.8, 128.4,
134.2, 135.1, 145.7, 163.5.
Preparation of 2,6-Bis(arylmethylidene)cycloalkanones (3);
General Procedure
To a mixture of 1-cycloalkenyltrimethylsilyl ether20 (2.35–5.35
mmol) and acylal (2.0 equiv) in anhydrous CH2Cl2 (10 mL) at 0 °C
was added BF3·OEt2 (1:1 mixture of BF3 in Et2O; density 1.15 g/mL;
1.0 equiv). The mixture was stirred overnight while the temperature
was allowed to rise to r.t., then the reaction was poured into H2O
(40–50 mL) and the products were extracted with Et2O (3 × 30 mL).
The combined organic extracts were washed with H2O (2 × 50 mL)
and dried (MgSO4). Filtration and concentration under vacuum
gave a crude product, which was purified by flash chromatography
on a silica gel (hexane–EtOAc, 95:5→80:20) as eluent.
MS (EI): m/z (%) = 294 (0.2) [M+], 259 (0.1), 228 (1), 227 (5), 226
(2), 225 (13), 209 (8), 155 (3), 142 (12), 141 (52), 140 (32), 139 82),
126 (4), 113 (13), 112 (6), 111 (33), 89 (4), 86 (8), 77 (15), 75 (18),
70 (25), 69 (100).
HRMS (EI): m/z [M+ – CH3CH=CHCO] calcd for C11H10O3Cl:
225.0318; found: 225.0318.
Anal. Calcd for C15H15ClO4: C, 61.13; H, 5.13. Found: C, 61.32; H,
4.85.
Synthesis 2007, No. 23, 3692–3696 © Thieme Stuttgart · New York

3696
L. K. Sydnes et al.
PAPER
The results are summarized in Table 2. Melting points and spectro-
scopic data are in accordance with those published in the litera-
ture.11–15,17 Yields of 3, obtained by condensation of cyclohexanone
and cyclopentanone with the appropriate aldehyde, using NaOH or
KOH as base, have been included for comparison.12,14
(5) Costi, R.; Di Santo, R.; Artico, M.; Miele, G.; Valentini, P.;
Novellino, E.; Cereseto, A. J. Med. Chem. 2007, 50, 1973.
(6) Sydnes, L. K.; Sandberg, M. Tetrahedron 1997, 53, 12679.
(7) Wegschneider, R.; Spath, E. Monatsh. Chem. 1909, 30, 825.
(8) Freeman, F.; Karchefsi, E. M. J. Chem. Eng. Data 1977, 22,
355.
(9) Pettersen, E. O.; Larsen, R. O.; Dornish, J. M.; Børretsen, B.;
Oftebro, R.; Ramdal, T.; Moen, V. PTC WO 9518607, 1995;
Chem. Abstr. 1995, 123, 188574a.
(10) Sandberg, M.; Sydnes, L. K. Org. Lett. 2000, 2, 687.
(11) Ionescu, M.; Makkay, K. Rev. Roum. Chim. 1970, 15, 265.
(12) Scanlon, W. B. DE 2245518, 1973; Chem. Abstr. 1973, 79,
53023x.
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Acknowledgment
Financial support from the Research Council of Norway and Nyco-
med Imaging (now GE Health), is gratefully acknowledged. Thanks
are also due to Ann Margot Whyatt at the University of Bergen, and
Dr. Dag Ekeberg at the Norwegian University of Life Sciences, for
skillful technical assistance.
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Synthesis 2007, No. 23, 3692–3696 © Thieme Stuttgart · New York