Synthesis of precursors for medium-ring aromatic lactones

Article abstract of DOI:10.1055/s-2005-865364

Hydroxyacids have been prepared via the nickel-catalysed electrochemical arylation of ethyl acrylate from an ortho-substituted aryl bromide. Protection and deprotection steps have been selected in terms of suitability and efficiency. The lactonisation was

Full text of DOI:10.1055/s-2005-865364

1682
PAPER
Synthesis of Precursors for Medium-Ring Aromatic Lactones
S
ynthesisof Pre
s
cursorsfo
t
r
M
ed
e
A
l
romati
l
c
L
acto
e
nes Métay,a Eric Léonel,*a Christine Sulpice-Gaillet,b Jean-Yves Nédéleca
a
Laboratoire d’Electrochimie, Catalyse et Synthèse Organique, UMR 7582, Institut des Sciences Chimiques Seine-Amont, IFR 1780,
CNRS – Université Paris XII, 2, Rue Henri Dunant, B.P. 28, 94320 Thiais, France
Fax +33(1)49781148; E-mail: leonel@glvt-cnrs.fr
Laboratoire de Recherche sur les Polymères, UMR 7581, Institut des Sciences Chimiques Seine-Amont, IFR 1780, CNRS – Université
Paris XII, 2, Rue Henri Dunant, B.P. 28, 94320 Thiais, France
b
Received 22 December 2004; revised 16 February 2005
to the expected fused benzolactone in only two steps. Un-
fortunately, this methodology is of low efficiency, as the
main products in the electrochemical step come from re-
duction and cleavage of the starting compound.8 As an al-
Abstract: Hydroxyacids have been prepared via the nickel-cata-
lysed electrochemical arylation of ethyl acrylate from an ortho-sub-
stituted aryl bromide. Protection and deprotection steps have been
selected in terms of suitability and efficiency. The lactonisation was
performed according to an already reported method. Two-dimen- ternative, the C–C bond could first be formed by a
sional NMR analysis has been used to ascertain the structure of the
lactones formed.
bimolecular process before closing the ring by lactonisa-
tion. Though the starting reagent is similar in these two
Key words: electrochemical arylation, nickel catalysis, medium
ring lactones
pathways, pathway II, however, requires additional steps,
as compared to pathway I, i.e. the protection/deprotection
of the hydroxy group and of the carboxylic group as well
as the lactonisation step. In addition to this, we could en-
Lactones are basic structures in many bioactive molecules vision some possible ortho-steric hindrance in the electro-
from plants, insects or bacteria.1 They are also intermedi- chemical arylation reaction.
ates in many synthetic applications. Lactones containing
up to a six-membered ring are easily prepared, either by
lactonisation or by Baeyer–Villiger oxidation of cycloal-
kanones.2 Also, macrocyclic lactones larger than 11-
membered rings can be efficiently obtained when high di-
lution reaction conditions are used. On the contrary, me-
dium-sized ring lactones, like other medium-size ring
compounds, are reported to be the most difficult to pre-
pare by cyclisation.3 In his extended review on the synthe-
sis of medium-sized ring lactones, Rousseau4 has pointed
out that in addition to the classical Pitzer or torsional
strain, and the Baeyer or angle strain, transannular inter-
Scheme 1
actions create an extra strain which is significatively more
important in medium than in small or large rings. As a re-
sult, tentative preparations of medium ring lactones fre-
quently lead to the formation of the macrocyclic diolide.5
Classical routes4 to lactones are either lactonisation from
hydroxy-5,6 or halo-acids,7 cyclisation by C–C bond for-
mation from a starting compound containing an ester
group in the chain or the ring expansion by ionic or radical
route.
Preliminary investigations on pathway II, revealed that
the bimolecular electrochemical arylation reaction is fea-
sible. This encouraged us to optimise this reaction for any
length of side-chain ortho to the halogen. In addition, we
studied more deeply the protecting groups with regard to
both the ease of formation and removal, as well as their
compatibility with the reaction conditions. Finally, we
had to not only carry out the lactonisation as efficiently as
possible, but also, as detailed below, to ascertain the struc-
ture of the benzolactone and, more precisely, the carboxyl
connection.
Our purpose was to apply an efficient C–C bond forming
electrochemical reaction, involving the nickel-catalysed
arylation of activated olefins, to the formation of medium
ring benzolactones. The first idea was to perform this re-
action in an intramolecular manner, as illustrated in
Scheme 1, pathway I. In such a simple route, the activated
olefin is first tethered to the aryl moiety before the electro-
chemical arylation of the C–C double bond, thus leading
The various steps of the synthesis via pathway II are indi-
cated in Scheme 2.
Our aim has been to have access to a series of benzolac-
tones from seven through to ten-membered rings, some of
which having not being described so far. Of the required
ortho-bromophenyl alkanols necessary as starting materi-
als, only 1a and 1b are commercially available. The others
were prepared (Scheme 3) according to the method re-
ported by Gibson for 1c and by Jordis for 1d,9 i.e. by per-
SYNTHESIS 2005, No. 10, pp 1682–1688
x
x.
x
x
.
2
0
0
5
Advanced online publication: 02.05.2005
DOI: 10.1055/s-2005-865364; Art ID: Z24004SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Precursors for Medium-Ring Aromatic Lactones
1683
O
b. electrochemical
Br
Br a.alcohol protection
coupling
OEt
O
n
quantitative
yields
O
n
OH
n
OEt
Pg
Pg
O
Pg : protective group
Me, THP, PMB
2 (Pg = THP)
3 (Pg = PMB)
4 (Pg = THP)
5 (Pg = PMB)
1a–d
yields: 45–80%
a (n = 1)
b (n = 2)
c (n = 3)
d (n = 4)
c. cleavage of
the protective group
d. saponification
e. lactonisation
n = 1, 2 commercialy available
n = 3, 4 not commercialy available
yields: 40–80%
O
6 (alcohol-esters)
7 (alcohol-acids)
8 (lactones)
O
n
total isolated yield
31–58%
Scheme 2
Br
forming a Wadsworth–Emmons condensation on a
suitable carbonyl compound, then the reduction of the C–
C double bond and ester group by super hydride
(LiBEt3H).
Br
a. alcohol protection
OH
O
Pg = THP; DHP, TsOH
Pg
n
n
Pg = PMB; NaH, PMBCl
isolated yield
3 (Pg = PMB)
1a (n = 1)
1b (n = 2)
1c (n = 3)
1d (n = 4)
The choice of the OH-protecting group is a key parameter
in this synthetic methodology. Notably, the electrochemi-
cal step requires a protecting group which is not easily re-
duced, nor sensitive to Lewis acids. THP derivatives are
easily prepared, but this was not a good general protection
method since the THP group is partially cleaved during
the electrolysis, and the overall yields are only moderate.8
The most convenient OH-protecting group for our pur-
pose is para-methoxybenzyl group (PMB),10 which is eas-
ily introduced, and can be cleaved efficiently by CAN.11
The isolated yields for the two methods are good to excel-
lent. The results are presented in Scheme 4.
The electrochemical step12 has been conducted with ethyl
acrylate as the Michael acceptor. The reaction conditions
are similar to those previously reported, i.e. DMF contain-
ing 10% pyridine, and with NiBr2 as the catalyst precur-
sor. A higher temperature (100 °C) was found to be more
efficient with these models, whereas 60 °C is usually
2 (Pg = THP)
3a (93%)
3b (95%)
3c (82%)
3d (61%)
2a (77%)
2b (85%)
-
-
Scheme 4
enough with the more simple structures. We can see
(Scheme 5) that yields are good and higher with PMB
than with THP as the protecting group. Also, the yields
decrease slightly with increasing side chain length; there
is no major steric effect due to the ortho substitution.
The next step is the cleavage of the PMB protecting group
using the methodology described in the literature11
(Scheme 6).
This reaction is easily and efficiently performed with
CAN in an acetonitrile–water mixture at room tempera-
Br
Br
Br
CH3OCH2P(C6H5)3Cl
HCl 3 N
H
O
t-BuOK
THF
OMe
O
10
9
H
(EtO)2P(O)CH2CO2Et
NaH, THF
(EtO)2P(O)CH2CO2Et
NaH, THF
Br
Br
12 84%
11 quantitative yield
CO2Et
CO2Et
i. LiBEt3H
ii. H2O
i. LiBEt3H
ii. H2O
iii. NaOH, H2O2
iii. NaOH, H2O2
Br
Br
OH
OH
1c 91%
1d 80%
Scheme 3
Synthesis 2005, No. 10, 1682–1688 © Thieme Stuttgart · New York

1684
E. Métay et al.
PAPER
b. electrochemical coupling
OEt
CO2H
OH
Sc(OTf)3, 10%
O
O
O
(p-NO2C6H4CO)2O (2 equiv)
CH3CN
n
n
Br
O
OEt
8a (52%)
8b (38%)
8c (66%)
8d (67%)
7a–d
O
O
n
NiBr H2O (10%)
⋅
2
Pg
Pg
n
I = 0.2 A, T = 100 °C, DMF, Py
isolated yield
4a (58%, partly cleaved)
5a (79%)
5b (76%)
5c (64%)
5d (54%)
Scheme 7
4b (46%, partly cleaved)
-
-
As mentioned above, the characterisation of the hydroxy-
acid by spectroscopy is not simple. We could only defi-
nitely ascertain the structure of the lactones by 2D NMR
spectroscopy using the HMBC program, which is based
Scheme 5
2
3
1
on the J and J H–13C couplings. Thus, each lactone
spectrum displays the coupling between the carbon of the
carbonyl and the protons of the methylene on the alcohol
side through the C–O bond (Figure 1). Such a coupling is
obviously not observed in the spectra of the hydroxyacids.
O
O
OEt
CAN
OEt
O
n
OH
MeCN/H2O
r.t.
Pg
n
isolated yield
5a–d
6a (mixture of 6a and 8a)
6b (80%)
O
C
6c (80%)
C
O
O
O
6d (70%)
H
H
H
H
Scheme 6
8a (38%)
8b (22%)
O
O
ture in one hour. From 6a, we have obtained, by purifica-
tion of the crude product on silica gel, the lactone along
with the expected hydroxyester. Based on this, we tried to
increase the amount of lactone obtained by simply using
acid catalysis, TsOH in toluene with a Dean–Stark appa-
ratus. This attempt, however, did not produce the expect-
ed lactone, but only the corresponding diolide. No lactone
was formed, either, in basic conditions. Similar results
were obtained with all substrates.
C
C
O
O
H
H
H
H
8c (28%)
8d (15%)
Overall yields based on compound 1
Figure 1
The best method for generating the hydroxyacid is the sa-
ponification of the ethyl ester in dioxane.13 This, however,
was the turning point in the characterisation of the prod-
ucts, we obtained odd spectroscopic data for the hydroxy-
acid. Indeed, the IR spectrum shows a C=O band at ca.
1730 cm–1, while the O–H bands of both the acid and the
alcohol are of lower intensity than expected. The typical
signals of the corresponding protons of these groups are
also absent in the 1H NMR spectrum in acetone-d6. Final-
ly, the high resolution mass spectrum (EI) gave as the
mass of the parent ion, the one corresponding to the loss
of H2O, which is also the mass of the lactone. These ob-
servations were indeed misleading and we could neither
confirm nor rule out the formation of the lactone during
the saponification. Actually, we could only notably char-
acterise each one unequivocally by 2D NMR spectrosco-
py as detailed below, and thus confirm that the product
obtained by saponification followed by neutralisation is
the hydroxyacid.
In conclusion, we have described in this paper a method-
ology to prepare precursors of medium-sized ring aromat-
ic lactones. The key step is the nickel-catalysed
electrochemical arylation of acrylic ester. Most of the lac-
tones prepared, as well as some intermediates, are new
products. This methodology can now be applied to the
preparation of new types of lactones having various sub-
stituents on the aryl ring or containing a heteroaryl moi-
ety.
All reagents and supporting electrolytes were used as obtained com-
mercially. All reactions were performed under an inert atmosphere
(argon) unless otherwise indicated. An iron rod was used as the an-
ode; the cathode was made of nickel foam.
1H, 13C NMR spectra were recorded on a Brucker AC-200 (200
MHz) or AVANCE 300 (300 MHz) spectrometer at r.t., except for
8d. Regarding the 13C NMR data, some of the aromatic signals are
missing, which may be a consequence of the overlapping of certain
signals. Infrared spectra were recorded on a Perkin Elmer Spectrum
BX II spectrometer. Mass spectra (electron impact) were obtained
on a Thermoquest GCQ spectrometer coupled to a Finnigan-GCQ
chromatograph with a CPSIL5CB/MS capillary column. High-res-
For preparing the lactone from the hydroxy acid, we tried
some reported methods and found that the method de-
scribed by Yamamoto14 scandium triflate catalysis in ace- olution mass spectral and elemental analyses were performed by
Service Central d’Analyses du CNRS, Lyon.
tonitrile under high dilution conditions afforded the
expected ring compound in good yields (Scheme 7).
Synthesis 2005, No. 10, 1682–1688 © Thieme Stuttgart · New York

PAPER
Synthesis of Precursors for Medium-Ring Aromatic Lactones
1685
3-(2-Bromophenyl)propan-1-ol (1c)
ethyl phosphonoacetate (24 mmol, 5.3 mL) was added to a stirred
suspension of NaH (22 mmol, 0.848 g) in THF (50 mL) at 0 °C to
give a white foam. The mixture was allowed to warm r.t. and after
30 min was re-cooled in an ice bath and the aldehyde in THF (50
mL) added slowly. After 4 h, the reaction mixture was allowed to
warm to r.t. and stirred for 1 h. Sat. aq NH4Cl (20 mL) was then add-
ed to the mixture. Et2O (30 mL) was added and the organic layers
were combined and washed with H2O (3 × 25 mL), dried (MgSO4)
and the solvent removed in vacuo. The residue was purified by col-
umn chromatography (silica gel; pentane–EtOAc, 40:1) to give eth-
yl (E)-3-(2-bromophenyl)but-2-enoate (12) as a pale yellow oil (4.5
g, 84%; E/Z, 3:1).
Triethyl phosphonoacetate (11.9 mL, 60 mmol) was added to a
stirred suspension of NaH (2.5 g, 65 mmol) in THF (70 mL) at 0 °C
to give a white foam. The mixture was allowed to warm to r.t. and
after 30 min was re-cooled in an ice bath and 2-bromobenzaldehyde
(5.83 mL, 50 mmol) was added as a solution in THF (70 mL). After
20 min the reaction mixture was allowed to warm to r.t. and stirred
for 1 h. Sat. aq NH4Cl (50 mL) was then added to the mixture. Et2O
(30 mL) was added and the organic phases were combined and
washed with H2O (3 × 25 mL), dried (MgSO4) and the solvent re-
moved in vacuo to give ethyl (E)-3-(2-bromophenyl)prop-2-enoate
(11) as a pale yellow oil (12.7 g, quantitative yield).
1115
E-1217
IR (CHCl3): 3025, 2985, 2874, 1708, 1637, 1586, 1562 cm–1.
IR (CHCl3): 3072, 2980, 2906, 1714, 1654, 1568, 1468 cm–1.
1H NMR (200 MHz, acetone-d6): d = 7.87 (d, J = 15.9 Hz, 1 H, CH),
7.75–7.17 (m, 4 H, ArH), 6.4 (d, J = 15.9 Hz, 1 H, CH), 4.1 (q,
J = 7.1 Hz, 2 H, CH2), 1.16 (t, J = 7.1 Hz, 3 H, CH3).
13C NMR (50 MHz, acetone-d6): d = 166.4, 143.0, 142.7, 135.0,
134.1, 132.4, 129.0, 125.6, 122.1, 61.0, 14.2.
1H NMR (200 MHz, acetone-d6): d = 7.73–7.63 (m, 1 H, CH), 7.44–
7.03 (m, 4 H, ArH), 5.84 (dt, J = 15.6, 1.6 Hz, 1 H, CH), 4.18 (q,
J = 7.1 Hz, 2 H), 3.76 (dd, J = 6.6, 1.6 Hz, 2 H, CH2), 1.27 (t, J = 7.1
Hz, 3 H).
13C NMR (50 MHz, acetone-d6): d = 166.3, 146.2, 138.5, 133.6,
132.0, 129.6, 128.8, 126.8, 123.6, 60.6, 38.9, 14.5.
EIMS: m/z (%) = 256 (3), 254 (3), 211 (12), 209 (12), 176 (11), 175
(75), 148 (11), 147 (100), 103 (35), 102 (30).
EIMS: m/z (%) = 270 (32), 268 (31), 224 (11), 195 (11), 190 (14),
189 (100), 161 (49), 144 (74), 143 (35), 133 (23), 117 (14), 116
(60), 115 (75).
To a solution of 11 (2.55 g, 10 mmol) in THF (14 mL) at –78 °C un-
der argon was added LiBEt3H (1 M soln in THF; 40 mL, 40 mmol)
dropwise over 1 h. The reaction mixture was then stirred for a fur-
ther hour at –78 °C and then allowed to warm to r.t. After stirring at
r.t. for 18 h, H2O (11 mL) was added carefully and the reaction mix-
ture was refluxed for 2 h. After cooling to r.t., aq NaOH (3 M, 26
mL) was added. Finally, after chilling to 0 °C, 27% aq H2O2 (30
mL) was added dropwise. When the reactivity had lessened, the ice
bath was removed and the reaction allowed to warm to r.t., the reac-
tion mixture was stirred for a further hour and then diluted with H2O
(30 mL). After extraction with Et2O (3 × 30 mL), the organic layers
were combined, washed with H2O (3 × 40 mL), dried (MgSO4) and
evaporated in vacuo to give, 3-(2-bromophenyl)propan-1-ol (1c), as
a pale yellow oil (2.13 g, 91%).
The reduction of 12 (15 mmol) was carried out as for the reduction
of 11 to yield 3-(2-bromophenyl)butan-1-ol (1d) (2.74 g, 80%).
1d16
IR (CHCl3): 3472, 3043, 2939, 2865, 1045 cm–1.
1H NMR (200 MHz, acetone-d6): d = 7.7–7.1 (m, 4 H, ArH), 3.63–
3.53 (m, 2 H, CH2), 2.93–2.75 (m, 2 H, CH2), 1.84–1.62 (m, 4 H,
2 × CH2).
13C NMR (50 MHz, acetone-d6): d = 142.7, 133.7, 133.5, 131.6,
128.6, 124.9, 62.4, 36.6, 33.4, 27.3.
EIMS: m/z (%) = 230 (<1), 228 (<1), 184 (53), 182 (55), 171 (24),
169 (27), 150 (11), 149 (100), 131 (77), 116 (26), 115 (18), 107
(21), 103 (34), 91 (34), 90 (23), 89 (22).
1c16
IR (CHCl3): 3435, 3062, 2940, 2880, 1053 cm–1.
Protection of Alcohols 1; General Procedure
1H NMR (200 MHz, acetone-d6): d = 7.43–6.92 (m, 4 H, ArH), 3.47
(t, J = 6.4 Hz, 2 H, CH2), 3.45 (br s, 1 H, OH), 2.68 (t, J = 7.7 Hz, 2
H, CH2), 1.75–1.60 (m, 2 H, CH2).
13C NMR (50 MHz, acetone-d6): d = 142.4, 133.6, 131.5, 128.6,
124.8, 61.8, 33.8, 33.2.
To a suspension of NaH (1.73 g, 45 mmol) in THF (30 mL) was
added alcohol (30 mmol) in THF (50 mL) at r.t. After the mixture
was stirred for 10 min, p-methoxybenzyl choride (4.6 mL, 36
mmol) and TBAI (1.6 g, 4.2 mmol) were added. The resulting mix-
ture was stirred for 4 h at 50 °C, and then H2O (20 mL) was added.
The mixture was extracted with Et2O several times (3 × 20 mL).
The combined extracts were dried (MgSO4) and evaporated to leave
a crude product, which was purified by column chromatography
(silica gel; pentane–Et2O, 95:5).
EIMS: m/z (%) = 216 (<1), 214 (<1), 171 (10), 169 (11), 135 (45),
134 (13), 117 (100), 115 (29), 107 (14), 91 (20), 90 (13).
3-(2-Bromophenyl)butan-1-ol (1d)
To a stirred suspension of CH3OCH2P(C6H5)3Cl (2.2 equiv, 44
mmol, 15 g) in anhyd THF (75 mL), t-BuOK (2 equiv, 40 mmol, 4.5
g) was added at 0 °C within 30 min and stirred for 30 min at this
temperature. o-Bromobenzaldehyde (20 mmol, 2.3 mL) was added
within 30 min, the resulting mixture was stirred for 5 h at r.t. and
then hydrolysed with H2O (20 mL). The solvent was removed in
vacuo, and the residue was acidified with HCl (2 N; 20 mL) and ex-
tracted with EtOAc (3 × 25 mL). The combined organic layers were
washed with H2O (15 mL) and brine (15 mL), dried (MgSO4), fil-
tered and concentrated. The residue was purified by column chro-
matography (silica gel; pentane–EtOAc, 20:1). The product was
diluted in THF (30 mL) and HCl (2 N; 10 mL) and this solution was
stirred under reflux for 2.5 h. H2O (20 mL) was added, and the so-
lution was concentrated in vacuo to a volume of 45 mL. The residue
was extracted with EtOAc (3 × 25 mL), the combined organic lay-
ers were washed with H2O (15 mL), sat. NaHCO3 (15 mL) and
brine, dried, filtered and evaporated in vacuo. At the same time, tri-
3a18
Yield: 8.9 g (93%); colourless oil.
IR (CHCl3): 3027, 2958, 2863, 1613, 1587, 1514, 1087, 1035 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.55–6.85 (m, 8 H, ArH), 4.59 (s,
2 H, CH2), 4.56 (s, 2 H, CH2), 3.80 (s, 3 H, CH3).
13C NMR (50 MHz, CDCl3): d = 159.1, 137.6, 130.0, 129.2, 128.7,
127.2, 122.6, 113.7, 72.3, 71.1, 55.1.
EIMS: m/z (%) = 308 (7), 306 (9), 150 (12), 137 (100), 122 (42),
121 (43), 119 (19), 91 (24), 77 (11).
Anal. Calcd for C15H15BrO2: C, 58.65; H, 4.92; O, 10.42; Br, 26.01;
Found: C, 58.83; H, 4.98; O, 10.80; Br, 26.11.
3b
Yield: 9.12 g (95%); colourless oil.
Synthesis 2005, No. 10, 1682–1688 © Thieme Stuttgart · New York

1686
E. Métay et al.
PAPER
IR (CHCl3): 3027, 2960, 2862, 1613, 1586, 1514, 1090, 1037 cm–1.
(s, 3 H, CH3), 3.23–3.15 (m, 2 H, CH2), 2.84–2.75 (m, 2 H, CH2),
1.43 (t, J = 7.1 Hz, 3 H, CH3).
1H NMR (200 MHz, CDCl3): d = 7.73–7.09 (m, 8 H, ArH), 4.67 (s,
2 H, CH2), 4.0 (s, 3 H, CH3), 3.91–3.87 (m, 2 H, CH2), 3.29–3.24
(m, 2 H, CH2).
13C NMR (50 MHz, CDCl3): d = 159.0, 138.1, 132.7, 130.3, 129.1,
128.9, 127.1, 124.5, 113.6, 72.4, 68.9, 55.1, 36.3.
13C NMR (50 MHz, CDCl3): d = 172.9, 159.1, 139.5, 135.8, 130.1,
129.5, 129.1, 128.1, 126.3, 113.7, 72.0, 70.0, 60.3, 55.1, 35.5, 27.5,
14.1.
EIMS: m/z (%) = 328 (<1), 192 (14), 161 (12), 146 (21), 137 (100),
133 (29), 122 (10), 121 (78), 118 (17), 117 (19), 115 (14), 109 (19),
105 (13), 91 (17), 77 (15).
EIMS: m/z (%) = 322 (5), 320 (4), 241 (26), 121 (100), 105 (9),
91(7), 77 (9).
Anal. Calcd for C20H24O4: C, 73.15; H, 7.37; O, 19.49. Found: C,
73.17; H, 7.52; O, 19.38.
Anal. Calcd for C16H17BrO2: C, 59.83; H, 5.33; O, 9.96; Br, 24.88.
Found: C, 60.09; H, 5.46; O, 10.21; Br, 24.97.
5b
3c
Yield: 2.6 g (76%); colourless oil.
IR (CHCl3): 3025, 2960, 2862, 1726, 1613, 1586, 1514, 1076 cm–1.
Yield: 8.2 g (82%); colourless oil.
IR (CHCl3): 3027, 2937, 2839, 1613, 1586, 1512, 1104.
1H NMR (200 MHz, CDCl3): d = 7.44–7.02 (m, 8 H, ArH), 4.64 (s,
2 H, CH2), 4.31 (q, J = 7.1 Hz, 2 H, CH2), 3.96 (s, 3 H, CH3), 3.83
(t, J = 7.4 Hz, 2 H, CH2), 3.15 (m, 4 H, 2 CH2), 2.79–2.71 (m, 2 H,
CH2), 1.42 (t, J = 7 Hz, 3 H, CH3).
13C NMR (50 MHz, CDCl3): d = 172.7, 159.0, 138.6, 136.5, 130.3,
129.7, 129.0, 126.4, 113.6, 72.5, 70.4, 60.3, 55.1, 35.3, 32.7, 27.6,
14.0.
1H NMR (200 MHz, acetone-d6): d = 7.49–6.81 (m, 8 H, ArH), 4.36
(s, 2 H, CH2), 3.69 (s, 3 H, CH3), 3.40 (t, J = 6.2 Hz, 2 H, CH2), 2.75
(t, J = 7.7 Hz, 2 H, CH2), 1.85–1.77 (m, 2 H, CH2).
13C NMR (50 MHz, acetone-d6): d = 160.0, 142.1, 133.6, 133.4,
131.8, 131.5, 130.0, 129.8, 128.6, 124.8, 114.4, 72.9, 69.5, 55.4,
33.4, 30.6.
EIMS: m/z (%) = 336 (2), 334 (2), 256 (17), 255 (86), 137 (21), 122
(15), 121 (100), 119 (11), 91 (24), 77 (15).
EIMS: m/z (%) = 342 (<1), 254 (18), 137 (15), 122 (13), 121 (100).
Anal. Calcd for C21H26O4: C, 73.66; H, 7.65; O, 18.69. Found: C,
73.67; H, 7.64; O, 18.91.
HRMS (ESI): m/z calcd for C17H19BrO4Na (M + Na): 389.0364;
found: 389.0343.
5c
3d
Yield: 1.59 g (64%); colourless oil.
IR (CHCl3: 3027, 2939, 2863, 1727, 1612, 1586, 1513, 1096 cm–1.
Yield: 6.43 g (61%); colourless oil.
IR (CHCl3): 3047, 2938, 2863, 1611, 1513, 1098 cm–1.
1H NMR (200 MHz, acetone-d6): d = 7.12–6.70 (m, 8 H, ArH), 4.25
(s, 2 H, CH2), 3.89 (q, J = 7.0 Hz, 2 H, CH2), 3.59 (s, 3 H, CH3), 3.29
(t, J = 5.9 Hz, 2 H, CH2), 2.77 (t, J = 7.7 Hz, 2 H, CH2), 2.60–2.52
(m, 2 H, CH2), 2.42–2.34 (m, 2 H, CH2), 1.73–1.63 (m, 2 H, CH2),
1.0 (t, J = 7.0 Hz, 3 H, CH3).
13C NMR (50 MHz, acetone-d6): d = 172.8, 160.0, 140.7, 139.3,
131.8, 129.9, 127.1, 114.3, 72.8, 69.7, 60.1, 55.4, 35.8, 31.9, 29.6,
28.1, 14.3.
1H NMR (300 MHz, acetone-d6): d = 7.91–6.92 (m, 8 H, ArH), 4.50
(s, 2 H, CH2), 3.85 (s, 3 H, CH3), 3.60–3.55 (m, 2 H, CH2), 2.84–
2.78 (m, 2 H, CH2), 1.81–1.67 (m, 4 H, 2 × CH2).
13C NMR (75 MHz, acetone-d6): d = 159.2, 141.7, 132.8, 130.7,
130.4, 129.3, 127.6, 127.5, 126.3, 114.4, 113.8, 74.4, 69.9, 55.3,
35.9, 29.5, 26.6.
EIMS: m/z (%) = 350 (2), 348 (2), 122 (33), 121 (100).
HRMS (ESI): m/z calcd for C18H21BrO2Na (M + Na): 371.0623;
found: 371.0603.
EIMS: m/z (%) = 268 (27), 205 (13), 171 (10), 137 (21), 129 (11),
122 (18), 121 (100), 117 (11), 91 (14).
Anal. Calcd for C22H28O4: C, 74.13; H, 7.92; O, 17.95. Found: C,
74.32; H, 8.09; O, 18.00.
Arylation of Electron-Deficient Olefins; General Procedure
Under argon, in an undivided cell equipped with nickel foam (area
40 cm2) as the cathode and an iron rod as the anode, TBAB (0.34
mmol) and TBAI (0.21 mmol) as supporting electrolytes were dis-
solved in a mixture of DMF (50 mL) and pyridine (5 mL). 1,2-Di-
bromoethane (0.1 mmol) was introduced; after a short electrolysis
run at constant current density (0.2 A·dm–2) at r.t. over 15 min a
small amount of iron ions resulted. The activated olefin (25 mmol),
NiBr2·3H2O (1 mmol) and aryl bromide (10 mmol) was added, and
the reaction mixture was heated at 100 °C. The electrosynthesis was
run at current density 0.2 A·dm–2. The reaction was monitored by
GC and stopped after the aryl bromide was consumed. The mixture
was then hydrolysed with HCl (1 N; 30 mL) and diluted with Et2O
(2 × 50 mL) and the combined organic layers were washed with
H2O (15 mL) and sat. NaCl soln, then dried with MgSO4. The oil
thus obtained was purified by column chromatography (silica gel;
pentane–Et2O, 90:10) to give the desired compound.
5d
Yield: 1.99 g (54%); colourless oil.
IR (CHCl3): 3027, 2939, 2863, 1727, 1612, 1586, 1513, 1096 cm–1.
1H NMR (300 MHz, acetone-d6): d = 7.31–6.89 (m, 8 H, ArH), 4.41
(s, 2 H, CH2), 4.07 (q, J = 7.2 Hz, 2 H, CH2), 3.78 (s, 3 H, CH3),
3.48–3.44 (m, 2 H, CH2), 2.98–2.92 (m, 2 H, CH2), 2.68–2.55 (m, 4
H, 2 CH2), 1.69–1.65 (m, 4 H, 2 × CH2), 1.19 (t, J = 7.2 Hz, 3 H,
CH3).
13C NMR (75 MHz, acetone-d6): d = 172.8, 159.8, 141.1, 139.1,
131.8, 129.9, 126.9, 114.2, 72.8, 70.3, 60.5, 55.4, 35.8, 32.8, 28.1,
14.5.
EIMS: m/z (%) = 268 (27), 205 (13), 171 (10), 137 (21), 129 (11),
122 (18), 121 (100), 117 (11), 91 (14).
HRMS (ESI): m/z calcd for C23H30O4Na (M + Na): 393.2042;
found: 393.2005.
5a
Yield: 2.6 g (79%); colourless oil.
IR (CHCl3): 3025, 1726, 1612, 1586, 1514 cm–1.
Deprotection of Alcohols 5; Typical Procedure
1H NMR (200 MHz, CDCl3): d = 7.55–7.09 (m, 8 H, ArH), 4.74 (s,
2 H, CH2), 4.70 (s, 2 H, CH2), 4.32 (q, J = 7.1 Hz, 2 H, CH2), 3.98
A solution of product 5a (2.6 g, 7.88 mmol) and CAN (8.64 g, 15.3
mmol) in MeCN–H2O (9:1, 37 mL) was stirred for 30 min at r.t. The
reaction mixture was diluted with CH2Cl2 (20 mL). The organic
Synthesis 2005, No. 10, 1682–1688 © Thieme Stuttgart · New York

PAPER
Synthesis of Precursors for Medium-Ring Aromatic Lactones
Saponification; Typical Procedure
1687
phase was washed with sat. aq NaHCO3 (20 mL), and the aqueous
phase was extracted with CH2Cl2 (2 × 20 mL). The combined or-
ganic phases were dried (MgSO4), filtered, concentrated, and puri-
fied by column chromatography (silica gel; pentane–EtOAc, ratio).
To a solution of 6a (1.46 g, 7 mmol) in dioxane–H2O (1:1, 70 mL)
was added a 20% soln of KOH in H2O (1.56 g, 24 mmol). The reac-
tion mixture was refluxed for 16 h, cooled to r.t., then H2SO4 was
added until pH = 1 was reached. The mixture was extracted with
Et2O (3 × 25 mL). The combined extracts were dried (MgSO4) and
evaporated to leave the crude product.
6a14
Isolated as a mixture of 6a and 8a.
EIMS: m/z (%) = 208 (5), 190 (54), 175 (12), 163 (17), 162 (30),
147 (10), 145 (50), 144 (53), 134 (17), 133 (100), 119 (32), 118
(14), 117 (84), 116 (93), 115 (72), 107 (20), 105 (27), 103 (11), 91
(48), 79 (27), 77 (20).
7a19
Yield: 1.26 g (quantitative).
IR (KBr): 3346, 1694 cm–1.
1H NMR (200 MHz, acetone-d6): d = 7.27–6.98 (m, 4 H, ArH), 4.56
6b
(s, 2 H, CH2), 2.88–2.80 (m, 2 H, CH2), 2.53–2.45 (m, 2 H, CH2).
Due to the instability of 6b, it was characterized by IR, NMR and
MS only.
13C NMR (50 MHz, acetone-d6): d = 174.3, 140.5, 139.7, 129.7,
129.1, 128.2, 126.8, 62.6, 35.4, 27.7.
Yield: 1.52 g (80%); colourless oil.
IR (CHCl3): 3462, 3032, 1727 cm–1.
7b
Yield: 1.36 g (quantitative).
IR (KBr): 3392, 2918, 2865, 1702 cm–1.
1H NMR (200 MHz, acetone-d6): d = 7.09–6.94 (m, 4 H, ArH), 3.62
(t, J = 7.3 Hz, 2 H, CH2), 2.87–2.79 (m, 2 H, CH2), 2.76 (t, J = 7.3
Hz, 2 H, CH2), 2.49–2.41 (m, 2 H, CH2).
1H NMR (200 MHz, acetone-d6): d = 7.21–7.00 (m, 4 H, ArH), 4.05
(q, J = 7.2 Hz, 2 H, CH2), 3.8 (br s, 1 H, OH under the next signal)
3.74 (t, J = 7.2 Hz, 2 H, CH2), 3.00–2.92 (m, 2 H, CH2), 2.87 (t,
J = 7.2 Hz, 2 H, CH2), 2.60–2.52 (m, 2 H, CH2), 1.16 (t, J = 7.2 Hz,
3 H, CH3).
13C NMR (50 MHz, acetone-d6): d = 173.1, 139.9, 138.0, 130.8,
129.7, 128.8, 127.1, 63.6, 60.7, 36.8, 35.9, 28.4, 14.5.
13C NMR (50 MHz, acetone-d6): d = 174.1, 139.9, 137.8, 130.6,
126.9, 126.6, 63.4, 36.5, 35.4, 28.1.
EIMS: m/z (%) = 222 (<1), 192 (51), 160 (40), 159 (51), 147 (18),
146 (100), 133 (18), 131 (47), 130 (38), 129 (28), 121 (13), 119
(21), 118 (88), 117 (78), 116 (16), 115 (53), 105 (29), 104 (25), 103
(11), 93 (11), 91 (37).
HRMS (ESI): m/z calcd for C11H14O3Na (M + Na): 217.0841;
found: 217.0840.
7c
Yield: 1.46 g (quantitative).
IR (KBr): 3300, 2936, 2865, 1720 cm–1.
6c
Yield: 1.03 g (80%); colourless oil.
1H NMR (200 MHz, acetone-d6): d = 7.09–6.93 (m, 4 H, ArH), 3.49
(t, J = 6.3 Hz, 2 H, CH2), 2.87–2.79 (m, 2 H, CH2), 2.61 (t, J = 7.7
Hz, 2 H, CH2), 2.49–2.41 (m, 2 H, CH2), 1.73–1.59 (m, 2 H, CH2).
13C NMR (50 MHz, acetone-d6): d = 174.0, 140.9, 139.4, 129.8,
126.9, 126.6, 61.8, 35.4, 35.0, 34.8, 28.1.
IR (CHCl3): 3474, 3034, 1723 cm–1.
1H NMR (200 MHz, acetone-d6): d = 7.11–6.98 (m, 4 H, ArH), 3.98
(q, J = 7.2 Hz, 2 H, CH2), 3.50 (br s, 1 H, OH under the signal), 3.50
(t, J = 6.3 Hz, 2 H, CH2), 2.90–2.82 (m, 2 H, CH2), 2.63 (t, J = 6.3
Hz, 2 H, CH2), 2.51–2.43 (m, 2 H, CH2), 1.76–1.62 (m, 2 H, CH2),
1.09 (t, J = 7.2 Hz, 3 H, CH3).
HRMS (ESI): m/z calcd for C12H16O3Na (M + Na): 231.0997;
13C NMR (50 MHz, acetone-d6): d = 172.7, 140.9, 139.1, 129.7,
found: 231.0976.
126.6, 61.7, 60.4, 35.7, 35.0, 30.0, 27.9, 14.3.
7d
EIMS: m/z (%) = 236 (9), 218 (54), 190 (15), 173 (26), 172 (92),
147 (10), 146 (37), 145 (46), 144 (92), 143 (17), 131 (34), 130 (47),
129 (100), 119 (11), 118 (22), 117 (79), 116 (23), 115 (54), 103
(12), 105 (38), 91 (39), 77 (12).
Yield: 1.55 g (quantitative).
IR (KBr): 3300, 2937, 2868, 1711 cm–1.
1H NMR (300 MHz, acetone-d6): d = 7.21–7.01 (m, 4 H, ArH), 3.60
(t, J = 6.2 Hz, 2 H, CH2), 2.98–2.93 (m, 2 H, CH2), 2.69 (t, J = 7.5
Hz, 2 H, CH2), 2.62–2.56 (m, 2 H, CH2), 1.65–1.62 (m, 2 H, CH2).
HRMS (ESI): m/z calcd for C14H20O3Na (M + Na): 259.1310;
found: 259.1321.
13C NMR (75 MHz, acetone-d6): d = 174.7, 141.4, 139.6, 127.0,
126.9, 62.5, 35.8, 33.6, 33.1, 32.8, 28.5, 28.3.
6d
Yield: 0.75 g (70%); colourless oil.
IR (CHCl3): 3474, 3034, 1723 cm–1.
HRMS (ESI): m/z calcd for C13H18O3Na (M + Na): 245.1154;
found: 245.0871.
1H NMR (300 MHz, acetone-d6): d = 7.20–7.09 (m, 4 H, ArH), 4.09
(q, J = 7.1 Hz, 2 H, CH2), 3.59 (t, J = 6.1 Hz, 2 H, CH2), 3.56 (br s,
1 H, OH), 2.98–2.93 (m, 2 H, CH2), 2.65 (t, J = 7.5 Hz, 2 H, CH2),
2.61–2.55 (m, 2 H, CH2), 1.67–1.61 (m, 4 H, 2 × CH2), 1.20 (t,
J = 7.1 Hz, 3 H, CH3).
13C NMR (75 MHz, acetone-d6): d = 172.2, 140.5, 138.4, 129.2,
128.8, 126.2, 125.9, 61.3, 59.8, 35.1, 32.7, 32.1, 27.6, 27.4, 13.6.
p-Nitrobenzoic Anhydride
To a mixture of p-nitrobenzoic acid (3.34 g, 20 mmol) and p-ni-
trobenzoic chloride (3.71g, 20 mmol) in CH2Cl2 (50 mL) was added
pyridine (2.02 mL, 25 mmol) dropwise at 0 °C. The reaction mix-
ture was stirred for 15 h at r.t. and then quenched with cold H2O (20
mL). The mixture was extracted with CH2Cl2 (3 × 30 mL), the or-
ganic phases were dried with MgSO4 and evaporated. The crude
product was purified by recrystallisation from CH2Cl2–hexane to
afford p-nitrobenzoic anhydride (5.4 g, 85% yied).
EIMS: m/z (%) = 250 (<1), 204 (16), 187 (15), 186 (100), 159 (13),
158 (49), 145 (28), 144 (27), 143 (23), 133 (12), 132 (11), 131 (27),
130 (34), 129 (33), 128 (13), 118 (11), 117 (38), 116 (15), 115 (28),
105 (11), 91 (17).
Lactonisation; Typical Procedure
p-Nitrobenzoic anhydride (506 mg, 1.6 mmol) was dissolved in an-
hyd MeCN (340 mL), and a cloudy solution of Sc(OTf)3 (1.6 mL,
HRMS (ESI): m/z calcd for C15H23O3 (M + H): 251.1647; found:
251.1664.
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1688
E. Métay et al.
PAPER
0.16 mmol, 0.1 M) in MeCN was added to the solution at r.t. under
argon. A solution of hydroxycarboxylic acid (20 mL, 0.8 mmol,
0.08 M) in THF was added slowly from a mechanically driven sy-
ringe over 15 h to the mixed solution at reflux under argon, and the
reaction mixture was stirred for a further 5 h at reflux. After cooling
to r.t., the solution was quenched with aq sat. NaHCO3 (8 mL). The
resulting mixture was concentrated under reduced pressure and ex-
tracted with Et2O (2 × 25 mL). The organic layers were dried over
MgSO4, filtered, and concentrated in vacuo. Purification by column
chromatography (silica gel; pentane–EtOAc) gave the desired lac-
tone.
HRMS (ESI): m/z calcd for C13H17O2 (M + H): 205.1229; found:
205.1232.
References
(1) (a) Corey, E. J.; Cheng, X.-M. The Logic of Chemical
Synthesis; Wiley: New York, 1989. (b) Davoli, P.;
Spaggiari, A.; Castagnetti, L.; Prati, F. Org. Biomol. Chem.
2004, 2, 38. (c) Fürstner, A.; Radkowski, K.; Wirtz, C.;
Goddard, R.; Lehmann, C. W.; Mynott, R. J. Am. Chem. Soc.
2002, 124, 7061. (d) Andrus, M. B.; Argade, A. B.
Tetrahedron Lett. 1996, 37, 5049.
(2) Cooper, M. S.; Heaney, H.; NewBold, A. J.; Sanderson, W.
R. Synlett 1990, 533.
(3) (a) Illuminati, G.; Mandolini, L. Acc. Chem. Res. 1981, 14,
95. (b) Brown, D. P.; Krishnamurthy, L. Heterocycles 2004,
5, 1185.
8a8,20
Yield: 0.067 g (52%); colourless oil.
IR (CHCl3): 3060, 2927, 1733, 1606, 1530 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.25–7.05 (m, 4 H, ArH), 5.18 (s,
2 H, CH2), 3.18–3.13 (m, 2 H, CH2), 3.01–2.96 (m, 2 H, CH2).
13C NMR (75 MHz, CDCl3): d = 173.2, 137.0, 133.2, 130.0, 129.2,
126.6, 70.2, 31.5, 28.4.
(4) Rousseau, G. Tetrahedron 1995, 51, 2777; and references
therein.
(5) (a) Vorbrüggen, H.; Krolikiewicz, K. Angew. Chem., Int. Ed.
Engl. 1977, 16, 876. (b) Steliou, K.; Szczygielska-
Nowosielska, A.; Favre, A.; Poupart, M. A.; Hanessian, S. J.
Am. Chem. Soc. 1980, 102, 7578. (c) Inanaga, J.; Hirata, K.;
Saeki, H.; Katsuki, T.; Yamaguchi, M. Bull. Chem. Soc. Jpn.
1979, 52, 1989. (d) Bartra, M.; Vilarasa, J. J. Org. Chem.
1991, 56, 5132. (e) Kurihara, T.; Nakajima, Y.; Mitsunobu,
O. Tetrahedron Lett. 1976, 28, 2455. (f) Corey, E. J.;
Nicolaou, K. C. J. Am. Chem. Soc. 1974, 96, 5614.
(6) (a) Mukaiyama, T.; Izumi, J.; Shiina, I. Chem. Lett. 1997,
187. (b) Gilbert, J.; Gault, H. C. R. Acad. Sci., Ser. C 1969,
268, 867. (c) Gilbert, J.; Douville, R. C. R. Acad. Sci., Ser. C
1970, 271, 1262.
EIMS: m/z (%) = 162 (26), 144 (27), 133 (19), 118 (19), 117 (100),
116 (50), 115 (50), 105 (17), 91 (42), 77 (12).
8b8
Yield: 0.053 g (38%); colourless oil.
IR (CHCl3): 3022, 2928, 1732, 1604, 1492 cm–1.
1H NMR (300 MHz, acetone-d6): d = 7.23–7.18 (m, 4 H, ArH), 4.29
(t, J = 5.5 Hz, 2 H, CH2), 3.07 (t, J = 6.5 Hz, 2 H, CH2), 2.98 (t,
J = 5.5 Hz, 2 H, CH2), 2.61 (t, J = 6.5 Hz, 2 H, CH2).
13C NMR (75 MHz, acetone-d6): d = 176.5, 139.9, 137.7, 130.9,
130.3, 127.2, 127.1, 67.2, 39.1, 35.8, 30.9.
(7) (a) Galli, C.; Giovannelli, G.; Illuminati, G.; Mandolini, L.
J. Org. Chem. 1979, 44, 1258. (b) Karim, M. R.; Sampson,
P. J. Org. Chem. 1990, 55, 598. (c) Chai, K. B.; Sampson,
P. J. Org. Chem. 1993, 58, 6807. (d) Kimura, Y.; Regen, S.
L. J. Org. Chem. 1983, 48, 1533.
EIMS: m/z (%) = 176 (57), 161 (11), 147 (13), 146 (36), 131 (52),
130 (40), 117 (31), 116 (11), 115 (29), 105 (10), 104 (100), 103
(14), 78 (27).
8c
(8) Cavalcanti, J. C. M.; Fonseca Goulart, M. O.; Léonel, E.;
Nédélec, J.-Y. Tetrahedron Lett. 2002, 43, 6343.
(9) (a) Gibson, S. E.; Guillo, N.; Middleton, R. J.; Thuilliez, A.;
Tozer, M. J. Chem. Soc., Perkin Trans. 1 1997, 447.
(b) Poschalko, A.; Welzig, S.; Treu, M.; Nerdinger, S.;
Mereiter, K.; Jordis, U. Tetrahedron 2002, 58, 1513.
(10) Asao, N.; Ohishi, T.; Sato, K.; Yamamoto, Y. Tetrahedron
2002, 58, 8195.
Yield: 0.100 g (66%); colourless oil.
IR (CHCl3): 3016, 2937, 2868, 1736, 1603, 1491 cm–1.
1H NMR (300 MHz, acetone-d6): d = 7.2–7.08 (m, 4 H, ArH), 4.21–
4.16 (m, 2 H, CH2), 3.05–2.98 (m, 2 H, CH2), 2.89–2.70 (m, 2 H,
CH2), 2.52–2.45 (m, 2 H, CH2), 2.19–2.05 (m, 2 H, CH2).
13C NMR (75 MHz, acetone-d6): d = 173.7, 142.6, 138.1, 130.4,
130.2, 126.8, 126.1, 62.3, 36.7, 31.1, 30.7, 26.7.
(11) Johanson, R.; Samuelson, B. J. Chem. Soc., Perkin Trans. 1
EIMS: m/z (%) = 191 (11), 190 (60), 173 (16), 172 (100), 157 (20),
146 (20), 145 (20), 144 (50), 133 (12), 131 (26), 130 (22), 129 (59),
128 (21), 118 (22), 117 (87), 116 (26), 115 (58), 105 (18), 91 (40).
1984, 2371.
(12) (a) Nédélec, J.-Y.; Périchon, J.; Troupel, M. Top. Curr.
Chem. 1997, 185, 141. (b) Condon-Gueugnot, S.; Dupré,
D.; Nédélec, J.-Y.; Périchon, J. Synthesis 1997, 1475.
(c) Condon, S.; Dupré, D.; Falgayrac, G.; Nédélec, J.-Y. Eur.
J. Org. Chem. 2002, 105.
HRMS (ESI): m/z calcd for C12H15O2 (M + H):191.1072; found:
191.1085.
(13) Miller, M. J.; Bajwa, J. S.; Mattingly, P. G.; Peterson, K. J.
8d
Org. Chem. 1982, 47, 4928.
(14) Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H. J.
Org. Chem. 1996, 61, 4560.
Yield: 0.109 g (67%); colourless oil.
IR (CHCl3): 3056, 2957, 2860, 1732, 1530, 1491 cm–1.
1H NMR (300 MHz, DMF-d7, 343 K): d = 7.27–7.10 (m, 4 H, ArH),
4.23–4.18 (m, 2 H, CH2), 3.05–2.91 (m, 4 H, 2 × CH2), 2.64–2.59
(m, 2 H, CH2), 2.08–1.99 (m, 2 H, CH2), 1.43–1.35 (m, 2 H, CH2).
(15) Chatterjee, A. K.; Choi, T. L.; Sanders, D. P.; Grubbs, R. H.
J. Am. Chem. Soc. 2003, 125, 11360.
(16) Wolfe, J. P.; Rennels, R. A.; Buchwald, S. L. Tetrahedron
1996, 52, 7525.
(17) (a) Huang, Q.; Larock, R. C. J. Org. Chem. 2003, 68, 7342.
(b) Huang, Q.; Larock, R. C. Org. Lett. 2002, 4, 2505.
(18) Martin-Matute, B.; Nevado, C.; Cardenas, D. J.; Echavarren,
A. M. J. Am. Chem. Soc. 2003, 125, 5757.
13C NMR (75 MHz, DMF-d7, 343 K): d = 171.1, 139.6, 138.7,
130.3, 128.5, 126.4, 125.8, 65.5, 37.2, 28.5, 28.4, 27.2, 24.4.
EIMS: m/z (%) = 204 (59), 187 (13), 186 (100), 171 (26), 158 (83),
157 (15), 145 (12), 143 (25), 142 (13), 131 (30), 130 (53), 129 (46),
128 (17), 117 (51), 116 (19), 115 (55), 105 (12), 91 (26).
(19) Arth, C.; Clemens, M.; Meise, W. Liebigs Ann. Chem. 1994,
3, 259.
(20) Meise, W.; Arth, C. Liebigs Ann. Chem. 1992, 2, 163.
Synthesis 2005, No. 10, 1682–1688 © Thieme Stuttgart · New York