An efficient synthetic route to novel 3-alkyl- and 3-aryl-4-iodophenols

Article abstract of DOI:10.1055/s-2007-1000860

An efficient method for the preparation of novel 3-alkyl-and 3-aryl-4-iodophenols from 3-alkyl- and 3-arylphenols is described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-1000860

PAPER
221
An Efficient Synthetic Route to Novel 3-Alkyl- and 3-Aryl-4-iodophenols
N
ovel 3-Alkyl- an
e
d 3-Aryl-4-
s
iodopheno
i
ls ne J. Hermann,*a Michael C. Annis,a Peter D. Edwards,a Marta Corrales,a Lucía Díaz,a Robert A. Goodnowb
a
ChemOvation Ltd., Graylands, Langhurstwood Road, Horsham, West Sussex, RH12 4QD, UK
Fax +44(1403)276501; E-mail: gesine.hermann@chemovation.com
Roche Research Center, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, USA
b
Received 4 September 2007; revised 2 October 2007
unsubstituted in the 3-position, utilising one equivalent of
sodium iodide and sodium hypochlorite in the presence of
sodium hydroxide in an aqueous methanolic solution.
Abstract: An efficient method for the preparation of novel 3-alkyl-
and 3-aryl-4-iodophenols from 3-alkyl- and 3-arylphenols is de-
scribed.
When this method was applied to the alkyl-substituted 3-
isopropylphenol (4a) the main product was 2-iodo-5-iso-
propylphenol (5a) with 2,4-diiodo-5-isopropylphenol
(6a) as a byproduct (Table 1). However, by changing to
acidic conditions and using one equivalent of iodine
monochloride in methanol the reactivity of the phenol was
decreased and 4-iodo-3-isopropylphenol (1a) and the 2-
iodo isomer 5a were obtained in good isolated yield ac-
companied by a minor amount of 2,4-diiodo-5-isopro-
pylphenol (6a) (Table 1).
Key words: phenols, halogenation, deiodination, iodine monochlo-
ride, Suzuki reaction
As part of an ongoing project it was necessary to access a
series of novel 4-arylphenols containing sterically de-
manding functionality at the 3-position; in particular phe-
nols with isopropyl, tert-butyl, and phenyl groups were of
interest for our work. A viable approach to these com-
pounds via palladium-catalysed coupling of the 3-alkyl-
and 3-aryl-4-halophenols 1 (Figure 1) was proposed.
However, literature searches revealed a paucity of infor-
mation regarding the synthesis of these 4-halogenated 3-
alkyl- and 3-arylphenols.
Table 1 Iodination of 3-Substituted Phenols 4a–c with Iodine
Monochloride in Methanol
I
I
OH
OH
+
OH
OH
I-Cl
I
OH
Br
+
MeOH
I
I
OH
OH
r.t
R
R
R
R
X
4
1
5
6
R
Br
1a R = i-Pr, X = I
1b R = Ph, X = I
1c R = t-Bu, X = I
1d R = t-Bu, X = Br
1,4–6
R
Yield (%)
1
5
2
3
a
b
c
i-Pr
Ph
41
12
0
28
62
86
Figure 1
A few methods have been reported for the direct para-io-
dination of phenols;1 these include the use of sodium io-
dide/Chloramine T, iodine/tert-butyl hypochlorite, and
iodine in trimethyl phosphate. Reagents such as iodine/
potassium iodate,2 bis(pyridine)iodonium tetrafluorobo-
rate,3 or potassium iodide/Oxone4 are also commonly
used. However, none of these methods refers to examples
wherein phenols bearing a 3-alkyl or 3-aryl substituent
and unsubstituted ortho-position(s) are directly and selec-
tively para-iodinated.
t-Bu
Isomers 1a and 5a were separated by column chromatog-
raphy and analysed by LCMS and NMR. NOE experi-
ments provided definite characterisation of the isomers.
Compound 1a showed one NOE signal between the aryl
proton H2 and the adjacent isopropyl group protons; com-
pound 5a showed two NOE signals between the isopropyl
group protons and the adjacent aryl protons H4 and H6.
This paper describes a procedure for selectively and effi-
ciently preparing the 4-halogenated compounds 1 from 3-
alkyl- and 3-arylphenols.
A similar result was obtained when biphenyl-3-ol (4b)
was iodinated with one equivalent of iodine monochloride
in methanol under acidic conditions. A mixture of 6-io-
dobiphenyl-3-ol (1b) and 4-iodobiphenyl-3-ol (5b) was
formed (Table 1) and the isomers were also separated by
column chromatography and characterised by LCMS and
NMR and the structure assigned by NOE.
Initial attempts were undertaken following a literature
procedure5 for the preparation of 4-iodophenols that are
SYNTHESIS 2008, No. 2, pp 0221–0224
x
x
.
x
x
.2
0
0
7
Applying the same method to the sterically most hindered
3-tert-butylphenol (4c), the sole product isolated was 5-
Advanced online publication: 18.12.2007
DOI: 10.1055/s-2007-1000860; Art ID: P10307SS
© Georg Thieme Verlag Stuttgart · New York

222
G. J. Hermann et al.
PAPER
tert-butyl-2-iodophenol (5c)6 with none of the desired iso- achieved under basic conditions to give products 6a–c
mer 1c.
(Table 2). Subsequent selective ortho-deiodination with
N-methylmorpholine9 furnished the desired products 1a–
c in good yields.
It was therefore necessary to pursue another approach to-
wards this template and attention was turned to the prepa-
ration of 4-bromo-3-tert-butylphenol (1d) (Figure 1). It
appeared likely that 1d could be prepared by the selective
dehalogenation of a 2,4-dihalophenol following a litera-
ture procedure.7 Thus 5-tert-butyl-2-iodophenol (5c) was
brominated with bromine in carbon tetrachloride to pro-
vide 4-bromo-5-tert-butyl-2-iodophenol (3). Compound 3
was subsequently deiodinated under reductive conditions
using either zinc in 10% hydrochloric acid and ethanol or
zinc in 10% aqueous sodium hydroxide solution. In our
hands these dehalogenation conditions did not lead to the
reported7 4-bromo-3-tert-butylphenol (1d). The product
isolated under acidic and basic conditions was 2-bromo-5-
tert-butylphenol (2) (Figure 1) and the structure was con-
firmed by NOE. It appears that under the applied reduc-
tive conditions selective deiodination takes place with
concomitant migration of bromine. An alternative litera-
ture method8 whereby 3-tert-butylphenol (4c) was esteri-
fied with boric acid and subsequently brominated with
bromine in chloroform also failed to produce the reported
isomer 1d; the undesired isomer 2 was isolated instead.
Finally, deiodination of 3 under nonreductive conditions9
using N-methylmorpholine afforded the desired 4-bromo-
3-tert-butylphenol (1d). N-Methylmorpholine initiates the
selective removal of iodine, the bromo functionality re-
mains unreacted and no migration of the bromine substit-
uent is observed. Mechanistically the deiodination can be
rationalised as proposed by Talekar et al.9 (Scheme 1);
however the fate of the iodine moiety remains somewhat
unclear. It also has to be noted that traces of water are es-
sential to the reaction, allowing for hypoiodic acid as a
possible temporary intermediate.
Table 2 Diiodination of Phenols 4a–c and Selective ortho-Deiodi-
nation of 6a–c
I
OH
OH
OH
I-Cl/NaOH
MeOH, r.t.
NMM
reflux
I
I
R
R
R
4
6
1
1,4,6
R
Yield (%)
6
1
a
b
c
i-Pr
Ph
60
58
99
74
37
51
t-Bu
4-Iodo- and 4-bromophenols 1a–d were subjected to stan-
dard Suzuki reaction conditions using a range of aryl- and
heteroarylboronic acids (Scheme 2). Tetrakis(triphenyl-
phosphine)palladium(0) was the preferred catalyst in the
presence of tripotassium phosphate or potassium carbon-
ate, in a mixture of toluene–water (9:1) at 90–95 °C; typ-
ically yields of 50–60% were obtained. As expected the 4-
bromophenol 1d was less reactive than the corresponding
4-iodophenol 1c.
OH
+
OH
Pd(PPh3)4
K3PO4 or K2CO3
OH
B
X
Ar
Ar
OH
Toluene/H2O
90–95 °C
R
R
1a–d
Ar = aryl or
heteroaryl
50–60%
H+
I
I
NMM
O–
OH
Scheme 2 Palladium-catalysed coupling reactions of 4-halophenols
1a–d with boronic acids
Br
Br
In summary an efficient and high yielding method to-
wards the synthesis of 3-alkyl- and 3-aryl-4-iodophenols
is described. This requires a diiodination step followed by
selective monodeiodination under nonreductive condi-
tions. These novel compounds are suitable building
blocks for palladium-catalysed coupling reactions under
standard conditions.
3
OH
H
I
NMM or OH–
O
Br
Br
1d
Reagents and solvents were purchased from Acros, Aldrich, or Alfa
Aesar and used without further purification. Flash column chroma-
tography was performed on silica gel 60 Å, Davisil, 35–70 micron
(Fisher Scientific). TLC was performed on silica gel 60 F254 plates
(Merck) and visualised with UV-light 254 nm. 1H NMR, 13C NMR,
and NOE spectra were recorded on a Jeol ECA 500 instrument.
HPLC/MS data were obtained using an HP1100 LC combined with
a Waters Micromass ZMD mass spectrometer operating in positive
and negative ion mode. HRMS data were obtained using a VG Au-
tospec instrument with a resolution <5000 ppm in EI mode.
Scheme 1 Mechanism for the deiodination with N-methylmorpho-
line proposed by Talekar et al9
Following the success of this approach for the preparation
of 4-bromophenol 1d, a more efficient procedure for the
preparation of 4-iodophenols 1a–c was developed. Diiod-
ination of compounds 4a–c with iodine monochloride was
Synthesis 2008, No. 2, 221–224 © Thieme Stuttgart · New York

PAPER
Novel 3-Alkyl- and 3-Aryl-4-iodophenols
223
4-Iodo-3-isopropylphenol (1a) and 2-Iodo-5-isopropylphenol
(5a)
4-Iodobiphenyl-3-ol (5b)
Yield: 2.15 g (62%); Rf = 0.43 (hexane–CH2Cl2, 4:1).
To a stirred soln of commercially available 3-isopropylphenol (4a,
10.0 g, 73.4 mmol) in MeOH (250 mL) was added a soln of ICl
(11.9 g, 73.4 mmol) in MeOH (100 mL) over 1 h. After stirring at
r.t. for 16 h, the mixture was quenched with 20% aq Na2S2O3 (50
mL), stirred for 20 min, and concentrated to give a two-phase mix-
ture. H2O (200 mL) was added and the mixture was extracted with
EtOAc (2 × 150 mL). The combined organic phases were dried
(MgSO4), filtered, and concentrated to dryness. The crude product
was purified by column chromatography (silica gel, gradient hexane
to hexane–CH2Cl2, 1:1).
1H NMR (500 MHz, CDCl3): d = 7.70 (d, J = 8 Hz, 1 H, H3), 7.55–
7.58 (m, 2 H, Haryl), 7.42–7.45 (m, 2 H, Haryl), 7.35–7.38 (m, 1 H,
Haryl), 7.23 (d, J = 2 Hz, 1 H, H6), 6.93 (dd, J = 8, 2.5 Hz, 1 H, H4),
5.30 (s, 1 H, OH); NOE cross peaks observed: H4 and H6 to
d = 7.55–7.58.
13C NMR (125 MHz, CDCl3): d = 155.07, 143.75, 139.74, 138.38,
128.87, 127.87, 126.95, 121.34, 113.69, 84.33.
HPLC/MS: m/z = 295 (M–).
Anal. Calcd for C12H9IO: C, 48.68; H, 3.06. Found: C, 48.65; H,
2.99.
4-Iodo-3-isopropylphenol (1a)
Yield: 7.88 g (41%); Rf = 0.26 (hexane–CH2Cl2, 2:3).
3-tert-Butyl-4-iodophenol (1c); Typical Procedure
1H NMR (500 MHz, CDCl3): d = 7.63 (d, J = 8.5 Hz, 1 H, H5), 6.76
(d, J = 3.5 Hz, 1 H, H2), 6.43 (dd, J = 3, 8.5 Hz, 1 H, H6), 4.69 (s,
1 H, OH), 3.12 (sept, J = 7 Hz, 1 H, CH), 1.21 (d, J = 7 Hz, 6 H,
CH3); NOE cross peaks observed: H2 to d = 1.21.
13C NMR (125 MHz, CDCl3): d = 156.11, 151.96, 140.03, 115.24,
113.42, 89.51, 37.94, 22.95.
A soln of 5-tert-butyl-2,4-diiodophenol (6c, 2.63 g, 6.54 mmol) in
NMM (27 mL) was heated to reflux for 8 h. The mixture was con-
centrated under vacuum. The residues were taken up in EtOAc (50
mL) and washed with 2 M HCl (25 mL) and 20% Na2S2O3 soln (30
mL). The organic phase was dried (MgSO4), filtered, and concen-
trated under vacuum. The resulting oil was purified by column chro-
matography (hexane–CH2Cl2, 7:3 to 1:1); yield: 922 mg (51%);
Rf = 0.42 (hexane–CH2Cl2, 3:7).
HPLC/MS: m/z = 261 (M–).
Anal. Calcd for C9H11IO: C, 41.25; H, 4.23. Found: C, 41.35; H,
4.19.
1H NMR (500 MHz, CDCl3): d = 7.79 (d, J = 8 Hz, 1 H, H5), 6.94
(d, J = 3 Hz, 1 H, H2), 6.38 (dd, J = 2.9, 8.4 Hz, 1 H, H6), 4.65 (s,
1 H, OH), 1.50 (s, 9 H, CH3); NOE cross peaks observed: H2 to
d = 1.50.
13C NMR (125 MHz, CDCl3): d =155.33, 151.93, 144.17, 115.50,
114.69, 83.49, 36.56, 29.70.
2-Iodo-5-isopropylphenol (5a)
Yield: 5.34 g (28%); Rf = 0.54 (hexane–CH2Cl2, 2:3);
1H NMR (500 MHz, CDCl3): d = 7.54 (d, J = 8 Hz, 1 H, H3), 6.88
(d, J = 2 Hz, 1 H, H6), 6.57 (dd, J = 2.5, 8.5 Hz, 1 H, H4), 5.18 (s,
1 H, OH), 2.83 (sept, J = 7 Hz, 1 H, CH), 1.22 (d, J = 7 Hz, 6 H,
CH3); NOE cross peaks observed: H4 and H6 to d = 1.22.
13C NMR (125 MHz, CDCl3): d = 154.67, 151.95, 137.83, 120.99,
113.23, 81.92, 33.75, 23.75.
HPLC/MS: m/z = 261 (M–).
HPLC/MS: m/z = 275 (M–).
Anal. Calcd for C10H13IO: C, 43.50; H, 4.75. Found: C, 43.42; H,
4.68.
4-Bromo-3-tert-butylphenol (1d)
4-Bromo-5-tert-butyl-2-iodophenol (3,7 100 mg, 0.281 mmol) was
taken up in NMM (2 mL) and heated to reflux for 16 h. The soln was
cooled to r.t. and concentrated to dryness. The obtained oil was tak-
en up in EtOAc (50 mL) and washed with 2 M HCl (20 mL). The
organic phase was dried (MgSO4), filtered, and concentrated to dry-
ness. The resulting oil was purified by chromatography (silica gel,
hexane–CH2Cl2, 9:1 to 1:1); yield: 34 mg (50%); Rf = 0.20 (hexane–
CH2Cl2, 1:1).
HRMS: m/z calcd for C9H11IO: 261.9854; found: 261.9846.
Anal. Calcd for C9H11IO: C, 41.25; H, 4.23. Found: C, 41.71; H,
4.34.
6-Iodobiphenyl-3-ol (1b) and 4-Iodobiphenyl-3-ol (5b)
A soln of ICl (2.28 g, 14.1 mmol) in MeOH (10 mL) was added
dropwise to a stirred soln of commercially available biphenyl-3-ol
(4b, 2.00 g, 11.7 mmol) in MeOH (40 mL) over 1 h. The mixture
was stirred at r.t. for 20 h, quenched with 20% Na2S2O3 soln (30
mL) and stirred for a further 15 min. The mixture was concentrated
under vacuum to half of its volume and extracted with EtOAc
(2 × 100 mL). The combined organic phases were dried (Na2SO4),
filtered, and concentrated under vacuum to dryness. The resulting
oil was purified by chromatography (silica gel, hexane–CH2Cl2, 4:1
to 100% CH2Cl2).
1H NMR (500 MHz, CDCl3): d = 7.42 (d, J = 8.5 Hz, 1 H, H5), 6.93
(d, J = 2.5 Hz, 1 H, H2), 6.53 (dd, J = 8.5, 2.5 Hz, 1 H, H6), 4.68 (s,
1 H, OH), 1.48 (s, 9 H, CH3); NOE cross peaks observed: H2 to
d = 1.48.
2-Bromo-5-tert-butylphenol (2)
4-Bromo-5-tert-butyl-2-iodophenol (3,7 1.97 g, 5.56 mmol) was
taken up in 10% aq NaOH (80 mL). Zn powder (4.36 g, 66.7 mmol)
was added in 1 portion and the resulting suspension was heated to
100 °C for 2.5 h. The mixture was cooled to r.t. and filtered through
a pad of Celite. The filtrate was acidified to pH 1–2 with concd HCl
and extracted with EtOAc (2 × 100 mL). The combined organic lay-
ers were dried (MgSO4), filtered, and concentrated to dryness. The
resulting oil was purified by chromatography (silica gel, hexane–
Et2O, 95:5 to 4:1); yield: 1.27 g (quantitative); Rf = 0.51 (hexane–
Et2O, 4:1).
6-Iodobiphenyl-3-ol (1b)
Yield:0.41 g (12%); Rf = 0.20 (hexane–CH2Cl2, 4:1).
1H NMR (500 MHz, CDCl3): d = 7.76 (d, J = 8.5 Hz, 1 H, H5),
7.39–7.43 (m, 3 H, Haryl), 7.31–7.33 (m, 2 H, Haryl), 6.83 (d, J = 3
Hz, 1 H, H2), 6.59 (dd, J = 8.5, 3 Hz, 1 H, H6) 4.77 (s, 1 H, OH);
NOE cross peaks observed: H2 to d = 7.31–7.33.
13C NMR (125 MHz, CDCl3): d = 155.63, 147.79, 143.75, 140.27,
129.11, 127.97, 127.77, 117.47, 116.41, 87.19.
HPLC/MS: m/z = 295 (M–).
1H NMR (500 MHz, CDCl3): d = 7.35 (d, J = 8.5 Hz, 1 H, H3), 7.06
(d, J = 2.5 Hz, 1 H, H6), 6.84 (dd, J = 8.5, 2.5 Hz, 1 H, H4), 5.41 (s,
1 H, OH), 1.29 (s, 9 H, CH3); NOE cross peaks observed: H4 and
H6 to d = 1.29.
HRMS: m/z calcd for C12H9IO: 295.9698; found: 295.9706.
Anal. Calcd for C12H9IO: C, 48.68; H, 3.06. Found: C, 49.26; H,
3.06.
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224
G. J. Hermann et al.
PAPER
5-tert-Butyl-2-iodophenol (5c); Typical Procedure6,7
1H NMR (500 MHz, CDCl3): d = 8.19 (s, 1 H, Haryl), 7.09 (s, 1 H,
A soln of ICl (1.07 g, 6.60 mmol) in MeOH (15 mL) was added
dropwise to a stirred soln of commercially available 3-tert-bu-
tylphenol (4c, 1.00 g, 6.60 mmol) and NaOH (266 mg, 6.60 mmol)
in MeOH (20 mL). The mixture was stirred at r.t. for 19 h, quenched
with 20% Na2S2O3 soln (25 mL), and stirred for a further 15 min.
The mixture was concentrated under vacuum to give a two-phase
mixture. 2 M HCl (20 mL) was added and the mixture was extracted
with EtOAc (2 × 50 mL). The combined organic phases were dried
(MgSO4), filtered, and concentrated under vacuum. The resulting
oil was purified by column chromatography (silica gel, hexane and
a gradient of hexane to hexane–EtOAc, 97:3); yield: 1.59 g (86%);
Rf = 0.29 (hexane–EtOAc, 9:1).
1H NMR (500 MHz, CDCl3): d = 7.54 (d, J = 8 Hz, 1 H, H3), 7.04
(d, J = 2 Hz, 1 H, H6), 6.73 (dd, J = 2.5, 8.5 Hz, 1 H, H4), 5.18 (s,
1 H, OH), 1.28 (s, 9 H, CH3); NOE cross peaks observed: H4 and
H6 to d = 1.28.
13C NMR (125 MHz, CDCl3): d = 154.45, 154.34, 137.52, 119.96,
112.52, 81.75, 34.63, 31.12.
Haryl), 5.15 (s, 1 H, OH), 1.49 (s, 9 H, CH3).
13C NMR (125 MHz, CDCl3): d = 154.94, 152.92, 150.26, 114.76,
83.76, 83.15, 36.57, 29.57.
HPLC/MS: m/z = 401 (M–).
HRMS: m/z calcd for C10H12I2O: 401.8977; found: 401.8962.
Anal. Calcd for C10H12I2O: C, 29.88; H, 3.01. Found: C, 30.63; H
3.06.
Suzuki Reaction
The phenol building block 1a–d (0.54 mmol) was taken up in tolu-
ene (8–10 mL), boronic acid (1.08 mmol) was added, followed by
K3PO4 (1.08 mmol), Pd(PPh3)4 (63 mg, 10 mol%), and H2O (1–2
mL). The mixture was heated to 90–95 °C for 14–16 h. The mixture
was filtered through a pad of Celite. After concentration of the fil-
trate the crude mixture was purified by column chromatography
(hexane–CH2Cl2, 9:1 to 6:4).
HPLC/MS: m/z = 275 (M–).
Acknowledgment
Anal. Calcd for C10H13IO: C, 43.50; H, 4.75. Found: C, 43.52; H,
4.68.
1H NMR, 13C NMR, and NOE analyses were carried out by Andrew
Mendham, School of Science, University of Greenwich, Kent. Ele-
mental analyses and high resolution mass analyses were carried out
by Warwick Analytical Services, University of Warwick Science
Park, Coventry. M.C. and L.D. thank the Spanish Ministerio de
Educación y Ciencia/Leonardo da Vinci Programme for financial
support.
2,4-Diiodo-5-isopropylphenol (6a)
Following the typical procedure for 5c using 3-isopropylphenol (4a,
20.0 g, 147 mmol) with ICl (47.7 g, 294 mmol) in MeOH in the
presence of NaOH (11.8 g, 294 mmol), the product was isolated af-
ter column chromatography (hexane–CH2Cl2, 4:1 to CH2Cl2) as a
beige-coloured solid; yield: 34.1 g (60%); Rf = 0.45 (hexane–
CH2Cl2, 1:1).
References
HPLC/MS: m/z = 387 (M–).
(1) Merkushev, E. B. Synthesis 1988, 923.
(2) Doad, G. J. S.; Barltrop, J. A.; Petty, C. M.; Owen, T. C.
4,6-Diiodobiphenyl-3-ol (6b)
Tetrahedron Lett. 1989, 30, 1597.
Following the typical procedure for 5c using biphenyl-3-ol (4b, 600
mg, 3.53 mmol) with ICl (1.14 g, 7.05 mmol) in MeOH in the pres-
ence of NaOH (282 mg, 7.05 mmol), the product was isolated after
column chromatography (hexane–CH2Cl2, 4:1 to CH2Cl2) as a co-
lourless oil; yield: 864 mg (58%); Rf = 0.49 (hexane–CH2Cl2, 1:1).
(3) Espuña, G.; Arsequell, G.; Valencia, G.; Barluenga, J.;
Pérez, M.; González, J. M. Chem. Commun. 2000, 1307.
(4) Narender, N.; Srinivasu, P.; Kulkarni, S. J.; Raghavan, K. V.
Synth. Commun. 2002, 32, 2319.
(5) Edgar, K. J.; Falling, S. N. J. Org. Chem. 1990, 55, 5287.
(6) Doad, G. J. S.; Barltrop, J. A.; Petty, C. M.; Owen, T. C.
Tetrahedron Lett. 1989, 30, 1597.
HPLC/MS: m/z = 421 (M–).
5-tert-Butyl-2,4-diiodophenol (6c)
(7) Fukata, G.; Kubota, Y.; Mataka, S.; Thiemann, T.; Tashiro,
Following the typical procedure for 5c using 3-tert-butylphenol (4c,
5.00 g, 33.3 mmol) with ICl (12.2 g, 75.2 mmol) in MeOH in the
presence of NaOH (4.33 g, 108 mmol), the product was isolated as
a beige-coloured solid without purification; yield: 13.3 g (99%).
M. Bull. Chem. Soc. Jpn. 1994, 67, 592.
(8) Morinaka, H.; Nakanishi, A.; Nonaka, Y. US 4,668,831,
1987.
(9) Talekar, R. S.; Chen, G. S.; Lai, S.-Y.; Chern, J.-W. J. Org.
Chem. 2005, 70, 8590.
For analytical purposes a sample was purified by column chroma-
tography (silica gel, hexane–CH2Cl2, 8:2 to 7:3); Rf = 0.27 (hexane–
CH2Cl2, 7:3).
Synthesis 2008, No. 2, 221–224 © Thieme Stuttgart · New York