Iodinated biaryls synthesized by the direct dehydrodimerization of iodoarenes using phenyliodine(III) bis(trifluoroacetate) (PIFA)

Article abstract of DOI:10.1002/adsc.200404024

Multiply iodinated biaryls can be prepared in yields up to 75% by direct oxidative coupling reaction of the iodinated arenes. The PIFA-mediated dehydrodimerization is superior to all other known methods. The developed protocol is reliable and easy to perform.

Full text of DOI:10.1002/adsc.200404024

FULL PAPERS
Iodinated Biaryls Synthesized by the Direct Dehydrodimerization
of Iodoarenes Using Phenyliodine(III) Bis(trifluoroacetate)
(PIFA)
Daniela Mirk, Alexander Willner, Roland Frˆhlich, Siegfried R. Waldvogel*
Organisch-Chemisches Institut, Westf‰lische Wilhelms-Universit‰t M¸nster, Corrensstrasse 40, 48149 M¸nster, Germany
Fax: (þ49)-251-833-9772, e-mail: waldvog@uni-muenster.de
Received: January 27, 2004; Accepted: April 2, 2004
À
Abstract: Multiply iodinated biaryls can be prepared Keywords: biaryls; C C coupling; hypervalent iodine
in yields up to 75% by direct oxidative coupling reac- reagents; iodoarenes; synthetic methods
tion of the iodinated arenes. The PIFA-mediated de-
hydrodimerization is superior to all other known
methods. The developed protocol is reliable and
easy to perform.
Introduction
as Lewis acid additive. The reaction occurs without
loss of the iodo moiety and tolerates a broad scope of
Iodoarenes represent valuable precursors in the syn- substrates leading to multiplyiodinated biaryls. The pro-
thesis of biaryl compounds. Due to the excellent leaving tocol for the transformation is highly reliable and easy to
group properties of the iodo moiety, this particular sub- perform.
stituent is lost under reductive coupling reaction condi-
tions.[1] The oxidative coupling process of electron-rich
aryls mediated by phenyliodine(III) bis(trifluoroace- Results and Discussion
tate) (PIFA), a hypervalent iodine reagent, was inten-
sively studied by Kita and co-workers.[2] Usually, PIFA
Synthesis of Iodoarenes
is activated by strong Lewis acids and acts as a two-elec-
tron-acceptor. This particular reagent has found wide
application in organic synthesis.[3]
The syntheses of diiodobenzenes 1 and 2 from guaiacol
Multiply iodinated biaryls are generally obtained by (19) were performed as published.[8] The synthesis of 3
linear multi-step syntheses and have recently attracted started with the known alkylation of catechol (17)[9] in
attention as novel contrast media for X-ray diagnos- good yields followed by iodination with iodine mono-
tics.[4] The direct oxidative coupling of iodoarenes to io- chloride, providing 48% of the desired product
dinated biaryls usually fails yielding deiodinated prod- (Scheme 2). Substrate 4 was obtained by alkylation of
ucts.[5] Generally, highly toxic thallium(III) or lead(IV) the corresponding phenol 20, that was accessible from
reagents are used to perform the dehydrodimerization guaiacol applying known procedures.[10]
without loss of the valuable iodo substituent.[6] Recently,
Diiodoarenes 5 and 6 were prepared according to
we reported an environmentally friendly alternative by Scheme 2. The first and common step involved the de-
using MoCl5 for the oxidative dimerization of iodovera- scribed multiple iodination of guaiacol providing the in-
trole derivatives.[7] Application of this methodology to stable intermediate 21.[11] Without further purification
substrate 9 even allows a direct synthesis of a 2,2’,6,6’-tet- the subsequent transformations gave on the one hand
raiodobiphenyl. To improve the solubility of the multiply by alkylation with (2-chloroethyl)tosylate product 5 in
iodinatedbiarylsforfurtherpurposes, theintroductionof a good yield and on the other hand demethylation and
solubilizing groups in the alkoxy side chains is of great in- direct formation of the dioxolane moiety afforded the
terest. Surprisingly, the MoCl5-mediated dehydrodimeri- benzodioxole derivative 6 which was obtained in a total
zation, e.g., of 1, provided not the desired biaryls but led yield of 24%. Compounds 8 and 16 were constructed
rather to a highly selective chlorination of the iodoar- similarly to described protocols,[12] while iodoarenes 7
enes, directed by the alkoxycarbonylmethyl side chain.[8] and 9 15 are known.[13] All employed substrates were
Here, we describe the dehydrodimerization of iodoar- obtained and used for further studies in analytically
enes mediated by PIFA in combination with BF3 ¥Et2O pure form.
Adv. Synth. Catal. 2004, 346, 675 681
DOI: 10.1002/adsc.200404024
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
675

Daniela Mirk et al.
FULL PAPERS
subjected to column chromatography. Using that partic-
ular substrate, the reaction conditions were investigat-
ed. Quenching of the reaction mixture with NaHCO3
solution at À408C and 08C, respectively, demonstrates
that there is almost no conversion at lower temperatures
(entries 2 and 3). Mainly substrate 1 was recovered un-
der these conditions. In contrast to the literature, we an-
ticipate that the oxidative coupling process occurs at
room temperature. The dehydrodimerization reaction
with PIFA seems to be very fast since the proto-deiodi-
nation process on arenes is known to be slow and was not
observed in these studies. By running the reaction at
258C for a few minutes, 56% of the desired product
and 31% of 1 could be isolated (entry 4). The best results
were obtained by slow addition of the oxidizing mixture
at room temperature. Removal of the solvent and sepa-
ration by column chromatography on silica provided
61% of the biaryl and 31% of the iodoarene (entry 5).
Elevated temperatures, prolonged reaction times, or us-
ing an excess of the coupling agent decreased the
amount of the desired product since over-oxidation
takes place.
These ameliorated reaction conditions were applied
on a variety of iodoarenes (Scheme 1). The conversion
of these substrates was performed in synthetically inter-
esting yields up to 75%. Generally, the amount of prod-
uct is significant higher when 2,2’,6,6’-tetrasubstituted
biaryls are formed compared to the yield of only 2,2’-di-
substituted biaryls (Table 2). The synthetic potential of
the PIFA/BF3 ¥Et2O mixture is apparent in the conver-
sion of 9 which provides remarkably better results
than the MoCl5-mediated process (entry 8).[7] By apply-
ing slightly milder reaction conditions, substrates with
benzodioxole moieties are successfully subjected to
the dehydrodimerization process (entries 5 and 6).
The multiply iodinated biaryls are obtained as color-
less solids that are stable towards light and heat. The
coupling reaction usually occurs para to an alkoxy sub-
stituent in spite of the steric demand of the iodine moi-
eties. Under the applied reaction conditions no side re-
actions were observed. This fact also makes the PIFA-
mediated oxidation superior compared to the MoCl5
methodology.[8] The solid state structure of 6a reveals
Scheme 1. Employed substrates.
Table 1. Investigation of the reaction conditions for the con-
version of 1.
Dehydrodimerization of Iodoarenes
Entry
T
Time
Recovered 1
Yield of
biaryl 1a
The dehydrodimerization of iodoarenes using PIFA/
BF3 ¥Et2O as oxidizing mixture leads directly to multiply
iodinated biaryls (Scheme 3). When applying the stand-
ard reaction conditions[2] on substrate 1, the correspond-
ing biaryl 1a was obtained in 55% besides 26% of non-
converted starting material (Table 1, entry 1). The reac-
tion was carried out for 90 minutes at À408C. After
warming up to room temperature, the volatile compo-
nents were evaporated and the products were directly
1
2
3
4
5
À408C
À408C
08C
258C
258C
90 min
26%
82%
74%
31%
31%
55%
7%
12%
56%
61%
90 min[a]
90 min[a]
5 min
30 min[b]
[a]
The reaction mixture was quenched with NaHCO3 solu-
tion.
[b]
Slow addition of PIFA/BF3 ¥Et2O.
676
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 675 681

Iodinated Biaryls by Direct Dehydrodimerization of Iodoarenes
FULL PAPERS
Scheme 2. Synthesis of iodoarenes.
ditions. Instead, a transiodination occurred leading to
triiodotrimethoxybenzene (23). The transiodination
product was achieved in 42% by using a two-fold excess
of the oxidizing agent. Iodoarene 13 was also transiodi-
nated yielding 14 in 16%. The conversion of 15 and 16
showed no formation of a defined product, only starting
material could be recovered in 51% and 71%, respec-
tively, whereas subjecting 14 to the protocol led to com-
plete decomposition.
Scheme 3. Dehydrodimerization of iodoarenes.
Table 2. Dehydrodimerization of iodoarenes.
Conclusion
Entry
Substrate
Recovered substrate
Yield of biaryl
1
2
3
4
5
6
7
8
9
2
3
4
5
6
7
8
9
10
11
23%
39%
6%
17%
39%
49%
20%
13%
23%
37%
66% (2a)
37% (3a)
40% (4a)
69% (5a)
46%[a] (6a)
38%[a] (7a)
60% (8a)
75% (9a)
66% (10a)
34% (11a)
Multiply iodinated biaryls can be prepared in syntheti-
cally interesting yields up to 75% by applying a very sim-
ple protocol employing a PIFA/BF3 ¥Et2O mixture for
the dehydrodimerization reaction. The valuable iodo
substituents are not lost during the procedure. The de-
veloped PIFA-mediated protocol is superior to other
10
[a]
Addition of PIFA/BF3 ¥Et2O at 08C, stirring at 258C for
1 2.5 h.
the orthogonality of the aromatic planes (Figure 1). Fur-
thermore, the iodo substituents are shielded by those of
the other aryl portion and also by the other aromatic
plane, which might explain the unusual stability of
such compounds.
Surprisingly, the electron-rich substrate 12 was not
converted to the corresponding biaryl under these con- Figure 1. Solid state structure of 6a.
Adv. Synth. Catal. 2004, 346, 675 681
asc.wiley-vch.de
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
677

Daniela Mirk et al.
FULL PAPERS
known methods since the reagent mixture is considered Methyl (5-Iodo-2-methoxy-phenoxy)acetate (4)
as environmentally benign and no side reactions are ob-
Guaiacol (11.1 mL, 100 mmol), pyridine (17.1 mL, 220 mmol)
served. The broad scope of this transformation in the
and DMAP (0.61 g, 5.0 mmol) were dissolved in CH2Cl2
substitution pattern of the arenes as well as in the side
chains offers a wide range of applications for the multi-
ply iodinated biaryls.
(200 mL). At 08C acetic acid anhydride (10.4 mL, 110 mmol)
was added dropwise. After stirring for 1 h, the reaction mixture
was brought to 258C and acidified with 1 M H3PO4 solution
(100 mL). The aqueous layer was extracted with CH2Cl2 (2Â
60 mL) and the combined organic layers were washed with
brine, dried over anhydrousCaCl2 and concentrated under vac-
uum. Distillation under high vacuum furnished the protected
guaiacol as a colorless oil; yield: 16.04 g (96.5 mmol, 97%); bp
648C/1.2Â10À2 mbar.
Experimental Section
General Remarks
The acetylguaiacol (15.62 g, 94.0 mmol) was dissolved in
CH2Cl2 (150 mL) and treated dropwise with a solution of ICl
(5.7 mL, 113 mmol) in CH2Cl2 (60 mL). The reaction mixture
was stirred at 258C under light exclusion for 7 d. The reaction
progress was controlled by GC. After addition of Na2S2O3 sol-
ution (100 mL, 10%) and standard work-up (see 3) the crude
product was dissolved in a 1:1 mixture of MeOH/THF
(180 mL) and a solution of lithium hydroxide monohydrate
(15.78 g, 376 mmol) in water (30 mL) was added. After stirring
at 258C for 5 d, the mixture was acidified with 2 N HCl solution
(160 mL) and extracted with Et2O (2Â100 mL). The com-
bined organic layers were washed with brine, dried over anhy-
drous MgSO4 and concentrated under vacuum. After purifica-
tion by column chromatography, the deprotected phenol 20
was obtained; yield: 17.14 g (68.6 mmol, 73%).
All reagents used were of analytical grade. Solvents were desic-
cated if necessary by standard methods. Column chromatogra-
phy was performed on silica gel 60 (particle size 63 200 mm)
using mixtures of cyclohexane and EtOAc as eluents. Melting
points were determined on a MFB 595 Gallenkamp apparatus
(UK) and are uncorrected. Microanalyses were performed us-
ing a Vario EL III (Elementar-Analysensysteme, Hanau, Ger-
many). NMR spectra were recorded at 258C on a Bruker ARX
300 using TMS as an internal standard. Chemical shifts (d) are
reported in parts per million (ppm) relative to TMS. Mass spec-
tra were obtained on a MAT8200 system (Finnigan-MAT, Bre-
men, D) (EI) or on a Quattro LC-Z (Micromass, Manchester,
UK) (ESI). Exact mass was determined with a GC-TOF (Mi-
cromass, Manchester, UK).
Phenol 20 (4.64 g, 18.6 mmol) was treated with methyl bro-
moacetate (2.6 mL, 27.9 mmol) and K2CO3 (5.00 g, 36.2 mmol)
as described for compound 3. Standard work-up and purifica-
tion by column chromatography afforded 4 as colorless crys-
tals; yield: 5.55 g (17.2 mmol, 93% from 20); mp 978C
(EtOH); 1H NMR (300 MHz, CDCl3): d¼3.80 (s, 3H,
OCH3), 3.84 (s, 3H, OCH3), 4.66 (s, 2H, CH2), 6.65 (d, 1H,
Methyl (4-Iodo-2-methoxycarbonylmethoxy-
phenoxy)acetate (3)
Catechol (10.00 g, 91.0 mmol) was dissolved in DMF. K2CO3
(40.0 g, 290 mmol) and methyl bromoacetate (26.0 mL,
272 mmol) were added. After stirring at 258C overnight,
Et2O (200 mL) was added and the mixture was washed several
times with water and brine, dried over anhydrous MgSO4 and
concentrated under vacuum. Compound 18 was obtained as a
colorless oil, which was used without further purification; yield:
20.03 g (78.8 mmol, 87%).
4
3J3,4 ¼8.4 Hz, 3-H), 7.10 (d, 1H, J4,6 ¼2.1 Hz, 6-H), 7.26 (dd,
3
4
1H, J3,4 ¼8.4 Hz, J4,6 ¼2.1 Hz, 4-H); 13C NMR (75 MHz,
CDCl3): d¼52.18 (OCH3), 55.95 (ArOCH3), 66.52 (CH2),
81.80 (C5), 114.06 (C3), 123.57 (C6), 131.53 (C4), 148.00
(C2), 149.89 (C1), 168.84 (CO); MS (EI, 70 eV): m/z (%)¼
322 (100) [Mþ], 263 (10) [Mþ ÀCO2CH3], 249 (26) [Mþ À
CH2CO2CH3]; anal. calcd. for C10H11IO4 (322.10): C 37.29, H
3.44; found: C 37.27, H 3.15.
Compound 18 (7.53 g, 29.4 mmol) was dissolved in CH3CN
(100 mL) and treated with ICl (1.5 mL, 29.4 mmol) at 258C
for 24 h under light exclusion. The reaction mixture was con-
centrated under vacuum and treated with Na2S2O3 solution
(50 mL, 10%) and Et2O (50 mL). The aqueous layer was re-ex-
tracted with Et2O (50 mL) and the combined organic layers
were washed with water (2Â50 mL) and brine and dried
over anhydrous MgSO4. After removal of the solvent, the
crude product was purified by distillation under high vacuum
to give 3 as a colorless oil, that crystallizes immediately; yield:
5.36 g (14.0 mmol, 48%); bp 155 1578C/2.7Â10À2 mbar; mp
2-(2-Chloroethoxy)-1,5-diiodo-3-methoxybenzene (5)
Iodine (23 g, 90.6 mmol) was dissolved in EtOH (120 mL) and
treated dropwise with morpholine (24 mL, 180 mmol). After
stirring for an additional hour guaiacol (19) (2.5 mL,
22.6 mmol) was added. The reaction mixture was stirred at
258C overnight under light exclusion and then concentrated
under vacuum. Saturated NH4Cl solution (250 mL) was added
and the aqueous phase was extracted with Et2O (3Â100 mL).
The combined organic layers were washed with Na2S2O3 solu-
tion (250 mL, 10%) and brine, dried over anhydrous MgSO4
and concentrated under vacuum.
Without further purification the crude product 21 was dis-
solved in DMF (90 mL) and deprotonated with NaH
(651 mg, 27.1 mmol; 60% in oil). After stirring at 258C for
30 min, 2-chloroethyl tosylate (4.9 mL, 27.1 mmol) was inject-
ed. The reaction mixture was stirred at 908C for 4 h. After cool-
ing to 258C, EtOAc (200 mL) was added and the mixture was
1
778C (EtOH); H NMR (300 MHz, CDCl3): d¼3.79 (s, 3H,
OCH3), 3.81 (s, 3H, OCH3), 4.71 (s, 2H, CH2), 4.72 (s, 2H,
3
4
CH2), 6.66 (d, 1H, J5,6 ¼8.4 Hz, 6-H), 7.19 (d, 1H, J3,5
¼
3
4
2.1 Hz, 3-H), 7.27 (dd, 1H, J5,6 ¼8.4 Hz, J3,5 ¼2.1 Hz, 5-H);
13C NMR (75 MHz, CDCl3): d¼51.92 (OCH3), 51.95
(OCH3), 66.25 (CH2), 66.40 (CH2), 83.94 (C4), 117.15 (C6),
124.39 (C3), 131.33 (C5), 147.95 (C1), 148.52 (C2), 168.61
(CO), 168.76 (CO); MS (EI, 70 eV): m/z (%)¼380 (100) [Mþ],
321 (3) [Mþ ÀCO2CH3], 307 (9) [Mþ ÀCH2CO2CH3], 249 (34)
[307ÀCO2CH3]; anal. calcd. for C12H13IO6 (380.13): C 37.92, H
3.45; found: C 37.97, H 3.21.
678
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 675 681

Iodinated Biaryls by Direct Dehydrodimerization of Iodoarenes
FULL PAPERS
washed with water (3Â100 mL) and brine, dried over anhy-
drous MgSO4 and concentrated under vacuum. Purification
by column chromatography furnished 5 as colorless crystals;
(CH2), 92.99 (C2), 98.06 (C6), 122.57 (C5), 147.15, 147.56
(C1, C4), 151.32 (C3), 168.82 (CO); MS [ESI(ES þ), Cap:
0.84 V; Cone: 52 V]: m/z¼917 [MþNaþ]; anal. calcd. for
C20H18I4O8 (893.97): C 26.87, H 2.03; found: C 26.80, H 2.11.
2,2’,6,6’-Tetraiodo-3,3’,4,4’-tetrakis(methoxycarbonylme-
thoxy)-biphenyl (2a): mp 2048C (EtOAc); 1H NMR
(300 MHz, DMSO-d6): d¼3.72 (s, 6H, OCH3), 3.73 (s, 6H,
OCH3), 4.70 (s, 4H, CH2), 4.98 (s, 4H, CH2), 7.63 (s, 2H, 5-H);
13C NMR (75 MHz, DMSO-d6): d¼51.72 (OCH3), 51.90
(OCH3), 65.19 (CH2), 68.51 (CH2), 93.65 (C2), 98.66 (C6),
123.19 (C5), 146.73, 147.17 (C1, C4), 148.84 (C3), 168.26
(CO), 168.54 (CO); MS (EI, 70 eV): m/z (%)¼1010 (100)
[Mþ]; anal. calcd. for C24H22I4O12 (1010.04): C 28.54, H 2.20;
found: C 28.44, H 2.00.
1
yield: 5.88 g (13.4 mmol, 59%); mp 708C (EtOH); H NMR
3
(300 MHz, CDCl3): d¼3.83 (t, 2H, JCH CH ¼6.3 Hz, CH2Cl),
2
2
3.83 (s, 3H, OCH3), 4.21 (t, 2H, 3JCH CH ¼6.3 Hz, OCH2), 7.14
2
2
4
4
(d, 1H, J4,6 ¼1.8 Hz, 4-H), 7.67 (d, 1H, J4,6 ¼1.8 Hz, 6-H);
13C NMR (75 MHz, CDCl3): d¼42.22 (CH2Cl), 56.29
(OCH3), 72.57 (OCH2), 88.02 (C1), 93.43 (C5), 122.14 (C4),
138.35 (C6), 147.80 (C3), 152.69 (C2); MS (EI, 70 eV): m/z
(%)¼438, 440 (100, 33) [Mþ], 375 (60) [Mþ ÀCH2CH2Cl];
anal. calcd. for C9H9ClI2O2 (438.43): C 24.66, H 2.07; found:
C 24.68, H 1.84.
2,2’-Diiodo-4,4’,5,5’-tetrakis(methoxycarbonylmethoxy)-
biphenyl (3a): mp 125 1268C (EtOAc); 1H NMR (300 MHz,
CDCl3): d¼3.78 (s, 6H, OCH3), 3.83 (s, 6H, OCH3), 4.70 (s,
4H, CH2), 4.75 (s, 4H, CH2), 6.69 (s, 2H, 6-H), 7.33 (s, 2H, 3-
H); 13C NMR (75 MHz, CDCl3): d¼52.27 (OCH3, OCH3),
66.44 (CH2), 66.70 (CH2), 89.68 (C2), 116.75 (C6), 125.11
(C3), 142.52 (C1), 147.80 (C4, C5), 168.78 (CO), 168.83
(CO); MS (EI, 70 eV): m/z (%)¼758 (100) [Mþ], 631 (41)
[Mþ ÀI], 499 (18) [Mþ ÀIÀCH2CO2CH3 ÀCO2CH3]; anal.
calcd. for C24H24I2O12 (758.25): C 38.02, H 3.19; found: C
37.94, H 2.85.
2,2’-Diiodo-5,5’-dimethoxy-4,4’-bis(methoxycarbonylme-
thoxy)-biphenyl (4a): mp 1968C (EtOAc); 1H NMR
(300 MHz, CDCl3): d¼3.83 (s, 6H, OCH3), 3.86 (s, 6H,
OCH3), 4.72 (s, 4H, CH2), 6.75 (s, 2H, 6-H), 7.28 (s, 2H, 3-H);
13C NMR (75 MHz, CDCl3): d¼52.25 (OCH3), 56.11 (Ar-
OCH3), 66.51 (CH2), 87.48 (C2), 113.92 (C6), 125.89 (C3),
142.87 (C1), 147.21 (C5), 149.63 (C4), 168.83 (CO); MS (EI,
70 eV): m/z (%)¼642 (100) [Mþ], 515 (61) [Mþ ÀI]; anal.
calcd. for C20H20I2O8 (642.18): C 37.41, H 3.14; found: C
37.16, H 2.93.
4,6-Diiodobenzo[1,3]dioxole (6)
The iodination of guaiacol (19) (5.8 mL, 52.3 mmol) was per-
formed according to the synthesis of compound 5. The crude
product 21 was dissolved in 150 mL anhydrous CH2Cl2 and
chilled to À788C. BBr3 (5.9 ml, 62.9 mmol) was added drop-
wise. The mixture was stirred for 30 min at À788C and 4 h at
À128C. After addition of Et2O (100 mL), the mixture was
brought to 258C, water (200 mL) was added and the aqueous
layer was extracted with EtOAc (2Â100 mL). The combined
organic layers were washed with Na2S2O3 solution (10%) and
brine, dried over anhydrous MgSO4 and concentrated under
vacuum.
The crude product 22 was dissolved in DMF (100 mL), anhy-
drous CH2Cl2 (4.0 mL, 62.8 mmol) and CsF (39.7 g, 262 mmol)
were added. The reaction mixture was refluxed for 90 min. Af-
ter cooling to 258C, water (100 mL) was added, followed by an
extraction with Et2O (2Â100 mL). The combined organic lay-
ers were washed with water (3Â100 mL) and brine, dried over
anhydrous MgSO4 and concentrated under vacuum. Column
chromatography gave 6 as colorless crystals; yield: 4.64 g
3,3’-Bis(2-chloroethoxy)-2,2’,6,6’-tetraiodo-4,4’-dimethoxy-
biphenyl (5a): mp 1708C (EtOAc); 1H NMR (300 MHz,
CDCl3): d¼3.87 (t, 4H, 3JCH CH ¼6.3 Hz, CH2Cl), 3.92 (s, 6H,
1
(12.4 mmol, 24%); mp 1088C (EtOH). H NMR (300 MHz,
CDCl3): d¼6.01 (s, 2H, CH2), 7.05 (d, 1H, 4J5,7 ¼1.8 Hz, 7-H),
2
2
4
7.75 (d, 1H, J5,7 ¼1.8 Hz, 5-H); 13C NMR (75 MHz, CDCl3):
3
OCH3), 4.29 (t, 4H, JCH CH ¼6.3 Hz, OCH2), 7.45 (s, 2H, 5-
2
H); 13C NMR (75 MHz,2 CDCl3): d¼42.25 (CH2Cl), 56.29
(OCH3), 72.46 (OCH2), 92.68 (C2), 98.74 (C6), 122.57 (C5),
147.18 (C1), 148.17 (C4), 151.67 (C3); MS (EI, 70 eV): m/z
(%)¼874, 876, 877 (100, 70, 25) [Mþ], 811 (27) [Mþ ÀCH2
CH2Cl], 63, 65 (23, 7) [CH2CH2Clþ]; anal. calcd. for
C18H16Cl2I4O4 (874.84): C 24.71, H 1.84; found: C 24.65, H 1.68.
4,4’,6,6’-Tetraiodo-[5,5’]bi(benzo[1,3]dioxolyl) (6a): The
oxidizing reagent mixture was added at 08C. After stirring
for 30 min at 08C, the reaction mixture was brought to 258C,
stirred for additional 2 h and purified following the general
d¼71.70 (C4), 83.00 (C6), 101.01 (C2), 117.52 (C7), 137.69
(C5), 147.28 (C7a), 149.86 (C3a); MS (EI, 70 eV): m/z (%)¼
374 (100) [Mþ], 247 (5) [Mþ ÀI]; anal. calcd. for C7H4I2O2
(373.91): C 22.49, H 1.08; found: C 22.81, H 1.08.
Dehydrodimerization with PIFA; General Procedure
The respective substrate (1.50 mmol) was dissolved in anhy-
drous CH2Cl2 (20 mL).
A solution of PIFA (323 mg,
1
protocol; mp 2158C (EtOAc); H NMR (300 MHz, CDCl3):
0.75 mmol) and BF3 ¥Et2O (0.19 mL, 1.50 mmol) in CH2Cl2
(5 mL) was added in small portions over a period of 15 minutes
at 258C. After stirring for additional 15 min the solvent was
evaporated under vacuum and without further work-up the
crude mixture was directly subjected to column chromatogra-
phy. All biaryls formed as colorless crystalline solids immedi-
ately upon evaporation of the solvents. The products were
dried under high vacuum.
2,2’,6,6’-Tetraiodo-4,4’-dimethoxy-3,3’-bis(methoxycarbo-
nylmethoxy)-biphenyl (1a): mp 1758C (EtOAc); 1H NMR
(300 MHz, CDCl3): d¼3.84 (s, 6H, OCH3), 3.90 (s, 6H, Ar-
OCH3), 4.65 (s, 4H, CH2), 7.45 (s, 2H, 5-H); 13C NMR
(75 MHz, CDCl3): d¼52.12 (OCH3), 56.27 (ArOCH3), 68.97
d¼6.13 (s, 4H, CH2), 7.34 (s, 2H, 7-H); 13C NMR (75 MHz,
CDCl3): d¼75.92 (C4), 88.48 (C6), 101.45 (C2), 118.17 (C7),
145.67 (C5), 146.27 (C7a), 150.92 (C3a); MS (EI, 70 eV): m/z
(%)¼746 (100) [Mþ], 492 (34) [Mþ À2 I]; HRMS: m/z calcd.
for C14H6I4O4 (Mþ): 745.6445; found: 745.6403.
6,6’-Diiodo-[5,5’]bi(benzo[1,3]dioxolyl) (7a):[14] 1H NMR
(300 MHz, CDCl3): d¼6.02 (s, 4H, CH2), 6.67 (s, 2H, 4-H),
7.32 (s, 2H, 7-H); 13C NMR (75 MHz, CDCl3): d¼88.59 (C6),
101.82 (C2), 110.25 (C4), 118.06 (C7), 142.25 (C5), 148.01,
148.14 (C3a, C7a); MS (EI, 70 eV): m/z (%)¼494 (100) [Mþ],
367 (57) [Mþ ÀI], 240 (58) [Mþ À2 I]; anal. calcd. for C14H8I2O4
(494.02): C 34.04, H 1.63; found: C 34.43, H 1.62.
Adv. Synth. Catal. 2004, 346, 675 681
asc.wiley-vch.de
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
679

Daniela Mirk et al.
FULL PAPERS
2,2’-Diiodo-3,3’,4,4’-tetramethoxy-6,6’-dimethylbiphenyl
(8a): mp 233 2348C (EtOAc); H NMR (300 MHz, CDCl3):
Road, Cambridge CB2 1EZ, UK [Fax: int. codeþ
1
44(1223)336 033; E-mail: deposit@ccdc.cam.ac.uk].
d¼1.96 (s, 6H, CH3), 3.85 (s, 6H, OCH3), 3.92 (s, 6H, OCH3),
6.82 (s, 2H, 5-H); 13C NMR (75 MHz, CDCl3): d¼21.23
(CH3), 55.92 (OCH3), 60.42 (OCH3), 100.29 (C2), 114.23
(C5), 133.24 (C6), 140.16 (C1), 147.40 (C3), 151.51 (C4); MS
(EI, 70 eV): m/z (%)¼554 (100) [Mþ], 427 (23) [Mþ ÀI];
anal. calcd. for C18H20I2O4 (554.16): C 39.01, H 3.64; found: C
39.30, H 3.48.
Acknowledgements
This work was supported by the Fonds der Chemischen Indus-
trie and by the International Graduate College ™Template Di-
rected Chemical Synthesis∫.
2,2’-Diiodo-4,4’,5,5’-tetramethoxybiphenyl (10a):[15] 1H
NMR (300 MHz, CDCl3): d¼3.86 (s, 6H, OCH3), 3.91 (s, 6H,
OCH3), 6.73 (s, 2H, 6-H), 7.31 (s, 2H, 3-H); 13C NMR
(75 MHz, CDCl3): d¼56.04 (OCH3), 56.17 (OCH3), 88.14
(C2), 113.26 (C6), 120.91 (C3), 141.45 (C1), 149.00 (C4, C5);
MS (EI, 70 eV): m/z (%)¼526 (100) [Mþ], 399 (58) [Mþ ÀI],
257 (30) [Mþ À2 IÀCH3].
References
[1] D. Astruc (Ed.), Modern Arene Chemistry, Wiley-VCH,
Weinheim, 2002.
2,2’-Diiodo-4,4’,5,5’-tetramethoxy-3,3’-dimethylbiphenyl
(11a):[6a] 1H NMR (300 MHz, CDCl3): d¼2.46 (s, 6H, CH3),
3.80 (s, 6H, OCH3), 3.81 (s, 6H, OCH3), 6.64 (s, 2H, 6-H);
13C NMR (75 MHz, CDCl3): d¼22.38 (CH3), 55.87 (OCH3),
60.49 (OCH3), 96.58 (C2), 111.70 (C6), 135.54 (C1, C3),
146.54 (C4), 152.26 (C5); MS (EI, 70 eV): m/z (%)¼554 (68)
[Mþ], 427 (100) [Mþ ÀI].
[2] a) Y. Kita, M. Gyoten, M. Ohtsubo, H. Tohma, T. Taka-
da, Chem. Commun. 1996, 1481 1482; b) T. Takada, M.
Arisawa, M. Gyoten, R. Hamada, H. Tohma, Y. Kita, J.
Org. Chem. 1998, 63, 7698 7706; c) H. Tohma, H. Mor-
ioka, S. Takizawa, M. Arisawa, Y. Kita, Tetrahedron
2001, 57, 345 352; d) H. Tohma, M. Iwata, T. Maegawa,
Y. Kita, Tetrahedron Lett. 2002, 43, 9241 9244.
[3] G. Pohnert, J. Prakt. Chem. 2000, 342, 731 734.
[4] a) P. L. Anelli, M. Brochetta, C. Maffezzoni, P. Paoli, P.
Rossi, F. Ugger, M. Visigalli, J. Chem. Soc. Perkin Trans.
1 2001, 1175 1181; b) M. Dugast-Zrihen, D. Meyer,
(Guerbet S. A.), US Patent 5,616,798, 1997; Chem. Abstr.
1993, 118, 38602r; c) M. Dugast-Zrihen, D. Meyer,
(Guerbet S. A.), US Patent 5,618,977, 1997; Chem. Abstr.
1994, 120, 322950p; d) F. Uggeri, L. Pier (BRACCO
S. P. A.), WO Patent 95/15307, 1995; Chem. Abstr. 1995,
123, 169364r.
[5] N. Boden, R. J. Bushby, Z. Lu, G. Headdock, Tetrahe-
dron Lett. 2000, 41, 10117 10120.
[6] a) A. McKillop, A. G. Turell, D. W. Young, E. C. Taylor,
J. Am. Chem. Soc. 1980, 102, 6504 6512; b) E. C. Taylor,
A. H. Katz, S. I. Alvarado, A. McKillop, J. Organomet.
Chem. 1985, 285, C9-C12.
[7] S. R. Waldvogel, E. Aits, C. Holst, R. Frˆhlich, Chem.
Commun. 2002, 1278 1279.
[8] D. Mirk, O. Kataeva, R. Frˆhlich, S. R. Waldvogel, Syn-
thesis 2003, 2410 2414.
[9] D. T. Gryko, P. Piatek, J. Jurczak, Tetrahedron 1997, 53,
7957 7966.
[10] R. Bushby, Z. Lu, Synthesis 2001, 763 767.
[11] P. Chabrier, J. Seyden-Penne, A.-M. Fouage, C. R. Hebd.
Sceances Acad. Sci. 1957, 245, 174 175.
[12] 8: T. Marti, B. R. Peterson, F. F¸rer, T. Mordasini-Denti,
J. Zarske, B. Jaun, F. Diederich, V. Gramlich, Helv. Chim.
Acta 1989, 72, 109 144; 16: see also Ref.[13] for 9.
[13] Synthesis of iodoarenes: 7: L. Crombie, M. A. Horsham,
R. J. Blade, Tetrahedron Lett. 1987, 28, 4879 4882 for 9:
J. Borgulya, H. Bruderer, K. Bernauer, G. Zuercher,
M. D. Prada, Helv. Chim. Acta 1989, 72, 952 968; 10:
H. O. Wirth, O. Kˆnigstein, W. Kern, Liebigs Ann.
Chem. 1960, 634, 84 104; 11: see Ref.[6a]; 12, 14 and 15:
K. Orito, T. Hatakeyama, M. Takea, H. Suginome, Syn-
thesis 1995, 1273 1277; 13: M. C. Carreno, J. L. G. Rua-
1,2,3-Triiodo-4,5,6-trimethoxybenzene (23): mp 1188C
(EtOAc); 1H NMR (300 MHz, CDCl3): d¼3.85 (s, 6H,
OCH3), 3.87 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3): d¼
60.77 (OCH3), 60.92 (OCH3), 100.67 (C1, C3), 114.15 (C2),
144.54 (C5), 155.19 (C4, C6); MS (EI, 70 eV): m/z (%)¼546
(100) [Mþ]; anal. calcd. for C9H9I3O3 (545.88): C 19.80, H
1.66; Found: C 20.03, H 1.42.
X-Ray Crystallographic Study
X-ray crystal structure analysis of 6a: formula C14H6I4O4 ¥
0.5 CH2Cl2, M¼788.25, yellow crystal 0.50Â0.30Â0.10 mm,
a¼20.020(1), b¼11.681(1), c¼17.336(1) ä, b¼111.10(1)8,
V¼3782.3(4) ä3, 1calcd. ¼2.769 g cmÀ3, m¼67.47 cmÀ1, empiri-
cal absorption correction (0.133 ꢀ T ꢀ 0.552), Z¼8, mono-
clinic, space group C2/c (No. 15), l¼0.71073 ä, T¼198 K, w
and f scans, 8111 reflections collected (ꢁh, ꢁk, ꢁl),
[(sinq)/l]¼0.66 äÀ1, 4479 independent (Rint ¼0.042) and
3450 observed reflections [I ꢂ 2 s(I)], 213 refined parameters,
R¼0.044, wR2 ¼0.115, max. residual electron density 1.78
(À1.71) e äÀ3 close to iodine, hydrogens calculated and re-
fined as riding atoms.
The data set was collected with a Nonius KappaCCD dif-
fractometer, equipped with a rotating anode generator Nonius
FR591. Programs used: data collection COLLECT (Nonius
B. V., 1998), data reduction Denzo-SMN (Z. Otwinowski, W.
Minor, Methods in Enzymology, 1997, 276, 307 326), absorp-
tion correction SORTAV (R. H. Blessing, Acta Cryst. 1995,
A51, 33 37; R. H. Blessing, J. Appl. Cryst. 1997, 30, 421
426), structure solution SHELXS-97 (G. M. Sheldrick, Acta
Cryst. 1990, A46, 467 473), structure refinement SHELXL-
97 (G. M. Sheldrick, Universit‰t Gˆttingen, 1997), graphics
SCHAKAL (E. Keller, Universit‰t Freiburg, 1997).
Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC-229654. Copies of the data can be ob-
tained free of charge on application to CCDC, 12 Union
680
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 675 681

Iodinated Biaryls by Direct Dehydrodimerization of Iodoarenes
FULL PAPERS
no, G. Sanz, M. A. Toledo, A. Urbano, Tetrahedron Lett.
1996, 37, 4081 4084.
[15] W. Baker, J. W. Barton, J. F. W. McOmie, R. J. Penneck,
M. L. Watts, J. Chem. Soc. 1961, 3986 3989.
[14] F. Dallacker, G. Adolphen, Liebigs Ann. Chem. 1966,
694, 110 116.
Adv. Synth. Catal. 2004, 346, 675 681
asc.wiley-vch.de
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
681