Ortho-directed lithiation of 3, 4-(alkylenedioxy)halobenzenes with LDA and LiTMP. The first ortho lithiation of 1 an lodobenzene

Full text of DOI:10.1021/jo9824955

8004
J . Org. Chem. 1999, 64, 8004-8007
There are many examples in the literature of the ortho
Or th o-Dir ected Lith ia tion of
lithiation of fluoro- and chlorobenzenes, but there are
fewer examples of the ortho lithiation of bromo-aromatics
with LiTMP and LDA.7 Even more rare are iodine-
directed ortho lithiations, which have been described for
iodothiophenes,8 iodoisothiazoles,9 and iodopyridines.10
We are unaware, however, of any examples of the ortho
lithiation of iodobenzenes.
3,4-(Alk ylen ed ioxy)h a loben zen es w ith LDA
a n d LiTMP . Th e F ir st Or th o Lith ia tion of
a n Iod oben zen e
Ronald J . Mattson,*,† Charles P. Sloan,†
Christopher C. Lockhart,†,‡ J ohn D. Catt,† Qi Gao,§ and
Stella Huang|
Pharmaceutical Research Institute, Bristol-Myers
Squibb Company, 5 Research Parkway,
Wallingford, Connecticut 06492-7660
Resu lts a n d Discu ssion
Since 1,2-(alkylenedioxy)benzenes readily halogenate
at the 4-position, we investigated whether the additional
halogen atom would increase the thermodynamic acid-
ity11 of the ortho hydrogen and shift the reaction with
lithium bases from ring-opening to ortho lithiation.
Schlosser’s ortho lithiation of 3-bromobenzotrifluoride7a
required 2 h at -100 °C and gave better yields with 2
equiv of LiTMP. In contrast, each of the 3,4-(alkylene-
dioxy)chlorobenzenes and -bromobenzenes used in the
present study (Table 1) underwent rapid deprotonation
with 1.1 equiv of either LDA or LiTMP in THF at -78
°C. Subsequent quenching of the aryllithiums with DMF
gave the expected benzaldehyde products, 1-6, in yields
of 68-81% for the chloro- and bromo-aromatics. Yields
did not significantly increase using LiTMP rather than
LDA. To investigate whether these aryllithium reagents
would efficiently trap other electrophiles, 5-bromoben-
zodioxole was metalated with LDA under the general
conditions and then treated with methyl iodide, TMS-
Cl, benzaldehyde, acetaldehyde, and acetone to give the
expected products, 7-11. The aryllithium was efficiently
trapped with even the enolizable electrophiles, acetalde-
hyde, and acetone.
The facile lithiation of the bromo- and chloro(alkylene-
dioxy)benzenes led us to attempt the lithiation of an iodo
case. Reaction of 5-iodobenzodioxole with LDA for 15 min
and quenching with DMF gave a 12.5% yield of 12, while
LiTMP (15 min) gave a 50% yield. Longer lithiation times
with LiTMP (40 min) gave only a slight increase in yield
(55%). Thus, even in the iodo case, lithiation is rapid and
the o-iodo aryllithium species appears to be stable at -78
°C for at least 40 min. 5-Iodobenzodioxole was also
metalated in a similar manner and treated with TMS-
Cl and with iodine to give the expected products, 13 and
14. Since we believe this to be the first example of an
iodine-directed ortho lithiation of a benzene ring, the
structure of 12 was confirmed by single-crystal X-ray
analysis. As further structural proof, catalytic hydroge-
nation of 12 gave benzodioxole-4-carboxaldehyde that
was identical with the commercially available material
Received December 22, 1998 (Revised Manuscript Received
August 4, 1999)
In tr od u ction
In comparison to other groups, the 1,2-methylenedioxy
and -ethylenedioxy groups are poor ortho-directed meta-
lation groups. Early attempts to ortho-lithiate 1,3-ben-
zodioxole failed,1 while later attempts with 1,3-benzo-
dioxole and 2,2-dimethyl-1,3-benzodioxole demonstrated
that the cleavage of the methylenedioxy ring competes
with ortho lithiation.2 Similarly, the attempted lithiation
of 1,4-benzodioxane gave only the ring-opened product,
catechol monovinyl ether.3 More recent work successfully
lithiated 2,2-dimethyl-1,3-benzodioxole using butyllith-
ium in ether, although the reaction was slow, requiring
32 h at room temperature.4a 2,2-Difluoro-1,3-benzodioxole
was also lithiated at -10 °C using butyllithium/TMEDA
in ether.4b While the ortho metalation of unsubstituted
(alkylenedioxy)benzenes is problematic, the ortho lithia-
tion of some substituted examples has been reported,5
and the related benzyne has been generated from 5-bromo-
1,3-benzodioxole and sodium amide.6 The ortho lithiation
of 3,4-(alkylenedioxy)halobenzenes, however, has not
been investigated.
* To whom correspondence should be addressed at Dept. 403, 5
Research Parkway, Wallingford, CT 06492-7660. Tel: (203) 677-6355.
Fax: (203) 677-7702. E-mail: mattsonr@bms.com.
† Neuroscience Chemistry.
‡ Present address: Schweizerhall, 1106 Perimeter Rd., Greenville,
SC 29605.
§ Analytical Research and Development.
| Discovery Analytical/Core Chemistry.
(1) Gensler, W. J .; Stouffer, J . E. J . Org. Chem. 1958, 23, 908-910.
(2) Cabiddu, S.; Maccioni, A.; Piras, P. P.; Secci, M. J . Organomet.
Chem. 1977, 136, 139-146.
(3) Ranade, A. C.; J ayalakshmi, S. Chem. Ind. (London) 1978, 234;
Chem. Abstr. 1978, 89, 108419.
(4) (a) Huang, D.-S.; Ting, S.-H. J . Chem. Res., Synop. 1994, 500-
501. (b) Ackermann, P.; Ka¨nel, H.-R.; Schaub, B. U.S. Patent 5,496,848,
1996.
(5) (a) Ranade, A. C.; Mali, R. S.; Bhide, S. R.; Mehta, S. R. Synthesis
1976, 123. (b) Guillaumet, G.; Hretani, M.; Coudert, G. Tetrahedron
Lett. 1988, 29, 475-6. (c) Tanigawa, Y.; Fuse, Y.; Murahashi, S.
Tetrahedron Lett. 1982, 23, 557-560.
(6) Liebeskind, L. S.; Lescosky, L. J .; McSwain, C. M., J r. J . Org.
Chem. 1989, 54, 1435-1439.
1
by H NMR and MS spectra.
In one reaction of 5-iodobenzodioxole with LDA and
DMF, the temperature was allowed to go above -70 °C.
(7) (a) Mongin, F.; Desponds, O.; Schlosser, M. Tetrahedron Lett.
1996, 37, 2767-2770. (b) Mongin, F.; Schlosser, M. Tetrahedron Lett.
1996, 37, 6551-6554. (c) Gribble, G. W.; Saulnier, M. G. Tetrahedron
Lett. 1980, 21, 4137-4140. (d) Gu, Y.-G.; Bayburt, E. K. Tetrahedron
Lett. 1996, 37, 2565-2568. (e) Aoyagi, Y.; Inariyama, T.; Arai, Y.;
Tsuchida, S.; Matuda, Y.; Kobayashi, H.; Ohta, A.; Kurihara, T.;
Fujihira, S. Tetrahedron 1994, 50, 13575-13582. (f) Goehring, R. R.
Tetrahedron Lett. 1992, 33, 6045-6048. (g) Effenberger, F.; Daub, W.
Chem. Ber. 1991, 124, 2119-2125. (h) Marsais, F.; Pineau, P.;
Nivolliers, F.; Mallet, M.; Turck, A.; Godard, A.; Que´guiner, G. J . Org.
Chem. 1992, 57, 565-573.
(8) Gjos, N.; Gronowitz, S. Acta Chem. Scand. 1971, 25, 2596-2608.
(9) Caton, M. P. L.; J ones, D. H.; Slack, R.; Woolridge, K. R. H. J .
Chem. Soc. 1964, 446-451.
(10) (a) Rocca, P.; Cochennec, C.; Marsais, F.; Thomas-dit-Dumont,
L.; Mallet, M.; Godard, A.; Que´guiner, G. J . Org. Chem. 1993, 58,
7832-7838. (b) Cochennec, C.; Rocca, P.; Marsais, F.; Godard, A.;
Que´guiner, G. Synthesis 1995, 321-324.
(11) Katsoulos, G.; Takagishi, S.; Schlosser, M. Synlett 1991, 731-
732.
10.1021/jo9824955 CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/10/1999

Notes
J . Org. Chem., Vol. 64, No. 21, 1999 8005
Ta ble 1. Or th o-Dir ected Lith ia tion s of 3,4-(Alk ylen ed ioxy)h a loben zen es
R
base
X
X′
electrophile
product
E
% yield
-CH2-
-CH2-
-CH2-
-CH2-
-(CH2)2-
-(CH2)2-
-(CH2)3-
-C(CH3)2-
-CH2-
-CH2-
-CH2-
-CH2-
-CH2-
-CH2-
-CH2-
-CH2-
-CH2-
-CH2-
LDA
LDA
LiTMP
LDA
LDA
LiTMP
LDA
LDA
LDA
LDA
LDA
LDA
LDA
LDA
LiTMP
LiTMP
LDA
Cl
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
I
H
H
H
Br
H
H
H
H
H
H
H
H
H
H
H
H
H
H
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
1
2
2
3
4
4
5
6
7
-CHO
76
72
75
69
68
77
77
81
94
83
89
78
78
12.5
50a
56b
57
85
-CHO
-CHO
-CHO
-CHO
-CHO
-CHO
-CHO
MeI
-CH3
TMS-Cl
PhCHO
CH3CHO
CH3COCH3
DMF
DMF
DMF
TMS-Cl
I2
8
9
-TMS
-CHOHPh
-CH(CH3)OH
-C(CH3)2OH
-CHO
10
11
12
12
12
13
14
I
I
I
I
-CHO
-CHO
-TMS
LiTMP
-I
a
b
Metalated for 15 min. Metalated for 40 min.
Sch em e 1
Sch em e 2
3-iodopyridines, Que´guiner observed a similar rearrange-
ment, isolating only 4-iodopyridine products.10 This shift
may occur through an elimination of lithium iodide, and
subsequent readdition12 in opposite regiochemistry, to the
intermediate benzyne. A more likely mechanism proposed
by Bunnett for this “halogen dance” involves the involve-
ment of trace amounts of a diiodo contaminant to give
scrambling of the regiochemistry.13
The in situ trapping of the 5-iodo-4-lithiobenzodioxole
with TMS-Cl gave the expected product, 13 (57%), along
with a small amount of a bis(trimethylsilyl) product
resulting from the excess LDA and TMS-Cl performing
a further deprotonation and trapping of 13. To further
investigate the position of this second subsequent lithia-
tion, the chloro-, bromo-, and iodobenzodioxoles were
metalated with 2.2 equiv of LDA and treated with excess
TMS-Cl to give high yields of the bis(trimethylsilyl)
products. The structure of 15c was confirmed both by
single-crystal X-ray analysis and by removal of the iodo
substituent by catalytic reduction to give a product that
showed a singlet in the 1H NMR for two equivalent
aromatic protons. Thus, the second lithiation occurs
adjacent to the methylenedioxy group to give 15c, which
upon catalytic hydrogenation gives the symmetrical
product 16 (Scheme 2).
Ta ble 2. Ch em ica l Sh ifts of 12 a n d th e Min or P r od u ct
(p p m ) in CDCl3 (500 MHz)
major component (12)
minor component
assignt
carbon
proton
assignt
carbon
proton
C2
C3a
C4
C5
C6
C7
C7a
C8
103.10
149.20
118.30
86.10
133.40
114.30
149.90
193.80
6.13
C2′
C3a′
C4′
C5′
C6′
C7′
C7a′
C8′
103.70
149.60
118.40
131.60
129.20
111.40
155.10
189.10
6.22
7.38
6.70
7.51
7.06
10.03
10.20
Before recrystallization of product 12, a minor component
(about 9%) was seen. While we were not able to separate
the minor component, the structure was characterized
by 1D and 2D NMR spectroscopic techniques. The
observed NMR data, including H-1, C-13, HMQC, and
HMBC spectra indicated that the structural difference
between the minor component and the major component
was in the position of the substituents. On the basis of
an interpretation of the NMR data, the minor component
is the isomeric 4-iodobenzodioxole-5-carboxaldehyde
(Scheme 1). This structure is supported by the observa-
tion of a C-H three-bond long-range correlation: from
the C-6′ proton (7.51 ppm) to the C8′ carbon (189.1 ppm)
and from the C-8′ proton (10.20 ppm) to the C-4′ carbon
(118.4 ppm). The total spectral assignments (Table 2) on
both components have also been made and are consistent
with the assigned structures. In his ortho lithiation of
The chloro-, bromo-, iodo-, and dibromo substrates were
all metalated efficiently, and no evidence of ring opening
(12) (a) Wittig, G.; Hoffmann, R. W. Chem. Ber. 1962, 95, 2729-
2734. (b) Hoffmann, R. W.; Vargas-Nunez, G. E.; Guhn, G.; Sieber, W.
Chem. Ber. 1965, 98, 2074-2085.
(13) Bunnett, J . F. Acc. Chem. Res. 1972, 5, 139-147.

8006 J . Org. Chem., Vol. 64, No. 21, 1999
Notes
1238, 1202 cm-1. Anal. Calcd for C8H4Br2O3: C, 31.20; H, 1.31;
N, 0.00. Found: C, 31.36; H, 1.33; N, <0.02.
was seen. Unlike previous studies, no significant differ-
ences in yields or purity of products from the chloro- and
bromo-aromatics were seen in the present study using
LiTMP rather than LDA as the base. Only in the iodo
case were significantly better yields obtained with LiT-
MP. These o-halo aryllithiums are easily generated at
-78 °C using only a slight excess of LDA or LiTMP, and
they can be reacted with a variety of electrophiles to form
2,3-(alkylenedioxy)phenyl compounds in quite good yields.
Moreover, the halogen substituents on these products are
useful for further synthetic manipulation, or they can be
removed by mild catalytic hydrogenation. This provides
a facile route to the products that would result from a
formal ortho lithiation of the unsubstituted (alkylene-
dioxy)benzenes.
6-Br om o-2,3-d ih yd r o-1,4-b en zod ioxa n e-5-ca r b oxa ld e-
h yd e (4): pale orange needles from cyclohexane/ethyl acetate;
1
mp 105-107 °C. H NMR: δ 4.28-4.31 (m, 2H), 4.35-4.38 (m,
2H), 6.92 (d, 1H, J ) 8.7 Hz), 7.11 (d, 1H, J ) 8.7 Hz), 10.34 (s,
1H). IR: 1689, 1291, 1255, 1221 cm-1. Anal. Calcd for C9H7-
BrO3: C, 44.47; H, 2.90; N, 0.00. Found: C, 44.57; H, 2.87; N,
<0.02.
7-Br om o-3,4-d ih yd r o-2H -1,5-b en zod ioxep in e-6-ca r b ox-
a ld eh yd e (5): pale yellow oil that solidified on standing
(chromatographed on silica gel using 10-30% ethyl acetate/
hexanes); mp 63-66 °C. 1H NMR: δ 2.28-2.31 (m, 2H), 4.26 (t,
2H, J ) 5.7 Hz), 4.36 (t, 2H, J ) 5.7 Hz), 7.02 (d, 1H, J ) 8.7
Hz), 7.20 (d, 1H, J ) 8.7 Hz), 10.34 (s, 1H). IR: 1700, 1472,
1455, 1265 cm-1. Anal. Calcd for C10H9BrO3‚0.1C6H12: C, 47.95;
H, 3.87; N, 0.00. Found: C, 47.94; H, 3.79; N, <0.02.
5-Br om o-2,2-d im et h yl-1,3-b en zod ioxole-4-ca r b oxa ld e-
h yd e (6): pale yellow needles from cyclohexane; mp 91-92.5
°C. 1H NMR: δ 1.74 (s, 6H), 6.75 (d, 1H, J ) 8.2 Hz), 7.04 (d,
Exp er im en ta l Section
1H, J ) 8.2 Hz), 10.27 (s, 1H). IR: 1694, 1686, 1458, 1241 cm-1
.
Anal. Calcd for C10H9BrO3: C, 46.72; H, 3.53; N, 0.00. Found:
C, 46.83; H, 3.53; N, <0.02.
Gen er a l Con sid er a tion s. The NMR spectra were deter-
mined using CDCl3 as a solvent and TMS as an internal
standard. All yields are of analytically pure material, and all
compounds had NMR, IR, and MS spectra and elemental
analyses ((0.4%) consistent with the assigned structures.
Several of the products were highly crystalline, and the struc-
tures of 2,14 12, and 14c were confirmed by single-crystal X-ray
analyses (enclosed as Supporting Information). The THF was
freshly distilled from Na-benzophenone ketyl under N2. The
lithium bases were prepared immediately before use from the
appropriate amine (distilled from calcium hydride) and n-
butyllithium (titrated15 with the tosyl hydrazone of benzophe-
none). Commercially available 5-chloro-, 5-bromo-, and 5-iodo-
benzodioxoles were used without purification. 6-Bromobenzo-
dioxane, 5-bromo-2,2-dimethylbenzodioxole, and 7-bromo-3,4-
dihydro-2H-1,5-benzodioxepine were prepared by literature
methods.16,17
Gen er a l P r oced u r e for 2-Su b st it u t ed 3,4-(Alk ylen e-
d ioxy)h a loben zen e. The 3,4-(alkylenedioxy)halobenzene (10
mmol) was added dropwise under dry nitrogen to a -78 °C
solution of the lithium dialkylamide (11 mmol) in THF (30 mL)
at a rate such that the temperature remained less than -70 °C.
The resulting solution was stirred for 15 min at -78 °C, and
then the electrophile (12.5 mmol) was added. The solution was
stirred for 15 min, and the -78 °C cooling bath was removed.
The reaction was warmed to room temperature over a 30 min
period, quenched with water, and diluted with ethyl acetate (30
mL). The organic layer was separated, washed twice with 1 N
HCl, twice with saturated sodium carbonate, and then dried with
brine. The organic layer was concentrated in vacuo to give the
crude products, which were purified by recrystallization or
column chromatography.
5-Br om o-4-m eth yl-1,3-ben zodioxole (7): white solid (Ku¨gel-
rohr distilled); mp 131-133 °C. 1H NMR: δ 2.24 (s, 3H), 5.95
(s, 2H), 6.55 (d 1H, J ) 8.3 Hz), 7.00 (d, 1H, J ) 8.3 Hz). IR:
1458, 1254, 1057, 800 cm-1. Anal. Calcd for C8H7BrO2: C, 44.69;
H, 3.28; N, 0.00. Found: C, 44.79; H, 3.19; N, <0.02.
5-Br om o-4-(tr im eth ylsilyl)-1,3-ben zod ioxole (8): pale yel-
low viscous oil (chromatographed on silica gel using 10-20%
ethyl acetate/hexanes). 1H NMR: δ 0.42 (s, 9H), 5.90 (s, 2H),
6.63 (d, 1H, J ) 8.2 Hz), 6.99 (d, 1H, J ) 8.2 Hz). IR: 1411,
1229, 1045, 853 cm-1. Anal. Calcd for C10H13BrO2Si: C, 43.96;
H, 4.80; N, 0.00. Found: C, 43.70; H, 4.73; N, <0.02.
1-(5-Br om o-1,3-b e n zod ioxol-4-yl)-1-p h e n ylm e t h a n ol
(9): pale yellow viscous oil (chromatographed on silica gel using
20% ethyl acetate/hexanes). 1H NMR: δ 3.11 (d, 1H, J ) 9.6
Hz), 5.95 (d, 1H, J ) 1.3 Hz), 6.00 (d, 1H, J ) 1.3 Hz), 6.18 (d,
1H, J ) 9.6 Hz), 6.66 (d, 1H, J ) 8.3 Hz), 7.06 (d, 1H, J ) 8.3
Hz), 7.25-7.43 (m, 5H). IR: 1454, 1241, 1052, 738 cm-1. Anal.
Calcd for C14H11BrO3: C, 54.75; H, 3.61; N, 0.00. Found: C,
55.12; H, 3.67; N, <0.02.
1-(5-Br om o-1,3-ben zod ioxol-4-yl)eth a n ol (10): pale yellow
viscous oil (chromatographed on silica gel using 20% ethyl
1
acetate/hexanes). H NMR: δ 1.54 (d, 3H, J ) 6.7 Hz), 5.17 (q,
1H, J ) 6.7 Hz), 6.00 (s, 2H), 6.60 (d, 1H, J ) 8.3 Hz), 6.99 (d,
1H, J ) 8.3 Hz). IR: 1453, 1241, 1058, 1035 cm-1. Anal. Calcd
for C9H9BrO3: C, 44.11; H, 3.70; N, 0.00. Found: C, 43.89; H,
3.53; N, <0.02.
1-(5-Br om o-1,3-ben zod ioxol-4-yl)-1-m eth yleth a n ol (11):
white solid (chromatographed on silica gel using 20% ethyl
1
acetate/hexanes); mp 41 °C. H NMR: δ 1.75 (s, 6H), 3.62 (br s,
1H), 5.93 (s, 2H), 6.58 (d, 1H, J ) 8.3 Hz), 7.08 (d, 1H, J ) 8.3
Hz). IR: 1427, 1327, 1234, 1041 cm-1. Anal. Calcd for C10H11
-
5-Ch lor o-1,3-ben zod ioxole-4-ca r boxa ld eh yd e (1): pale
yellow needles from cyclohexane; mp 129.5-131.5 °C. 1H NMR:
δ 6.16 (s, 2H), 6.90 (s, 2H), 10.40 (s, 1H). IR: 1678, 1459, 1246
cm-1. Anal. Calcd for C8H5ClO3: C, 52.06; H, 2.73; N, 0.00.
Found: C, 51.80; H, 2.65; N, <0.02.
5-Br om o-1,3-ben zod ioxole-4-ca r boxa ld eh yd e (2): pale
yellow needles from isopropyl acetate; mp 160-162 °C. 1H
NMR: δ 6.16 (s, 2H), 6.85 (d, 1H, J ) 8.2 Hz), 7.10 (d, 1H, J )
8.2 Hz), 10.28 (s, 1H). IR: 1681, 1454, 1244 cm-1. Anal. Calcd
for C8H5BrO3: C, 41.95; H, 2.20; N, 0.00. Found: C, 41.99; H,
2.16; N, <0.02.
BrO3: C, 46.36; H, 4.28; N, 0.00. Found: C, 46.42; H, 4.07; N,
<0.02.
5-Iod o-1,3-ben zod ioxole-4-ca r boxa ld eh yd e (12): pale yel-
low needles from cyclohexane; mp 162-165 °C. 1H NMR: δ 6.13
(s, 2H), 6.70 (d, 1H, J ) 8.2 Hz), 7.38 (d, 1H, J ) 8.2 Hz), 10.03
(s, 1H). IR: 1674, 1582, 1451, 1242 cm-1. Anal. Calcd for C8H5-
IO3‚0.12 C6H12: C, 36.60; H, 2.27; N, 0.00. Found: C, 36.82; H,
2.00; N, <0.02.
5-Iod o-4-(tr im eth ylsilyl)-1,3-ben zod ioxole (13): clear oil
(chromatographed on silica gel using 0-5% ethyl acetate/
hexanes). 1H NMR: δ 0.44 (s, 9H), 5.89 (s, 2H), 6.49 (d, 1H, J )
5,6-Dibr om o-1,3-ben zodioxole-4-car boxaldeh yde (3): pale
yellow powder from isopropyl acetate; mp 200-202 °C. 1H
NMR: δ 6.18 (s, 2H), 7.25 (s, 1H), 10.28 (s, 1H). IR: 1681, 1462,
8.1 Hz), 7.33 (d, 1H, J ) 8.1 Hz). IR: 1408, 1394, 1228, 846 cm-1
.
Anal. Calcd for C10H13IO2Si: C, 37.51; H, 4.09; N, 0.00. Found:
C, 37.60; H, 4.09; N, <0.02.
4,5-Diiod o-1,3-ben zod ioxole (14): pale yellow oil that
solidified on cooling (purified by Ku¨gelrohr distillation). 1H
NMR: δ 6.05 (s, 2H), 6.60 (d, 1H, J ) 8.0 Hz), 7.38 (d, 1H, J )
8.0 Hz). IR: 1445, 1234, 1033, 934 cm-1. Anal. Calcd for
C7H4I2O2: C, 22.49; H, 1.08; N, 0.00. Found: C, 22.62; H, 1.26;
N, <0.02.
Gen er a l P r oced u r e for 4,7-Bis(tr im eth ylsilyl)-5-h a lo-1,3-
ben zod ioxoles. The 3,4-(alkylenedioxy)halobenzene (4 mmol)
was added dropwise under dry nitrogen to a -78 °C solution of
(14) Smidrkal, J . Collect. Czech. Chem. Commun. 1982, 47, 2140-
2144; Chem. Abstr. 1983, 98, 34817.
(15) Miranda, R.; Hernandez, A.; Angeles, E.; Cabrera, A.; Salmon,
M.; J oseph-Nathan, P. Analyst (London) 1990, 115, 1483-1485; Chem.
Abstr. 1991, 114, 55044.
(16) Dauksas, V.; Udrenaite, E.; Labanauskas, L.; Gasperaviciene,
G. Chemija 1994, 70-72; Chem. Abstr. 1995, 122, 159883.
(17) Ding, Y. S.; Shiue, C. Y.; Fowler, J . S.; Wolf, A. P.; Plenevaux,
A. J . Fluorine Chem. 1990, 48, 189-206.

Notes
J . Org. Chem., Vol. 64, No. 21, 1999 8007
9H), 5.81 (s, 2H), 7.26 (s, 1H). IR: 1364, 1249, 1048, 839 cm-1
Anal. Calcd for C13H21IO2Si2: C, 39.79; H, 5.39; N, 0.00. Found:
C, 39.65; H, 5.43; N, <0.02.
the lithium dialkylamide (8.8 mmol) and TMS-Cl (2 mL) in THF
(30 mL) at a rate such that the temperature remained less than
-70 °C. The solution was stirred for 15 min, and the -78 °C
cooling bath was removed. The reaction mixture was warmed
to room temperature over a 30 min period, quenched with water,
and diluted with ethyl acetate (30 mL). The organic layer was
separated, washed twice with water, and then dried with brine.
The organic layer was concentrated in vacuo to give the crude
products, which were purified by column chromatography.
4,7-Bis(tr im eth ylsilyl)-5-ch lor o-1,3-ben zod ioxole (15a ):
clear oil that solidified on standing (chromatographed on silica
gel using hexanes); mp 44-47 °C. 1H NMR: δ 0.27 (s, 9H), 0.38
(s, 9H), 5.89, (s, 2H), 6.79 (s, 1H). IR: 1374, 1249, 1056, 841
cm-1. Anal. Calcd for C13H21ClO2Si2: C, 51.89; H, 7.03; N, 0.00.
Found: C, 52.08; H, 7.08; N, <0.02.
.
Hyd r ogen a tion of 5-Iod o-1,3-ben zod ioxole-4-ca r boxa l-
d eh yd e (12). An ethanol solution of 12 (50 mg) was stirred with
10% Pd/C (50 mg) and potassium carbonate (50 mg) under
hydrogen (balloon pressure) for 3 h. The mixture was filtered
and the filtrate concentrated in vacuo to give 1,3-benzodioxole-
4-carboxaldehyde (25 mg, 92%) by 1H NMR and MS spectra.
4,6-Bis(tr im eth ylsilyl)-1,3-ben zod ioxole (16). An ethanol
solution of 15c (100 mg) was hydrogenated (60 psi) over 10%
Pd/C (100 mg) for 2 h. The mixture was filtered and concentrated
in vacuo to give 4,6-bis(trimethylsilyl)-1,3-benzodioxole (16) as
1
a clear oil that solidified on standing (60 mg, 88%). H NMR: δ
0.32 (s, 18H), 5.94 (s, 2H), 6.90 (s, 2H). IR: 1370, 1249, 1197,
839 cm-1. Anal. Calcd for C13H22O2Si2: C, 58.59; H, 8.32; N, 0.00.
Found: C, 58.30; H, 8.15; N, <0.02.
4,7-Bis(tr im eth ylsilyl)-5-br om o-1,3-ben zod ioxole (15b):
clear oil that solidified on standing (chromatographed on silica
gel using hexanes); mp 36-39 °C. 1H NMR: δ 0.26 (s, 9H), 0.39
(s, 9H), 5.88, (s, 2H), 6.98 (s, 1H). IR: 1368, 1250, 1052, 840
cm-1. Anal. Calcd for C13H21BrO2Si2: C, 45.21; H, 6.13; N, 0.00.
Found: C, 45.48; H, 6.12; N, <0.02.
Su p p or tin g In for m a tion Ava ila ble: Tables giving details
of the single-crystal X-ray analyses of 2, 12, and 14c. This
material is available free of charge via the Internet at
http://pubs.acs.org.
4,7-Bis(tr im eth ylsilyl)-5-iodo-1,3-ben zodioxole (15c): clear
oil that solidified on standing (chromatographed on silica gel
1
using hexanes); mp 66-68 °C. H NMR: δ 0.20 (s, 9H), 0.38 (s,
J O9824955