Intermediates Offering Access to New Organofluorine Compounds
FULL PAPER
R. Maggi, M. Schlosser, Tetrahedron Lett. 1999, 40,
[4]
[5]
6.7 Hz, 2 H). Ϫ C9H7F3O3 (202.12): calcd. C 49.10, H 3.20; found
C 49.62, H 3.32.
8797Ϫ8800.
M. Schlosser, J. H. Choi, S. Takagishi, Tetrahedron 1990, 46,
5633Ϫ5648.
Z.-P. Liu, M. Schlosser, Heteroatom Chem. 1991, 2, 515Ϫ519;
2,2,5-Trifluoro-1,3-benzodioxole-4-carboxylic Acid: Obtained from
2,2,5-trifluoro-1,3-benzodioxole (4.4 g, 25 mmol) and isolated as
described above (see the preparation of 2,2-difluoro-1,3-benzodiox-
ole-4-carboxylic acid); colorless needles; m.p. 137Ϫ138 °C (from a
[6]
Chem. Abstr. 1992, 116, 83793y.
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J. D. Roberts, D. Y. Curtin, J. Am. Chem. Soc. 1946, 68,
1658Ϫ1660.
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1
[8]
1:4 mixture of ethyl acetate and hexanes); yield 5.2 g (94%). Ϫ H
1968, 11, 209Ϫ226.
NMR: δ ϭ 7.25 (dd, J ϭ 9.0, 4.8 Hz, 1 H), 6.97 (dd, J ϭ 8.9 Hz,
1 H). Ϫ C8H3F3O4 (220.11): calcd. C 43.66, H 1.37; found C 43.64,
H 1.24.
[9]
S. Takagishi, G. Katsoulos, M. Schlosser, Synlett 1992,
360Ϫ361.
[10]
[11]
M. Schlosser, F. Mongin, J. Porwisiak, W. Dmowski, H. H.
Büker, N. M. M. Nibbering, Chem. Eur. J. 1998, 4, 1281Ϫ1286.
Postulated binding interactions between metals and carbon-
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3425Ϫ3468 (general); T. Ooi, N. Kagoshima, K. Maruoka, J.
Am. Chem. Soc. 1997, 119, 5754Ϫ5755 (aluminum); J. Karl, G.
Erker, R. Fröhlich, J. Am. Chem. Soc. 1997, 119, 11165Ϫ11173
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Tetrahedron Lett. 1998, 39, 7105Ϫ7108 (aluminum); H. Take-
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Inazu, Angew. Chem. 1999, 111, 1012Ϫ1014; Angew. Chem. Int.
Ed. 1999, 38, 959Ϫ961 (potassium); D. R. Click, B. L. Scott,
J. G. Watkin, Chem. Commun. 1999, 633Ϫ634 (samarium); H.-
J. Buschmann, J. Hermann, M. Kaupp, H. Plenio, Chem. Eur.
J. 1999, 5, 2566Ϫ2572 (lithium).
H. Felkin, G. Roussi, Tetrahedron Lett. 1965, 6, 4153Ϫ4159;
H. Felkin, C. Frajerman, Tetrahedron Lett. 1970, 11,
1045Ϫ1048; H. Felkin, C. Frajerman, G. Roussi, Bull. Soc.
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333658 (to Ciba Geigy AG; filed 20. Sept. 1989); Chem. Abstr.
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1989); Chem. Abstr. 1990, 112, 13901n.
2-(5-Bromo-2,2-difluoro-1,3-benzodioxol-4-yl)ethanol (7g): Butyl-
lithium (25 mmol) in hexanes (16 mL) and 5-bromo-2,2-difluoro-
1,3-benzodioxole (5.9 g, 25 mmol) were added consecutively to
2,2,6,6-tetramethylpiperidine (4.2 mL, 3.5 g, 25 mmol) in tetrahy-
drofuran (50 mL), cooled in a dry ice/acetone bath. After 2 h at
Ϫ75 °C, the mixture was treated with oxirane (1.3 mL, 1.1 g,
25 mmol) and the colorless product isolated as described above (see
preparation of 5g); m.p. 59Ϫ60 °C (needles; from hexanes); b.p.
122Ϫ124 °C/2 Torr; yield 5.3 g (76%). Ϫ 1H NMR: δ ϭ 7.32 (d,
J ϭ 8.5 Hz, 1 H), 6.86 (d, J ϭ 8.6 Hz, 1 H), 3.93 (t, J ϭ 6.7 Hz, 2
H), 3.10 (t, J ϭ 6.7 Hz, 2 H). Ϫ C9H7BrF2O3 (281.06): calcd. 38.46,
H 2.51; found C 38.61, H 2.21.
5-Bromo-2,2-difluoro-1,3-benzodioxole-4-carboxylic Acid: A reac-
tion mixture, prepared as described in the preceding paragraph,
was poured onto an excess of freshly crushed solid CO2 in place of
the treatment with oxirane. The colorless product was isolated as
before (see above); m.p. 148Ϫ149 °C (cubes; from toluene); yield
[12]
[13]
1
6.2 g (88%). Ϫ H NMR: δ ϭ 7.44 (d, J 8.5 Hz, 1 H), 7.09 (d, J ϭ
8.6 Hz, 1 H). Ϫ C8H3BrF2O4 (281.02): calcd. C 34.19, H 1.08;
found C 34.13, H 1.18.
[14]
[15]
[16]
[17]
O. Desponds, L. Franzini, M. Schlosser, Synthesis 1997,
2-(2,2-Difluoro-1,3-benzodioxol-5-yl)ethanol: A solution of tert-bu-
tyllithium (50 mmol) in pentanes (30 mL) was added at Ϫ75 °C to
5-bromo-2,2-difluoro-1,3-benzodioxole (5.9 g, 25 mmol) in tetrahy-
drofuran (50 mL), followed 15 min later by oxirane (1.3 mL, 1.1 g,
25 mmol). When the mixture had reached ϩ25 °C, it was worked
up as before (see preparation of 5g) to obtain a colorless oil; b.p.
106Ϫ108 °C/3 Torr. Ϫ n2D0 ϭ 1.4836; yield 3.7 g (73%). Ϫ 1H NMR:
δ ϭ 6.98 (d, J ϭ 8.1 Hz, 1 H), 6.97 (d, J ϭ 1.1 Hz, 1 H), 6.91 (dd,
J ϭ 8.2, 1.3 Hz, 1 H), 3.83 (t, J ϭ 6.2 Hz, 2 H), 2.84 (t, J ϭ 6.4 Hz,
2 H). Ϫ C9H8F2O3 (202.16): calcd. C 53.47, H 3.99; found C 53.33,
H 4.16.
150Ϫ152.
M. Schlosser, J. Porwisiak, F. Mongin, Tetrahedron 1998, 54,
895Ϫ900.
Q. Wang, H.-x. Wei, M. Schlosser, Eur. J. Org. Chem. 1999,
3263Ϫ3268.
G. Rauchschwalbe, M. Schlosser, Helv. Chim. Acta 1975, 58,
1094Ϫ1099; see also: M. Schlosser, L. Franzini, Synthesis 1998,
707Ϫ709, footnote 14.
V. P. Nazaretyan, V. I. Troizkaya, L. M. Jagupolskii, Ukr. Khim.
Zh. 1974, 40, 545Ϫ546; Chem. Abstr. 1974, 81, 91169y.
A. I. Ponomarev, S. V. Sokolov, J. A. Larionova, A. L. Kleban-
skii, V. V. Berenblit, J. P. Dolnakov, L. M. Yagupolskii, V. V.
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F. Mathey, J. Bensoam, Tetrahedron Lett. 1973, 25, 2253Ϫ2256.
L. M. Yagupolskii, V. I. Troizkaya, Zhur. Obshche. Khim. 1957,
27, 518Ϫ523; Chem. Abstr. 1957, 51, 15517i.
E. Grigat, R. Pütter, Chem. Ber. 1964, 97, 3012Ϫ3017.
G. Köbrich, H. Trapp, A. Akhtar, Chem. Ber. 1968, 101,
[18]
[19]
Acknowledgments
[20]
[21]
This work was financially supported by the Schweizerische Na-
tionalfonds zur Förderung der wissenschaftlichen Forschung, Bern
(grant 20Ϫ55Ј303Ϫ98) and the Bundesamt für Bildung und Wis-
senschaft, Bern (grant 97.0083 linked to the TMR project
FMRXCT970129).
[22]
[23]
2644Ϫ2659.
[24]
[25]
E. L. Stogryn, J. Med. Chem. 1973, 16, 1399Ϫ1401.
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M. Schlosser, G. Katsoulos, S. Takagishi, Synlett 1990,
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747Ϫ748.
[2]
G. Katsoulos, S. Takagishi, M. Schlosser, Synlett 1991,
731Ϫ732.
M. Schlosser, P. Maccaroni, E. Marzi, Tetrahedron 1998, 54,
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M. J. Thomas, J. Org. Chem. 1981, 46, 5431Ϫ5434.
[3]
Received August 7, 2000
[O00414]
Eur. J. Org. Chem. 2001, 691Ϫ695
695