7876
H. Awad et al. / Tetrahedron Letters 45 (2004) 7873–7877
Table 3. Deprotonation of 12 and 13 using lithium magnesates
´
cited therein; (b) Mongin, F.; Queguiner, G. Tetrahedron
2001, 57, 4059–4090, and references cited therein; (c)
N
N
R
R'
Cl
´
´
Turck, A.; Ple, N.; Mongin, F.; Queguiner, G. Tetrahe-
dron 2001, 57, 4489–4505, and references cited therein.
3. (a) Schlecker, W.; Huth, A.; Ottow, E.; Mulzer, J. J. Org.
Chem. 1995, 60, 8414–8416; (b) Schlecker, W.; Huth, A.;
Ottow, E.; Mulzer, J. Liebigs Ann. 1995, 1441–1446; (c)
Schlecker, W.; Huth, A.; Ottow, E.; Mulzer, J. Synthesis
1995, 1225–1227.
I
1) base, THF
-10 °C, 2 h
Cl
R'
Cl
R'
Cl
R'
+
2) I2 3) H2O
R
N
R
R
N
12: R= Cl, R'= H
13: R= H, R'= F
14a: R= Cl, R'= H 14b: R= Cl, R'= H
15b: R= H, R'= F
´
´
4. (a) Bonnet, V.; Mongin, F.; Trecourt, F.; Queguiner, G. J.
Chem. Soc., Perkin Trans. 1 2000, 4245–4249; (b) Schlec-
ker, W.; Huth, A.; Ottow, E.; Mulzer, J. Tetrahedron 1995,
51, 9531–9542.
15a: R= H, R'= F
Products (yields)
Entry Substrate Base
1
2
3
4
5
6
7
8
12
12
12
12
13
13
13
13
1/3equiv
Bu2(DA)MgLi
1equiv
14a (64%),
5. (a) Kondo, Y.; Shilai, M.; Uchiyama, M.; Sakamoto, T. J.
Am. Chem. Soc. 1999, 121, 3539–3540; (b) Imahori, T.;
Uchiyama, M.; Sakamoto, T.; Kondo, Y. Chem. Commun.
2001, 2450–2451; (c) Schwab, P. F. H.; Fleischer, F.;
Michl, J. J. Org. Chem. 2002, 67, 443–449; Concerning the
deprotonation of substituted benzenes, see: (a) Uchiyama,
M.; Miyoshi, T.; Kajihara, Y.; Sakamoto, T.; Otani, Y.;
Ohwada, T.; Kondo, Y. J. Am. Chem. Soc. 2002, 124,
8514–8515.
6. Wittig, G.; Meyer, F. J.; Lange, G. Liebigs Ann. Chem.
1951, 571, 167–201.
7. For a synopsis, see: Mulvey, R. E. Chem. Commun. 2001,
1049–1056.
8. (a) Ashby, E. C.; Chao, L.-C.; Laemmle, J. J. Org. Chem.
1974, 39, 3258–3263; (b) Kamienski, C. W.; Gastonia, N.
C.; Eastham, J. F. U.S. Patent 3,847,883, 1974; Chem.
Abstr. 1975, 82, 58590; (c) Richey, H. G., Jr.; Farkas, J.,
Jr. Tetrahedron Lett. 1985, 26, 275–278; (d) Richey, H. G.,
Jr.; Farkas, J., Jr. Organometallics 1990, 9, 1778–1784; (e)
Castaldi, G.; Borsotti, G. Eur. Pat. Appl. EP 491,326,
1992; Chem. Abstr. 1992, 117, 150667; (f) Yasuda, M.; Ide,
M.; Matsumoto, Y.; Nakata, M. Synlett 1997, 899–902;
(g) Yasuda, M.; Ide, M.; Matsumoto, Y.; Nakata, M. Bull.
Chem. Soc. Jpn. 1998, 71, 1417–1429; (h) Ide, M.; Yasuda,
M.; Nakata, M. Synlett 1998, 936–938; (i) Kitagawa, K.;
Inoue, A.; Shinokubo, H.; Oshima, K. Angew. Chem., Int.
Ed. 2000, 39, 2481–2483; (j) Iida, T.; Wada, T.; Mase, T.
Japan Application No. JP 2000–024613 20000202, 2000;
Chem. Abstr. 2001, 135, 152370(k) Kondo, J.; Inoue, A.;
Shinokubo, H.; Oshima, K. Angew. Chem., Int. Ed. 2001,
40, 2085–2087; (l) Inoue, A.; Kitagawa, K.; Shinokubo,
H.; Oshima, K. J. Org. Chem. 2001, 66, 4333–4339; (m)
Iida, T.; Wada, T.; Tomimoto, K.; Mase, T. Tetrahedron
Lett. 2001, 42, 4841–4844; (n) Inoue, A.; Kondo, J.;
Shinokubo, H.; Oshima, K. Chem. Eur. J. 2002, 8, 1730–
1740; (o) Fukuhara, K.; Takayama, Y.; Sato, F. J. Am.
Chem. Soc. 2003, 125, 6884–6885; (p) Dumouchel, S.;
14b not detected
14a (traces),
14b (41%)
Bu2(TMP)MgLi
1equiv
Bu(TMP)2MgLi
14a not detected,
14b (60%)
1equiv (TMP)3MgLi 14a not determined,
14b (51%)
1/3equiv
Bu2(TMP)MgLi
1/2equiv
15a (42%),
15b (traces)
15a (27%),
15b (traces)
15a (traces),
15b (44%)
Bu(TMP)2MgLi
1equiv
Bu2(TMP)MgLi
1equiv (TMP)3MgLi 15a (traces),
15b (56%)
Bu3(TMP)MgLi2 in THF at ꢀ10°C, as evidenced by
trapping with I2. The use of Bu(TMP)2MgLi in Et2O
allowed the reaction of 2-chloropyridine, giving the 3-
functionalized derivative as the main product. Mixtures
of 3- and 4-functionalized derivatives were obtained
when 2,6-dichloropyridine was involved in the reaction.
Surprisingly, by performing the reaction on 3-chloropyri-
dine with lithium magnesates in THF, either the
4,40-dimer or the 4-iodo derivative was formed after
quenching by I2, the former using 1/3equiv of
Bu2(TMP)MgLi and the latter 1equiv of (TMP)3MgLi.
Intramolecular 1,2-migration of the sterically congested
lithium arylmagnesate formed by deprotonation was
proposed to justify the dimer formation. Similar results
were observed with 3,5-dichloropyridine, 2,5-dichloro-
pyridine and 3-chloro-2-fluoropyridine.
Deprotonation using Bu3MgLi, typical procedure. BuLi
(6.0mmol) was added to a solution of MgBr2 (2.0mmol)
in THF (3mL) at ꢀ10°C. After stirring for 1h at
ꢀ10°C, 3,5-dichloropyridine (0.88g, 6.0mmol) was
introduced at ꢀ30°C. After 2h at ꢀ10°C, a solution
of I2 (1.5g, 6.0mmol) in THF (3mL) was added and
the mixture was stirred for 18h at rt. Addition of water
(0.5mL) and Na2S2O3 (until bleaching), dilution with
CH2Cl2 (50mL), drying over MgSO4 and column chro-
matography using CH2Cl2 as an eluent afforded com-
pound 10a (88% yield).
´
Mongin, F.; Trecourt, F.; Queguiner, G. Tetrahedron Lett.
2003, 44, 2033–2035; (q) Dumouchel, S.; Mongin, F.;
´
´
Trecourt, F.; Queguiner, G. Tetrahedron Lett. 2003, 44,
3877–3880; (r) Dumouchel, S.; Mongin, F.; Trecourt, F.;
´
´
´
Queguiner, G. Tetrahedron 2003, 59, 8629–8640; (s)
Farkas, J., Jr.; Stoudt, S. J.; Hanawalt, E. M.; Pajerski,
A. D.; Richey, H. G., Jr. Organometallics 2004, 23, 423–
427; (t) Ito, S.; Kubo, T.; Morita, N.; Matsui, Y.;
Watanabe, T.; Ohta, A.; Fujimori, K.; Murafuji, T.;
Sugihara, Y.; Tajiri, A. Tetrahedron Lett. 2004, 45, 2891–
2894; (u) Therkelsen, F. D.; Rottla¨nder, M.; Thorup, N.;
Pedersen, E. B. Org. Lett. 2004, 6, 1991–1994.
References and notes
9. Armstrong, D. R.; Kennedy, A. R.; Mulvey, R. E.;
Rowlings, R. B. Angew. Chem., Int. Ed. 1999, 38, 131–133.
´
´
1. Katritzky, A. R.; Rees, C. W. In Comprehensive Hetero-
cyclic Chemistry; Boulton, A. J., McKillop, A., Eds.;
Pergamon, 1984; Vol. 2.
10. Awad, H.; Mongin, F.; Trecourt, F.; Queguiner, G.;
Marsais, F.; Blanco, F.; Abarca, B.; Ballesteros, R.
Tetrahedron Lett. 2004, 45, 6697–6701.
´
2. (a) Queguiner, G.; Marsais, F.; Snieckus, V.; Epsztajn, J.
Adv. Heterocycl. Chem. 1991, 52, 187–304, and references
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