- Email: [email protected]
First cross-coupling reactions of arylmagnesates: a convenient access to heteroarylquinolines
TETRAHEDRON LETTERS Pergamon
Tetrahedron Letters 44 (2003) 3877–3880
First cross-coupling reactions of arylmagnesates: a convenient access to heteroarylquinolines Sylvain Dumouchel, Florence Mongin,* Franc¸ois Tre´court and Guy Que´guiner Laboratoire de Chimie Organique Fine et He´te´rocyclique, UMR 6014, IRCOF, Place E. Blondel, BP 08, 76131 Mont-Saint-Aignan Ce´dex, France Received 17 December 2002; accepted 8 February 2003
Abstract—2-, 3- and 4-Bromoquinolines were converted to the corresponding lithium tri(quinolyl)magnesates at −10°C on treatment with Bu3MgLi in THF. The resulting organomagnesium derivatives were involved in catalyzed cross-coupling reactions with heteroaryl bromides and chlorides to afford functionalized quinolines. © 2003 Elsevier Science Ltd. All rights reserved.
We describe the first cross-couplings with lithium triarylmagnesates. Interest in azine and diazine natural products either for pharmaceuticals or as building blocks for various applications within materials science and supramolecular chemistry has led to extensive efforts devoted to a variety of synthetic methodologies.1 In these series, the development of transition metal-catalyzed cross-couplings, such as Negishi,2,3 Suzuki,2,4 Stille2,4d,f,5 and Kharasch2,6 reactions, is of crucial importance. An organomagnesate (R3MgLi) was first published in 1951.7 However, while the structure of such complexes has long been investigated,8 their synthetic applications remained unexplored until very recently.9 In 2001, the first halogen–magnesium exchanges via organomagnesates were published by Oshima in the benzene, pyridine and thiophene series.9i,l The method has since been extended to the mono-exchange of dibromobenzenes and dibromoheteroarenes (pyridine and thiophene series) by Iida and Mase using lithium tributylmagnesate.9m We have been interested in the bromine–magnesium exchange of 2-, 3- and 4-bromoquinolines using lithium tributylmagnesate.10 Herein, we describe the behavior of the lithium tri(quinolyl)magnesates thus prepared in the catalyzed cross-coupling reactions with heteroaromatic bromides and chlorides.
Keywords: cross-coupling; ate complexes; magnesium; quinoline. * Corresponding author. Tel.: +33 (0) 2 35 52 29 00; fax: +33 (0) 2 35 52 29 62; e-mail: [email protected]
The first experiments were conducted on lithium tri(3quinolyl)magnesate (1a), prepared by treating 3-bromoquinoline (1) with lithium tributylmagnesate in THF at −10°C.10 Under palladium catalysis, reactions between arylmagnesium halides and aryl chlorides, bromides, or iodides are possible at rt.6f,i,l,m,11 Nickel, which is harder than palladium, was most often chosen for chlorides6d,h,l and fluorides,12 which are harder than bromides and iodides. Indeed, attempts to realize the subsequent cross-coupling reactions of 1a in a ‘one-pot’ procedure with heteroaromatic bromides under nickel catalysis were unsuccessful. So we turned our attention to palladium catalysis. The reaction could be achieved when catalytic amounts of bis(dibenzylideneacetone)palladium(0) (Pd(dba)2) and 1,1%-bis(diphenylphosphino)ferrocene (dppf) were used.6i,l,m,13 The low to medium yields observed are based on 3-bromoquinoline (1). The first step proceeds in 85–90% yield, as demonstrated by quenching the intermediate 1a with benzaldehyde, the remaining 10–15% being essentially butylated products formed through addition of the residual butylmagnesium species to the quinoline ring.10 The coupling step results of the successive reactions of the lithium tri(3-quinolyl)magnesate, the bi(3-quinolyl)magnesium, and the 3-quinolylmagnesium bromide with the bromo substrate. It appears that less than 10% of 3,3%-biquinoline could be detected, the main by-product being quinoline, obtained in 15 to 50% yield depending on the reactivity of the bromide involved. The best results were observed with p-deficient substrates such as bromopyridines and bromoquinolines, for which the oxidative addition step is easier (Table 1, entries 1–5), while lower yields were obtained with less activated bromothiophenes (Table 1, entries 6 and 7). Moreover, the
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0040-4039(03)00786-X
3878
S. Dumouchel et al. / Tetrahedron Letters 44 (2003) 3877–3880
Table 1. Cross-coupling reactions of 1a with bromides
Scheme 2. Table 2. Cross-coupling reactions of 1a with chlorides
yields depend on the position of the bromine atom on the ring, better results being noted with 2-bromo substrates (Scheme 1, Table 1). We then investigated the reaction with chlorides. In this case, we have shown that it is advantageous to use bis(acetylacetonate)nickel(II) (Ni(acac)2) instead of Pd(dba)2; 1,3-bis(diphenylphosphino)propane (dppp) was found to be the best ligand.6a–i,l,m The reaction of 1a with heteroaromatic chlorides was carried out in THF, in a ‘one-pot’ procedure at rt. It generally proceeds in modest yields, depending on the substrate used (better yields with diazines, for which the oxidative addition step is easier), but also on the position of the chlorine atom on the ring (Scheme 2, Table 2). To evaluate the scope of this reaction, it was applied to the lithium tri(quinolyl)magnesates 3a and 4a, respectively, derived from 2- and 4-bromoquinolines (3 and 4).16 It appears that the yields obtained from magnesate 3a are lower:10 this may be attributed to its incomplete
Scheme 1.
synthesis through bromine-magnesium exchange, but also to a lower reactivity, when compared to magnesates 1a and 4a (Scheme 3, Table 3). In conclusion, 2-, 3- and 4-substituted quinolines could be synthesized from the corresponding bromo derivatives in a ‘one-pot’ procedure through bromine-magnesium exchange reaction and subsequent cross-coupling with heteroaryl halides. Even if the yields are not high,
Scheme 3.
S. Dumouchel et al. / Tetrahedron Letters 44 (2003) 3877–3880
3879
Table 3. Cross-coupling reactions of 3a and 4a with bromides
our method is interesting since it avoids a preliminary synthesis of the organometallic substrate, usually at low temperatures via its corresponding lithio derivative. Cross-coupling typical procedure: BuLi (1.6 M in hexanes, 1.3 mmol) was added to a solution of BuMgCl (2.0 M in diethyl ether, 0.65 mmol) in THF (4 mL) at −10°C. After stirring for 1 h at −10°C, 3-bromoquinoline (1, 0.23 mL, 1.7 mmol) was introduced at −30°C. After 2.5 h at −10°C, 2-bromopyridine (0.16 mL, 1.7 mmol) in THF (3 mL), Pd(dba)2 (48 mg, 85 mmol) and dppf (47 mg, 85 mmol) were added and the mixture was stirred for 18 h at rt. Addition of water saturated with NH4Cl (0.5 mL), dilution with CH2Cl2 (50 mL), drying over MgSO4 and column chromatography using CH2Cl2/Et2O (80:20) as an eluent afforded compound 2a (56% yield).
References 1. (a) Katritzky, A. R.; Rees, C. W. Comprehensive Heterocyclic Chemistry; Boulton, A. J.; McKillop, A., Eds., Pergamon Press, 1984; Vol. 2; (b) Que´ guiner, G.; Marsais, F.; Snieckus, V.; Epsztajn, J. Adv. Heterocycl. Chem. 1991, 52, 187–304; (c) Mongin, F.; Que´ guiner, G. Tetrahedron 2001, 57, 4059–4090; (d) Turck, A.; Ple´ , N.; Mongin, F.; Que´ guiner, G. Tetrahedron 2001, 57, 4489– 4505. 2. Stanforth, S. P. Tetrahedron 1998, 54, 263–303 and references cited therein. 3. (a) Negishi, E.; King, A. O.; Okukado, N. J. J. Org. Chem. 1977, 42, 1821–1823; (b) Sakamoto, T.; Kondo, Y.; Murata, N.; Yamanaka, H. Tetrahedron 1993, 49, 9713–9720; (c) Tre´ court, F.; Gervais, B.; Mallet, M.; Que´ guiner, G. J. Org. Chem. 1996, 61, 1673–1676; (d) Tre´ court, F.; Gervais, B.; Mongin, O.; Le Gal, C.; Mongin, F.; Que´ guiner, G. J. Org. Chem. 1998, 63,
2892–2897; (e) Hargreaves, S. L.; Pilkington, B. L.; Russel, S. E.; Worthington, P. A. Tetrahedron Lett. 2000, 41, 1653–1656; (f) Loren, J. C.; Siegel, J. S. Angew. Chem., Int. Ed. 2001, 40, 754–757; (g) Karig, G.; Spencer, J. A.; Gallagher, T. Org. Lett. 2001, 3, 835–838; (h) Karig, G.; Thasana, N.; Gallagher, T. Synlett 2002, 808–810. 4. (a) Ishikura, M.; Kamada, M.; Terashima, M. Synthesis 1984, 936–938; (b) Ishikura, M.; Oda, I.; Terashima, M. Heterocycles 1985, 23, 2375–2386; (c) Deshayes, K.; Broene, R. D.; Chao, I.; Knobler, C. B.; Diederich, F. J. Org. Chem. 1991, 56, 6787–6795; (d) Godard, A.; Turck, A.; Ple´ , N.; Marsais, F.; Que´ guiner, G. Trends Heterocycl. Chem. 1993, 3, 19–29; (e) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483; (f) Godard, A.; Marsais, F.; Ple´ , N.; Tre´ court, F.; Turck, A.; Que´ guiner, G. Heterocycles 1995, 40, 1055–1091; (g) Fernando, S. R. L.; Maharoof, U. S. M.; Deshayes, K. D.; Kinstle, T. H.; Ogawa, M. Y. J. Am. Chem. Soc. 1996, 118, 5783–5790; (h) Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168; (i) Schomaker, J. M.; Thomas, T. J. J. Org. Chem. 2001, 66, 7125–7128; (j) Bouillon, A.; Lancelot, J.-C.; Collot, V.; Bovy, P. R.; Rault, S. Tetrahedron 2002, 58, 2885– 2890; (k) Bouillon, A.; Lancelot, J.-C.; Collot, V.; Bovy, P. R.; Rault, S. Tetrahedron 2002, 58, 3323–3328; (l) Bouillon, A.; Lancelot, J.-C.; Collot, V.; Bovy, P. R.; Rault, S. Tetrahedron 2002, 58, 4369–4373. 5. (a) Stille, J. K. Angew. Chem. 1986, 98, 504–519; (b) Schubert, U. S.; Eschbaumer, C.; Heller, M. Org. Lett. 2000, 2, 3373–3376; (c) Fallahpour, R.-A. Synthesis 2000, 1138–1142; (d) Kimber, M.; Anderberg, P. I.; Harding, M. M. Tetrahedron 2000, 56, 3575–3581; (e) Fallahpour, R.-A.; Neuburger, N. Eur. J. Org. Chem. 2001, 1853– 1856; (f) Mathieu, J.; Gros, P.; Fort, Y. Tetrahedron Lett. 2001, 42, 1879–1881. 6. (a) Pridgen, L. N. J. Heterocycl. Chem. 1975, 12, 443– 444; (b) Takei, H.; Miura, M.; Sugimura, H.; Okamura, H. Chem. Lett. 1979, 1447–1450; (c) Tamao, K.; Kodama, S.; Nakajima, I.; Kumada, M.; Minato, A.;
3880
S. Dumouchel et al. / Tetrahedron Letters 44 (2003) 3877–3880
Suzuki, K. Tetrahedron 1982, 38, 3347–3354; (d) Sengupta, S.; Leite, M.; Raslan, D. S.; Quesnelle, C.; Snieckus, V. J. Org. Chem. 1992, 57, 4066–4068; (e) Albers, W. M.; Canters, G. W.; Reedijk, J. Tetrahedron 1995, 51, 3895–3904; (f) Meth-Cohn, O.; Jiang, H. J. Chem. Soc., Perkin Trans. 1 1998, 3737–3745; (g) MetalCatalyzed Cross-Coupling Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; (h) Bo¨ hm, V. P. W.; Weskamp, T.; Gsto¨ ttmayr, C. W. K.; Herrmann, W. A. Angew. Chem., Int. Ed. 2000, 39, 1602–1604; (i) Bonnet, V.; Mongin, F.; Tre´ court, F.; Que´ guiner, G.; Knochel, P. Tetrahedron Lett. 2001, 42, 5717–5719; (j) Fu¨ rstner, A.; Leitner, A. Angew. Chem., Int. Ed. 2002, 41, 609–612; (k) Fu¨ rstner, A.; Leitner, A.; Me´ ndez, M.; Krause, H. J. Am. Chem. Soc. 2002, 124, 13856–13863; (l) Bonnet, V.; Mongin, F.; Tre´ court, F.; Breton, G.; Marsais, F.; Knochel, P.; Que´ guiner, G. Synlett 2002, 1008–1010; (m) Bonnet, V.; Mongin, F.; Tre´ court, F.; Que´ guiner, G.; Knochel, P. Tetrahedron 2002, 58, 4429–4438; (n) Quintin, J.; Franck, X.; Hocquemiller, R.; Figade`re, B. Tetrahedron Lett. 2002, 43, 3547–3549. 7. Wittig, G.; Meyer, F. J.; Lange, G. Liebigs Ann. Chem. 1951, 571, 167–201. 8. (a) Seitz, L. M.; Brown, T. L. J. Am. Chem. Soc. 1966, 88, 4140–4147; (b) Coates, G. E.; Heslop, J. A. J. Chem. Soc. (A) 1968, 514–518; (c) Thoennes, D.; Weiss, E. Chem. Ber. 1978, 111, 3726–3731; (d) Greiser, T.; Kopf, J.; Thoennes, D.; Weiss, E. Chem. Ber. 1981, 114, 209– 213; (e) Mulvey, R. E. Chem. Commun. 2001, 1049–1056. 9. (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. US 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;
10. 11.
12.
13.
14.
15. 16. 17.
(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. Dumouchel, S.; Mongin, F.; Tre´ court, F.; Que´ guiner, G. Tetrahedron Lett. 2003, 44, 2033–2035. (a) Sekiya, A.; Ishikawa, N. J. Organomet. Chem. 1976, 118, 349–354; (b) Widdowson, D. A.; Zhang, Y. Z. Tetrahedron 1986, 42, 2111–2116; (c) Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889–9890. (a) Kiso, Y.; Tamao, K.; Kumada, M. J. Organomet. Chem. 1973, 50, C12–C14; (b) Cahiez, G.; Lepifre, F.; Ramiandrasoa, P. Synthesis 1999, 2138–2144; (c) Bo¨ hm, V. P. W.; Gsto¨ ttmayr, C. W. K.; Weskamp, T.; Herrmann, W. A. Angew. Chem., Int. Ed. 2001, 40, 3387– 3389; (d) Mongin, F.; Mojovic, L.; Guillamet, B.; Tre´ court, F.; Que´ guiner, G. J. Org. Chem. 2002, 67, 8991–8994. Concerning the use of this catalyst, see: (a) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.; Hirotsu, K. J. Am. Chem. Soc. 1984, 106, 158–163; (b) Amatore, C.; Jutand, A. J. Organomet. Chem. 1999, 576, 254–278; (c) Sato, F.; Urabe, H.; Okamoto, S. Chem. Rev. 2000, 100, 2835–2886. Compound 2c: 1H NMR (CDCl3): 9.34 (d, 1H, J=2.2), 8.68 (d, 1H, J=8.3), 8.58 (d, 1H, J=2.2), 8.03 (d, 1H, J=8.3), 7.79 (m, 2H), 7.75 (m, 2H), 7.46 (m, 1H). Compound 2h: 1H NMR (CDCl3): 9.85 (d, 1H, J=1.0), 9.12 (d, 1H, J=1.0), 8.78 (d, 2H, J=1.5), 8.09 (d, 1H, J=8.0), 7.88 (d, 1H, J=7.0), 7.69 (m, 1H), 7.50 (m, 1H), 7.18 (m, 1H). Compound 2i: 1H NMR (CDCl3): 9.51 (d, 1H, J=2.5), 9.14 (d, 1H, J=1.5), 8.73 (d, 1H, J=2.0), 8.66 (d, 1H, J=1.5), 8.55 (d, 1H, J=2.5), 8.10 (d, 1H, J=8.0), 7.89 (d, 1H, J=8.3), 7.75 (m, 1H), 7.55 (m, 1H). Compound 6a: 1H NMR (CDCl3): 8.92 (d, 1H, J=4.3), 8.74 (d, 1H, J=4.5), 8.11 (d, 1H, J=8.5), 8.05 (d, 1H, J=8.5), 7.79 (t, 1H, J=7.6), 7.66 (t, 1H, J=7.2), 7.4 (m, 4H). Compound 6b: 1H NMR (CDCl3): 8.93 (d, 1H, J=4.4), 8.82 (d, 1H, J=2.1), 8.12 (d, 1H, J=8.3), 8.02 (d, 1H, J=7.8), 7.95 (dd, 1H, J=8.3, 2.4), 7.68 (m, 1H), 7.5 (m, 2H), 7.42 (d, 1H, J=4.4). Fort, Y.; Becker, S.; Caube`re, P. Tetrahedron 1994, 50, 11893–11902. Prepared using a published procedure: Grundmann, G. Chem. Ber. 1948, 81, 7. The physical and spectral data are analogous to those obtained for a commercial sample.
Tetrahedron Letters 44 (2003) 3877–3880
First cross-coupling reactions of arylmagnesates: a convenient access to heteroarylquinolines Sylvain Dumouchel, Florence Mongin,* Franc¸ois Tre´court and Guy Que´guiner Laboratoire de Chimie Organique Fine et He´te´rocyclique, UMR 6014, IRCOF, Place E. Blondel, BP 08, 76131 Mont-Saint-Aignan Ce´dex, France Received 17 December 2002; accepted 8 February 2003
Abstract—2-, 3- and 4-Bromoquinolines were converted to the corresponding lithium tri(quinolyl)magnesates at −10°C on treatment with Bu3MgLi in THF. The resulting organomagnesium derivatives were involved in catalyzed cross-coupling reactions with heteroaryl bromides and chlorides to afford functionalized quinolines. © 2003 Elsevier Science Ltd. All rights reserved.
We describe the first cross-couplings with lithium triarylmagnesates. Interest in azine and diazine natural products either for pharmaceuticals or as building blocks for various applications within materials science and supramolecular chemistry has led to extensive efforts devoted to a variety of synthetic methodologies.1 In these series, the development of transition metal-catalyzed cross-couplings, such as Negishi,2,3 Suzuki,2,4 Stille2,4d,f,5 and Kharasch2,6 reactions, is of crucial importance. An organomagnesate (R3MgLi) was first published in 1951.7 However, while the structure of such complexes has long been investigated,8 their synthetic applications remained unexplored until very recently.9 In 2001, the first halogen–magnesium exchanges via organomagnesates were published by Oshima in the benzene, pyridine and thiophene series.9i,l The method has since been extended to the mono-exchange of dibromobenzenes and dibromoheteroarenes (pyridine and thiophene series) by Iida and Mase using lithium tributylmagnesate.9m We have been interested in the bromine–magnesium exchange of 2-, 3- and 4-bromoquinolines using lithium tributylmagnesate.10 Herein, we describe the behavior of the lithium tri(quinolyl)magnesates thus prepared in the catalyzed cross-coupling reactions with heteroaromatic bromides and chlorides.
Keywords: cross-coupling; ate complexes; magnesium; quinoline. * Corresponding author. Tel.: +33 (0) 2 35 52 29 00; fax: +33 (0) 2 35 52 29 62; e-mail: [email protected]
The first experiments were conducted on lithium tri(3quinolyl)magnesate (1a), prepared by treating 3-bromoquinoline (1) with lithium tributylmagnesate in THF at −10°C.10 Under palladium catalysis, reactions between arylmagnesium halides and aryl chlorides, bromides, or iodides are possible at rt.6f,i,l,m,11 Nickel, which is harder than palladium, was most often chosen for chlorides6d,h,l and fluorides,12 which are harder than bromides and iodides. Indeed, attempts to realize the subsequent cross-coupling reactions of 1a in a ‘one-pot’ procedure with heteroaromatic bromides under nickel catalysis were unsuccessful. So we turned our attention to palladium catalysis. The reaction could be achieved when catalytic amounts of bis(dibenzylideneacetone)palladium(0) (Pd(dba)2) and 1,1%-bis(diphenylphosphino)ferrocene (dppf) were used.6i,l,m,13 The low to medium yields observed are based on 3-bromoquinoline (1). The first step proceeds in 85–90% yield, as demonstrated by quenching the intermediate 1a with benzaldehyde, the remaining 10–15% being essentially butylated products formed through addition of the residual butylmagnesium species to the quinoline ring.10 The coupling step results of the successive reactions of the lithium tri(3-quinolyl)magnesate, the bi(3-quinolyl)magnesium, and the 3-quinolylmagnesium bromide with the bromo substrate. It appears that less than 10% of 3,3%-biquinoline could be detected, the main by-product being quinoline, obtained in 15 to 50% yield depending on the reactivity of the bromide involved. The best results were observed with p-deficient substrates such as bromopyridines and bromoquinolines, for which the oxidative addition step is easier (Table 1, entries 1–5), while lower yields were obtained with less activated bromothiophenes (Table 1, entries 6 and 7). Moreover, the
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0040-4039(03)00786-X
3878
S. Dumouchel et al. / Tetrahedron Letters 44 (2003) 3877–3880
Table 1. Cross-coupling reactions of 1a with bromides
Scheme 2. Table 2. Cross-coupling reactions of 1a with chlorides
yields depend on the position of the bromine atom on the ring, better results being noted with 2-bromo substrates (Scheme 1, Table 1). We then investigated the reaction with chlorides. In this case, we have shown that it is advantageous to use bis(acetylacetonate)nickel(II) (Ni(acac)2) instead of Pd(dba)2; 1,3-bis(diphenylphosphino)propane (dppp) was found to be the best ligand.6a–i,l,m The reaction of 1a with heteroaromatic chlorides was carried out in THF, in a ‘one-pot’ procedure at rt. It generally proceeds in modest yields, depending on the substrate used (better yields with diazines, for which the oxidative addition step is easier), but also on the position of the chlorine atom on the ring (Scheme 2, Table 2). To evaluate the scope of this reaction, it was applied to the lithium tri(quinolyl)magnesates 3a and 4a, respectively, derived from 2- and 4-bromoquinolines (3 and 4).16 It appears that the yields obtained from magnesate 3a are lower:10 this may be attributed to its incomplete
Scheme 1.
synthesis through bromine-magnesium exchange, but also to a lower reactivity, when compared to magnesates 1a and 4a (Scheme 3, Table 3). In conclusion, 2-, 3- and 4-substituted quinolines could be synthesized from the corresponding bromo derivatives in a ‘one-pot’ procedure through bromine-magnesium exchange reaction and subsequent cross-coupling with heteroaryl halides. Even if the yields are not high,
Scheme 3.
S. Dumouchel et al. / Tetrahedron Letters 44 (2003) 3877–3880
3879
Table 3. Cross-coupling reactions of 3a and 4a with bromides
our method is interesting since it avoids a preliminary synthesis of the organometallic substrate, usually at low temperatures via its corresponding lithio derivative. Cross-coupling typical procedure: BuLi (1.6 M in hexanes, 1.3 mmol) was added to a solution of BuMgCl (2.0 M in diethyl ether, 0.65 mmol) in THF (4 mL) at −10°C. After stirring for 1 h at −10°C, 3-bromoquinoline (1, 0.23 mL, 1.7 mmol) was introduced at −30°C. After 2.5 h at −10°C, 2-bromopyridine (0.16 mL, 1.7 mmol) in THF (3 mL), Pd(dba)2 (48 mg, 85 mmol) and dppf (47 mg, 85 mmol) were added and the mixture was stirred for 18 h at rt. Addition of water saturated with NH4Cl (0.5 mL), dilution with CH2Cl2 (50 mL), drying over MgSO4 and column chromatography using CH2Cl2/Et2O (80:20) as an eluent afforded compound 2a (56% yield).
References 1. (a) Katritzky, A. R.; Rees, C. W. Comprehensive Heterocyclic Chemistry; Boulton, A. J.; McKillop, A., Eds., Pergamon Press, 1984; Vol. 2; (b) Que´ guiner, G.; Marsais, F.; Snieckus, V.; Epsztajn, J. Adv. Heterocycl. Chem. 1991, 52, 187–304; (c) Mongin, F.; Que´ guiner, G. Tetrahedron 2001, 57, 4059–4090; (d) Turck, A.; Ple´ , N.; Mongin, F.; Que´ guiner, G. Tetrahedron 2001, 57, 4489– 4505. 2. Stanforth, S. P. Tetrahedron 1998, 54, 263–303 and references cited therein. 3. (a) Negishi, E.; King, A. O.; Okukado, N. J. J. Org. Chem. 1977, 42, 1821–1823; (b) Sakamoto, T.; Kondo, Y.; Murata, N.; Yamanaka, H. Tetrahedron 1993, 49, 9713–9720; (c) Tre´ court, F.; Gervais, B.; Mallet, M.; Que´ guiner, G. J. Org. Chem. 1996, 61, 1673–1676; (d) Tre´ court, F.; Gervais, B.; Mongin, O.; Le Gal, C.; Mongin, F.; Que´ guiner, G. J. Org. Chem. 1998, 63,
2892–2897; (e) Hargreaves, S. L.; Pilkington, B. L.; Russel, S. E.; Worthington, P. A. Tetrahedron Lett. 2000, 41, 1653–1656; (f) Loren, J. C.; Siegel, J. S. Angew. Chem., Int. Ed. 2001, 40, 754–757; (g) Karig, G.; Spencer, J. A.; Gallagher, T. Org. Lett. 2001, 3, 835–838; (h) Karig, G.; Thasana, N.; Gallagher, T. Synlett 2002, 808–810. 4. (a) Ishikura, M.; Kamada, M.; Terashima, M. Synthesis 1984, 936–938; (b) Ishikura, M.; Oda, I.; Terashima, M. Heterocycles 1985, 23, 2375–2386; (c) Deshayes, K.; Broene, R. D.; Chao, I.; Knobler, C. B.; Diederich, F. J. Org. Chem. 1991, 56, 6787–6795; (d) Godard, A.; Turck, A.; Ple´ , N.; Marsais, F.; Que´ guiner, G. Trends Heterocycl. Chem. 1993, 3, 19–29; (e) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483; (f) Godard, A.; Marsais, F.; Ple´ , N.; Tre´ court, F.; Turck, A.; Que´ guiner, G. Heterocycles 1995, 40, 1055–1091; (g) Fernando, S. R. L.; Maharoof, U. S. M.; Deshayes, K. D.; Kinstle, T. H.; Ogawa, M. Y. J. Am. Chem. Soc. 1996, 118, 5783–5790; (h) Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168; (i) Schomaker, J. M.; Thomas, T. J. J. Org. Chem. 2001, 66, 7125–7128; (j) Bouillon, A.; Lancelot, J.-C.; Collot, V.; Bovy, P. R.; Rault, S. Tetrahedron 2002, 58, 2885– 2890; (k) Bouillon, A.; Lancelot, J.-C.; Collot, V.; Bovy, P. R.; Rault, S. Tetrahedron 2002, 58, 3323–3328; (l) Bouillon, A.; Lancelot, J.-C.; Collot, V.; Bovy, P. R.; Rault, S. Tetrahedron 2002, 58, 4369–4373. 5. (a) Stille, J. K. Angew. Chem. 1986, 98, 504–519; (b) Schubert, U. S.; Eschbaumer, C.; Heller, M. Org. Lett. 2000, 2, 3373–3376; (c) Fallahpour, R.-A. Synthesis 2000, 1138–1142; (d) Kimber, M.; Anderberg, P. I.; Harding, M. M. Tetrahedron 2000, 56, 3575–3581; (e) Fallahpour, R.-A.; Neuburger, N. Eur. J. Org. Chem. 2001, 1853– 1856; (f) Mathieu, J.; Gros, P.; Fort, Y. Tetrahedron Lett. 2001, 42, 1879–1881. 6. (a) Pridgen, L. N. J. Heterocycl. Chem. 1975, 12, 443– 444; (b) Takei, H.; Miura, M.; Sugimura, H.; Okamura, H. Chem. Lett. 1979, 1447–1450; (c) Tamao, K.; Kodama, S.; Nakajima, I.; Kumada, M.; Minato, A.;
3880
S. Dumouchel et al. / Tetrahedron Letters 44 (2003) 3877–3880
Suzuki, K. Tetrahedron 1982, 38, 3347–3354; (d) Sengupta, S.; Leite, M.; Raslan, D. S.; Quesnelle, C.; Snieckus, V. J. Org. Chem. 1992, 57, 4066–4068; (e) Albers, W. M.; Canters, G. W.; Reedijk, J. Tetrahedron 1995, 51, 3895–3904; (f) Meth-Cohn, O.; Jiang, H. J. Chem. Soc., Perkin Trans. 1 1998, 3737–3745; (g) MetalCatalyzed Cross-Coupling Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; (h) Bo¨ hm, V. P. W.; Weskamp, T.; Gsto¨ ttmayr, C. W. K.; Herrmann, W. A. Angew. Chem., Int. Ed. 2000, 39, 1602–1604; (i) Bonnet, V.; Mongin, F.; Tre´ court, F.; Que´ guiner, G.; Knochel, P. Tetrahedron Lett. 2001, 42, 5717–5719; (j) Fu¨ rstner, A.; Leitner, A. Angew. Chem., Int. Ed. 2002, 41, 609–612; (k) Fu¨ rstner, A.; Leitner, A.; Me´ ndez, M.; Krause, H. J. Am. Chem. Soc. 2002, 124, 13856–13863; (l) Bonnet, V.; Mongin, F.; Tre´ court, F.; Breton, G.; Marsais, F.; Knochel, P.; Que´ guiner, G. Synlett 2002, 1008–1010; (m) Bonnet, V.; Mongin, F.; Tre´ court, F.; Que´ guiner, G.; Knochel, P. Tetrahedron 2002, 58, 4429–4438; (n) Quintin, J.; Franck, X.; Hocquemiller, R.; Figade`re, B. Tetrahedron Lett. 2002, 43, 3547–3549. 7. Wittig, G.; Meyer, F. J.; Lange, G. Liebigs Ann. Chem. 1951, 571, 167–201. 8. (a) Seitz, L. M.; Brown, T. L. J. Am. Chem. Soc. 1966, 88, 4140–4147; (b) Coates, G. E.; Heslop, J. A. J. Chem. Soc. (A) 1968, 514–518; (c) Thoennes, D.; Weiss, E. Chem. Ber. 1978, 111, 3726–3731; (d) Greiser, T.; Kopf, J.; Thoennes, D.; Weiss, E. Chem. Ber. 1981, 114, 209– 213; (e) Mulvey, R. E. Chem. Commun. 2001, 1049–1056. 9. (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. US 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;
10. 11.
12.
13.
14.
15. 16. 17.
(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. Dumouchel, S.; Mongin, F.; Tre´ court, F.; Que´ guiner, G. Tetrahedron Lett. 2003, 44, 2033–2035. (a) Sekiya, A.; Ishikawa, N. J. Organomet. Chem. 1976, 118, 349–354; (b) Widdowson, D. A.; Zhang, Y. Z. Tetrahedron 1986, 42, 2111–2116; (c) Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889–9890. (a) Kiso, Y.; Tamao, K.; Kumada, M. J. Organomet. Chem. 1973, 50, C12–C14; (b) Cahiez, G.; Lepifre, F.; Ramiandrasoa, P. Synthesis 1999, 2138–2144; (c) Bo¨ hm, V. P. W.; Gsto¨ ttmayr, C. W. K.; Weskamp, T.; Herrmann, W. A. Angew. Chem., Int. Ed. 2001, 40, 3387– 3389; (d) Mongin, F.; Mojovic, L.; Guillamet, B.; Tre´ court, F.; Que´ guiner, G. J. Org. Chem. 2002, 67, 8991–8994. Concerning the use of this catalyst, see: (a) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.; Hirotsu, K. J. Am. Chem. Soc. 1984, 106, 158–163; (b) Amatore, C.; Jutand, A. J. Organomet. Chem. 1999, 576, 254–278; (c) Sato, F.; Urabe, H.; Okamoto, S. Chem. Rev. 2000, 100, 2835–2886. Compound 2c: 1H NMR (CDCl3): 9.34 (d, 1H, J=2.2), 8.68 (d, 1H, J=8.3), 8.58 (d, 1H, J=2.2), 8.03 (d, 1H, J=8.3), 7.79 (m, 2H), 7.75 (m, 2H), 7.46 (m, 1H). Compound 2h: 1H NMR (CDCl3): 9.85 (d, 1H, J=1.0), 9.12 (d, 1H, J=1.0), 8.78 (d, 2H, J=1.5), 8.09 (d, 1H, J=8.0), 7.88 (d, 1H, J=7.0), 7.69 (m, 1H), 7.50 (m, 1H), 7.18 (m, 1H). Compound 2i: 1H NMR (CDCl3): 9.51 (d, 1H, J=2.5), 9.14 (d, 1H, J=1.5), 8.73 (d, 1H, J=2.0), 8.66 (d, 1H, J=1.5), 8.55 (d, 1H, J=2.5), 8.10 (d, 1H, J=8.0), 7.89 (d, 1H, J=8.3), 7.75 (m, 1H), 7.55 (m, 1H). Compound 6a: 1H NMR (CDCl3): 8.92 (d, 1H, J=4.3), 8.74 (d, 1H, J=4.5), 8.11 (d, 1H, J=8.5), 8.05 (d, 1H, J=8.5), 7.79 (t, 1H, J=7.6), 7.66 (t, 1H, J=7.2), 7.4 (m, 4H). Compound 6b: 1H NMR (CDCl3): 8.93 (d, 1H, J=4.4), 8.82 (d, 1H, J=2.1), 8.12 (d, 1H, J=8.3), 8.02 (d, 1H, J=7.8), 7.95 (dd, 1H, J=8.3, 2.4), 7.68 (m, 1H), 7.5 (m, 2H), 7.42 (d, 1H, J=4.4). Fort, Y.; Becker, S.; Caube`re, P. Tetrahedron 1994, 50, 11893–11902. Prepared using a published procedure: Grundmann, G. Chem. Ber. 1948, 81, 7. The physical and spectral data are analogous to those obtained for a commercial sample.