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O
O
References and notes
NH2
S
R
i, BuLi (1 eqv), THF, 0ºC
NH
1. (a) Guillena, G.; Ramón, D. J.; Yus, M. Angew. Chem., Int. Ed. 2007, 46, 2358–
2364; (b) Hamid, M. H. S. A.; Slatford, P. A.; Williams, J. M. J. Adv. Synth. Catal.
2007, 349, 1555–1575; (c) Nixon, T. D.; Whittlesey, M. K.; Williams, J. M. J.
Dalton Trans. 2009, 753–762.
R
ii, Li(excess)/C10H8(4 mol%),
THF, -78 to 20ºC
6a: R = Ph, >99%
5
6b: R = C6H11, 94%
2. Guerbet, M. C. R. C.R. Chim. 1908, 146, 298–300.
3. For recent examples from our laboratory, see: (a) Martínez, R.; Brand, G. J.;
Ramón, D. J.; Yus, M. Tetrahedron Lett. 2005, 46, 3683–3686; (b) Martínez, R.;
Ramón, D. J.; Yus, M. Tetrahedron 2006, 62, 8982–8987; (c) Martínez, R.; Ramón,
D. J.; Yus, M. Tetrahedron 2006, 62, 8988–9001.
Scheme 2. Deprotection of sulfonamides 5.
4. For reviews on the synthesis of amines, see: (a) Malpass, J. R.. In Comprehensive
Organic Chemistry; Barton, D., Ollis, W. D., Eds.; Pergamon: Oxford, 1979; Vol. 2,
pp 3–59; (b) Gladych, J. M. Z.; Hartley, D.. In Comprehensive Organic Chemistry;
Barton, D., Ollis, W. D., Eds.; Pergamon: Oxford, 1979; Vol. 2, pp 61–130; (c)
Lindsay, R. J.. In Comprehensive Organic Chemistry; Barton, D., Ollis, W. D., Eds.;
Pergamon: Oxford, 1979; Vol. 2, pp 131–184; (d) Mitsunobu, O.. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon
Press: Oxford, 1991; Vol. 6, pp 65–101; (e) Gilchrist, T. L.. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991;
Vol. 8, pp 381–402; (f) Salvatore, R. N.; Yoon, C. H.; Jung, K. W. Tetrahedron
2001, 57, 7785–7811; (g) Schlummer, B.; Scholz, U. Adv. Synth. Catal. 2004, 346,
1599–1626; (h) Muñiz, K.; Hövelmann, C. H.; Streuff, J.; Campos-Gómez, E. Pure
Appl. Chem. 2008, 80, 1089–1096; (i) Müller, T. E.; Hultzsch, K. C.; Yus, M.;
Foubelo, F.; Tada, M. Chem. Rev. 2008, 108, 3795–3892; (j) Hartwig, J. F. H. Acc.
Chem. Res. 2008, 41, 1534–1544.
5. (a) Klyuev, M. V.; Khidekel’, M. L. Russ. Chem. Rev. Engl. Transl. 1980, 49, 14–27;
(b) Baiker, A.; Kijenski, J. Cat. Rev.-Sci. Eng. 1985, 27, 653–697; (c) Roundhill, D.
M. Chem. Rev. 1992, 92, 1–27.
6. Schwoegler, E. J.; Adkins, H. J. Am. Chem. Soc. 1939, 61, 3499–3502.
7. Baiker, A.; Richarz, W. Tetrahedron Lett. 1977, 1937–1938.
8. (a) Runeberg, J.; Baiker, A.; Kijenski, J. Appl. Catal. 1985, 17, 309–319; (b)
Vultier, R.; Baiker, A.; Wokaun, A. Appl. Catal. 1987, 30, 167–176.
9. Abe, H.; Yokota, Y.; Okabe, K. Appl. Catal. 1989, 52, 171–179.
can also be carried out with aliphatic alcohols such as 1-heptanol,
although in this case the reaction time should be increased up to
6 days. Finally, the reaction of secondary N-methylaniline with
benzyl alcohol failed after 6 days under standard conditions, show-
ing the selectivity of the process.
Once the catalytic activity and scope of the copper(II) acetate
were demonstrated, we faced the problem of using other less
nucleophilic amino derivatives such as sulfonamides14,15 (Table
3). The best conditions were obtained when a strong base in tolu-
ene was used (compare entries 1–4). Under these conditions other
amides and alcohols were submitted to the alkylation process,
obtaining similar results independently on the use of either ali-
phatic or aromatic sulfonamide or alcohol (entries 5–10).
Finally, the above-mentioned sulfonamides 5 were deprotected
to give the corresponding primary amines 6 with excellent re-
sults,16 by a protocol which implied the initial deprotonation of
amide followed by a reductive cleavage of N–S bond through a
naphthalene-catalyzed lithiation17 reaction (Scheme 2). The whole
process, N-alkylation of sulfonamide and deprotective reduction, is
an interesting alternative to the direct monoalkylation of ammo-
nia, which is a difficult task.
In conclusion, cheap and commercially available copper(II) ace-
tate has been shown to be an active, stable, versatile, and highly
selective catalyst for the selective monoalkylation of aromatic
amines and amides through a hydrogen autotransfer process. The
simplicity of the protocol and the wide scope of substrates, which
could be used, permitted us to anticipate a good future for the pro-
cess shown in this Letter not only in the academia but also in
industries. The combined alkylation–deprotection process is an
alternative to the direct monoalkylation of ammonia.
10. Kimura, H.; Taniguchi, H. Appl. Catal., A 2005, 287, 191–196.
11. (a) Kimura, H.; Tsutsumi, S.-i.; Tsukada, K. Appl. Catal., A 2005, 292, 281–286;
(b) Kimura, H.; Yokota, Y.; Sawamoto, Y. Catal. Lett. 2005, 99, 133–140.
12. (a) Kimura, H.; Matsutani, K.; Tsutsumi, S.-i.; Nomura, S.; Ishikawa, K.; Hattori,
Y.; Itahashi, M.; Hoshino, H. Catal. Lett. 2005, 99, 119–131; (b) Kimura, H.;
Ishikawa, K.; Nishino, K.; Nomura, S. Appl. Catal., A 2005, 286, 120–127.
13. (a) Pratt, E. F.; Frazza, E. J. J. Am. Chem. Soc. 1954, 76, 6174–6179; (b) Sprinzak,
Y. J. Am. Chem. Soc. 1956, 78, 3207–3208; (c) Watanabe, Y.; Morisaki, Y.; Kondo,
T.; Mitsudo, T.-a. J. Org. Chem. 1996, 61, 4214–4218; (d) Fujita, K.-i.; Li, Z.;
Ozeki, N.; Yamaguchi, R. Tetrahedron Lett. 2003, 44, 2687–2690; (e) Blank, B.;
Madalska, M.; Kempe, R. Adv. Synth. Catal. 2008, 350, 749–758; (f) Martínez, R.;
Ramón, D. J.; Yus, M. Org. Biomol. Chem. 2009, 7, 2176–2181.
14. The first protocol of alkylation of sulfonamides using copper(II) acetate
appeared during the preparation of this article: Shi, F.; Tse, M. K.; Cui, X.;
Gördes, D.; Michalik, D.; Thurow, K.; Deng, Y.; Beller, M. Angew. Chem., Int. Ed.
2009, 48, 5912–5915.
15. For examples of N-alkylation of different sulfonamides using
a hydrogen
autotransfer process, see: (a) Hamid, M. H.; Allen, C. L.; Lamb, G. W.; Maxwell,
A. C.; Maytum, H. C.; Watson, A. J. A.; Williams, J. M. J. J. Am. Chem. Soc. 2009,
131, 1766–1774; (b) Shi, F.; Tse, M. K.; Zhou, S.; Pohl, M.-M.; Radnik, J.; Hübner,
S.; Jähnisch, K.; Brückner, A.; Beller, M. J. Am. Chem. Soc. 2009, 131, 1775–1779.
16. Alonso, E.; Ramón, D. J.; Yus, M. Tetrahedron 1997, 42, 14355–14368.
17. (a) Ramón, D. J.; Yus, M. Eur. J. Org. Chem. 2000, 225–237; (b) Gómez, I.; Alonso,
E.; Ramón, D. J.; Yus, M. Tetrahedron 2000, 56, 4043–4052; (c) Yus, M.; Ramón,
D. J.; Gómez, I. Tetrahedron 2002, 58, 5163–5172; (d) Yus, M.; Ramón, D. J.;
Gómez, I. J. Organomet. Chem. 2002, 663, 21–31; (e) Yus, M.; Ramón, D. J.;
Gómez, I. Tetrahedron 2003, 59, 3219–3225; (f) Yus, M.; Ramón, D. J.; Prieto, O.
Eur. J. Org. Chem. 2003, 2745–2748.
Acknowledgments
This work was supported by the Spanish Ministerio de Ciencia y
Tecnología (Consolider Ingenio 2010 CSD2007-00006, CTQ2007-
65218/BQU). A.M.-A. thanks the Consolider Ingenio program for a
fellowship.