C O M M U N I C A T I O N S
References
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Based on the mechanisms proposed for the Cp*Ir-catalyzed
N-alkylation of amines,10 a plausible mechanism for the first
monoalkylation cycle transiently affording primary amine is
depicted in Scheme 1.19 The second and third N-alkylations to
produce secondary and tertiary amines, respectively, would proceed
through similar sequential processes.
(6) Nagano, T.; Kobayashi, S. J. Am. Chem. Soc. 2009, 131, 4200.
(7) Prinz, T.; Driessen-Ho¨lscher, B. Chem.sEur. J. 1999, 5, 2069.
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Scheme 1. A Plausible Mechanism for the N-Alkylation of Aqueous
Ammonia with an Alcohol
(9) Rao, H.; Fu, H.; Jiang, Y.; Zhao, Y. Amgew. Chem., Int. Ed. 2009, 48,
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(10) (a) Fujita, K.; Yamaguchi, R. Synlett 2005, 560. (b) Fujita, K.; Yamaguchi,
R. In Iridium Complexes in Organic Synthesis; Oro, L. A., Claver, C., Eds.;
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(11) N-Alkylation reactions of amines with alcohols using ruthenium, iridium,
and other transition metals as catalyst have also been reported by other
research groups. (a) Grigg, R.; Mitchell, T. R. B.; Sutthivaiyakit, S.;
Tongpenyai, N. J. Chem. Soc., Chem. Commun. 1981, 611. (b) Naota, T.;
Takaya, H.; Murahashi, S.-I. Chem. ReV. 1998, 98, 2599, and references
cited therein. (c) Hollmann, D.; Tillack, A.; Michalik, D.; Jackstell, R.;
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J. M. J. Tetrahedron Lett. 2007, 48, 8263. (e) Tillack, A.; Hollmann, D.;
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4745. (f) Balcells, D.; Nova, A.; Clot, E.; Gnanamgari, D.; Crabtree, R. H.;
Eisenstein, O. Organometallics 2008, 27, 2529. (g) Hamid, M. H. S. A.;
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. (h) Blank,
B.; Michlik, S.; Kempe, R. Chem.sEur. J. 2009, 15, 3790. (i) Nixon, T. D.;
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Yus, M. Chem. ReV. 2010, 110, 1611, and references cited therein.
(12) N-Alkylation of amines with alcohols or diols in aqueous media catalyzed
by Cp*Ir complexes has been reported by Madsen and Williams,
respectively. However, none of the reaction using ammonia as a nitrogen
source was reported in these publications. (a) Nordstrøm, L. U.; Madsen,
R. Chem. Commun. 2007, 5034. (b) Saidi, O.; Blacker, A. J.; Farah, M. M.;
Marsden, S. P.; Williams, J. M. J. Chem. Commun. 2010, 1541. (c) Saidi,
O.; Blacker, A. J.; Lamb, G. W.; Marsden, S. P.; Taylor, J. E.; Williams,
J. M. J. Org. Process Res. DeV. 2010, 14, 1046.
The superiority of catalyst 3 having iodide (I-) as a counteranion
among the water-soluble catalysts 1-3 could be attributed to the
differences of activities for the hydrogenation of the iminic
intermediate. When the transfer hydrogenations of N-benzylideneben-
zylamine (11) were carried out in the presence of 1-3 as catalysts,
the highest yield of the dibenzylamine (6a) was obtained in the
reaction using 3 (eq 4). There have been many examples that iodide
often exhibits a positive effect in the transition-metal-catalyzed
hydrogenation of imines.20
(13) Reductive amination of R-keto acids with aqueous ammonia leading to
R-amino acids catalyzed by a Cp*Ir complex has been reported by Ogo
and Fukuzumi et al. Ogo, S.; Uehara, K.; Abura, T.; Fukuzumi, S. J. Am.
Chem. Soc. 2004, 126, 3020.
In summary, novel water-soluble Cp*Ir-ammine complexes have
been synthesized and a new and highly atom-economical system
for the synthesis of organic amines using aqueous ammonia as a
nitrogen source has been developed. With a water-soluble and air-
stable Cp*Ir-ammine catalyst, [Cp*Ir(NH3)3][I]2 (3), a variety of
tertiary and secondary amines were synthesized by the multialkyl-
ation of aqueous ammonia with theoretical equivalents of primary
and secondary alcohols. A one-flask synthesis of quinolizidine
starting with triol was also demonstrated. This new catalytic system
would provide a practical and environmentally benign methodology
for the synthesis of various organic amines.
(14) Very recently, Mizuno et al. reported an efficient system for the synthesis
of tertiary and secondary amines by the reaction of alcohols with urea,
aqueous ammonia, or ammonium salt catalyzed by ruthenium hydroxide
supported on titanium dioxide in organic solvent. (a) He, J.; Kim, J. W.;
Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed. 2009, 48, 9888. (b)
Yamaguchi, K.; He, J.; Oishi, T.; Mizuno, N. Chem.sEur. J. 2010, 16,
7199.
(15) The Cp*Ir monoammine complex, Cp*Ir(NH3)I2, has previously been
reported by Blacker et al. Blacker, A. J.; Brown, S.; Cligue, B.; Gourlay,
B.; Headley, C. E.; Ingham, S.; Ritson, D.; Screen, T.; Stirling, M. J.; Taylor,
D.; Thompson, G. Org. Process Res. DeV. 2009, 13, 1370.
(16) There are several examples of the transition-metal-catalyzed multialkylation
of ammonia equivalent (aqueous ammonia, ammonium salt, and urea) with
alcohols (refs 10f, 11d, 14a, and 14b and this work). A summary and
comparison of these catalytic systems are shown in Table S1 in the
Supporting Information. See also ruthenium-catalyzed monoalkylation of
ammonia with alcohol (ref 2d).
Acknowledgment. This research was supported financially in
part by the Mitsubishi Chemical Corporation Fund. We also thank
Johnson Matthey, Inc., for a generous loan of iridium trichloride.
(17) Secondary amines were selectively obtained even in the reactions using
excess amounts of the secondary alcohol.
(18) The synthesis of quinolizidines usually requires noncatalytic multistep
reactions. (a) Comins, D. L.; O’Connor, S. Tetrahedron Lett. 1987, 28,
1843. (b) Ojima, I.; Iula, D. M.; Tzamarioudaki, M. Tetrahedron Lett. 1998,
39, 4599. (c) Tehrani, K. A.; D’hooghe, M.; De Kimpe, N. Tetrahedron
2003, 59, 3099.
Supporting Information Available: Experimental procedures,
characterization data of the products, and X-ray data for 3. This material
9
15110 J. AM. CHEM. SOC. VOL. 132, NO. 43, 2010