ORGANIC LETTERS
Ruthenium(II) Porphyrin-Catalyzed Amidation of Aromatic Heterocycles
2004 Vol. 6, No. 14 2405-2408
Ling He, Philip Wai Hong Chan, Wai-Man Tsui, Wing-Yiu Yu, and Chi-Ming Che* Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug DiscoVery and Synthesis, The UniVersity of Hong Kong, Pokfulam Road, Hong Kong, P. R. China
[email protected] Received April 27, 2004
ABSTRACT
Ruthenium(II) porphyrin-catalyzed amidation of aromatic heterocycles with iminoiodanes under mild conditions (CH2Cl2, 4 Å molecular sieves, ultrasound, 40 °C) was achieved in moderate to good yields (up to 84%) and conversions (up to 99%). Only the N,N-ditosylamidated product was obtained for reactions involving heteroarenes, where X ) O, S, or NTs. N-Alkyl- and N-aryl-substituted pyrroles, on the other hand, were shown to give the 3,4-diaminated adduct.
Transition metal-catalyzed nitrene insertion into C-H bonds is increasingly attractive as a C-N bond formation strategy.1-6 Innovative works by Breslow,2 Mu¨ller,3 and Du Bois4 showed that dirhodium(II,II) complexes with bridging carboxylate ligands and derivatives are effective catalysts for amidation of saturated C(sp3)-H bonds using N-(p-toluenesulfonyl)imino-phenyliodinane (PhIdNTs) or “PhI(OAc)2 + NH2SO2R” (usually R ) Ar) as a nitrogen source. Studies in our laboratory demonstrated that highly enantioselective amidation of saturated C-H bonds can be accomplished using chiral ruthenium porphyrin catalysts.5 Despite these (1) (a) Mu¨ller, P. In AdVances in Catalytic Processes; Doyle, M. P., Ed.; JAI Press: Greenwich, CT, 1997; Vol. 2, p 113. (b) Jacobsen, E. N. In ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Berlin, 1999; Vol. 2, p 607. (c) Mu¨ller, P.; Fruit, C. Chem. ReV. 2003, 103, 2905 and references therein. (2) (a) Breslow, R.; Gellman, S. H. Chem. Commun. 1982, 1400. (b) Breslow, R.; Gellman, S. H. J. Am. Chem. Soc. 1983, 105, 6728. (c) Yang, J.; Weinberg, R.; Breslow, R. Chem. Commun. 2000, 531. (3) Nageli, I.; Baud, C.; Bernardinelli, G.; Jacquier, Y.; Moran, M.; Mu¨ller, P. HelV. Chim. Acta 1997, 80, 1087. (4) (a) Espino, C. G.; Du Bois, J. Angew. Chem., Int. Ed. 2001, 40, 598. (b) Espino, C. G.; Wehn, P. M.; Chow, J.; Du Bois, J. J. Am. Chem. Soc. 2001, 123, 6935. 10.1021/ol049232j CCC: $27.50 Published on Web 06/08/2004
© 2004 American Chemical Society
advances, examples of amidation of aromatic C(sp2)-H bonds are sparse in the literature. A recent notable achievement is that of Pe´rez and co-workers showing that copper(I)homoscorpionate complexes can effect benzene amidation by PhIdNTs in moderate yields.6 In the present work, we describe amidation of C(sp2)-H bonds of heteroarenes such as furan, pyrrole and thiophene using ruthenium(II) porphyrin as a catalyst and PhIdNTs as a nitrogen source. Although reactions of these heterocycles with metallocarbenoids to give cyclopropanes are known,7 examples of protocols for catalytic amidation of heteroarenes have limited precedent in the literature. It is well-known that amino-functionalized het(5) (a) Au, S.-M.; Huang, J.-S.; Yu, W.-Y.; Fung, W.-H.; Che, C.-M. J. Am. Chem. Soc. 1999, 121, 9120. (b) Zhou, X.-G.; Yu, X.-Q.; Huang, J.-S.; Che, C.-M. Chem. Commun. 1999, 2377. (c) Liang, J.-L.; Yu, X.-Q.; Che, C.-M. Chem. Commun. 2002, 124. (d) Liang, J.-L.; Yuan, S.-X.; Huang, J.-S.; Yu, W.-Y.; Che, C.-M. Angew. Chem., Int. Ed. 2002, 41, 3465. (6) Dı´az-Requejo, M. M.; Belderraı´n, T. R.; Nicasio, M. C.; Trofimenko, S.; Pe´rez, P. J. J. Am. Chem. Soc. 2003, 125, 12078. (7) Selected examples: (a) Doyle, M. P.; Chapman, B. J.; Hu, W.; Peterson, C. S.; McKervey, M. A.; Garcia, C. F. Org. Lett. 1999, 1, 1327 and references therein. (b) Hughes, C. C.; Kennedy-Smith, J. J.; Trauner, D. Org. Lett. 2003, 5, 4113.
erocycles are prevalent in many natural and therapeutic products of biological significance.8
Scheme 1
At the outset of this study, we found that ultrasound treatment of furan (1 equiv) with 10 mol % [RuII(TTP)(CO)] [H2(TTP) ) meso-tetrakis(tolyl)porphyrin] and PhIdNTs (1.5 equiv) in CH2Cl2 containing 4 Å molecular sieves9 at 40 °C gave N,N-ditosylamido-2-furan (1) in 73% isolated yield (Table 1, entry 1).10 The molecular structure of 1 has
Table 1. Optimization of Reaction Conditionsa
entry
temp (οC)
catalyst loading (mol %)
product
% yieldb
1c 2 3c,d 4c 5 6 7e
40 40 40 40 40 65 40
10 10 10 2 2 2 10
1 1 1 1 1 1 2
73 41 10 40 43 45 63
a All reactions were performed in CH Cl for 2 h with a catalyst: 2 2 heteroarene:PhIdNTs ratio of 1:1:5 in the absence of ultrasound. b Isolated yield based on the amount of heteroarene consumed. c Reaction conducted with ultrasound treatment. d Reaction conducted with 5 equiv of PhIdNTs. e Reaction conducted with PhIdNNs.
been established by X-ray crystal analysis (Figure 1).11 Analysis of the crude reaction mixture by 1H NMR spectroscopy and mass spectrometry revealed that 1 was the sole product. Under our experimental conditions, formation of (8) Selected examples: (a) Lipshutz, B. H. Chem. ReV. 1986, 86, 795. (b) Reymond, J. L.; Pinkerton, A. A.; Vogel, P. J. Org. Chem. 1991, 56, 2128. (c) Bossio, R.; Marcaccini, S.; Pepino, R.; Torroba, T. J. Org. Chem. 1996, 61, 2202. (d) Marcotte, F.-A.; Rombouts, F. J. R.; Lubell, W. D. J. Org. Chem. 2003, 68, 6984. (9) Amount of 4 Å molecular sieves employed is equivalent to the amount (by mass) of PhIdNTs used. (10) See Supporting Information for full experimental details. (11) See Supporting Information. Also, CCDC 219719-219720 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033; e-mail:
[email protected]). 2406
Figure 1. Perspective view of 1. Selected bond lengths (Å) and angles (deg): O(5)-C(1) 1.347(3), N(1)-C(1) 1.404(3), S(1)N(1) 1.689(2), C(1)-C(2) 1.334(4), C(2)-C(3) 1.447(5), S(1)N(1)-S(2) 122.7(1), C(2)-C(1)-N(1) 128.9(3), C(1)-C(2)-C(3) 103.1(3).11
the monotosylated amide (i.e., N-furan-2-yl-tolylsulfonamide) was not detected. The reason for formation of the N,N-ditosylamidated product remains ill understood. However, attempts to obtain the putative monotosylated compound were futile. For example, conducting the above catalytic reaction in the presence of a proton source such as TsOH (1.5 equiv) led to compound 1 in a trace amount (
