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Organometallics 2009, 28, 956–959
A Copper-Catalyzed Azide-Alkyne Cycloaddition Approach to the Synthesis of Bimetallic Chromium(0) (Fischer) Carbene Complexes Beatriz Baeza,† Luis Casarrubios,*,† Pedro Ramı´rez-Lo´pez,‡ Mar Go´mez-Gallego,† and Miguel A. Sierra*,† Departamento de Quı´mica Orga´nica, Facultad de Quı´mica, UniVersidad Complutense de Madrid, 28040 Madrid, Spain, and Instituto de Quı´mica Orga´nica, Consejo Superior de InVestigaciones Cientı´ficas (CSIC), Juan de la CierVa 3, 28006 Madrid, Spain ReceiVed December 10, 2008 Summary: The Cu(I)-catalyzed 1,3-dipolar cycloaddition of bisazides to alkynyl chromium(0) (Fischer) carbene complexes has been deVeloped. The method is a new entry to the synthesis of highly functionalized chromium(0) bis-carbene complexes bearing different tethers joining both metal centers. The use of complex bis- and polymetallic Fischer carbenes in organic synthesis has been hampered by the difficulties in the preparation of these types of compounds.1,2 The potential of these complexes as reagents in organic synthesis is demonstrated by the use of group 6 bis-carbene complexes in the synthesis of complex organic molecules. The key for the utility of these compounds in synthesis is their bidirectional reactivity derived from the presence of two metal-carbene fragments in the same molecule.1 The diastereoselective preparation of helicenes3 and biaryls4 by a double-benzannulation reaction, unsymmetrical [n,m]cyclophanes from the macrocyclization of bis-carbene complexes and diynes,5 and the sequential photochemical reaction of bis-carbene complexes and imidazolines followed by acid isomerization to produce bis-oxocyclams6 are paramount examples of the use of these types of group 6 metal complexes in synthesis. The simplest strategies, based on the catalytic coupling of two moieties having the carbene metal fragments, are generally of little value to prepare bis-carbene complexes, due to the fast transmetalation reaction experienced by the group 6 metal carbenes when they are exposed to latetransition-metal reagents.7 The only reported cross-coupling * To whom correspondence should be addressed. E-mail: luis_casarrubios@ quim.ucm.es (L.C.);
[email protected] (M.A.S.). † Universidad Complutense de Madrid. ‡ Consejo Superior de Investigaciones Cientı´ficas (CSIC). (1) Sierra, M. A. Chem. ReV. 2000, 100, 3591. (2) The chemistry of group 6 mononuclear carbene complexes and their application in organic synthesis is well established and it has been profusely reviewed. For selected, recent reviews, see: (a) Wulff, W. D. In ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford, U.K., 1995; Vol. 12, p 470. (b) Hegedus, L. S. In ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds. Pergamon: Oxford, U.K., 1995; Vol. 12, p 549. (c) Harvey, D. F.; Sigano, D. M. Chem. ReV. 1996, 96, 271. (d) Aumann, R.; Nienaber, H. AdV. Organomet. Chem. 1997, 41, 163. (e) de Meijere, A.; Schirmer, H.; Duetsch, M. Angew. Chem., Int. Ed. 2000, 39, 3964. (f) Barluenga, J.; Flo´rez, J.; Fan˜ana´s, F. J. J. Organomet. Chem. 2001, 624, 5. (g) Barluenga, J.; Santamarı´a, J.; Toma´s, M. Chem. ReV. 2004, 104, 2259. (3) Tomuschat, P.; Kro¨ner, L.; Steckhan, E.; Nieger, M.; Do¨tz, K. H. Chem. Eur. J. 1999, 5, 700. (4) Bao, J.; Wulff, W.; Fumo, M. J.; Grant, E. B.; Heller, D. P.; Whitcomb, M. C.; Yeung, S.-M. J. Am. Chem. Soc. 1996, 118, 2166. (5) Wang, H.; Wulff, W. D. J. Am. Chem. Soc. 1998, 120, 10573. (6) (a) Dumas, S.; Lastra, E.; Hegedus, L. S. J. Am. Chem. Soc. 1995, 117, 3368. (b) Hsiao, Y.; Hegedus, L. S. J. Org. Chem. 1997, 62, 3586. (7) Go´mez-Gallego, M.; Manchen˜o, M. J.; Sierra, M. A. Acc. Chem. Res. 2005, 38, 44.
Scheme 1
reaction to date is the Stille reaction between alkynylaminocarbene complexes 1 and 2 to yield alkyne-tethered complexes 3 and other higher homologues (Scheme 1).8 The reaction takes advantage of the fact that transmetalation from group 6 (Fischer) aminocarbene complexes to Pd(0) is considerably more difficult than from alkoxycarbenes. Recently, we have also succeeded9 in the preparation of symmetrical bis-carbene complexes 5, having different bis-alkynyl tethers, by means of Hay’s10 oxidative coupling of alkynylchromium(0) carbene complexes 4 (Scheme 1). By use of the double carbene functionality present in complexes 5, efficient synthesis of bis-pyrazoles and bimetallic bis-uracyls by reaction with tosylhydrazine and N,N′dimethylurea, respectively, were developed. The synthesis of complexes 5 demonstrates the compatibility of group 6 Fischer carbene complexes with a late-transition-metal catalyst, provided that the appropriate reaction conditions are used. Considering these precedents, alkynyl complexes 4 are optimal substrates to use the Cu-catalyzed azide-alkyne cycloaddition (CuAAC)11 approach to prepare bis-carbene complexes. The reactivity of alkynyl group 6 Fischer carbene complexes and 1,3-dipoles is known to depend on the nature (8) Hartbaum, C.; Mauz, E.; Roth, G.; Weissenbach, K.; Fischer, H. Organometallics 1999, 18, 2619. (9) Lo´pez-Alberca, M. P.; Manchen˜o, M. J.; Ferna´ndez, I.; Go´mezGallego, M.; Sierra, M. A. Org. Lett. 2008, 10, 365. (10) Hay, A. S. J. Org. Chem. 1962, 27, 3320. (11) Recent revisions: (a) Meldal, M.; Tornøe, C. W. Chem. ReV. 2008, 108, 2952. (b) Stanley, L. M.; Sibi, M. P. Chem. ReV. 2008, 2887. (c) Binder, W. H.; Sachsenhofer, R. Macromol. Rapid Commun. 2007, 28, 15. (d) Lutz, J. F. Angew. Chem., Int. Ed. 2007, 46, 1018. (e) Gil, M. V.; Are´valo, M. J.; Lo´pez, O. Synthesis 2007, 1589. (f) Li, Y.; Ju, Y.; Zhao, Y. F. Chin. J. Org. Chem. 2006, 26, 1640. (g) Bock, V. D.; Hiemstra, H.; Van Maarseveen, J. H. Eur. J. Org. Chem. 2006, 51. (h) Kolb, H. C.; Sharpless, K. B. Drug DiscoVery Today 2003, 8, 1128.
10.1021/om801171x CCC: $40.75 2009 American Chemical Society Publication on Web 01/29/2009
Communications
Organometallics, Vol. 28, No. 4, 2009 957 Scheme 2
Table 1 cat.
of both reagents and often produces mixtures of compounds.12,2g However, the incorporation of Cu as a catalyst in the process should drive the reaction through a different mechanistic pathway, leading to products with total regioselectivity.13 What is more attractive from this methodology is that although it has been thoroughly applied to a full range of chemical transformations,7 there are only scarce examples reported for transitionmetal complexes bearing alkyne moieties.14 The application of the CuAAC approach to the reaction between alkynyl carbenes 4 and bis-azides should constitute a new route to prepare bimetallic bis-carbene complexes, as long as the metal-carbeneCu transmetalation would be avoided. Reported in this communication is the successful implementation of this approach to prepare a series of bis-carbene complexes 7 having diverse tethers joining both metal centers, as well as a preliminary study of their electrochemical properties. A deaerated DMF solution of complex 4a5,15 and azide 6a16 was treated with CuSO4 · 5H2O (10 mol %) in the presence of sodium ascorbate (20 mol %). Monitoring of the reaction (TLC) showed the complete disappearance of 4a after 2 h. However, NMR analysis of the reaction mixture indicated that only small amounts of the desired bis-carbene complex 7a were formed (Scheme 2). The reaction was also carried out in other solvents, including THF, MeCN, and Et2O, maintaining the system CuSO4 · 5H2O/ sodium ascorbate as the Cu(I) source, but again with poor results. The combination CuI/base was next investigated. Different mixtures of CuI and bases (Et3N, 2,6-lutidine, DIPEA, and K2CO3) in different solvents (CHCl3, MeCN, THF, Et2O, CH2Cl2) were screened. Under these conditions, complex 7a was obtained. The best results (34% isolated yield) were obtained with Et3N, in anhydrous CHCl3 and using 20 mol % (12) For a review, see: Alcaide, B.; Casarrubios, L.; Domı´nguez, G.; Sierra, M. A. Curr. Org. Chem. 1998, 2, 551. (13) (a) Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210. (b) Rodionov, V. O.; Fokin, V. V.; Finn, M. G. Angew. Chem., Int. Ed. 2005, 44, 2210. (14) (a) Chen, W. Z.; Fanwick, P. E.; Ren, T. Inorg. Chem. 2007, 46, 3429. (b) Ornelas, C.; Ruiz Aranzaes, J.; Cloutet, E.; Alves, S.; Astruc, D. Angew. Chem., Int. Ed. 2007, 46, 872. (15) (a) Ferna´ndez, I.; Manchen˜o, M. J.; Go´mez-Gallego, M.; Sierra, M. A. Org. Lett. 2003, 5, 1237. (b) Ferna´ndez, I.; Sierra, M. A.; Manchen˜o, M. J.; Go´mez-Gallego, M.; Ricart, S. Organometallics 2001, 20, 4304. (c) Llordes, A.; Sierra, M. A.; Lo´pez-Alberca, M. P.; Molins, E.; Ricart, S. J. Organomet. Chem. 2005, 690, 6096. (16) Ramı´rez-Lo´pez, P.; de la Torre, M. C.; Montenegro, H. E.; Asenjo, M.; Sierra, M. A. Org. Lett. 2008, 10, 3555.
base
CuSO4 · 5H2O sodium ascorbate
-
CuCl CuI CuI
2,6-lutidine 2,6-lutidine Et3N
CuCl CuI CuI
Et3N DIPEA K2CO3
solvent
yield of 7a (%)
time (h)
DMF THF MeCN CHCl3 CHCl3 CHCl3 MeCN THF CHCl3 CHCl3 CHCl3
