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Organometallics 2010, 29, 5744–5747 DOI: 10.1021/om1006853
Iridafurans by Coupling of Alkynes and Aldehydes on a TpMe2Ir System. Facile Demethoxycarbonylation of a β-CO2Me Substituent Crispı´ n Crist obal,† Silvia Garcı´ a-Rubı´ n,‡ Yohar A. Hernandez,† Joaquı´ n L opez-Serrano,† ,† † ,† Margarita Paneque,* Cristina M. Posadas, Manuel L. Poveda,* Nuria Rend on,† and † Eleuterio Alvarez †
Instituto de Investigaciones Quı´micas and Departamento de Quı´mica Inorg anica, Consejo Superior de Investigaciones Cientı´ficas (CSIC) and Universidad de Sevilla, Avda. Am erico Vespucio 49, Isla de la Cartuja, 41092 Sevilla, Spain, and ‡Departamento de Quı´mica Org anica, Facultad de Quı´mica, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain Received July 13, 2010 Me2
Me2
Summary: The reaction of Tp Ir(C2H4)2 (Tp =hydrotris(3,5-dimethylpyrazolyl )borate) with 1 equiv of DMAD (DMAD= dimethyl acetylenedicarboxylate) and 1 equiv of an aromatic aldehyde cleanly yields iridafuran derivatives, characterized by spectroscopy and X-ray analysis. These derivatives experience a stepwise selective hydrolysis-decarboxylation of the CO2Me group located at the β-carbon of the metallacycle, which proceeds through two isolable intermediates: a water adduct of an iridaenolate and an iridium carboxylate bicyclic species. Dealkoxycarbonylation of β-keto esters (eq 1) is a common useful process in organic synthesis.1 It is normally carried out in water-containing polar aprotic solvents such as DMSO, DMF, and HMPA at elevated temperatures, with the aid of a salt catalyst such as NaCl or LiCl. In accord with resonance form A shown in Scheme 1, the iridafurans2 reported in this paper can be considered as β-keto esters. We report herein their stepwise demethoxycarbonylation along with detailed experimental and computational mechanistic studies that have allowed detection, isolation, and characterization of two key intermediates.
R1 CðOÞCR2 R3 CðOÞOR Δ
þ H2 O f R1 CðOÞCR2 R3 H þ ROH þ CO2
ð1Þ
Metallafurans were reported to form in the reactions of aldehydes and Ta-alkyne adducts in 1990.3 Many other synthetic *To whom correspondence should be addressed. E-mail: paneque@ iiq.csic.es. (1) (a) Krapcho, A. P. Arkivoc 2007, 54 (part ii). (b) Krapcho, A. P. Synthesis 1982, 893. (c) Levin, S.; Nani, R. R.; Reisman, S. E. Org. Lett. 2010, 12, 780. (2) Metallafurans are the most common aromatic metallacycles. See: Bleeke, J. R. Acc. Chem. Res. 2007, 40, 1035. (3) Strickler, J. R.; Bruck, M. A.; Wexler, P. A.; Wigley, D. E. Organometallics 1990, 9, 266. (4) See: (a) Li, X.; Chen, P.; Faller, J. W.; Crabtree, R. H. Organometallics 2005, 24, 4810. (b) Esteruelas, M. A.; Hernandez, Y. A.; Lopez, A. M.; Olivan, M.; O~ nate, E. Organometallics 2005, 24, 5989. (5) See: (a) Behamou, L.; Cesar, V.; Lugan, N.; Lavigne, G. Organometallics 2007, 26, 4673. (b) Kataoka, Y.; Iwato, Y.; Shibahara, A.; Yamagata, T.; Tani, K. Chem. Commun. 2000, 841. (c) Carmona, E.; Gutierrez-Puebla, E.; Monge, A.; Marín, J. M.; Paneque, M.; Poveda, M. L. Organometallics 1989, 8, 967. (6) See: (a) Stack, J. G.; Simpons, R. D.; Hollander, F. J.; Bergman, R. G.; Heathcock, C. H. J. Am. Chem. Soc. 1990, 112, 2716. (b) Bleeke, J. R.; New, P. R.; Blanchard, J. M. B.; Haile, T.; Beatty, A. M. Organometallics 1995, 14, 5127. (c) Stone, K. C.; Jamison, G. M.; White, P. S.; Templeton, J. L. Organometallics 2003, 22, 3083. (d) Lin, Y.; Gong, L.; Xu, H.; He, X.; Wen, T. B.; Xia, H. Organometallics 2009, 28, 1524. pubs.acs.org/Organometallics
Published on Web 10/25/2010
Scheme 1. Resonance Forms of the Iridafurans Studied in This Paper
methodologies are available that, in general, consist of the activation of organic molecules such as R,β-unsaturated carbonyl derivatives,4 the insertion of alkynes into M-acyl bonds,5 the combination or isomerization of other different carbon fragments,6 or other procedures.7 In addition, zirconafurans have been reported to form from the reaction of Cp2ZrEt2 with alkynes and chloroformates.8 The iridafurans reported herein result from the iridium-mediated coupling of an alkyne (dimethyl acetylenedicarboxylate (DMAD) or methyl propiolate (MP)) with aromatic aldehydes. As depicted in Scheme 2, hydride-iridafuran 1a results from the stepwise reaction of TpMe2Ir(C2H4)29 (TpMe2 = hydrotris(3,5-dimethylpyrazolyl)borate) with 1 equiv of DMAD (to result in TpMe2Ir(C2H4)(DMAD)10 ) and then p-anisaldehyde (excess). Related derivatives (1b, Ar=C6H4-p-Me; 1c, Ar=C6H5; 1d, Ar= C6H4-p-F) have also been obtained by this procedure. The hydride ligand of 1a gives rise to a 1H NMR signal at -20.35 ppm (CDCl3) and an IR absorption at 2168 cm-1. The most remarkable 13C{1H} NMR signals of this complex are those corresponding to two of the sp2-hybridized carbon (7) Bierstedt, A.; Clark, G. R.; Roper, W. R.; Wright, L. J. J. Organomet. Chem. 2006, 691, 3846. (8) Takahashi, T.; Xi, C.; Ura, Y.; Nakajima, K. J. Am. Chem. Soc. 2000, 122, 3228. (9) Alvarado, Y.; Boutry, O.; Gutierrez, E.; Monge, A.; Nicasio, M. C.; Poveda, M. L.; Perez, P. J.; Ruiz, C.; Bianchini, C.; Carmona, E. Chem. Eur. J. 1997, 3, 860. (10) Paneque, M.; Posadas, C. M.; Poveda, M. L.; Rend on, N.; Mereiter, K. Organometallics 2007, 26, 3120. r 2010 American Chemical Society
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Scheme 2. Reaction of TpMe2Ir(C2H4)2 with DMAD and p-Anisaldehyde
atoms of the metallacycle: 219.1 (Ir-C) and 202.7 (C-O) ppm. The very low field chemical shift of the Ir-bonded C atom is in accord with its partial carbene nature (see below), as the corresponding resonance for a σ-bound IrC(CO2Me)d group is typically in the range 140-170 ppm.11 Figure 1 shows the solid-state X-ray molecular structure of 1a.12 The Ir-C(25) bond distance of 1.961(3) A˚ is intermediate between values expected for single7 and double13 Ir-C bonds, while the C-C bonds of the ring also have lengths that suggest partial double-bond character: 1.389(4) A˚ for C(24)C(25) and 1.431(4) A˚ for C(16)-C(24). The iridacycle is almost planar (the largest deviation out of the mean plane defined by Ir(1), O(1), C(16), C(24), and C(25) is 0.08 A˚, which corresponds to C(25)). These data along with NMR data indicate an important electronic delocalization within the metallacycle. Hence, the structure of complexes 1 can be considered as a resonance hybrid of the forms shown in Scheme 1. Heating compounds 1 in a mixture of acetone and water generates the related iridafurans 2 (Scheme 3) as the result of formal replacement of the β-carbon CO2Me substituent by a hydrogen atom. X-ray data in support of the structure of compounds 2 have been obtained for 2a (see the Supporting Information). NMR monitoring for the conversion of 1a (8:1 CD3COCD3/D2O, ca. 6 M in D2O) reveals the formation of two other complexes that have been isolated and characterized as the species 3a and 4a of Scheme 4. The first, 3a, is the water adduct of an enolate that derives from stereospecific migration of the hydride ligand to the R-carbon atom of the metallacycle and exists at 60 °C in equilibrium14 with its hydride iridafuran precursor 1a. At higher temperatures (110 °C) compound 2a-d1 gradually appears and the bicyclic iridium carboxylate 4a-d1 is observed as a low-concentration, steady-state species. (11) (a) Paneque, M.; Posadas, C. M.; Poveda, M. L.; Rend on, N.; Alvarez, E.; Mereiter, K. Chem. Eur. J. 2007, 13, 5160. (b) Paneque, M.; Posadas, C. M.; Poveda, M. L.; Rendon, N.; Santos, L. L.; Alvarez, E.; Salazar, V.; Mereiter, K.; O~nate, E. Organometallics 2007, 26, 3403. (12) The hydride ligand for 1a was not located but was predicted by potential energy calculations (HYDEX program) (see: (a) Orpen, A. G. Program HYDEX; University of Bristol, Bristol, U.K., 1986; (b) Orpen, A. G. J. Chem. Soc., Dalton Trans., 1980, 2509) to be situated at the vacant octahedral axial position around the metal atom. Thereby, in the final steps of the refinement the hydride ligand was included in the model and was refined riding on the iridium metal center with a free isotropic displacement parameter. The calculated Ir-H distance is 1.702 Å, a value that falls within the range 1.49-1.81 Å of the Ir-H bond lengths from crystal structures of similar complexes reported in the Cambridge Structural Database (CSD) but which is a bit long compared to the only known Ir-H distance (Ir-H = 1.486 Å) determined by neutron diffraction. See: (c) Xu, W.; Logh, A. J.; Morris, R. H. Can. J. Chem. 1977, 75, 475. (13) For some examples of TpMe2Ir compounds containing IrdC bonds, see: (a) Ilg, K.; Paneque, M.; Poveda, M. L.; Rend on, N.; Santos, L. L.; Carmona, E.; Mereiter, K. Organometallics 2006, 25, 2230. (b) Alvarez, E.; Paneque, M.; Petronilho, A. G.; Poveda, M. L.; Santos, L. L.; Carmona, E.; Mereiter, K. Organometallics 2007, 26, 1231. (14) Under these conditions, the equilibrium is fully established in ca. 2 h.
Figure 1. Solid-state structure of 1a. H atoms, other than the hydride ligand, have been omitted for clarity. Ellipsoids are shown at the 30% probability level. Selected distances (A˚) and angles (deg): Ir-N(1) =2.120(2), Ir-N(3) =2.033(2), Ir-N(5) =2.180(2), IrO(1)=2.038(2), Ir-C(25)=1.961(3), Ir-H = 1.70, C(24)-C(25)= 1.389(4), C(16)-C(24)=1.431(4), C(16)-O(1)=1.284(3); C(25)Ir(1)-O(1)=78.86(10), C(25)-Ir(1)-H=85.0, O(1)-Ir(1)-H= 85.3, C(16)-O(1)-Ir(1)=115.13(17), C(16)-C(24)-C(26)= 123.6(3), O(1)-C(16)-C(24) = 116.6(2), C(24)-C(25)-Ir(1)= 115.5(2). Scheme 3. Reaction of Complexes 1 with Water at 110 °C
Formation of compound 4a-d1 requires hydrolysis of the CO2Me group at the β-position of the ring, with liberation of MeOD (detected by 1H and 13C{1H} NMR), deuteration at the β-position, and coordination of the carboxylate group to Ir. Its decarboxylation, followed by R-H elimination, gives the iridafuran 2a-d1, which, as expected, retains the deuterium label at the same site. By using equimolecular amounts of H2O and D2O a kinetic isotopic effect kH/kD of ca. 1.8 was obtained.15 A competition experiment carried out with 1a and 1d (8:1 CD3COCD3/D2O) reveals that the latter experiences the demethoxycarbonylation process at a rate ca. 10 times slower than 1a. (15) Further heating slowly increases the deuterium content in the βposition of 2a until the equilibrium 2a þ DOH (average) h 2a-d1 þ H2O is fully achieved, with, as expected, deuterium being favored at the carbon position.
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Scheme 4. Stepwise Transformation of Complex 1a into 2a in CD3COCD3/D2O Mixtures
Figure 2. Species stable toward the demethoxycarbonylation. Scheme 6. Proposed Mechanism for the Hydrolytic Decarboxylation of Compounds 1
Scheme 5. Demethoxycarbonylation of the Iridafuran 5a
The related less-substituted iridafuran 5a, formed in the reaction of TpMe2Ir(C2H4)2 with MP and p-anisaldehyde, undergoes the same hydrolysis-decarboxylation sequence in acetone/water, as depicted in Scheme 5. The absence of the CO2Me substituent at the R-carbon of the metallacycle strongly disfavors the process (the reaction is ca. 150 times slower than for 1a). The hydride iridafuran-water adduct equilibria are very sensitive to the nature of the substituents on the ring. Thus, the equilibrium constant for adduct formation in the case of 1d is almost 15 times larger than for 1a (7.5 vs 0.5 M-1).16 More compelling evidence that electron-withdrawing groups in the ring stabilize the water adducts rely on the fact that both 5a and 6a do not form any measurable amount of the corresponding adduct (NMR monitoring, 8:1 CD3COCD3/D2O, 60 °C). To understand the mechanism of this hydrolytic decarboxylation, additional studies were carried out. First, we attempted without success the same reaction with the iridacyclopentadiene derivative C,11a which contains a coordinated water molecule (Figure 2). Second, we prepared the nonlabile CO adduct D, related to 3a, and subjected it to the reaction conditions of Scheme 3 to recover only the starting material. Therefore, it can be concluded that the presence of the delocalized keto group within the metallacycle is required and that the hydrolysis is most probably intramolecular. Scheme 6 shows a plausible mechanistic pathway for this transformation. Either enolate 3 undergoes protonation at the β-C atom of the ring to give intermediate E or, alternatively, this latter species is formed by a similar protonation of the iridafuran, followed by fast adduct formation, as was the case for (16) A van’t Hoff plot of Keq vs T (40-110 °C) gives the following parameters: ΔH = -7.1 kcal mol-1 and ΔS = -22.7 cal mol-1 K-1.
related iridapyrroles.17 Whatever the case, the close proximity of the ester group and the coordinated molecule of water in the stereoisomer E,18 shown in Scheme 6, permits the subsequent lactonization to yield 4, which then decarboxylates to the final product 2 via intermediate F. In accord with this proposal, the hydrolytic step is catalyzed by the addition of protic acids (even silica gel is effective for this purpose). Computational support for the mechanistic route that leads to 2 has been sought. The solid-state geometry of 3d 3 H2O 3 CH3COCH3 was used as the starting point for gas-phase calculations at the ONIOM(BHandH:UFF) level (see the Supporting Information). The gas-phase optimized geometry for 3d 3 H2O compares well with the solid-state geometry; therefore, this DFT method was considered appropriate for this system. The calculations indicate that the protonation of the metallacycle takes place on the β-carbon, in agreement with the experimental observations. Moreover, protonation can take place on both faces of the ring, but protonation on the upper face (i.e., that opposite to the coordinated water, Figure S5 in the Supporting Information) leads to an intermediate which is 19 kcal/mol more stable than the species resulting from protonation on the lower face (Figure S6 in the (17) Alı´ as, F. M.; Daff, P. J.; Paneque, M.; Poveda, M. L.; Carmona, E.; Perez, P. J.; Salazar, V.; Alvarado, Y.; Atencio, R.; SanchezDelgado, R. Chem. Eur. J. 2002, 8, 5132. (18) The epimer of E may be formed under the reaction conditions,17 but this would be an unproductive species that would revert to 3.
Communication
Supporting Information). The bond lengths in the protonated ring are consistent with the located ketone structure E of Scheme 6. The higher relative stability of this species is likely due to the formation of an intramolecular hydrogen bond between its H2O ligand and the C(O) moiety of the carboxylate substituent on the β-carbon of the protonated iridafuran. This conformation (see Scheme 6 and Figure S5) favors attack of the coordinated H2O at the ester, which may lead to the observed hydrolysis. In summary, a variety of iridafurans, prepared by the oxidative coupling of alkynes and aldehydes in a TpMe2IrI system, experience an easy hydrolytic process of a β-CO2Me group of the ring. This reaction is followed by decarboxylation, which regenerates a less-substituted iridafuran structure.
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Acknowledgment. Financial support (FEDER contribution) from the Spanish MICINN (Grants CTQ2007-62814 and Consolider Ingenio 2010 CSD 2007-0006) and the Junta de Andalucı´ a (FQM119, P09-FQM-4832) is acknowledged. The use of computational facilities of the Centro Informatico Cientı´ fico de Andalucı´ a (CICA) and the Centro de Supercomputaci on de Galicia (CESGA) is also appreciated. N.R. and J.L.-S. thank the MICINN for Ram on y Cajal contracts. Supporting Information Available: Text, figures, and tables giving experimental procedures and theoretical calculations and a CIF file giving X-ray crystallographic data for 1a, 2a, 3d 3 C3H6O 3 H2O, and 4b. This material is available free of charge via the Internet at http://pubs.acs.org.
