A Simple Route to Keto-Substituted (η5 ... - ACS Publications

Organometallics 2009, 28, 925–928

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A Simple Route to Keto-Substituted (η5-Cyclohexadienyl)Mn(CO)3 Complexes Using Organomanganese Transmetalation: Structural and Theoretical Characterizations Antoine Eloi,† Franc¸oise Rose-Munch,*,† Eric Rose,*,† Murielle Chavarot-Kerlidou,† and He´le`ne Ge´rard‡ UPMC UniV Paris 06, CNRS UMR 7611, Laboratoire de Chimie Organique, Tour 44, 1er Etage, Case 181, 4 place Jussieu, 75252 Paris, France, and UPMC UniV Paris 06, CNRS UMR 7616, Laboratoire de Chimie The´orique, 4 place Jussieu, 75252 Paris, France ReceiVed September 16, 2008 Summary: Efficient synthesis of keto-substituted (η5-cyclohexadienyl)Mn(CO)3 complexes is achieVed by organomanganese transmetalation catalyzed by Fe(acac)3. Density functional theory (DFT) calculations highlight the influence of the keto group position on the strength of conjugation between the RCO function and the cyclohexadienyl ring and shed light on the regioselectiVity of nucleophilic attacks on such complexes.

Scheme 1. Reactivity Features of (η5-Cyclohexadienyl)Mn(Co)3 Complexes

Introduction

During these past five years, tremendous strides have been made in the study of the reactivity of (η5-cyclohexadienyl)Mn(CO)3 complexes with the development of efficient synthetic procedures such as Pd cross-coupling reactions5 and lithiation/ electrophilic quench sequence,6 thus giving rise to the formation of unprecedented functionalized complexes. Among them the η5 complexes substituted by synthetically useful keto groups appeared to be of crucial importance in the development of applications of such complexes.7 Starting from halogeno substrates, we have synthesized several keto-substituted η5 complexes using Stille Pd coupling under carbonylative conditions,5a but limitations concerning the presence of the halide on the arene ring of the starting material, the experimental conditions requiring a CO atmosphere, and the use of stannous derivatives narrow the convenience of the method. As for the lithiation/electrophilic quench sequence, only sterically demanding electrophiles such as 2,2-dimethylpropionic acid chloride were shown to react efficiently with the lithiated anion of η5 Mn complexes to give rise to the formation of the corresponding keto-substituted (η5-cyclohexadienyl)Mn(CO)3 complexes in high yield.6b All the other attempts using less bulky acid chlorides (thienyl or phenyl acid chlorides, for example)8 led to the formation of a mixture of unidentifiable products and a significant quantity of unreacted starting material. We therefore modified the nature of the electrophile and chose a Weinreb amide.9 Indeed, to prevent further addition of the anion to the

Transition metal complexes containing η6-arene ligands constitute an important class of organometallic compounds whose properties have been investigated for many years. Among them, (η6-arene)tricarbonylchromium and isoelectronic cationic (η6-arene)tricarbonylmanganese complexes1 present a decreased electron density of the arene ring coordinated to the M(CO)3 entity and, consequently, a very high electrophilicity, which found widespread applications in organic as well as in organometallic synthesis.2 In this context, cationic (η6-arenetricarbonyl)Mn(CO)3+ complexes and, in particular, the neutral (η5cyclohexadienyl)Mn(CO)3 derivatives formed by nucleophilic addition to the arene ring have received considerable attention because of their strategic importance in both fields.3 For example, treatment of an η5 complex with a nucleophile Nufollowed by oxidation results in the formation of highly functionalized cis-disubstituted cyclohexadienes (Scheme 1, path a),4a whereas its rearomatization occurs upon hydride abstraction by [CPh3][BF4] (Scheme 1, path b). 4b-d * To whom correspondence should be addressed. E-mail: francoise.rose@ upmc.fr; [email protected]. † Laboratoire de Chimie Organique. ‡ Laboratoire de Chimie The´orique. (1) (a) McGlinchey, M. J.; Ortin, Y. Seward, C. M. ComprehensiVe Organometallic Chemistry III; Crabtree, R. H., Mingos, D. M. P., Eds.; Elsevier Science, Ltd.: Oxford, 2006; Vol. 5, p 201. (b) Sweigart, D. A.; Reingold, J. A.; Son, S. U. ComprehensiVe Organometallic Chemistry III; Crabtree, R. H., Mingos, D. M. P., Eds.; Elsevier Science, Ltd.: Oxford, 2006; Vol. 5, p 761. (2) (a) McQuillin, F. J.; Parker, D. G.; Stephenson, G. R. Transition Metal Organometallics for Organic Synthesis; Cambridge University Press: Cambridge, U.K., 1991. (b) Djukic, J. P.; Rose-Munch, F.; Rose, E. Organometallics 1995, 14, 2027. (c) Rose-Munch, F.; Gagliardini, V.; Renard, C.; Rose, E Coord. Chem. ReV. 1998, 249, 178–180. (d) Pape, A. R.; Kaliappan, K. P.; Ku¨ndig, E. P. Chem. ReV. 2000, 100, 2917. (e) Giner Planas, J.; Prim, D.; Rose-Munch, F.; Rose, E.; Monchaud, D.; Lacour, J. Organometallics 2001, 20, 4107. (f) Ku¨ndig, E. P. Topics in Organometallic Chemistry; Springer: Berlin, 2004; Vol. 7. (g) Rosillo, M.; Domı´nguez, G.; Pe´rez-Castells, J. Chem. Soc. ReV. 2007, 36, 1589. (3) For recent reviews, see (a) McDaniel, K. F. ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon Press: Oxford, U.K., 1995; Vol. 6, p 93. (b) Pike, R. D.; Sweigart, D. A. Coord. Chem. ReV. 1999, 187, 183. (c) Rose-Munch, F.; Rose, E. Eur. J. Inorg. Chem. 2002, 1269.

(4) See, for example, (a) Roell, B. C.; M; Daniel, K. F.; Vaughan, W. S.; Macy, T. S Organometallics 1993, 12, 224. (b) Pearson, A. J.; Bruhn, P. R. J. Org. Chem. 1991, 56, 7092. (c) Pearson, A. J.; Shin, H. Tetrahedron 1992, 48 (36), 7527. (d) Pearson, A. J.; Vickerman, R. J. Tetrahedron Lett. 1998, 39, 5931. (5) (a) Auffrant, A.; Prim, D.; Rose-Munch, F.; Rose, E.; Schouteeten, S.; Vaisserman, J. Organometallics 2003, 22, 1898. (b) Prim, D.; Andrioletti, B.; Rose-Munch, F.; Rose, E.; Couty, F. Tetrahedron 2004, 60, 3325. (6) (a) Jacques, B.; Chavarot, M.; Rose-Munch, F.; Rose, E. Angew. Chem., Int. Ed. 2006, 45, 3481. (b) Jacques, B.; Chanaewa, A.; ChavarotKerlidou, M.; Rose-Munch, F.; Rose, E.; Ge´rard, H. Organometallics 2008, 27, 626. (c) Jacques, B.; Eloi, A.; Chavarot-Kerlidou, M.; Rose-Munch, F.; Rose, E.; Ge´rard, H.; Herson, P. Organometallics 2008, 27, 2505. (7) Eloi, A.; Rose-Munch, F.; Rose, E.; Herson, P. Organometallics 2006, 25, 4554. (8) Eloi, A.; Rose-Munch, F.; Rose, E. Unpublished results. (9) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22 (39), 3815.

10.1021/om800863t CCC: $40.75  2009 American Chemical Society Publication on Web 01/08/2009

926 Organometallics, Vol. 28, No. 3, 2009 Scheme 2. Transmetallation Procedure

keto group of the final product, this electrophile has been shown to be efficient for the synthesis of benzoyl-substituted (η6arene)Cr(CO)3 complexes.10 Unfortunately, only very low yields of the expected Mn complexes and low conversion were observed when using the 2-thienyl Weinreb amide ThCON(Me)OMe (Th ) thienyl), for example.8 One of the problems we had to face was the very high instability of the anions formed on the η5 system, thus it was impossible to reach a suitable temperature to react them with acid chlorides without degradation of these anions or without recovering a significant quantity of the starting material. Thus, we decided to use an organomanganese route involving the formation of a manganese chloride intermediate that could react with the acid chloride in the presence of Fe(acac)3 as the catalyst,11,12 and our results are reported herein.

Results and Discussion The lithiation of the three (η5-cyclohexadienyl)Mn(CO)3 complexes 1, 3, and 6 was achieved by reaction with an excess of n-butyllithium at -78 °C in the presence of tetramethylethylenediamine (TMEDA). After stirring with MnCl4Li2 for 30 min at the same temperature, the acid chloride (phenyl or thienyl acid chlorides) and the iron-based catalyst were added. These reactions give efficient access to the corresponding ketones with yields ranging from 45 to 91% (Scheme 2). Without the presence of Fe(acac)3, the yields of ketosubstituted complexes dramatically decreased (for example, only 25% yield in the case of complex 3), and a significant quantity of the starting material was recovered. This is in a good agreement with the catalytic role of the iron (III) complex, which increased the reactivity of the η5 complex intermediate obtained after lithium-manganese exchange. The regioselectivity is governed by the control of the formation of the lithiated anion: 6b in the case of the unsubstituted η5 system (complex 1) two regioisomers were formed in a 2/1 ratio in favor of the C2 position. When an activating group such as a methoxy (complex 3) or a chloride (complex 6) group is present at C2, only the regioisomer at the C3 position was isolated. Selected 1H NMR data of complexes 1, 2a-b, 3, and 4 are gathered in Table 1 as well as those of complex 2c obtained via a Pd cross-coupling reaction following the procedure (10) Eloi, A.; Rose-Munch, F.; Rose, E.; Herson, P. J. Organomet. Chem. 2007, 26, 5727. (11) (a) Cahiez, G.; Chavant, P. Y.; Metais, E. Tetrahedron Lett. 1992, 33, 36–5245. (b) Cahiez, G.; Alami, M.; Tetrahedron, 1989, 45, 4163. (c) Cahiez, G. Encyclopedia of Reagents for Organic Synthesis; Paquette, L., Ed.; Wiley: Chichester, U.K., 1995; p 3227. (d) Cahiez, G. Encyclopedia of Reagents for Organic Synthesis; Paquette, L., Ed.; Wiley: Chichester, U.K., 1995; p 925. (12) Cardellichio, C.; Fiandanese, V.; Marchese, G.; Ronzini, L. Tetrahedron Lett. 1987, 28, 2053.

Notes

reported in the literature5a and those of complex 12 whose synthesis has been already published.5a Indeed it was interesting to compare, first of all, the proton chemical shifts of the three regioisomers 2a, 2b, and 2c with those of the unsubstituted complex 1, and then, the proton chemical shifts of the regioisomers 4 and 12 with those of the monosubstituted complex 3. It is clear that the deshielding effects ∆δ ) δHi(2)-δHi(1) indicated in brackets can reach impressive values, and the highest ones correspond to the keto function at the C1 and C3 carbon atoms: 1.75 and 1.51 ppm for 2c and 2a, respectively (entries 2 and 4), and the lowest one to the keto group at the C2 carbon atom: 1.00 ppm for each proton β to the ketone of complex 2b (entries 1 and 3). Again, the same trend is observed for the second set of complexes (4, 12 and 3): the highest value is observed for the keto group linked to the C1 carbon atom (1.06 ppm for 12 compared to 0.50 for 4, entry 4). Thus, the electronic effects of the keto group on the β protons depend on the position of this functionality with respect to the η5 system. An alternative approach for the synthesis of complexes 4 or 5 is based on the ,Pd. methodology that we applied successfully to prepare complex 4 (Scheme 3) under the experimental conditions described for the Stille reaction of (η5cyclohexadienyl)Mn(CO)3 complexes.5a The reaction of 10 with 2-thienyltributyltin in the presence of Pd2dba3, AsPh3 as catalyst, under CO atmosphere delivered complex 4 in 86% yield. This last yield can be favorably compared with the 91% yield obtained with the transmetalation method (Scheme 2). Nevertheless, the higher yield of the preparation of complex 3 (90%)13 in comparison with that of 10 (46% yield) and the regioisomer 11 (39% yield) after addition of Grignard reagent to cationic complex 9, increases the importance of the much more environmentally friendly transmetalation method to give access to 4. The procedure described here is particularly valuable to afford the chloro complexes 7 and 8 because they cannot be synthesized via the Stille reaction. Indeed, to our knowledge, no synthesis of the starting dichloro (η5-cyclohexadienyl)Mn(CO)3 complex has been reported up to now. Furthermore, the chlorine atom in these two complexes remains available for subsequent functionalization.5a Complex 4 was crystallized from diethyl ether by a two-well diffusion procedure (petroleum ether in the outer well).14 The ORTEP view of the structure (Figure 1) confirms that the keto function is indeed located at the C3 position adjacent to the methoxy group. The η5 system is represented by five coplanar sp2 carbon atoms, while the remaining sp3 carbon atom is located 35° above this plane. The C7-O2 bond of the thienyl group (COTh) is not in the cyclohexadienyl plane but is deviated by 39° toward the Mn(CO)3 entity, and the dihedral angle between the [C3, C7, O2] and [C8, C9, C10, C11] planes is 12°. Whereas the Mn-C3 bond is usually the shortest Mn-cyclohexadienyl bond length, in the example reported here, the shortest distance is the Mn-C4 bond. The same observation can be made in the case of two X-ray structures of other η5 complexes substituted by a keto7 or a thio-ester group5a where the shortest distance is also the one between the Mn atom and the carbon β to the keto group. With these two methods in hand (Pd catalysis and transmeta(13) Chung, Y. K.; Williard, P. G.; Sweigart, D. A. Organometallics 1982, 1, 1053. (14) Crystal data for 4. C21H15MnO5S, M ) 434.34, monoclinic, P21, a ) 9.8801 (13) Å, b ) 15.8666 (15) Å, c ) 12.4541 (9) Å, R (deg) ) 90, β (deg)) 98.608 (8), γ (deg) ) 90, V (Å3) ) 1930,.4 (3), Z ) 4, density F (g cm3) ) 1.494, θ limits (°) ) 2-32, nb of data collected ) 19737, nb of unique data collected ) 6658, nb of unique data used for refinement 5603(F0)2 > 3σ(F0)2, R(F) ) 0.0334, Rw(F2) ) 0.0294.

Notes

Organometallics, Vol. 28, No. 3, 2009 927 Table 1. Selected 1H NMR Data (δ in ppm) for Complexes 1, 2a-c, 3, 4, and 12 ([Mn] ) Mn(CO)3)

a

In C6D6. b In CDCl3. c δHi(2a)-δHi(1). d δHi(2b)-δHi(1). e δHi(2c)-δHi (1). f δHi(4)-δHi(3). g δHi(12)-δHi(3).

Scheme 3. Alternative Synthesis of 4

lation), it is possible now to introduce a keto function at any of the carbons of the η5 system. A theoretical study of the influence of the position of the keto group on the stability and on the reactivity of the corresponding complexes was undertaken for the three ketosubstituted regioisomers 2a-c. As no effect of the Ph substituent at C6 was observed in the course of previous theoretical studies dealing with either lithiation6b or aldehyde formation6c in the η5 Mn complex series, computations were carried out on the H-substituted complexes. First, the preferred conformations and the relative stabilities of the three regioisomers were examined and compared to those obtained in the case of the analogous aldehydes.6c Two conformations of the CdO/C-S bonds can be proposed, s-cis or s-trans, as well as two conformations, noted

Figure 1. ORTEP view (ellipsoids at 30% probability) of complex 4. Selected interatomic distances: Mn-C1: 2.231(3); Mn-C2: 2.211(3); Mn-C3: 2.156(3); Mn-C4: 2.143(4); Mn-C5: 2.240(4).

Figure 2. Energies relative to the most stable regioisomer and νCO computed vibrational frequencies (in parenthesis, reported unscaled) for the three aldehyde (left) or ketone (right) derivatives. The most stable conformer is used and represented for each regioisomer. Scheme 4. Relative Conformations of CdO/C-S Bonds and CdO/C6 Carbon Atom

as syn or anti, of the CdO group in the plane of the η5 cycle, depending on the direction of the CdO bond with respect to the C6 sp3 carbon (Scheme 4). Whatever the complex, the S-cis conformer is slightly more stable. This is consistent with the conformation obtained for the X-ray structures of compound 4 and its regioisomer with the keto function at the C1 carbon atom7 showing that, despite the small energy difference between the S-cis and S-trans isomers, no crystal effect seems to alter the gas phase preference. In contrast, the Syn/Anti conformational preference is regiodependent, and opposite conformation is obtained compared to the most stable isomer in the case of the aldehyde analogues, as shown in Figure 2, most probably due to steric factors. The most stable conformers are then used to study the regiopreference of the functionalization. Substitution in position 2 (to form a keto-complex referred to as b) leads to the less stable regioisomer (by 4 kcal · mol-1), whereas a (keto-complex substituted in position 3) and c (position 1) are isoenergetic. The stability of a and c can be related to the participation of the CdO group within the metal-ligand coordination. Indeed, the highest occupied molecular orbital (HOMO) exhibits a strong binding interaction between the metal center and atoms C1, C3, and C5. As a consequence, substitution by a CdO group on one of these carbon leads to further delocalization of the HOMO to the carbonyl, and thus larger stabilization. Despite their

928 Organometallics, Vol. 28, No. 3, 2009

Figure 3. LUMO isodensity representation for the three regioisomers.

energetic similarity, a exhibits a νCO vibrational frequency 20 cm-1 higher than c. This is consistent with the proposal that substitution in position 3 allows less conjugation of the CdO bond with the π-system than in position 1. This is in a good agreement with the 1H NMR data, which show a strong electronic effect of the ketone on the β proton when the function is linked to the C1 carbon atom. At the same time, the CdO bond in c exhibits a smaller tilt angle with respect to the cyclohexadienyl plane (16°) than in a (23°). This can be linked to a larger steric hindrance in position C1 than in C3. Competition between conjugation and steric hindrance results in the small energy difference between a and c. This is consistent with the fact that a is 1.5 kcal · mol-1 above c in the case of the aldehyde, where less steric hindrance is at stake. As a consequence, the relative stability of keto-complexes substituted in C1 and C3 positions is most probably highly sensitive to the exact nature of the substituent at the keto-group. Insight within the reactive properties toward nucleophilic attack on these ketones is now searched by examining various reactivity indexes. Charge control is probed by computing the charges within the framework of the natural population analysis (NPA)15 or atoms in molecules (AIM)16 approaches, whereas orbital control is probed by plotting the lowest unoccupied molecular orbital (LUMO)17 and the nucleophilic Fukui indexes (F+)18 of the system (Figure 3). Whatever the regioisomer, only the C(O) carbon bears a positive charge (averaging to 0.55e for NPA and 1.01e for AIM) and exhibits a significant nucleophilic Fukui index (0.19 in average). In addition, the LUMO of all three regioisomers presents the largest coefficient on the carbonyl carbon. The F+ indexes in positions 1 and 5 are very small (below 0.05) compared to that of the nonsubstituted complex (0.17), so that nucleophilic attack on these positions, as shown in Scheme 1 (path a), is expected to be deactivated in these species. No clear-cut evidence concerning the reactivity in the β position of the keto carbon can be found, except for compound c. In that case, the negative charge at C2 (15) (a) Reed, A. E.; Weinhold, F. J. Chem. Phys. 1983, 78, 4066. (b) Reed, A. E.; Weinstock, R. B.; Weinhold, F. J. Chem. Phys. 1985, 83, 735. (16) Popelier, P. L. A. Atoms in Molecules: An Introduction; PrenticeHall: Harlow, U.K., 2000. (17) (a) Semmelhack, M. F.; Garcia, J. L.; Cortes, D.; Farina, R.; Hong, R.; Carpenter, B. K. Organometallics 1983, 2, 467. (b) Eisenstein, O.; Butler, W. M.; Pearson, A. J. Organometallics 1984, 3, 1150. (c) Pfletschinger, A.; Koch, W.; Schmalz, H.-G. New J. Chem. 2001, 25, 446. (18) (a) Fukui, K. Theory of Orientation and Stereoselection; Springer: Berlin, 1973. (b) Lee, C.; Yang, W.; Parr, R. G. J. Mol. Struct. 1988, 163, 305. (c) Bulat, F. A.; Chamorro, E.; Fuentealba, P.; Toro-Labbe´, A. J. Phys. Chem. A 2004, 108, 342.

Notes

is very close to zero (-0.05e with respect to -0.16e in a and -0.25e in b), and the LUMO exhibits a significant weight on this atom, in opposition to what is observed for a. As a consequence, nucleophilic addition should occur cleanly with full regioselectivity on the C(O) carbon for compounds b and a. Some 1,4-addition may be observed in the case of c. This in a good agreement with a relevant experimental result obtained by reacting NaBH4 (or NaBD4) with (η5-cyclohexadienyl)Mn(CO)3 complexes substituted at the C1 carbon atom by the thienone group:7 addition of the nucleophile mainly occurred to the keto group yielding the corresponding alcohol derivatives, but also to the C2 carbon atom, giving rise to the formation of cyclohexadienes in yields ranging from 13 to 20%. In conclusion, these results have shown that tools used for functionalization of arenes in organic synthesis can also be applied in organometallic chemistry for the π system of η5 Mn complexes. Thus, organomanganese transmetalation is an easy and complementary method to prepare keto η5 Mn complexes that cannot be made by Pd cross-coupling reactions. Density functional theory (DFT) calculations highlighted that, despite the influence of the RCO position on the strength of conjugation between the keto group and the cyclohexadienyl ring (evidenced from computed vibrational frequencies of the CdO bond), the carbonyl atom remains the favored site for nucleophilic attack, whatever the position it is branched on. These two strategies will be of interest for the synthesis of new η5 Mn complexes, as building blocks for highly functionalized cyclohexadiene targets.

Experimental Section Complexes 1, 3, and 6 were prepared according to literature procedures.13 Complex 2c was prepared using Pd coupling reaction.5a Typical procedure for the transmetalation process (preparation of 2a, 2b, 4, 5, 7, and 8): A solution of (η5cyclohexadienyl)Mn(CO)3 complex (0.80 mmol) and freshly distilled TMEDA (2.65 mmol, 3.3 equiv) in 8 mL of tetrahydrofuran (THF) was cooled to -78 °C. A solution of n-BuLi (2.40 mmol, 3 equiv) was slowly added. After stirring for 1 h at -78 °C, MnCl4Li211b (2.41 mmol, 3 equiv) was added. The mixture was stirred for 30 min at -78 °C. A solution of Fe(acac)3 (0.15 mmol, 0.2 equiv) in 2 mL of THF was then added followed by the addition of acid chloride (3.28 mmol, 4.1 equiv). After stirring for 1 h at the same temperature, before warming at room tempetrature, the reaction was hydrolyzed with an aqueous HCl solution (2 mol.L-1). Usual work up and purification by flash chromatography on silica gel led to the isolation of the pure keto-substituted η5 complexes.

Acknowledgment. This work was supported by the CNRS. We thank P. Herson (CIM2, UMR 7071, UPMC Univ Paris 06) for the X-Ray structure analysis and the Ecole Normale Supe´rieure (Paris) for financial support to A.E. The calculations have been performed at the CCRE of the University Paris 06 and at the CRIHAN (76800 SaintEtienne-du-Rouvray, France) regional supercomputing centre. Supporting Information Available: Spectroscopic data, 1H NMR and 13C NMR spectra for all new complexes, computational details as well as text giving X-ray crystallographic data, and the CIF files for complex 4. This material is available free of charge via the Internet at http://pubs.acs.org. OM800863T