A Simple Route to Keto-Substituted (η5-Cyclohexadienyl)Mn(CO)3

Complexes Using Organomanganese Transmetalation: Structuraland Theoretical Characterizations

Antoine Eloi,† Francoise Rose-Munch,*,† Eric Rose,*,† Murielle Chavarot-Kerlidou,† andHelene Gerard‡

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 Theorique, 4 place Jussieu, 75252 Paris, France

ReceiVed September 16, 2008

Summary: Efficient synthesis of keto-substituted (η5-cyclohexa-dienyl)Mn(CO)3 complexes is achieVed by organomanganesetransmetalation catalyzed by Fe(acac)3. Density functionaltheory (DFT) calculations highlight the influence of the ketogroup position on the strength of conjugation between the RCOfunction and the cyclohexadienyl ring and shed light on theregioselectiVity of nucleophilic attacks on such complexes.

Introduction

Transition metal complexes containing η6-arene ligandsconstitute an important class of organometallic compoundswhose properties have been investigated for many years. Amongthem, (η6-arene)tricarbonylchromium and isoelectronic cationic(η6-arene)tricarbonylmanganese complexes1 present a decreasedelectron density of the arene ring coordinated to the M(CO)3

entity and, consequently, a very high electrophilicity, whichfound widespread applications in organic as well as in orga-nometallic synthesis.2 In this context, cationic (η6-arenetricar-bonyl)Mn(CO)3

+ complexes and, in particular, the neutral (η5-cyclohexadienyl)Mn(CO)3 derivatives formed by nucleophilicaddition to the arene ring have received considerable attentionbecause of their strategic importance in both fields.3 Forexample, treatment of an η5 complex with a nucleophile Nu-

followed by oxidation results in the formation of highlyfunctionalized cis-disubstituted cyclohexadienes (Scheme 1, patha),4a whereas its rearomatization occurs upon hydride abstractionby [CPh3][BF4] (Scheme 1, path b). 4b-d

During these past five years, tremendous strides have beenmade in the study of the reactivity of (η5-cyclohexadienyl)Mn-(CO)3 complexes with the development of efficient syntheticprocedures such as Pd cross-coupling reactions5 and lithiation/electrophilic quench sequence,6 thus giving rise to the formationof unprecedented functionalized complexes. Among them theη5 complexes substituted by synthetically useful keto groupsappeared to be of crucial importance in the development ofapplications of such complexes.7 Starting from halogenosubstrates, we have synthesized several keto-substituted η5

complexes using Stille Pd coupling under carbonylativeconditions,5a but limitations concerning the presence of thehalide on the arene ring of the starting material, the experimentalconditions requiring a CO atmosphere, and the use of stannousderivatives narrow the convenience of the method. As for thelithiation/electrophilic quench sequence, only sterically demand-ing electrophiles such as 2,2-dimethylpropionic acid chloridewere shown to react efficiently with the lithiated anion of η5

Mn complexes to give rise to the formation of the correspondingketo-substituted (η5-cyclohexadienyl)Mn(CO)3 complexes inhigh yield.6b All the other attempts using less bulky acidchlorides (thienyl or phenyl acid chlorides, for example)8 ledto the formation of a mixture of unidentifiable products and asignificant quantity of unreacted starting material. We thereforemodified the nature of the electrophile and chose a Weinrebamide.9 Indeed, to prevent further addition of the anion to the

* To whom correspondence should be addressed. E-mail: francoise.rose@upmc.fr; eric.rose@upmc.fr.

† Laboratoire de Chimie Organique.‡ Laboratoire de Chimie Theorique.(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. TransitionMetal 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.; Kundig, 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) Kundig, E. P. Topics in Organo-metallic Chemistry; Springer: Berlin, 2004; Vol. 7. (g) Rosillo, M.;Domınguez, G.; Perez-Castells, J. Chem. Soc. ReV. 2007, 36, 1589.

(3) For recent reviews, see (a) McDaniel, K. F. ComprehensiVeOrganometallic 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. Tetrahedron1992, 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.; Chavarot-Kerlidou, M.; Rose-Munch, F.; Rose, E.; Gerard, H. Organometallics 2008,27, 626. (c) Jacques, B.; Eloi, A.; Chavarot-Kerlidou, M.; Rose-Munch,F.; Rose, E.; Gerard, H.; Herson, P. Organometallics 2008, 27, 2505.

(7) Eloi, A.; Rose-Munch, F.; Rose, E.; Herson, P. Organometallics2006, 25, 4554.

(8) Eloi, A.; Rose-Munch, F.; Rose, E. Unpublished results.(9) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22 (39), 3815.

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

Complexes

Organometallics 2009, 28, 925–928 925

10.1021/om800863t CCC: $40.75 2009 American Chemical SocietyPublication on Web 01/08/2009

keto group of the final product, this electrophile has been shownto be efficient for the synthesis of benzoyl-substituted (η6-arene)Cr(CO)3 complexes.10 Unfortunately, only very low yieldsof the expected Mn complexes and low conversion wereobserved when using the 2-thienyl Weinreb amide ThCON-(Me)OMe (Th ) thienyl), for example.8 One of the problemswe had to face was the very high instability of the anions formedon the η5 system, thus it was impossible to reach a suitabletemperature to react them with acid chlorides without degrada-tion of these anions or without recovering a significant quantityof the starting material. Thus, we decided to use an organoman-ganese route involving the formation of a manganese chlorideintermediate that could react with the acid chloride in thepresence of Fe(acac)3 as the catalyst,11,12 and our results arereported 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 excessof n-butyllithium at -78 °C in the presence of tetramethyleth-ylenediamine (TMEDA). After stirring with MnCl4Li2 for 30min at the same temperature, the acid chloride (phenyl or thienylacid chlorides) and the iron-based catalyst were added. Thesereactions give efficient access to the corresponding ketones withyields ranging from 45 to 91% (Scheme 2).

Without the presence of Fe(acac)3, the yields of keto-substituted complexes dramatically decreased (for example, only25% yield in the case of complex 3), and a significant quantityof the starting material was recovered. This is in a goodagreement with the catalytic role of the iron (III) complex, whichincreased the reactivity of the η5 complex intermediate obtainedafter lithium-manganese exchange. The regioselectivity isgoverned by the control of the formation of the lithiated anion:6b in the case of the unsubstituted η5 system (complex 1) tworegioisomers were formed in a 2/1 ratio in favor of the C2

position. When an activating group such as a methoxy (complex3) or a chloride (complex 6) group is present at C2, only theregioisomer at the C3 position was isolated.

Selected 1H NMR data of complexes 1, 2a-b, 3, and 4 aregathered in Table 1 as well as those of complex 2c obtainedvia a Pd cross-coupling reaction following the procedure

reported in the literature5a and those of complex 12 whosesynthesis has been already published.5a Indeed it was interestingto compare, first of all, the proton chemical shifts of the threeregioisomers 2a, 2b, and 2c with those of the unsubstitutedcomplex 1, and then, the proton chemical shifts of theregioisomers 4 and 12 with those of the monosubstitutedcomplex 3.

It is clear that the deshielding effects ∆δ ) δHi(2)-δHi(1)indicated in brackets can reach impressive values, and thehighest 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 � to the ketone ofcomplex 2b (entries 1 and 3). Again, the same trend is observedfor the second set of complexes (4, 12 and 3): the highest valueis 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, theelectronic effects of the keto group on the � protons depend onthe position of this functionality with respect to the η5 system.

An alternative approach for the synthesis of complexes 4 or5 is based on the ,Pd. methodology that we appliedsuccessfully to prepare complex 4 (Scheme 3) under theexperimental conditions described for the Stille reaction of (η5-cyclohexadienyl)Mn(CO)3 complexes.5a The reaction of 10 with2-thienyltributyltin in the presence of Pd2dba3, AsPh3 as catalyst,under CO atmosphere delivered complex 4 in 86% yield. Thislast yield can be favorably compared with the 91% yieldobtained with the transmetalation method (Scheme 2). Never-theless, the higher yield of the preparation of complex 3 (90%)13

in comparison with that of 10 (46% yield) and the regioisomer11 (39% yield) after addition of Grignard reagent to cationiccomplex 9, increases the importance of the much moreenvironmentally friendly transmetalation method to give accessto 4. The procedure described here is particularly valuable toafford the chloro complexes 7 and 8 because they cannot besynthesized 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, thechlorine atom in these two complexes remains available forsubsequent functionalization.5a Complex 4 was crystallized fromdiethyl ether by a two-well diffusion procedure (petroleum etherin the outer well).14 The ORTEP view of the structure (Figure1) 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° abovethis plane. The C7-O2 bond of the thienyl group (COTh) is notin the cyclohexadienyl plane but is deviated by 39° toward theMn(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 twoX-ray structures of other η5 complexes substituted by a keto7

or a thio-ester group5a where the shortest distance is also theone between the Mn atom and the carbon � to the keto group.With these two methods in hand (Pd catalysis and transmeta-

(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. Encyclopediaof 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.

(13) Chung, Y. K.; Williard, P. G.; Sweigart, D. A. Organometallics1982, 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,� (deg)) 98.608 (8), γ (deg) ) 90, V (Å3) ) 1930,.4 (3), Z ) 4, densityF (g cm3) ) 1.494, θ limits (°) ) 2-32, nb of data collected ) 19737, nbof unique data collected ) 6658, nb of unique data used for refinement5603(F0)2 > 3σ(F0)2, R(F) ) 0.0334, Rw(F2) ) 0.0294.

Scheme 2. Transmetallation Procedure

926 Organometallics, Vol. 28, No. 3, 2009 Notes

lation), it is possible now to introduce a keto function at any ofthe carbons of the η5 system.

A theoretical study of the influence of the position of theketo group on the stability and on the reactivity of thecorresponding complexes was undertaken for the three keto-substituted regioisomers 2a-c. As no effect of the Ph substituentat C6 was observed in the course of previous theoretical studiesdealing with either lithiation6b or aldehyde formation6c in theη5 Mn complex series, computations were carried out on theH-substituted complexes. First, the preferred conformations andthe relative stabilities of the three regioisomers were examinedand compared to those obtained in the case of the analogousaldehydes.6c Two conformations of the CdO/C-S bonds canbe proposed, s-cis or s-trans, as well as two conformations, noted 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 tothe C6 sp3 carbon (Scheme 4). Whatever the complex, the S-cisconformer is slightly more stable. This is consistent with theconformation obtained for the X-ray structures of compound 4and its regioisomer with the keto function at the C1 carbon atom7

showing that, despite the small energy difference between theS-cis and S-trans isomers, no crystal effect seems to alter thegas phase preference. In contrast, the Syn/Anti conformationalpreference is regiodependent, and opposite conformation isobtained compared to the most stable isomer in the case of thealdehyde analogues, as shown in Figure 2, most probably dueto steric factors.

The most stable conformers are then used to study theregiopreference of the functionalization. Substitution in position2 (to form a keto-complex referred to as b) leads to the lessstable regioisomer (by 4 kcal · mol-1), whereas a (keto-complexsubstituted in position 3) and c (position 1) are isoenergetic.The stability of a and c can be related to the participation of theCdO group within the metal-ligand coordination. Indeed, thehighest occupied molecular orbital (HOMO) exhibits a strongbinding interaction between the metal center and atoms C1, C3,and C5. As a consequence, substitution by a CdO group onone of these carbon leads to further delocalization of the HOMOto the carbonyl, and thus larger stabilization. Despite their

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

Figure 1. ORTEP view (ellipsoids at 30% probability) ofcomplex 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 moststable conformer is used and represented for each regioisomer.

Scheme 4. Relative Conformations of CdO/C-S Bonds andCdO/C6 Carbon Atom

Notes Organometallics, Vol. 28, No. 3, 2009 927

energetic similarity, a exhibits a νCO vibrational frequency 20cm-1 higher than c. This is consistent with the proposal thatsubstitution in position 3 allows less conjugation of the CdObond with the π-system than in position 1. This is in a goodagreement with the 1H NMR data, which show a strongelectronic effect of the ketone on the � proton when the functionis linked to the C1 carbon atom. At the same time, the CdObond in c exhibits a smaller tilt angle with respect to thecyclohexadienyl plane (16°) than in a (23°). This can be linkedto a larger steric hindrance in position C1 than in C3. Competitionbetween conjugation and steric hindrance results in the smallenergy difference between a and c. This is consistent with thefact 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, therelative stability of keto-complexes substituted in C1 and C3

positions is most probably highly sensitive to the exact natureof the substituent at the keto-group.

Insight within the reactive properties toward nucleophilicattack on these ketones is now searched by examining variousreactivity indexes. Charge control is probed by computing thecharges within the framework of the natural population analysis(NPA)15 or atoms in molecules (AIM)16 approaches, whereasorbital control is probed by plotting the lowest unoccupiedmolecular orbital (LUMO)17 and the nucleophilic Fukui indexes(F+)18 of the system (Figure 3). Whatever the regioisomer, onlythe C(O) carbon bears a positive charge (averaging to 0.55efor NPA and 1.01e for AIM) and exhibits a significantnucleophilic Fukui index (0.19 in average). In addition, theLUMO of all three regioisomers presents the largest coefficienton the carbonyl carbon. The F+ indexes in positions 1 and 5are very small (below 0.05) compared to that of the nonsub-stituted complex (0.17), so that nucleophilic attack on thesepositions, as shown in Scheme 1 (path a), is expected to bedeactivated in these species. No clear-cut evidence concerningthe reactivity in the � position of the keto carbon can be found,except for compound c. In that case, the negative charge at C2

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 onthis atom, in opposition to what is observed for a. As aconsequence, nucleophilic addition should occur cleanly withfull regioselectivity on the C(O) carbon for compounds b anda. Some 1,4-addition may be observed in the case of c. This ina good agreement with a relevant experimental result obtainedby reacting NaBH4 (or NaBD4) with (η5-cyclohexadienyl)Mn-(CO)3 complexes substituted at the C1 carbon atom by thethienone group:7 addition of the nucleophile mainly occurredto the keto group yielding the corresponding alcohol derivatives,but also to the C2 carbon atom, giving rise to the formation ofcyclohexadienes in yields ranging from 13 to 20%.

In conclusion, these results have shown that tools used forfunctionalization of arenes in organic synthesis can also beapplied in organometallic chemistry for the π system of η5 Mncomplexes. Thus, organomanganese transmetalation is an easyand complementary method to prepare keto η5 Mn complexesthat cannot be made by Pd cross-coupling reactions. Densityfunctional theory (DFT) calculations highlighted that, despitethe influence of the RCO position on the strength of conjugationbetween the keto group and the cyclohexadienyl ring (evidencedfrom computed vibrational frequencies of the CdO bond), thecarbonyl atom remains the favored site for nucleophilic attack,whatever the position it is branched on. These two strategieswill be of interest for the synthesis of new η5 Mn complexes,as building blocks for highly functionalized cyclohexadienetargets.

Experimental Section

Complexes 1, 3, and 6 were prepared according to literatureprocedures.13 Complex 2c was prepared using Pd couplingreaction.5a Typical procedure for the transmetalation process(preparation of 2a, 2b, 4, 5, 7, and 8): A solution of (η5-cyclohexadienyl)Mn(CO)3 complex (0.80 mmol) and freshly dis-tilled 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, 3equiv) was slowly added. After stirring for 1 h at -78 °C,MnCl4Li2

11b (2.41 mmol, 3 equiv) was added. The mixture wasstirred 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 additionof acid chloride (3.28 mmol, 4.1 equiv). After stirring for 1 h atthe same temperature, before warming at room tempetrature, thereaction was hydrolyzed with an aqueous HCl solution (2 mol.L-1).Usual work up and purification by flash chromatography on silicagel led to the isolation of the pure keto-substituted η5 complexes.

Acknowledgment. This work was supported by theCNRS. We thank P. Herson (CIM2, UMR 7071, UPMC UnivParis 06) for the X-Ray structure analysis and the EcoleNormale Superieure (Paris) for financial support to A.E. Thecalculations have been performed at the CCRE of theUniversity Paris 06 and at the CRIHAN (76800 Saint-Etienne-du-Rouvray, France) regional supercomputing centre.

Supporting Information Available: Spectroscopic data, 1HNMR and 13C NMR spectra for all new complexes, computationaldetails as well as text giving X-ray crystallographic data, and theCIF files for complex 4. This material is available free of chargevia the Internet at http://pubs.acs.org.

OM800863T

(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; Prentice-Hall: 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.

Figure 3. LUMO isodensity representation for the three regioisomers.

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