pubs.acs.org/OrganometallicsPublished on Web 09/30/2010r 2010 American Chemical Society

Organometallics 2010, 29, 4643–4646 4643

DOI: 10.1021/om1005269

Lithiation/Electrophilic Quench Sequence of “Benzylic” Position of(η5-Methylcyclohexadienyl)Mn(CO)3 Complexes

Julien Dubarle Offner,† Franc-oise Rose-Munch,*,† Eric Rose,*,† No�emie Elgrishi,† andH�el�ene Rousseli�ere§

†Equipe de Chimie Organique et Organom�etallique, Institut Parisien de Chimie Mol�eculaire IPCM,UMR CNRS 7201, Universite Pierre and Marie Curie Paris 06, Case 181, 4 Place Jussieu, 75005 Paris,

France, and §Centre de R�esolution de Structures, Universite Pierre and Marie Curie Paris 06,Case 42, 4 Place Jussieu, 75005 Paris, France

Received May 28, 2010

Summary: [(η6-Pentamethylbenzene)Mn(CO)3]þBF4

- 1 and[(η6-1,2,4,5-tetramethylbenzene)Mn(CO)3]

þBF4- 2 complexes

were prepared and reacted with nucleophiles to provide neutralexo-substituted (η5-polymethylcyclohexadienyl)Mn(CO)3 com-plexes 3-6. To study the regioselectivity of the deprotonation ata “benzylic” position of (η5-methylcyclohexadienyl)Mn(CO)3complexes, compounds 3-6were submitted to a lithiation/electro-philic quench sequence, and functionalized complexes 9-18 wereobtained in good yields and with a total regioselectivity. A secondsequence gave rise to the formation of unprecedented bifunctiona-lized (η5-1,2,4,5-tetramethylcyclohexadienyl)Mn(CO)3 and (η5-pentamethylcyclohexadienyl)Mn(CO)3 complexes 19-22.

Introduction

Coordination of the tricarbonylmanganese moiety to arenesconsiderably modifies their chemical properties and conse-quently their reactivity. Indeed, the presence of the electron-deficient Mn(CO)3

þ fragment implies a decrease of the electro-nic density of the arene and thus dramatically enhances theelectrophilic character of the ligand and the acidity of its pro-tons.1Furthermore, additionofnucleophilesR1 to cationic [(η6-arene)Mn(CO)3]

þ complexes leads to the formation of neutralexo-substituted (η5-6-R1-cyclohexadienyl)Mn(CO)3 complexes(Scheme 1, path a),2 whose chemistry has been intensivelydeveloped in the past decade to provide access to a wide rangeof organic andorganometallicmolecules.Nucleophilic additionto the (η5-cyclohexadienyl)Mn(CO)3 affords a cis-disubstitutedcyclohexadiene with a complete control of stereoselectivity(Scheme 1, path b),3 and oxidation leads to the decoordination

of themanganese unit, giving access to the substituted free arene(Scheme 1, path c). If the η5 complex is substituted by a goodleaving group such as R=OMe or Cl and if it is treated with ahydride and then an acid, cine or tele nucleophilic substitutionoccurs (Scheme 1, path d).4a-g Palladium-catalyzed couplingreactions can be achieved in (η5-halogenocyclohexadienyl)-Mn(CO)3 complexes and allows the introduction on the η5

system of many different functional groups, as well as a secondorganometallic unit (Scheme 1, path e).4h-j

Finally (η5-cyclohexadienyl)Mn(CO)3 complexes can also beeasily functionalizedbya lithiation/electrophilicquenchsequence(Scheme1,path f).4k,lThediversely substitutedη5 complexespro-videaneasyaccess to thecorrespondingη6 complexesafter rearo-matization by exo-hydride abstraction at the sp3 carbon atombyusing CPh3

þBF4- (Scheme 1, path g).

Having discovered the lithiation/electrophilic quenchsequence methodology that allows substitution of the ring pro-tons of (η5-cyclohexadienyl)Mn(CO)3 complexes, wewonderedwhether this reaction could be applied to functionalize“benzylic” positions, i.e., positions R to the η5-π system of suchcomplexes. Indeed, the studyof thebenzylic positionhas alreadybeen reported for the cationic [(η6-arene)Mn(CO)3]

þ series5 and

*To whom correspondence should be addressed. E-mail: franc-oise.rose@upmc.fr; eric.rose@upmc.fr.(1) (a) McDaniel, K. F. In Comprehensive Organometallic Chemistry

II; Abel, E.W.; Stone, F. G. A.;Wilkinson, G.,Eds.; Pergamon Press: Oxford,UK, 1995; Vol. 6, pp 93-107. (b) Pike, R. D.; Sweigart, D. A. Coord.Chem. Rev. 1999, 187, 183. (c) Pape, A. R.; Kaliappan, K. P.; K€undig, E. P.Chem. Rev. 2000, 100, 2917. (d) Giner-Planas, J.; Prim, D.; Rose-Munch, F.;Rose, E.; Monchaud, D.; Lacour, J. Organometallics 2001, 20, 4107. (e)Rose-Munch, F.; Rose, E. Eur. J. Inorg. Chem. 2002, 1269. (f) Prim, D.;Andrioletti, B.; Rose-Munch, F.; Rose, E.; Couty, F. Tetrahedron 2004, 60,3925. (g) Sweigart, D. A.; Reingold, J. A.; Son, S. U. In ComprehensiveOrganometallic Chemistry, 3rd ed.; Crabtree, R. H. Mingos, D. M. P., Eds.;Elsevier: Oxford, 2006; Vol. 5, Chapter 10, pp 761-814.(2) (a) Semmelhack, M. F. In Comprehensive Organometallic Chemistry

II; Abel, E. W.; Stone, F. G. A.; Wilkinson, G., Eds.; Pergamon Press: Oxford,1995; Vol. 12, p 979. (b) Pike, R. D.; Sweigart, D. A. Synlett 1990, 565.(3) See for example: (a) Pearson, A. J.; Bruhn, P. R. J. Org. Chem.

1991, 56, 7092. (b) Miles, W. H.; Brinkman, H. R. Tetrahedron Lett. 1992,33, 589. (c) Pearson, A. J.; Shin, H. Tetrahedron 1992, 48, 7527.

(4) (a) Balssa, F.; Gagliardini, V.; Rose-Munch, F.; Rose, E.Organome-tallics 1996, 15, 4373. For Cr complexes, see: (b)Boutonnet, J. C.; Rose-Munch,F.; Rose, E. Tetrahedron Lett. 1985, 26, 3989. (c) Rose-Munch, F.; Rose, E.;Semra, A. J. Chem. Soc., Chem. Commun. 1986, 1551. (d) Rose-Munch, F.;Rose, E.; Semra, A. J.Chem. Soc., Chem.Commun. 1987, 942. (e) Djukic, J.-P.;Rose-Munch, F.; Rose, E.Organometallics 1995, 14, 2027. (f) Rose-Munch, F.;Rose, E.; Semra, A.; Garcia-Oricain, J.; Knobler, K. J. Organomet. Chem. 1989,363, 297. (g) Rose-Munch, F.; Rose, E.; Semra, A.; Garcia-Oricain, J.; Bois, C.J.Organomet.Chem.1989,363, 103. (h)Auffrant,A.; Prim,D.;Rose-Munch,F.;Rose, E.; Schouteeten, S.; Vaissermann, J. Organometallics 2003, 22, 1898. (i)Jacques, B.; Tranchier, J.-P.; Rose-Munch, F.; Rose, E.; Stephenson, G. R.;Guyard-Duhayon, C. Organometallics 2004, 23, 184. (j) Schouteeten, S.;Tranchier, J.-P.; Rose-Munch, F.; Rose, E.; Auffrant, A.; Stephenson, G. R.Organometallics 2004, 23, 4308. (k) Jacques, B.; Chavarot,M.; Rose-Munch, F.;Rose, E.Angew. Chem., Int. Ed. 2006, 45, 3481. (l) Jacques, B.; Chanaewa, A.;Chavarot-Kerlidou, M.; Rose-Munch, F.; Rose, E.; G�erard, H. Organometallics2008, 27, 626. (m) Boutonnet, J.-C.; Rose-Munch, F.; Rose, E.; Jeannin, Y.;Robert, F. J. Organomet. Chem. 1985, 297, 185. For an anti-eclipsed conforma-tion of a bulky group, see: (n) Renard, C.; Valentic, R.; Rose-Munch, F.; Rose, E.Organometallics 1998, 17, 1587. For a staggered conformation, see: (o)Boutonnet, J. C.; Levisalles, J.; Rose, E.; Precigoux, G.; Courseille, C.; Platzer,N. J. Organomet. Chem. 1983, 255, 317.

(5) (a) Johnson, J.W.; Treichel, P.M. J. Chem. Soc., Chem. Commun.1976, 688. (b) Treichel, P. M.; Johnson, J.W. Inorg. Chem. 1977, 16, 749. (c)Treichel, P. M.; Fivizzani, K. P.; Haller, K. J.Organometallics 1982, 1, 931.(d) Bernhardt, R. J.; Eyman, D. P. Organometallics 1984, 3, 1445. (e)Bernhardt, R. J.; Wilmoth, M. A.; Weers, J. J.; LaBrush, D. M.; Eyman, D. P.Organometallics 1986, 5, 883. (f) LaBrush, D. M.; Eyman, D. P.; Baenziger,N. C.; Mallis, L. M. Organometallics 1991, 10, 1026. (g) Hull, J. W.;Roesselet, K. J.; Gladfelter, W. L. Organometallics 1992, 11, 3630.

4644 Organometallics, Vol. 29, No. 20, 2010 Dubarle Offner et al.

has been well developed in the (η6-arene)Cr(CO)3 series.6 In the

early 1990s, Eyman et al.5e and then Gladfelter et al.5f investi-gated the generality of deprotonation of organometallic com-plexes at a benzylic position using a large excess of strong base-such as potassium hydride or potassium tert-butoxide-andworked on different [(η6-alkylarene)Mn(CO)3]

þ complexes.They observed the formation of (η5-alkylbenzyl)Mn(CO)3 com-plexes presenting a highly activated exocyclic double bond(Scheme 2). However, to our knowledge, a deprotonation at a“benzylic” position has never been performed with (η5-cyclo-hexadienyl)Mn(CO)3 complexes; thereforewe applied the lithia-tion/electrophilic quench sequence to (η5-polymethylcyclohexa-dienyl)Mn(CO)3 complexes in order to study the reactivity ofthese positions. Here we report on the synthesis of a series ofη5-Mn complexes diversely substituted at a benzylic position aswell as the structure of two of them.

Results and Discussion

Synthesis of the Starting Materials. The (η5-cyclohexadie-nyl)Mn(CO)3 complexes used as starting materials in thepresent study were synthesized on one side from the (η6-pentamethylbenzene)Mn(CO)3

þBF4- complex 1 to settle the

proper experimental conditions for a “benzylic” deprotonationand, on the other side, from the (η6-tetramethylbenzene)-Mn(CO)3

þBF4- complex 2 to determine if there is any

competition between the deprotonation at the ring positionand the “benzylic” position. The [(η6-pentamethylbenzene)-Mn(CO)3]

þBF4- 1 and [(η6-1,2,4,5-tetramethylbenzene)-

Mn(CO)3]þBF4

- 2 complexes were readily obtained in 90%

and 88% yields respectively, via the “silver(I) method” usingBrMn(CO)5, AgBF4

-, and the corresponding free arenes.7 Sub-sequently, each of these cationic complexes underwent twodifferent nucleophilic additions, the first one with phenylGrignard reagent at 0 �C and the other one with n-butyllithiumat -78 �C.4l Two sets of η5 complexes were thus isolated: the(6-exo-substituted-η5-pentamethylcyclohexadienyl) Mn(CO)3complexes 3 and 4 from 1 in 47% and 67% isolated yields,respectively, and the (6-exo-substituted-η5-1,2,4,5-tetramethyl-cyclohexadienyl)Mn(CO)3 complexes 5 and 6 from 2 in 80%and 72% isolated yields, respectively (Scheme 3). An X-rayanalysis of the yellow crystals of the (6-phenyl-η5-1,2,4,5-tetramethylcyclohexadienyl)Mn(CO)3 complex 5 highlights theusual conformation of a Mn(CO)3 tripod with a CO ligandeclipsing the sp3 carbon C6, which is located 41.05(9)� above theplane formed by the five sp2 carbons (Figure 1).8

Lithiation/Electrophilic Quench Sequence. We first per-formed a lithiation/electrophilic quench sequence on the (η5-pentamethylcyclohexadienyl)Mn(CO)3 complexes 3 and 4 inorder to know whether the reaction takes place or not at anybenzylic position. We first followed the operating mode des-cribed in the case of deprotonation of the η5-cyclohexadienylring,4k,l where 1.4 to 2 equiv of nBuLi and 1.6 to 2.5 equiv ofthe electrophile were introduced at -78 �C, but we thenslightly modified the procedure because it appeared that thedeprotonation at the benzylic position was more difficult toperform than at the cyclohexadienylic position. We thusoptimized the reaction by adding an excess of n-BuLi at-40 �C to a THF solution of a η5 complex and TMEDA;then the reaction was stirred for two hours at this tem-perature, and finally a larger excess of the electrophile wasintroduced. After an extra hour of stirring at -40 �C themixture was warmed to room temperature and quenched byaddition of water. We found out that the “benzylic” carba-nion was stable up to -20 �C; nevertheless the best yields wereobserved at a reaction temperature of -40 �C. Different trialswere run with various electrophiles: chlorotrimethylsilane,N,N-dimethylformamide, chlorodiphenylphosphine, and Eschenmo-ser’s salt. The reaction was feasible with this large range ofreactants. Chromatography on silica gel afforded in each case a

Scheme 1. Reactivity Features of the(Cyclohexadienyl)tricarbonylmanganese Complexes

Scheme 2. Monodeprotonation of [(η6-alkylarene)Mn(CO)3]þ

Complexes

Scheme 3. Nucleophilic Addition to(η6-pentamethylbenzene)Mn(CO)3

þBF4- Complex 1 and

(η6-tetramethylbenzene)Mn(CO)3þBF4

- Complex 2

(6) (a)Davies, S.G.;Coote, S. J.;Goodfellow,C.L. InAdvances inMetalOrganicChemistry; Liebeskind,L.S.,Ed.; JAIPress:Greenwich, 1991;Vol.2, pp1-57. (b) Davies, S. G.;McCarthy, T. D. InComprehensive OrganometallicChemistry II; Abel, E.W.; Stone, F. G. A.; Wilkinson, G., Eds.; Pergamon Press:Oxford, UK, 1995; Vol. 12, pp 1039-1070. (c) Volk, T.; Bernicke, D.; Bats,J. W.; Schmalz, H.-G. Eur. J. Inorg. Chem. 1998, 1883–1905.

(7) Jackson, J. D.; Villa, S. J.; Bacon, D. S.; Pike, R. D.; Carpenter,G. B. Organometallics 1994, 13, 3972.

(8) For the first X-ray analyses of (η5-cyclohexadienyl)Mn(CO)3 com-plexes, see: (a) Churchill, M. R.; Scholer, F. R. Inorg. Chem. 1969, 8, 1950.(b) Mawby, A.; Walker, P. J. C.; Mawby, R. J. J. Organomet. Chem. 1973, 55,C39. For the first theorical study of (η5-cyclohexadienyl)Mn(CO)3 complexes,see: (c) Hoffmann, R.; Hofmann, P. J. Am. Chem. Soc. 1976, 98, 598.

Note Organometallics, Vol. 29, No. 20, 2010 4645

unique monofunctionalized complex. These new complexes7-12 were isolated in 15% to 71% yields, and some startingmaterial was always recovered in 10% to 42% isolated yieldsdependingon the electrophileused (Scheme4).Furthermore, noformationofacylmetalate, resulting fromapossiblenucleophilicattack of n-butyllithium on a carbonyl ligand, was detected.9

Interestingly the lithiation/electrophilic quench sequence iscompletely regioselective and occurred only at the equivalentcarbons C9 and C10 (it affords a couple of enantiomers), what-ever the electrophile. This regioselectivity was evidenced by asimpleNMRstudy, performing aHMBC (heteronuclearmulti-ple bond correlation) experiment between carbon C3 andprotons H9 (or H10) and between C6 and protons H7 (orH8),which confirmed the positionof the substituents on carbonC9 (or C10). Furthermore, crystallization of complex 9 fromdiethyl ether at 4 �C afforded yellow crystals suitable for X-rayanalyses. In this structure, theMn(CO)3 tripod eclipses carbonsC4-C10, the sp3 carbonC6 (located 42.52�(15) above the planedescribed by the five sp2 carbons), and carbons C2-C9 bearingthe diphenylphosphine group, which is on the opposite sidefrom the Mn(CO)3 group (Figure 2, left).

These preliminary observations do not reveal if the confor-mation of the Mn(CO)3-tripod favors the formation of the“benzylic” carbanions eclipsed by a Mn-CO bond and conse-quently the regioselective deprotonation observed in the presentstudy or if the steric effect of the exo-phenyl group at the C6carbon inhibits the approachof nBuLi at theC7 andC8 carbons.These results are relevant to those obtained a couple of yearsago4l in the case of a (η5-6-phenylcyclohexadienyl)Mn(CO)3complex, which could be efficiently silylated via a lithiation/electrophilic quench sequence. Two regioisomers resulting fromthe lithiation at C2/C4 and at C3 were isolated in a 80:20 ratio,respectively. It is interesting to notice that only amonocarbanionis produced, even if four equivalents of n-butyllithium wasintroduced; double or triple deprotonation was never observed,

in contrast with the experiments reported in the literature with(η6-arene)Cr(CO)3 complexes at aromatic positions10a or atbenzylic positions of benzyl allyl ethers.10b

We then performed this sequence using (η5-1,2,4,5-tetra-methylcyclohexadienyl)Mn(CO)3 complexes 5 and 6 and syn-thesized the monofunctionalized (η5-pentamethylcyclohexa-dienyl)Mn(CO)3 complexes 13-18 as unique products in48% to 69% isolated yields (starting material was also recov-eredwith yields ranging from 11% to 28%) (Scheme 5). To oursurprise, no deprotonation occurred at the C3 cyclohexadienylcarbon, in good agreement with the 1HNMR spectrum, whichshows the H3 proton signal around 5 ppm for each complex.

The reaction was also totally regioselective and took placeonly at the same benzylic position as in the previous example,on carbons C9 or C10 (Scheme 5). Again this total regios-electivity might be explained by a great difference of reactiv-ity between ring and benzylic protons. Yellow crystals of 13suitable for X-ray analysis were grown from diethyl ether at4 �C. The Mn(CO)3 tripod shows the typical conformationeclipsing carbons C2, C4, and C6, which is located 41.69(2)�above theplanedescribedby the five sp2 carbons.The trimethyl-silyl group is located on carbon C9, confirming the regioselec-tivity of this reaction, and the C9-Si bond points in the direc-tion opposite the Mn(CO)3 entity (Figure 2, right). Such aneclipsed bulky group has been also observed in (arene)Cr(CO)3complexes.4m

Second Lithiation/Electrophilic Quench Sequence. Takinginto account these results, we decided to perform a secondlithiation/electrophilic quench sequence using a monofunc-tionalized complex from the “tetramethylbenzene series”,the most interesting one, because the yields of the firstlithtiation/electrophilic quench sequence in this series werebetter than those observed in the “pentamethylbenzeneseries”. Futhermore, CD3ODwas chosen as electrophile, know-ing the excellent yields obtained with it in the first sequence. Thereaction conditionswere slightlymodified, anda strict control of

Figure 1. Molecular structure of 5with thermal ellipsoids at the50% probability level.

Scheme 4. Lithiation/Electrophilic Quench Sequence onComplexes 3 and 4

Figure 2. Molecular structures of 9 and 13 with thermal ellip-soids at the 50% probability level.

Scheme 5. Lithiation/Electrophilic Quench Sequence onComplexes 5 and 6

(9) Sheridan, J. B.; Padda, R. S.; Chaffee, K.; Wang, C.; Huang, Y.;Lalancette, R. J. Chem. Soc., Dalton Trans. 1992, 1539.(10) (a) Gibson, S. E.; Saladin, S. A.; Sur, S. Chem. Commun. 2000,

2011. (b) Abecassis, K.; Gibson, S. E.; Martin-Fontecha, M. Eur. J. Org.Chem. 2009, 1606.

(11) (a) Duisenberg, A. J. M.; Kroon-Batenburg, L. M. J.; Schreurs,A. M. M. J. Appl. Crystallogr. 2003, 36, 220. (b) Blessing, R. H. ActaCrystallogr. 1995, A51, 33. (c) Altomare, A.; Cascarano, G.; Giacovazzo,C.; Guagliardi, A. J. Appl. Crystallogr. 1993, 26, 343–350. (d) Sheldrick,G. M. Acta Crystallogr. 2008, 64, 112–122.

4646 Organometallics, Vol. 29, No. 20, 2010 Dubarle Offner et al.

the temperature and a very slow warming to room temperaturewere necessary. Thus, starting from (6-phenyl-η5-2-methylene-trimethylsilyl-1,4,5-trimethylcyclohexadienyl)Mn(CO)3 com-plex 13 and (6-phenyl-η5-2-methylenediphenylphosphine-1,4,5-trimethylcyclohexadienyl)Mn(CO)3 complex 15, complexes 19and 20 were isolated in 65% and 43% yields, respectively(Scheme 6). In both cases, 1H NMR spectra indicated clearlythe substitution of a proton atom H10 by a deuterium atom: itwas exhibited by the change of integration from 3 to 2 of itssinglet signal and by the two doublets for the diastereotopicH9aand H9b, which remained unchanged. Furthermore, by using13C-DEPT NMR spectroscopy, the CH3 signal of C10 turnedinto a CH2 signal. All these observations excluded a secondfunctionalization on the same carbon C9 and were in goodagreement with a substitution of the C10 carbon.

The formation of the two complexes 19 and 20 validatedthe principle of our methodology. We thus extended thesecond sequence starting from complex 13 to other electro-philes, DMFandClPPh2, and obtained bifunctionalized (η

5-cyclohexadienyl)Mn(CO)3 complexes 21 and 22 in low iso-lated yields. But in both cases, we recovered about 40% of

the monofunctionalized starting material. A total regioselec-tivity was still observed, and the reaction took place only oncarbon C10 (and not on carbons C3, C9, and C7 or C8)(Scheme 6). In both cases, 1H NMR of the products 21 and22 showed two sets of diastereotopic protons, H9a/H9b andH10a/H10b. Moreover, two methyl groups and two methy-lene groups were present in the 13C-DEPT NMR spectra.Again, these analyses were a proof that we synthesized thedesired bifunctionalized compounds.

Conclusion

We successfully developed amethod of lithiation/electrophilicquench sequence for mono- and bifunctionalized (η5-poly-methylcyclohexadienyl)Mn(CO)3 complexes at “benzylic” posi-tions, stressing the strong electron-withdrawing effect of theMn(CO)3 entity. These reactions are completely regioselective inthe studied examples, as evidencedbyNMRandX-rayanalyses,and occur only at themethyl groups substituting the C2/C4 car-bons of the cyclohexadienyl ring. This methodology opens newpossibilities on the application of (arene)tricarbonylmanganesecomplexes in organic and organometallic syntheses.

Acknowledgment. J.D.O. thanks the CNRS for a finan-cial grant. F.R. and E.R. thank the CNRS for financialsupport and Z. Ahmadi, an Erasmus student in collabora-tion with Prof. Dr. J. Heck (Hamburg).

Supporting Information Available: Experimental part andcrystal data for complexes 5, 9, and 13. This material is availablefree of charge via the Internet at http://pubs.acs.org.

Scheme 6. Second Lithiation/Electrophilic Sequence