π-arene/metal binding: An issue not only of structure but also of reactivity

Article abstract of DOI:10.1021/ol0502580

(Chemical Equation Presented) A trimethyl-, triethyl-, or triisopropylsilyl group attached to the meta position of toluene retards the rate of permutational hydrogen/metal interconversion with butyllithium in the presence of potassium tert-butoxide by fac

Full text of DOI:10.1021/ol0502580

ORGANIC
LETTERS
2005
Vol. 7, No. 10
1923-1925
π
-Arene/Metal Binding: An Issue Not
Only of Structure but Also of Reactivity
Eric Masson and Manfred Schlosser*
Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fe´de´rale,
(BCh), CH-1015 Lausanne, Switzerland
manfred.schlosser@epfl.ch
Received February 7, 2005
ABSTRACT
A trimethyl-, triethyl-, or triisopropylsilyl group attached to the meta position of toluene retards the rate of permutational hydrogen/metal
interconversion with butyllithium in the presence of potassium tert-butoxide by factors of 1.7, 3, and 7, respectively. Although remote from the
reaction center, the substituents sterically impede the coordination of potassium to the arene electron sextet.
play a major role in modulating chemical and, by extension, biochemical reactivity.
π-Arene/metal bonding may
To rationalize and even predict chemical reactivity requires
detailed knowledge about the involved transition states. As
part of our continuing efforts to probe the composition and
geometry of such elusive species in the context of organo-
metallic reactions,1a,2 we have carried out a new series of
toluene parent compound. In addition, triisopropyl-3-tolyl-
silane was included in the study. The superbasic mixed-metal
(“LIC-KOR”) reagent is known to produce benzylmetal
species that retain most of the potassium, whereas most of
the lithium, although not all, combines with tert-butoxide
(the alcoholate thus formed being removable by extraction
of the residue with toluene).4 The organometallic intermedi-
ates 1 (see Scheme 1) were trapped with iodomethane. The
3
competition kinetic experiments. In this way, we have
measured the rates of the permutational hydrogen/metal
interconversion (“metalation”) between trimethylsilyl- and
triethylsilyl-substituted toluenes and butyllithium in the
presence of potassium tert-butoxide relative to that of the
Scheme 1. Metalation of Trialkylsilyl-Substituted Toluenes
with the Superbasic Mixed-Metal LIC-KOR Reagent
(1) (a) Schlosser, M. In Organometallics in Synthesis: A Manual, 2nd
ed.; Schlosser, M., Ed.; Wiley: Chichester, 2002; pp 45-84; (b) pp 249-
251.
(2) (a) Schlosser, M.; Franzini, L.; Bauer, C.; Leroux, F. Chem. Eur. J.
2001, 7, 1909-1914. (b) Baston, E.; Maggi, R.; Friedrich, K.; Schlosser,
M. Eur. J. Org. Chem. 2001, 3985-3989. (c) Castagnetti, E.; Schlosser,
M. Chem. Eur. J. 2002, 8, 799-804. (d) Heiss, C.; Schlosser, M. Manuscript
in preparation. (e) Lefebvre, O.; Marull, M.; Cottet, F.; Schlosser, M.
Manuscript in preparation. (f) Gorecka, J.; Heiss, C.; Scopelliti, R.;
Schlosser, M. Org. Lett. 2004, 6, 4591-4593.
(3) (a) Bu¨ker, H. H.; Nibbering, N. M. M.; Espinosa, D.; Mongin, F.;
Schlosser, M. Tetrahedron Lett. 1997, 38, 8519-8522. (b) Schlosser, M.;
Mongin, F.; Porwisiak, J.; Dmowski, W.; Bu¨ker, H. H.; Nibbering, N. M.
M. Chem. Eur. J. 1998, 4, 1281-1286. (c) Baston, E.; Wang, Q.; Schlosser,
M. Tetrahedron Lett. 2000, 41, 667-700. (d) Faigl, F.; Marzi, E.; Schlosser,
M. Chem. Eur. J. 2000, 6, 771-777. (e) Schlosser, M.; Marzi, E.; Cottet,
F.; Bu¨ker, H. H.; Nibbering, N. M. M. Chem. Eur. J. 2001, 7, 3511-3516.
kinetically relevant substrate concentrations before and after
the reaction and, as a check, the product concentrations were
determined by high-accuracy gas chromatography.2c,3e,5
10.1021/ol0502580 CCC: $30.25
© 2005 American Chemical Society
Published on Web 04/19/2005

Table 1. Metalation of Trialkyltolylsilanes with Butyllithium
in the Presence of Potassium tert-Butoxidea or, as Indicated by
Values in Brackets, with Butyllithium in the Presence of
N,N,N′,N′′,N′′-Pentamethyldiethylenetriamine (PMDTA):b Rates
Relative to Toluene (krel ) 1.0)
isomer
R ) CH3
R ) C2H5
R ) CH(CH3)
ortho
meta
para
0.70 [0.50]
0.60 [1.3 ]
3.5 [4.3 ]
0.26 [0.33]
0.34 [1.0 ]
2.5 [4.1 ]
0.14 [-]
Figure 1. Metalation of toluenes with butyllithium/potassium tert-
butoxide: π-arene/potassium interaction at the transition state.
a In tetrahydrofuran (THF) at -75 °C. b In THF at 0 °C.
The results compiled in Table 1 are remarkable in several
aspects. They reveal a rate enhancement brought about by
para-positioned trialkylsilyl groups but also a strong rate
retardation if such substituents are located at the meta posi-
tion. However, the latter effect is restricted to the potassium-
containing mixed-metal reagent, being absent when the
similarly polar butyllithium/PMDTA (N,N′,N′,N′′,N′′-pen-
tamethyldiethylenetriamine) complex is employed (Table 1).
The reaction-inhibiting action of the meta-trialkylsilyl
groups proved to be cumulative. 1-Methyl-3,5-phenylenebis-
(triethylsilane) was found to undergo the LIC-KOR-promoted
metalation, generating intermediate 2, 0.14 () 0.372) times
as rapidly as toluene (Scheme 2).
the assumption of an η6-type coordination of potassium by
the arene π-electrons at the transition state 3 (Figure 1).
Under such circumstances, the bulky trialkylsilyl substituents
will inevitably become repulsive.
Potassium/π-arene interactions have been postulated for
the first time in an attempt to rationalize why the crowded
endo-4,4,4-triphenyl-2-butenylpotassium can compete with
its unstrained exo isomer at the conformational equilibrium
on equal terms.7 Later, several X-ray structures of organo-
potassiums,8 organosodiums,9 and even alkali metal amides10
have been published that feature η6-metal coordination as a
key factor modeling the crystallographic architecture. In
contrast, evidence for η6-lithium coordination is scarce11 if
one disregards “radical-anions”12 and “arene-dianions”.12c,13
It can only manifest itself if no better donor components are
Scheme 2. Metalation of
1-Methyl-3,5-phenylenebis(triethylsilane) with LIC-KOR
(7) Moret, E.; Fu¨rrer, J.; Schlosser, M. Tetrahedron 1988, 44, 3539-
3550.
(8) (a) Hoffmann, D.; Bauer, W.; Schleyer, P. V. R.; Pieper, U.; Stalke,
D. Organometallics 1993, 12, 1193-1200. (b) Hoffmann, D.; Bauer, W.;
Hampel, F.; van Eikema Hommes, N. J. R.; Schleyer, P. V. R.; Otto, P.;
Pieper, U.; Stalke, D.; Wright, D. S.; Snaith, R. J. Am. Chem. Soc. 1994,
116, 528-536. (c) Luinstra, G. A.; Wang, L.; Stahl, S. S.; Labinger, J. A.;
Bercaw, J. E. Organometallics 1994, 13, 755-756. (d) Scho¨n, J. C. Angew.
Chem. 1995, 107, 1183-1185; Angew. Chem., Int. Ed. Engl. 1995, 34,
1081-1083.
(9) (a) Bock, H.; Ruppert, K.; Fenske, D. Angew. Chem. 1989, 101,
1717-1720; Angew. Chem., Int. Ed. Engl. 1989, 28, 1685-1688. (b) Bock,
H.; Ruppert, K.; Havlas, Z.; Fenske, D. Angew. Chem. 1990, 102, 1095-
1097; Angew. Chem., Int. Ed. Engl. 1990, 29, 1042-1044. (c) Corbelin,
S.; Kopf, J.; Lorenzen, N. P.; Weiss, E. Angew. Chem. 1991, 103, 875-
876; Angew. Chem., Int. Ed. Engl. 1991, 30, 825-826. (d) Bock, H.;
Ruppert, K.; Havlas, Z.; Bensch, W.; Ho¨nle, W.; von Schnering, H. G.
Angew. Chem. 1991, 103, 1197-1200; Angew. Chem., Int. Ed. Engl. 1991,
30, 1183-1186. (e) Jost, W.; Adam, M.; Enkelmann, V.; Mu¨llen, K. Angew.
Chem. 1992, 104, 883-884; Angew. Chem., Int. Ed. Engl. 1992, 31, 878-
879. (f) Bock, H.; Na¨ther, C.; Ruppert, K.; Havlas, Z. J. Am. Chem. Soc.
1992, 114, 6907-6908. (g) Bock, H.; Ruppert, K.; Herdtweck, E.;
Herrmann, W. A. HelV. Chim. Acta 1992, 75, 1816-1824.
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2001, 113, 3345-3347; Angew. Chem., Int. Ed. 2001, 40, 3245-3247.
(11) (a) Bladauski, D.; Dietrich, H.; Hecht, H. J.; Rewicki, D. Angew.
Chem. 1977, 89, 490-491; Angew. Chem., Int. Ed. Engl. 1977, 16, 474-
475. (b) Bladauski, D.; Rewicki, D. Chem. Ber. 1977, 110, 3920-3929.
(c) Barr, D.; Clegg, W.; Mulvey, R. E.; Snaith, R.; Wright, D. S. J. Chem.
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1430-1433.
The rate decrease caused by meta-trialkylsilyl is too large
to be attributed to an electronic interaction. Actually, the
average σm of -0.056 would require an unreasonably high
reaction constant F of +4.4 to support the hypothesis of a
simple inductive effect [log 0.60 ) 4.4(-0.05)]. Moreover,
this F value would have to grow to +9.4 and +17 when
meta-triethylsilyl and meta-triisopropylsilyl are considered,
respectively. On the other hand, how could one evoke a steric
effect if the silyl substituent occupies the meta position,
which is distant from the exocyclic reaction center? In our
opinion, the only plausible explanation has to be based on
(4) Schlosser, M.; Hartmann, J. Angew. Chem. 1973, 85, 544-545;
Angew. Chem., Int. Ed. Engl. 1973, 12, 508-509.
(5) Schlosser, M.; Marzi, E. Chem. Eur J., in press, published online
March 30, 2005.
(6) (a) Roberts, J. D.; McElhill, E. A.; Armstrong, R. J. Am. Chem. Soc.
1949, 71, 2923-2926. (b) Benkeser, R. A.; Krysiak, H. R. J. Am. Chem.
Soc. 1953, 75, 2421-2425. (c) Bassindale, A. R.; Taylor, P. G. In The
Chemistry of Organosilicon Compounds; Patai S.; Rappoport, Z., Eds.;
Wiley: Chichester, 1989; Part II, pp 893-963, spec. pp 893-903.
(12) (a) DeBoer, E. AdV. Organomet. Chem. 1964, 2, 115-155. (b)
Manceron, L.; Andrews, L. J. Am. Chem. Soc. 1988, 110, 3840-3846.
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Renken, B.; Andres, W.; Gu¨nther, H. Angew. Chem. 1988, 100, 1212-
1213; Angew. Chem., Int. Ed. Engl. 1988, 27, 1182-1183.
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Org. Lett., Vol. 7, No. 10, 2005

available. The solvation provided by ether- or amine-type
donors is strong enough to override any π-complex interac-
tion and favor the formation of coordinatively saturated
monomers or µ-bound dimers and tetramers. Thus, it
becomes intelligible why the butyllithium/PMDTA-mediated
metalation of toluenes does not mirror adverse meta-
trialkylsilyl effects.
trimethylsilyl and para-triethylsilyl group falls in the 0.6 kcal/
mol range (∆∆Gq -0.59 and -0.57 kcal/mol).
If an ortho-trialkylsilyl group stabilizes charge excess to
the same extent as a para-trialkylsilyl, we can evaluate the
steric hindrance affecting the metalation of trimethyl-2-
tolylsilane and triethyl-2-tolylsilane. The numbers obtained
by adding 0.59 and 0.57 kcal/mol (see the preceding
paragraph) to the experimental relative activation energies
(∆∆Gq +0.14 and +0.53 kcal/mol) are amazingly moderate
(0.73-1.1 kcal/mol). This may be attributed at least in part
to the extreme in-plane deformability of C-Si bonds.2f
A seminal review by G. W. Gokel et al.18 culminated in
the conclusion that “Future studies in molecular recognition
and supramolecular chemistry must include cation-π inter-
actions in the panoply of feeble forces. The consequences
of this interaction are potentially profound for biology.”
While fully endorsing this statement, we feel tempted to add
“... and for synthesis-oriented mechanistic investigations as
well.”
Although of unusual magnitude, the rate-enhancing effect
of para-trialkylsilyl is in perfect agreement with the electron-
withdrawing capacity of this substituent. It is irrelevant in
the present context whether the stabilization of electron
excess by adjacent second-row (or heavier) elements is
described by the arguably misleading concepts of d-orbital
resonance6,14 or hyperconjugation6,15 or by “polarization” (in
the sense of an nfσ* mixing). 1b Whatever the exact nature
of the phenomenon may be, it lowers the activation energy
for the LIC-KOR-promoted metalation of trimethyl-4-tolyl-
silane and triethyl-4-tolylsilane. If the potassium was placed
perfectly over the middle of the arene ring, the steric
hindrance exhibited by a meta- or para-trialkylsilyl group
should be identical. In this case, the electronic bonus
provided by a para-trimethylsilyl and para-triethylsilyl
substituent would represent the difference (∆∆Gq -0.69 and
-0.78 kcal/mol relative to the toluene parent compound)
between the compensated steric hindrance (∆∆Gq +0.20 and
+0.42 kcal/mol) and the experimentally observed net rate
enhancement of 3.5-fold and 2.5-fold (∆∆Gq -0.49 and
-0.36 kcal/mol). However, as testified by X-ray structures,
11e,f the metal may prefer to reside somewhat outside of the
arene center in order to minimize steric repulsion while still
maintaining an η6-coordination.16 We assume the potassium
to choose indeed such an asymmetric location at the transition
state 3, staying closer to the ipso and more distant from the
para carbon atom. Therefore, we believe that the steric
hindrance is diminished when the trimethylsilyl or triethyl-
silyl substituent is moved from the meta to the para position
(say, for the sake of argument, to one-half of the meta values:
∆∆Gq +0.10 and +0.21 kcal/mol). Thus, the lowering of
the metalation barrier due to the electronic effect of a para-
Acknowledgment. This work was supported by the
Schweizerische Nationalfonds zur Fo¨rderung der wissen-
schaftlichen Forschung, Bern (Grant 20-100’336-02).
Supporting Information Available: Experimental pro-
cedures and characterization data for silane-type starting
materials and products. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL0502580
(15) (a) Pitt, C. G. J. Organomet. Chem. 1973, 61, 49-70. (b) Traylor,
T. G.; Hanstein, W.; Berwin, H. J.; Clinton, N. A.; Brown, R. S. J. Am.
Chem. Soc. 1971, 93, 5715-5725.
(16) It is of course a matter of semantics whether the term η6-coordination
is still appropriate when the distances of the metal to the para and ipso
positions are not equal but differ slightly (by 5-20%11e,f). This will have
to be decided from case to case. For example, there are model structures
such as the KCl, RbCl, and CsCl complexes of uranyl-salophen “receptors”17
that keep the metal relatively remote from the benzyl ligand. As a
consequence, the mode of interaction is no longer η6- but rather η1- or
η2-like, thus marking the other extreme of the π-arene coordination
continuum.
(14) (a) Cason, L. F.; Brooks, H. G. J. Org. Chem. 1954, 19, 1278-
1282. (b) Peterson, D. J. J. Organomet. Chem. 1967, 8, 199-208. (c)
Peterson, D. J. J. Organomet. Chem. 1967, 9, 373-374. (d) Doering, W.
V. E.; Hoffmann, A. K. J. Am. Chem. Soc. 1955, 77, 521-526.
(17) Cametti, M.; Nissinen, M.; Dalla Cort, A.; Mandolini, L.; Rissanen,
K. J. Am. Chem. Soc. 2005, 127, 3831-3837.
(18) Gokel, G. W.; Barbour, L. J.; Ferdani, R.; Hu, J. Acc. Chem. Res.
2002, 35, 878-886.
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