Regiocontrol of cyclometalation in a P4Ru(II) system. Unusual base-induced metalation within a chelate ring versus activation of a methyl group

Article abstract of DOI:10.1021/om0202470

The internally cyclometalated complex (MeSi-(CH₂PMe₂)₂CHPMe₂(PMe₃ )RuH has been prepared by the treatment of MeSi(CH₂PMe₂)₃PMe₃Ru(H)(Cl) with base, and an analogue has been structurally characterized by X-ray diffraction. The externally cyclometalated isomer MeSi(CH₂PMe₂)₃PMe₂CH₂RuH has been cleanly generated by the thermolysis of MeSi(CH₂PMe₂)₃PMe₃Ru(H)(Me), and the two isomers have been contrasted in terms of their spectroscopic features, calculated energies, and relative reactivities toward cresol and H₂. The two isomers are surprisingly resistant to interconversion. A chloride derivative, (MeSi(CH₂PMe₂)₂CHPMe₂)(PMe₃ )RuCl, has also been prepared, and its reactivity has shown the internally cyclometalated framework to be surprisingly stable.

Full text of DOI:10.1021/om0202470

© Copyright 2002
Volume 21, Number 11, May 27, 2002
American Chemical Society
Communications
Regiocon tr ol of Cyclom eta la tion in a P 4Ru (II) System .
Un u su a l Ba se-In d u ced Meta la tion w ith in a Ch ela te Rin g
ver su s Activa tion of a Meth yl Gr ou p
Andrew W. Holland and Robert G. Bergman*
Department of Chemistry and Center for New Directions in Organic Synthesis,
University of California, Berkeley, California 94720
Received April 1, 2002
Summary: The internally cyclometalated complex (MeSi-
(CH2PMe2)2CHPMe2)(PMe3)RuH has been prepared by
the treatment of MeSi(CH2PMe2)3PMe3Ru(H)(Cl) with
base, and an analogue has been structurally character-
ized by X-ray diffraction. The externally cyclometalated
isomer MeSi(CH2PMe2)3PMe2CH2RuH has been cleanly
generated by the thermolysis of MeSi(CH2PMe2)3PMe3-
Ru(H)(Me), and the two isomers have been contrasted
in terms of their spectroscopic features, calculated ener-
gies, and relative reactivities toward cresol and H2. The
two isomers are surprisingly resistant to interconversion.
A chloride derivative, (MeSi(CH2PMe2)2CHPMe2)(PMe3)-
RuCl, has also been prepared, and its reactivity has
shown the internally cyclometalated framework to be
surprisingly stable.
ration of various targets including catalysts,9-12 optical
materials,13 and biological agents.14 Cyclometalation
reactions may be triggered by a variety of events,
including ligand dissociation or elimination, group
abstraction, and deprotonation,1,2 but in the vast major-
ity of reported systems these reactions are complemen-
tary processes: they convert structurally similar start-
ing materials to a common product. Herein we report
evidence that this need not be the case and describe a
system in which thermolysis and deprotonation of
similar precursors yield two different cyclometalation
isomers. Despite the fact that one of them has a novel,
unusually strained structure, we find that it is es-
sentially impossible to interconvert them.
Cyclometalation reactions are ubiquitous in the chem-
istry of reactive transition metal centers1,2 and can
function either as obstacles to the development of
catalytic processes3,4 or as key components within
them.5-8 Intramolecular activation of precoordinated
groups can also be employed synthetically in the prepa-
(6) Murai, S.; Chatani, N.; Kakiuchi, F. Bull. Chem. Soc. J pn. 1997,
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(1) Collman, J . P.; Hegedus, L. S.; Norton, J . R.; Finke, R. G.
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(3) Hill, C., Ed. Activation and Functionalization of Alkanes; J ohn
Wiley and Sons: New York, 1989.
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Selective Hydrocarbon Activation; VCH Publishers: Toldeo, OH, 1989.
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Sonoda, M.; Chatani, N. Nature 1993, 366, 529.
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Ruano, J . L.; Raithby, P. R.; Masaguer, J . R.; Alonso, C. J . Med. Chem.
1993, 36, 3795.
10.1021/om0202470 CCC: $22.00 © 2002 American Chemical Society
Publication on Web 05/03/2002

2150 Organometallics, Vol. 21, No. 11, 2002
Communications
Sch em e 1
In the course of efforts to synthesize ruthenium
alkoxide and amide complexes bearing a variety of
phosphine ligands,15 we have prepared compounds of
the general type (MeSi(CH2PMe2)3)(PMe3)Ru(H)(X) (X-
) Cl-, NH3BPh4-) and found that they undergo cyclo-
metalation upon addition of strong base (Scheme 1).
Treatment of the dichloride complex 1 with LiBEt3H
yields the corresponding hydridochloride complex 2 in
36% isolated yield. Alternatively, the dihydride complex
3 can be prepared in 91% yield by treating 1 with
LiAlH4, and addition of 1 equiv of NH4BPh4 to 3
provides ammonia complex 4 in 83% yield.16 Treatment
of either 4 or chloride 2 with strong base (KOtBu or KN-
(SiMe3)2) does not result in attack on the PMe3 or NH3
protons. Instead, the internally cyclometalated complex
5 is formed in >70% isolated yield. No other cyclo-
metalation products are observed in these reactions. The
1H NMR spectrum of 5 is characterized by a broad
singlet at δ -0.96 ppm integrating to one proton
(relative to the three-proton Si-Me resonance at δ 0.48
ppm and the Ru-H signal at δ -8.63 ppm) and
corresponding to the remaining hydrogen on the ruthe-
nium-bound carbon. The 13C NMR spectrum also fea-
tures a characteristic upfield resonance at δ -15.0 ppm
associated with the corresponding methine carbon.
The solid-state structure of product 5 was confirmed
by an X-ray diffraction study of the tBu analogue (Figure
1). The molecule possesses a strongly distorted octahe-
dral geometry (P1-Ru1-P2 ) 129.25(6)°, P1-Ru1-P4
) 120.25(7)°, P4-Ru1-C1 ) 163.4(2)°), but its Ru-P
bonds are not substantially elongated relative to those
of other complexes bearing the intact ligand set.17 While
the Ru-C bond is long (2.282(6) Å; 2.18(1) Å was
observed for a Ru-C bond in a related complex17), the
Ru-P bond involved in cyclometalation is rather short
(2.243(2) Å) and the bonds from the activated carbon to
silicon and phosphorus (1.822(6) and 1.766(6) Å, respec-
F igu r e 1. ORTEP diagram of 5-tBu (thermal ellipsoids
are shown at 50% probability). Hydrogen atoms have been
omitted for clarity. Selected bond distances (Å) and angles
(deg): Ru1-P1, 2.243(2); Ru1-P2, 2.279(2); Ru1-P3,
2.326(2); Ru1-P4, 2.258(2); Ru1-C1, 2.282(2); P1-C1,
1.766(6), P1-C8, 1.822(7); P2-C2, 1.838(6); Si1-C1, 1.822-
(6), Si1-C3, 1.880(7); P1-Ru1-P2, 129.25(6); P1-Ru-P3,
93.16(6); P1-Ru-P4, 120.25(7); P2-Ru-P3, 93.66(6); P2-
Ru1-P4, 107.93(6); P3-Ru1-P4, 99.69(7); P1-Ru1-C1,
45.9(1); P1-C1-Si1, 130.8(3).
tively) are 0.05 Å shorter than CH2-Si and CH2-P
bonds elsewhere in the molecule. This suggests that
delocalization may significantly relieve strain and sta-
bilize the molecule.
While the synthetic route to complex 5 is well prece-
dented, its actual structure is less so. Deprotonation is
an established method of inducing the cyclometalation
of aryl groups,18 and similar reactions involving methyl-
substituted phosphines have also been observed.19-22
There are, however, very few examples of cyclometala-
tion within the chelate ring of an alkyl multidentate
phosphine ligand. Even activation of any secondary
C-H bond is relatively rare: Field has observed cyclo-
metalation involving a methylene unit of an ethyl
substituent in the (DEPE)2Fe system,23,24 although in
a similar n-propyl-substituted system no methylene
positions are activated.25 In a related system with an
expanded six-membered chelate ring investigated by
Karsch, the occurrence of internal cyclometalation was
proposed, but the regiochemistry of cyclometalation
could not be definitively established.26 Deprotonation of
(18) Cardenas, D. J .; Mateo, C.; Echevarren, A. M. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 2445.
(19) Karsch, H. H.; Klein, H.-F.; Kreiter, C. G.; Schmidbaur, H.
Chem. Ber. 1974, 107, 3692.
(20) Al-J ibori, S.; Crocker, C.; McDonald, W. S.; Shaw, B. L. Chem.
Soc., Dalton Trans. 1981.
(21) Mainz, V. V.; Andersen, R. A. Organometallics 1984, 3, 675.
(22) Bryndza, H. E.; Fong, L. K.; Paciello, R. C.; Tam, W.; Bercaw,
J . E. J . Am. Chem. Soc. 1987, 109, 1444.
(23) Baker, M. V.; Field, L. D. Organometallics 1986, 5, 821.
(24) Baker, M. V.; Field, L. D. J . Organomet. Chem. 1988, 354, 351.
(25) Baker, M. V.; Field, L. D. Aust. J . Chem. 1999, 52, 1005.
(26) Karsch, H. H. Chem. Ber. 1984, 117, 3123.
(15) Fulton, J . R.; Holland, A. W.; Fox, D. J .; Bergman, R. G. Acc.
Chem. Res. 2002, 35, 44.
(16) Ammonia complexes in a related system have been prepared
similarly: Rappert, T.; Yamamoto, A. Organometallics 1994, 13, 4984.
(17) McNeill, K.; Andersen, R. A.; Bergman, R. G. J . Am. Chem.
Soc. 1997, 119, 11244.

Communications
Organometallics, Vol. 21, No. 11, 2002 2151
Sch em e 2
Sch em e 3
methylene-bridged bis-phosphines is well known, and
Karsch has observed cyclometalation within a six-
membered chelate ring at a methylene group activated
by two adjacent phosphorus atoms.27 As silicon is known
to enhance the acidity of adjacent C-H bonds, and base-
induced cyclometalation of Si-Me groups is known,28
it seems likely that the presence of silicon plays a key
role in activating precursors 2 and 4 toward deproto-
nation-induced cyclometalation at the methylene posi-
tion.
from complex 5. A competition experiment showed that
cresol reacts much more rapidly with externally cyclo-
metalated complex 7 than with 5. Both species also
undergo addition of H2 to yield the dihydride 3 (Scheme
2), although in this case the reaction is dramatically
slower for externally cyclometalated complex 7 than for
isomer 5.
Perhaps the most striking aspect of the chemistry of
the two cyclometalated complexes 5 and 7 is that we
have been unable to induce their interconversion by any
means. Treatment of either isomer with a catalytic
amount of acid, base, buffer, silane, arene, or hydrogen
yields no reaction or irreversible conversion to new
products, as does the thermolysis or photolysis of either
complex. Interconversion via a Ru(0) intermediate
would be unlikely in this system due to the inacces-
sibility of a square-planar coordination geometry32
(without dechelation), but it is not evident why isomer-
ization through a Ru(IV) complex or Ru(II) cation does
not occur.
To better understand the unusual regiochemistry of
cyclometalation that yields complex 5, we sought to
effect cyclometalation in the (MeSi(CH2PMe2)3)(PMe3)-
Ru system in the absence of base. Chloride 2 reacts with
MeMgCl to afford the methyl hydride 6, and thermolysis
of this compound at 100 °C for 10 h induces elimination
of methane to generate exclusively the externally cy-
clometalated isomer 7. This complex has been reported
previously,29,30 but a brief discussion of its characteriza-
tion is warranted for the purpose of comparison to
1
isomer 5. The H NMR spectrum of complex 7 features
two broad signals at δ 0.30 and -0.47 ppm, correspond-
ing to the diastereotopic protons of the ruthenium-bound
methylene, and eight phosphorus-bound methyl signals
(δ 1.7-1.1 ppm, eight doublets integrating to 3H each)
indicating that the PMe3 ligand (rather than another
PMe group) has been activated. Both the 31P and 13C
NMR spectra include upfield peaks consistent with
cyclometalation at a methyl group, and all of these
spectroscopic features are similar to those observed for
the known analogue (PMe3)3(PMe2CH2)RuH.31
The isomeric nature of products 5 and 7 presents an
opportunity to contrast the two modes of cyclometalation
represented. The deprotonation product 5 appears much
more strained, and DFT calculations (BP86/LACVP**)
suggest that it is less stable than 7 by approximately 7
kcal/mol. The two isomers can also be compared in terms
of their reactivity. Both complexes react with cresol to
yield cresolate complex 8 (Scheme 2). When TolOD is
used in this reaction, D incorporation is observed in the
PMe3 group (δ 1.23 ppm) of the product formed from 7
and in both the methylene and hydride positions (δ 0.35
and -6.71 ppm, respectively) of the product 8 derived
To further explore the stability of the cyclometalated
framework in 5, we prepared the chloride analogue 9
via the reaction of dichloride 1 with KN(SiMe3)2 (Scheme
1). The crystalline yellow product was isolated in 84%
yield from pentane. This complex reacts with dihydro-
gen (Scheme 1), affording hydridochloride complex 2 in
1
95% yield by H NMR spectroscopy. The chloride 9 can
be treated with LiBEt3H to yield the hydride analogue
5 or with MeMgCl to afford the methyl analogue 10
(Scheme 3). Perhaps most surprisingly, treatment of 9
with MeOTf does not result in addition across the
presumably highly polarized Ru-C bond, but rather
anion metathesis to yield ruthenium triflate 11 and
MeCl. This further demonstrates the remarkable kinetic
stability of the internally cyclometalated complex.
In summary, we have observed that deprotonation of
ruthenium complexes bearing tripod MeSi(CH2PMe2)3
and a suitable leaving group yields an unusual cyclo-
metalation product bound to ruthenium through a
bridging methine rather than a methylene group. In
contrast, thermolysis of the corresponding methyl hy-
dride yields exclusively the more conventionally cyclo-
metalated isomer. Although the internal deprotonation
product appears strained (and is indeed calculated to
be less thermodynamically stable), it is not always more
reactive than its isomer and even features a Ru-C bond
that is stable to substitution chemistry elsewhere in the
(27) Karsch, H. H.; Neugebauer, D. Angew. Chem., Int. Ed. Engl.
1982, 21, 312.
(28) Karsch, H. H.; Grauvogl, G.; Kawecki, M.; Bissinger, P. Orga-
nometallics 1993, 12, 2757.
(29) Dahlenburg, L.; Kerstan, S.; Werner, D. J . Organomet. Chem.
1991, 411, 457.
(30) In the above reference complex 7 was prepared by Na/Hg
reduction of the dichloride, but we have found that this procedure also
yields a significant amount of complex 5.
(32) According to DFT calculations, the Ru(0) intermediate resulting
from reductive elimination of either cyclometalation product 5 or 7
would be 34 kcal/mol less stable than isomer 5.
(31) Grotzig, J .; Werner, H.; Werner, R. J . Organomet. Chem. 1981,
209, c60.

2152 Organometallics, Vol. 21, No. 11, 2002
Communications
molecule. Most significantly, the two cyclometalated
complexes resist interconversion when subjected to heat,
light, and a variety of reagents. These results demon-
strate that in contrast to the general observation that
all routes to cyclometalation in a given system lead to
the same product, the specific route by which intramo-
lecular M-C bond formation occurs can play a critical
role in determining the structure, and thus subsequent
reactivity, of a cyclometalated product.
Hollander and Dr. Allen Oliver of the UC Berkeley
CHEXRAY facility for performing the X-ray structure
determination, Dr. Benjamin King and Dr. Bernd
Straub for providing indispensable assistance with DFT
calculations, and Dr. Kristopher McNeill for performing
some preliminary experimental work.
Su p p or tin g In for m a tion Ava ila ble: Complete details for
the synthesis of all compounds, spectroscopic data, and X-ray
crystallographic data for 5-tBu . This material is available free
of charge via the Internet at http://pubs.acs.org.
Ack n ow led gm en t. This work was supported by
NSF Grant No. CHE-0094349. We thank Dr. Fred
OM0202470