A cationic Rh(III) complex that efficiently catalyzes hydrogen isotope exchange in hydrosilanes

Article abstract of DOI:10.1021/ja108521b

The synthesis and structural characterization of a mixed-sandwich (η⁵-C₅Me₅)Rh(III) complex of the cyclometalated phosphine PMeXyl₂ (Xyl = 2,6-C₆H ₃Me₂) with unusual κ⁴

Full text of DOI:10.1021/ja108521b

Published on Web 11/09/2010
A Cationic Rh(III) Complex That Efficiently Catalyzes Hydrogen Isotope
Exchange in Hydrosilanes
Jesu´s Campos,† Ana C. Esqueda,† Joaqu´ın Lo´pez-Serrano,† Luis Sa´nchez,† Fernando P. Cossio,‡
‡
†
†
,†
´
Abel de Cozar, Eleuterio Alvarez, Celia Maya, and Ernesto Carmona*
Departamento de Qu´ımica Inorga´nica-Instituto de InVestigaciones Qu´ımicas, UniVersidad de SeVilla-Consejo
Superior de InVestigaciones Cient´ıficas, AVda. Ame´rico Vespucio 49, Isla de la Cartuja, 41092 SeVilla, Spain, and
Kimika Organikoa I Saila, UniVersidad del Pa´ıs Vasco-Euskal Herriko Unibertsitatea (UPV-EHU), P. K. 1072,
20018 San Sebastia´n-Donostia, Spain
Received September 21, 2010; E-mail: guzman@us.es
Scheme 1
Abstract: The synthesis and structural characterization of a mixed-
sandwich (η5-C5Me5)Rh(III) complex of the cyclometalated phos-
phine PMeXyl2 (Xyl ) 2,6-C6H3Me2) with unusual κ4-P,C,C′,C′′
coordination (compound 1-BArf; BArf ) B(3,5-C6H3(CF3)2)4) are
reported. A reversible κ4 to κ2 change in the binding of the chelating
phosphine in cation 1+ induced by dihydrogen and hydrosilanes
triggers a highly efficient Si-H/Si-D (or Si-T) exchange applicable
to a wide range of hydrosilanes. Catalysis can be carried out in an
organic solvent solution or without solvent, with catalyst loadings
as low as 0.001 mol %, and the catalyst may be recycled a number
of times.
contains less than 50% of 1-Cl, the latter compound is best obtained
by chlorination (CH2Cl2 or CHCl3) of hydride 1-H (Scheme 2), which
in turn results from the stepwise reaction of [RhCl(C2H4)2]2 with
There is increased demand for isotopically labeled compounds
PMeXyl2 and Zn(C5Me5)216. Characterization by spectroscopy and
as internal standards for mass spectrometric studies, as well as for
X-ray studies has been achieved. A CH2Cl2 solution of 1-Cl reacts
other modern technologies that include agrochemical, biological,
with NaBArF (BArF ) B(3,5-C6H3(CF3)2)4) and acetonitrile (or other
and pharmaceutical investigations of the interaction of small
Lewis bases, L, like for example NH3, PMe3, or CO) with formation
molecules with receptors, enzymes, and other biomolecules.1
of the corresponding adducts (isolated as BArF salts), whereas, in the
Compounds labeled with both stable and radioactive isotopes are
absence of L, 1-BArF is the only isolable product. Consequently, for
critical to the drug development process and have become essential
poorly coordinating CH2Cl2 the equilibrium of Scheme 1 shifts to the
in many clinical studies.2,3
left and the unusual κ4-P,C,C′,C′′ structure prevails over CH2Cl2 adduct
Labeling organic molecules with deuterium (D) and tritium (T)
formation, which might be expected on the basis of previous
is a common, important practice for the pharmaceutical industry.4,5
reports14,15 for related cationic rhodium and iridium compounds.
Hydrosilanes, SiR4-nHn (n ) 1-3), provide one of the most
Moreover cations 1+ and 1-L+ feature characteristic 31P{1H} NMR
powerful tools in synthetic organic chemistry6 and are able to add
signals with chemical shifts δ of -14.7 and ca. 37-43 ppm,
catalytically to C-C, C-N, and C-O multiple bonds in the wide-
respectively. Hence, equilibria between 1+ and adducts 1-L+ can be
scope hydrosilylation reaction7-9 and to reduce, also catalytically,
readily ascertained by 31P{1H} NMR spectroscopy (for 1-L+ two
carbon-halogen bonds,10 including unreactive C-F bonds.11-13
a
Therefore, they are ideal reagents for D and T labeling procedures.
Herein we describe the synthesis and properties of the cationic
Rh(III) complex 1+ (Scheme 1) that catalyzes with high efficacy
hydrogen isotope exchange (H/D/T) in a wide range of hydrosilanes
(see eq 1 and Table 1 for selected H/D exchanges), employing D2
or T2 as the hydrogen isotope source.
Table 1. H/D Exchange in Hydrosilanes Catalyzed by 1-BArF
Cat.
(mol %) Solventb
Temp
(°C)
D
T (h) incorp. (%)
Entry
Silane
1
2
3
4
5
6
7
8
SiEt3H
SiEt3H
SiEt3H
SiPh3H
1
A
B
B
A
A
A
A
A
A
A
A
A
25
50
60
50
50
50
50
25
25
25
50
25
3
24
48
5
5
5
16
16
5
16
5
g99
g99
89
g99
g99
g99
98
80
g99
90
0.01
0.001
0.1
0.1
0.1
2
1
0.1
1
0.01 mol% 1-BArF
SiPh2H2
SiEt3H + D2
8 SiEt3D + HD
(1)
SiPhH3
Si(SiMe3)3Hd
SiiPr3Hd
9
PMHSe
In the search for analogues of the unusual iridium and rhodium
cations [(η5-C5Me5)M(Me)(PMe3)(ClCH2Cl)]+,14,15 we have focused
on rhodium precursor 1-Cl that contains a metalated PMeXyl2 ligand.
A preliminary report on the synthesis and reactivity of the iridium
analogue has appeared recently.16a Since the reaction between
[(η5-C5Me5)RhCl2]2 and PMeXyl2 gives a mixture of complexes that
10
11
12
1,2-C6H4(SiMe2H)2
SiEt2H2
Si(EtO)3H
0.1
1
g99
g99
5
a To ensure full deuteration three D2 loadings are routinely employed,
each consisting of cooling
0 °C/vacuum (0.1 bar)/0.5 bar of D2.
b Solvent: A, CD2Cl2 (0.6 mL); B, neat silane. c Determined by IR and
NMR (1H and 29Si) spectroscopy. d Catalyst decomposition occurs.
e Polymethylhydrosiloxane.
† Universidad de Sevilla-Consejo Superior de Investigaciones Cient´ıficas.
‡ Universidad del Pa´ıs Vasco-Euskal Herriko Unibertsitatea.
9
10.1021/ja108521b  2010 American Chemical Society
J. AM. CHEM. SOC. 2010, 132, 16765–16767 16765

C O M M U N I C A T I O N S
Scheme 2
diastereomers are commonly observed). Cation 1+ exhibits fluxional
behavior in solution, to be described in due course. It is, however,
appropriate mentioning at this stage that the solution dynamics of 1+
implies exchange of the roles of the metalated and nonmetalated xylyl
rings. Theoretical calculations support this degenerate exchange to
occur through agostic intermediate A (Figure 1), with an energy of
only 7.4 kcal ·mol-1 above 1+. Indeed, this rearrangement seems to
be crucial for the chemical reactivity to be described below.
Studying the reactivity of 1+ toward molecules like dihydrogen
and hydrosilanes that have only σ-bonded electrons18,19 was of
evident interest. At room temperature there is no observable reaction
between 1+ and either type of molecule. However, exposure of
solutions of 1+ to D2 yields 1(D11)+ almost instantly, due to fast
H/D exchange of all sp3-hybridized C-H bonds of the phosphine
xylyl units. Low-temperature (-90 °C) NMR monitoring of the
reaction of 1+ and H2 does not provide experimental evidence for
the formation of a σ-H2 complex but unveils the existence of a
cationic agostic hydride 1-H+ (1+:1-H+ ratio of ca. 85:15) that is
1
in equilibrium with 1+ (Scheme 3). Examination of its H NMR
spectrum shows a doublet of doublet resonance at -9.43 ppm due
to the hydride ligand (with spin-lattice relaxation time T1 ) 300
ms) that undergoes exchange with a signal with δ -0.02 ppm
attributed to the agostic methyl protons. A corresponding 31P{1H}
signal at 29.8 ppm can be observed in the range of -90 to -70 °C
but disappears above the latter temperature, although cooling at
-90 °C restores the original spectrum. Cation 1+ also undergoes
exchange with SiEt3D yielding 1(D11)+, but for this system neither
a σ-silane complex nor an agostic silyl related to 1-H+ can be
detected by NMR spectroscopy. Nevertheless, DFT calculations
reveal that both σ-H2 and σ-HSiEt3 complexes are key intermediates
in these reactions.
Figure 1. Agostic intermediate proposed for the exchange of the two xylyl
rings of the phosphine moiety.
Figure 2 compares the X-ray structures of 1+and 1-CO+. The
coordinated atoms of the metalated phosphine ligand of 1+, that is,
P(1), C(17), C(12), and C(11), form an essentially planar arrange-
ment which is nearly parallel to the C5Me5 ring plane (dihedral
angle 7.3°). Accordingly, the Rh-C distances to C(11), 2.135(5)
Å; C(12), 2.200(5) Å; and C(17), 2.254(4) Å are clearly bonding,
while for 1-CO+ only the Rh-C (11) distance of 2.124(2) Å is
bonding. In this compound the Rh-C(12) and Rh-C(17) separa-
tions are 3.112 and 3.290 Å, respectively. Despite the simplicity
of the metalated ligand in 1+, the mixed-sandwich structure of the
cation is unique. AIM analysis of its DFT-optimized structure shows
the expected (3, -1) Bond Critical Points (BCPs) between Rh-P(1)
and Rh-C(11). Furthermore, a third BCP17 has been located
between Rh and C(17), but not between Rh and C(12), in spite of
the short experimental (2.200(5) Å) and calculated (2.245 Å)
distances found for this linkage. Instead, two (3, +1) ring critical
pointshavebeenfoundroughlyatthecentroidsoftheRh-P(1)-C(17)
and Rh-C(17)-C(12) triangles.
Scheme 3
The H/D exchange between 1+ and D2 or SiEt3D suggests that
a catalytic synthesis of deuterated silanes can be developed (eq 1).
This is an important target as it can lead to labeling procedures
that are alternative to current practices.20,21 Although catalytic
Si-H/Si-D exchange is known,22-25 present information is scarce
and to our knowledge an efficient catalytic process for the synthesis
of labeled hydrosilanes, SiR4-nDn (n ) 1-3), has not yet been
developed. Table 1 presents a summary of the Si-H/Si-D
exchanges catalyzed by 1-BArF that have been investigated.
Deuteration of hydrosilanes may be carried out in CH2Cl2
solution or in the neat silane, using D2 (0.5 bar) as the source of
deuterium, at room temperature or above (40-60 °C), and with
catalyst loadings between 1 and 0.001 mol %. Deuteration is equally
effective for secondary and tertiary silanes (entries 5, 6, and 11).
Polymethylhydrosiloxane (PMHS, entry 9), an inexpensive, non-
toxic, and environmentally benign reagent,26 becomes deuterated
under similar conditions. As revealed by NMR studies, compound
Figure 2. X-ray molecular structures of 1-SbF6 and [1-CO]BArF, with H
atoms and anions omitted for clarity.
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C O M M U N I C A T I O N S
1-BArF is recovered unaltered after the catalytic runs (see entries
7 and 8 in Table 1 for exceptions). Furthermore, the catalyst can
be recycled at least eight times (tested for deuteration of SiEt3H)
without loss of efficacy. These and other data that include the Hg
test are indicative of a homogeneous process. Since compound
1-BArF is also an efficient catalyst for hydrosilylation of
carbon-oxygen and carbon-nitrogen multiple bonds, direct one-
flask addition of a Si-D bond to these functionalities (for some
examples, see eq 2 and Supporting Information) can be achieved.
be carried out in an organic solvent solution or in a solvent-free
manner, and the catalyst may be recycled a number of times. The
catalyst is also effective for hydrosilylation of C-O and C-N
multiple bonds and permits D or T incorporation into a wide class
of organic molecules employing one-flask procedures. All these
properties make the new method an environmentally benign,
technically robust, short, and atom-efficient technology for incor-
poration of deuterium and tritium into organic molecules.
Acknowledgment. Financial support (FEDER support) from the
Spanish Ministerio de Educacio´n (Project No. CTQ2007-62814),
Consolider-Ingenio 2010 (No. CSD2007-0000), and the Junta de
Andalucia (Projects Nos.FQM-119 and P09-FQM-4832) is grate-
fully acknowledged. J.C. thanks the Ministerio de Educacio´n for a
research grant (Ref. AP20080256), and A.C.E. thanks CONACYT
(Mexico) for a research grant (Ref. No. 22934).
C6H5C(O)CH3 + SiEt3H +
1 mol% 1-BArF
D2
8 C6H5C(D)(OSiEt3)CH3 + HD (2)
25 °C, 6 h
Tritiated silanes are convenient tritiation reagents,5 but their
synthesis requires treatment of the corresponding chlorosilanes with
LiT or complex metal hydrides.27 Catalyst 1+ allows facile tritium
incorporation into hydrosilanes and overcomes many of the
disadvantages of commonly used tritiation methods.28 A catalytic
procedure similar to that described for deuterium exchanges may
be utilized. However to avoid frequent use of tritium gas, which is
a dangerous and difficult substance to manipulate,28 complex 1+
may be used as a tritium carrier for low specific activity tritium
labeling. Thus, exposure of CH2Cl2 solutions of 1+ (200 mg; 148
µmol) to 1 Ci (18 µmol) of T2 permits T-incorporation (g85%)
into the CH2 and CH3(xylyl) sites of the catalyst to yield 1(Tn)+,
which can be stored safely. Then, heating for example 1 mg (0.74
µmol, 4.5 mCi) of the tritiated rhodium complex with an excess of
SiEt3H (1.2 mL, 7.5 mmol; 50 °C, 5 days) permits T transfer to
the silane that can be separated from the catalyst by trap-to-trap
distillation; the resulting tritiated silane features a specific activity
of 0.5 mCi/mmol.
Competition experiments with different silanes show that SiEt3H,
SiPh3H, and Si(OEt)3H undergo deuteration with comparable rates.
However, Si-H/Si-D exchange for SiEt3H is ca. 500 times faster
than that for SiiPr3H or Si(SiMe3)3H. The rate of incorporation of
D into phenyl silanes qualitatively follows the order SiPhH3 >
SiPh2H2 > SiPh3H. It thus seems that steric effects may be
responsible for the observed differences.
Mechanistic studies on the Si-H/Si-D exchange are underway
and will be reported in due course. The exchange may require the
operation of eqs 3 and 4 that have been demonstrated experimen-
tally. In accord with theoretical calculations these reactions imply,
as already mentioned, participation of reactive σ-H2 and σ-silane
complex intermediates.18,19,29 In view of the lability of the agostic
interaction in 1-H+, it is also plausible that a σ-silane complex may
result from coordination of the silane to 1-H+. However present
data indicate that such species is kinetically unstable toward
dissociation into 1-H+ and silane. Regardless of the precise
mechanism, our catalytic Si-H/Si-D exchange constitutes a new
example of metal-ligand cooperation30 that implies reversible
Rh-C bond cleavage and formation by action of dihydrogen and
hydrosilanes.
Supporting Information Available: Experimental methods; syn-
thesis and structural characterization of new compounds; X-ray structure
analysis of complexes 1+, 1-CO+, and 1-NCMe+; catalytic Si-H/D/T
exchanges procedures; and computational details are included in the
Supporting Information. This material is available free of charge via
the Internet at http://pubs.acs.org.
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1+ + D2 h 1-(D11)+ + HD
(3)
(4)
1-(D11)+ + SiR3H h 1-(D10)+ + SiR3D
In conclusion, a very productive catalytic procedure for hydrogen
isotope exchange in hydrosilanes has been developed. Catalysis can
JA108521B
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J. AM. CHEM. SOC. VOL. 132, NO. 47, 2010 16767