High oxidation state organocobalt complexes: Synthesis and characterization of dihydridodisilyl cobalt(V) species

Article abstract of DOI:10.1002/(SICI)1521-3773(20000502)39:9<1676::AID-ANIE1676>3.0.CO;2-M

Surprising stability toward reductive elimination of diphenylsilane is exhibited by [(C₅Me₅)Co(SiHPh₂)₂(H)₂] (1), which is a rare example of an organocobalt complex in the +5 oxidation state. This stability likely also accounts for its inactivity as a hydrosilylation catalyst.

Full text of DOI:10.1002/(SICI)1521-3773(20000502)39:9<1676::AID-ANIE1676>3.0.CO;2-M

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[16] Back-dissociation of the hydrogen-bonded adducts opens the way for
the competing nucleophilic substitutions mentioned in reference [13],
involving reattack of N(CH3)3 at the carbon centers of the freed onium
ion. Thus, only a fraction of the back-dissociating hydrogen-bonded
adducts collapse again to another hydrogen-bonded adduct.
[17] Interaction of (CH3)3N with the ring hydrogen atoms of II generates
an initial distribution of [IVat] ꢀ [IVst] which is not far from that
corresponding to the thermodynamic equilibrium ([IVat]eq ꢀ [IVst]eq).
Thus, the slight positive temperature dependence of the 4E:4Z ratios
from 2 reflects the effect of temperature on the ring-opening processes
and on the limited IVst $ IVat interconversion. In contrast, inter-
action of (CH3)3N with the ring hydrogen atoms of the Is/Ia pair
generates the corresponding adducts in an initial distribution of [IVac]
and [IVsc] which is far away from the equilibrium distribution
([IVsc]eq > [IVac]eq). In this case, the steeper positive temperature
dependence of the 4E:4Z ratios from 1 is much more sensitive to the
effect of temperature on the IVac !IVsc conversion, which efficiently
competes with the ring-opening reactions.
[18] M. J. Frish, G. W. Trucks, H. B. Schlegel, P. M. W. Gill, B. G. Johnson,
M. A. Robb, J. R. Cheeseman, T. A. Keith, G. A. Petersson, J. A.
Montgomery, K. Raghavachari, M. A. Al-Laham, V. G. Zakrzewski,
J. V. Ortiz, J. B. Foresman, J. Cioslowski, B. B. Stefanov, A. Nanayak-
kara, M. Challacombe, C. Y. Peng, P. Y. Ayala, W. Chen, M. W. Wong,
J. L. Andres, E. S. Repogle, R. Gomperts, R. L. Martin, D. J. Fox, J. S.
Binkley, D. J. Defrees, J. Baker, J. P. Stewart, M. Head-Gordon, C.
Gonzales, J. A. Pople, Gaussian 94, Revision E. 2, Gaussian, Inc.,
Pittsburg, PA, 1995.
state intermediates, as opposed to the traditionally formulated
redox pairs.[1±4] Some of the most thoroughly investigated
examples in this class are the high oxidation state neutral
iridium(v) and rhodium(v) complexes studied initially by
Maitlis et al. such as [(C5Me5)IrMe4],[5] [(C5Me5)Ir(H)2-
(SiR3)2], and [(C5Me5)Rh(H)2(SiR3)2][6±10] and the IrV complex
‡
cation [(C5Me5)IrMe3L] reported later by Bergman and
Aliamo.[11] Higher oxidation states of first-row metals have
been discussed as reactive intermediates, but isolated exam-
ples are rare.[12] We showed that cationic cobalt(iii) alkyl
‡
complexes [(C5Me5){P(OMe)3}CoR] are olefin hydrosilyla-
tion catalysts and must proceed through the CoV intermediate
‡
[(C5Me5){P(OMe)3}Co(R)(H)(SiR3)] or the CoIII intermedi-
2
‡
[13, 14]
À
ate [(C5Me5){P(OMe)3}Co(R)(h -H SiR3)] .
Here we
report the synthesis and X-ray crystallographic character-
ization of a bis-hydrido bis-silyl cobalt(v) complex.
For cobalt-mediated bond-activation reactions we have
used olefin complexes of the type [(C5Me5)Co(olefin)2] (1) as
catalysts,[13, 15±17] which provides a source of [(C5Me5)Co]
through olefin dissociation.[18] Heating a solution of 1a in
C6D6 (olefin ˆ C2H4) with 5 equiv of Ph2SiH2 (15 min, 708C)
led to a rapid disappearance of starting material and, along
with the appearance of ethylene and Ph2(Et)SiH, the for-
mation of two products 2a and 3 in approximately 1:1 molar
[19] a) A. D. Becke, J. Chem. Phys. 1993, 98, 1372, 5648; b) C. Lee, W.
Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785.
[20] C. Gonzales, H. B. Schlegel, J. Phys. Chem. 1990, 94, 5523.
1
ratio, as determined by H NMR spectroscopy [Eq. (1)].[19]
Equivalent hydrido ligands and silyl methylene protons
support a trans configuration of 2a, while a single set of 13C
phenyl signals indicates a trans configuration for 3.
High Oxidation State Organocobalt
Complexes: Synthesis and Characterization of
Dihydridodisilyl Cobalt(v) Species**
Heating 1a with an excess of Ph2SiH2 (5 ± 10 equiv) in
toluene at 858C for 60 min and removal of volatiles resulted in
quantitative formation of 3. Extraction with pentane and
crystallization at À258C produces white crystals that are
stable to air in the solid state and can be stored indefinitely at
208C in an argon atmosphere. In the temperature range of
À8 0 to 708C no reactivity or dynamic behavior of 3 was
observed by NMR spectroscopy. No exchange or magnet-
Maurice Brookhart,* Brian E. Grant,
Christian P. Lenges, Marc H. Prosenc, and
Peter S. White
Recently there has been considerable interest in the
organometallic chemistry of late transition metals in high
oxidation states. Second- and third-row metals in particular
were stabilized in high oxidation states by using organic ligand
environments. Certain catalytic reactions mediated by these
late metals were proposed to occur through high oxidation
À
À
ization transfer between the Co H and the Si H groups was
observed on the NMR timescale, and silicon satellites for the
À
Co H signals were absent. On the basis of this spectroscopic
evidence, the new cobalt silyl hydrido complexes are formu-
lated as rare examples of organocobalt(v) species which
contribute to a now complete series of silyl hydride complexes
of the type [(C5Me5)M(SiR3)2(H)2] (M ˆ Co, Rh, Ir).[6±10]
[*] Prof. M. Brookhart, Dr. B. E. Grant, Dipl.-Chem. C. P. Lenges,
Dr. M. H. Prosenc, Dr. P. S. White
Department of Chemistry, Venable and Kenan Laboratories
University of North Carolina at Chapel Hill
Chapel Hill, NC 27599-3290 (USA)
À
The activation of the Si H bond is facile in this process, as is
suggested by the reactivity of the more labile cobalt(i)
precursor [(C5Me5)Co(C2H3SiMe3)2] (1b). The reaction of
1b with Ph2SiH2 (15 equiv) in C6D6 at 308C for 10 h gave a
reaction mixture consisting of [(C5Me5)Co(SiPh2C2H4Si-
Me3)(SiPh2H)(H)2] (2b) (70%) and a minor amount of 3.
Heating this reaction mixture at 808C for 2 h resulted in
quantitative formation of 3. The reaction of Ph2SiH2 with
Fax : (‡1)919-962-2476
E-mail: mbrookhart@unc.edu
[**] We thank the National Institutes of Health (Grant GM 28938) for
financial support. C.P.L. thanks the Fonds der Chemischen Industrie,
Â
Germany, for a Kekule fellowship. Allocation of computing time by
the North Carolina Supercomputing Center is gratefully acknowl-
edged.
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C2H3SiMe3 in the presence of a catalytic amount of 1b
(5 mol%, 508C, 24 h) resulted in only 15% conversion to the
hydrosilylation product Ph2Si(H)CH2CH2SiMe3. During this
process, 1b is converted to 3. This indicates that these new
cobalt(v) silyl hydrides are not active at 508C in the catalytic
hydrosilylation of olefins.[20]
Scheme 1 outlines two possible routes for the formation of 3
from 1a, b. Since intermediates 2a,b are precursors to 3, the
mechanism must incorporate hydrosilylation of one of the
olefin ligands of 1a,b. Formation of 5a,b by oxidative
addition of silane to 4a,b is certainly the first step. Silyl
(path a; Scheme 1) or hydride (path b) migration may occur
to produce 6a,b or 7a,b, respectively, which can both be
converted to 9a,b. Path b for 5b is consistent with the
previously observed regiochemistry of insertion of vinyl-
trimethylsilane into a cobalt ± hydrogen bond,[21, 22a] which
could be followed by a-elimination and subsequent alkyl ±
silylene coupling to form 9a,b.[22b] Alternatively, it is reason-
able to suggest that the bulky SiPh2H group might migrate to
Cb (path a; Scheme 1). Conversion of 7a,b to 9a,b may occur
via formation of the metallacycle 8a,b. Oxidative addition of
Figure 1. ORTEP diagram of complex 3 (50% probability ellipsoids).
À
À
Selected bond lengths [Š] and angles [8]: Co Si1 2.2492(21), Co Si2
À
À
À
À
2.2536(19), Si1 C11 1.894(6), Si1 C21 1.922(7), Si2 C31 1.885(7), Si2 C41
1.895(6); Si1-Co-Si2 107.21(8), Co-Si1-C11 117.58(21), Co-Si1-C21
116.58(21), Co-Si2-C31 119.76(21), Co-Si2-C41 117.04(20).
[24]
À
The Co Si distances
are slightly shorter than
those of related CoIII silyl complexes (2.28± 2.30 Š) as
expected for the smaller ionic radius of cobalt in the
higher oxidation state.[25, 26] The Si1-Co-Si2 angle in 3
of 107.28 is slightly smaller than the corresponding
angle of the rhodium complex, and this could be
attributed to the larger nonbonding repulsions in the
ligands around the smaller Co center. Especially
interesting in 3 is the arrangement of the SiPh2H
group around the cobalt center. To reduce steric
crowding, one of the phenyl groups on each Si atom is
oriented parallel to the C5Me5 ligand. The other two
phenyl groups are roughly perpendicular (1058) to the
C5Me5 ring and parallel to each other with a distance
of 3.7 Š between the best planes of the six carbon
atoms of each ring. The C-Si-Co angles of 117 ± 1208
are significantly larger than 109.58; we suppose that
this also contributes to reduction of nonbonding
repulsions around the Co center. Similar large C-Si-
Co angles (114 ± 1208) were also found in the calcu-
lated structure (see below) in which intermolecular
interactions were not taken into account.
Scheme 1. Proposed mechanism for formation of 3 from 1a,b.
Table 1. Comparison of selected interatomic distances [Š] and bond
angles [8] in [(C5Me5)M(H)2(SiR3)2] (M ˆ Rh, Ir and SiR3 ˆ SiEt3; M ˆ
Co, SiR3 ˆ SiPh2H).
Ph2SiH2 to 9a,b results in 2a,b.[23] Reductive elimination of
Ph2Si(C2H4R)(H) from 2a,b followed by oxidative addition of
Ph2SiH2 produces 3.
Ir
Rh
Co[a]
Co[b]
To support the spectroscopic and chemical evidence for
these cobalt(v) complexes, single crystals of 3 were subjected
to X-ray structural analysis. The unit cell contains four
independent molecules, one of which is shown in Figure 1.
The X-ray structure verifies the proposed structure for 3. The
hydrido ligands attached to the cobalt center and the H atoms
bound to silicon atoms could not be located in the difference
Fourier map. Key structural parameters of 3 are listed in
Table 1 and compared to those of related Rh and Ir
complexes.
À
M Si
2.390(1)
2.379(2)
2.256 ± 2.261
2.243 ± 2.247
2.29
2.28
1.49
1.90
100
109
2.24
À
M H
1.581(1)
1.901(2)
99.50(2)
109.49(6)
2.272(2)
2.384(2)
2.433(4)
1.594(1)
1.900(1)
94.84(2)
107.90(8)
2.212(2)
2.336(2)
2.328(4)
À
Si C
1.880 ± 1.922
H1-M-H2
Si1-M-Si2
H1 ´´´ Si1
H2 ´´´ Si1
H1 ´´´ H2
107.2
2.25
2.28
[a] Averaged for the four molecules in the unit cell. [b] Data are based on
DFT calculations (see text).
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mentary publication no. CCDC-136182. Copies of the data can be obtained
free of charge on application to CCDC, 12 Union Road, Cambridge
CB21EZ, UK (fax: (‡44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
To further investigate structural details of complex 3,
density functional theory (DFT) calculations were conduct-
ed[27±30], as were successfully employed for related organo-
metallic complexes.[31±34] Some geometrical parameters ob-
tained after geometry optimization are listed in Table 1. The
main structural features of the calculated geometry of 3 and
Received: November 5, 1999 [Z14238]
[1] Pd-catalyzed Heck reactions were recently explained by invoking PdIV
intermediates; see for example: M. Ohff, A. Ohff, M. E. van der
Boom, D. Milstein, J. Am. Chem. Soc. 1997, 119, 1168 7.
[2] Shilov-type alkane oxidation involves Pt(iv) intermediates: J. E.
Bercaw, J. A. Labinger, S. Stahl, Angew. Chem. 1998, 110, 2298;
Angew. Chem. Int. Ed. 1998, 37, 2180.
[3] Hydrosilylation of olefins was explained by invoking RhV intermedi-
ates: R. N. Perutz, S. B. Duckett, Organometallics 1992, 11, 90.
[4] The dehydrogenative coupling of arenes and silanes is catalyzed by the
RhV complex [C5Me5Rh(H)2(SiEt3)2]: K. Ezbiansky, P. I. Djurovich,
M. LaForest, D. J. Sinning, R. Zayes, D. H. Berry, Organometallics
1998, 11, 1455.
[5] P. M. Maitlis, N. Dudeney, O. N. Kirchner, J. C. Green, J. Chem. Soc.
Dalton Trans. 1984, 1877.
[6] T. F. Koetzle, J. S. Ricci, P. M. Maitlis, M.-J. Fernandez, J. Organomet.
Chem. 1986, 299, 383.
[7] P. M. Maitlis, C. M. Spencer, B. E. Mann, J. Ruiz, P. O. Bentz, J. Chem.
Soc. Chem. Commun. 1985, 1985.
À
the X-ray structure of 3 are in good agreement. The Co Si
À
bond lengths in the calculated structure (Co Si 2.29 Š) are
À
slightly longer than those observed experimentally (Co Si
2.26 Š). The pseudo-square-pyramidal structure of the ML5
complex is clearly evident from the calculation. The calcu-
À
À
lated H H distance for complex 3 of 2.28Š and the H Si
distances of 2.24 and 2.25 Š indicate the complete oxidative
addition of the two Ph2SiH2 molecules to the cobalt center.[35]
We compared the CoV species 3 with other high oxidation
state silyl hydrido complexes. Interestingly, the rare iron(iv)
complex 10 also has a trans configuration around the Fe
center.[36] Complex 11, an Ru analogue of 3, was recently
reported[37] and also structurally characterized.
[8] P. M. Maitlis, M.-J. Fernandez, Organometallics 1983, 2, 164.
[9] P. M. Maitlis, M.-J. Fernandez, J. Chem. Soc. Chem. Commun. 1982,
1982.
[10] P. M. Maitlis, B. F. Taylor, C. M. Spencer, B. E. Mann, J. Ruiz, J. Chem.
Soc. Dalton Trans. 1987, 1963.
[11] P. J. Aliamo, R. G. Bergman, Organometallics 1999, 18, 2707.
[12] Rare CoIV and CoV tetrakis(1-norbornyl) complexes have been
isolated: a) B. K. Bower, H. G. Tennent, J. Am. Chem. Soc. 1972, 94,
2512; b) E. K. Byrne, D. S. Richeson, K. H. Theopold, J. Chem. Soc.
Chem. Commun. 1986, 1491; c) E. K. Byrne, K. H. Theopold, J. Am.
Chem. Soc. 1987, 109, 1282.
In summary, we have prepared and structurally character-
ized rare examples of organometallic Co complexes in the
formal oxidation state ‡5. Our DFT calculations fully support
the assigned structure and oxidation state of these cobalt
complexes. These species are remarkably stable towards
reductive elimination, and this is consistent with the well-
established ability of silyl and hydrido ligands to stabilize
metals in high oxidation states.
[13] M. Brookhart, B. E. Grant, J. Am. Chem. Soc. 1993, 115, 2151.
[14] Bergman et al. discussed a similar mechanistic controversy in C H
activation reactions mediated by cationic Ir complexes: P. Burger,
R. G. Bergman, J. Am. Chem. Soc. 1993, 115, 10462; see also ref. [11].
[15] C. P. Lenges, P. S. White, M. Brookhart, J. Am. Chem. Soc. 1998, 120,
6965.
À
[16] C. P. Lenges, P. S. White, M. Brookhart, Angew. Chem. 1999, 111, 535;
Angew. Chem. Int. Ed. 1999, 38, 552.
[17] C. P. Lenges, B. E. Grant, M. Brookhart, J. Organomet. Chem. 1997,
528, 199.
[18] J. L. Spencer, R. G. Beevor, S. A. Frith, J. Organomet. Chem. 1981,
Experimental Section
All operations were carried out under an Ar atmosphere. All solvents were
degassed and purified by standard methods.
221, C25.
1
À
[19] H NMR (300 MHz, [D6]benzene, 208C) of 2a: d ˆ 5.92 (s, 2H, Si H),
À
1.41 (s, 15H, C5Me5), À16.0 (s, 2H, Co H), and triplet and quartet
3: Ten equivalents of diphenylsilane were added to a solution of 1a (0.15 g,
O.6 mmol) in toluene (5 mL). The mixture was stirred for 1 h at 808C. After
cooling to 208C and removal of all volatile materials, the resulting solids
were dissolved in pentane and filtered. The clear, pale yellow solution was
cooled to À788C for 24 h; white crystalline material was obtained (72%
yield). Crystals for the X-ray structure analysis were obtained from pentane
at À258C.
signals diagnostic of a (silyl)ethyl group. For 3, see Experimental
Section.
[20] Interestingly 1b is an active catalyst for the hydrosilylation of
aromatic ketones with HSiEt3; however, hydrosilylation with Ph2SiH2
is not observed, and complex 3 is generated instead. Complex 3 is not
significantly active in catalytic hydrosilylation of aromatic ketones.
[21] The expected CoIII olefin silyl hydrido complex was not observed, and
this is in clear contrast to the analogous rhodium(iii) complex
[(C5Me5)Rh(C2H4)(H)(SiEt3)] prepared by Maitlis et al.[8, 22, 23]. With
HSi(OEt)3 as substrate; however, this type of intermediate was
Spectroscopic data for 3: 1H NMR (300 MHz, [D6]benzene, 208C) d ˆ 1.53
À
(s, 15H, C5Me5), 5.92 (s, 2H, Si H), 7.15 (m, 12H, Ph), 7.71 (m, 8H, Ph)
À15.51 (s, 2H, Co H); 13C{1H} NMR: d ˆ 95.46 (C5Me5), 9.65 (C5Me5),
À
140.90, 136.40, 135.88, 134.99 (Ar); elemental analysis: calcd: H 6.99, C
72.57; found: H 7.11, C 72.32.
observed in
unpublished results.
a reaction with 1b: C. P. Lenges, M. Brookhart,
Structural data for 3: crystals from pentane; C34H39Si2Co, Mr ˆ 562.76;
monoclinic, space group Cc; Z ˆ 16; a ˆ 60.673(3), b ˆ 10.0978(5), c ˆ
[22] a) Catalytic H/D exchange reactions of 1b in [D6]benzene result in
selective deuteration of the a-position of vinyltrimethylsilane; see
ref. [16]; b) the formation of silylenes by a-elimination from silyl
hydrides has been discussed, and examples of this reactive species
have recently been isolated: G. P. Mitchell, T. D. Tilley, Angew. Chem.
1998, 110, 2602; Angew. Chem. Int. Ed. 1998, 37, 2524.
20.8573(10) Š, b ˆ 109.264(1)8, Vˆ 12063.1(10) Š3; 1calcd ˆ 1.235 gcmÀ1
;
Tˆ À1108C; 2qmax ˆ 508; MoKa radiation (l ˆ 0.71073 Š), 50673 reflec-
tions were measured; 21315 unique reflections were obtained, and 14248of
these with I > 3.0s(I) were used in the refinement; data were collected on a
Siemens SMART diffractometer by the W scan method. For significant
reflections, the merging R value was 0.052; residuals: RF ˆ 0.046, Rw ˆ 0.054
(significant reflections); GOF 1.42. Crystallographic data (excluding
structure factors) for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as supple-
[23] The formation of the Rh silyl hydrido analogues follows a similar
mechanism[5±10]. Si H bond activation occurs after dissociation of
À
DMSO from [(C5Me5)RhMe2(dmso)] to generate
a rhodium(v)
intermediate: M. Gomez, J. M. Kisenyi, G. J. Sunley, P. M. Maitlis, J.
Organomet. Chem. 1985, 296, 197.
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[24] The geometries of the four independent molecules of 3 in the unit cell
Under this impulse, new tools for SPS were rapidly
developed, for example, new generations of robots and
synthesizers, resins, linkers, reactions, and building blocks.
However, most of the chemistry performed derives from
solution and peptide synthetic studies and do not make full
benefit of the use of the solid-support technique. In particular,
the most frequently used linkers were designed for peptide-
like synthesis. Substrates are therefore linked to the solid
support through either an ester, amide, or ether bond. Thus,
the cleaved products contain an acid, amide, or hydroxyl
residue, respectively, at the former linkage site (Scheme 1,
path A).[2]
À
show very similar values for the Co Si distances. However, small
À
À
deviations between 2.25 Š (Co Si1) and 2.26 Š (Co Si2) are
observed within each molecule in the unit cell.
[25] The steric effect of the more bulky SiEt3 group in the Rh complex
À
elongates the Rh Si bond distance increasing the expected difference
À
À
between Rh Si and Co Si (see Table 1).
[26] J. Y. Corey, J. Braddock-Wilking, Chem. Rev. 1999, 99, 175.
[27] For calculations of energies and gradients we used the hybrid nonlocal
density functional according to Becke and Lee, Yang, and Parr
(B3LYP). For all calculations the program Gaussian94 was used with
the fine integration grid option. For geometry optimization a gradient
convergence criterion of 0.1E À 6 was used. For C, H, and Si we used
the 6-31G* split-valence basis set supplied by the program. For Co we
used an effective core potential basis set according to Hay and Wadt
with double zeta quality in the valence region.
[28] C. Lee, W. Yang, R. G. Parr, Phys. Rev. Sect. B 1988, 37, 785.
[29] P. J. Hay, W. R. Wadt, J. Chem. Phys. 1985, 82, 299.
[30] Gaussian 94, Revision E.2, Gaussian, Inc., Carnegie Office Park,
Building 6, Pittsburgh, PA 15106, USA, 1995.
[31] M. R. Bloomberg, P. E. M. Siegbahn, M. Svensson, J. Chem. Phys.
1996, 104, 9546.
[32] P. E. M. Siegbahn, J. Am. Chem. Soc. 1996, 118, 1487.
[33] R. Poli, K. M. Smith, Eur. J. Inorg. Chem. 1999, 877.
[34] M.-D. Su, S.-Y. Chu, Chem. Eur. J. 1999, 5, 198.
[35] Orbital population analysis revealed that the main bonding contribu-
tion between the metal atom and the hydrido and silyl ligands arises
from their s bonds. A very small p backbonding from a metal dxz
orbital into a Si px orbital (about 2% of the s bond) also contributes to
À
the Co Si bond. Some contribution to the stability of the complex
appears to arise from the overlap population of Si and the hydrido
ligands of 0.1 electrons.
Scheme 1. Anchoring ± cleavage strategies used in SPS.
[36] K. J. Klabunde, Z. Yao, A. C. Hupton, Inorg. Chim. Acta 1997, 259,
119.
[37] P. I. Djurovich, P. J. Carroll, D. H. Berry, Organometallics 1994, 13,
To avoid a residual functionality on the cleaved product,
traceless cleavage strategies were developed (Scheme 1
path B).[3] These strategies result in the formation of a
carbon ± hygrogen or heteroatom ± hydrogen bond and often
rely on cyclization/cleavage or ipso-aromatic-substitution
reactions.[4]
Recently developed synthetic procedures for SPS have
allowed the introduction of diversity concomitantly with the
release of the target compound (Scheme 1, path C).[5] These
advantageous double transformations are generally achieved
through nucleophilic cleavage. The resin is thus used both as a
protecting group during all preliminary SPS steps, and as a
leaving group during the cleavage. These two properties,
stability during SPS and reactivity towards cleavage, are
somewhat antinomic. The linkages so far reported for such
functionalizing cleavage suffer from an enhanced reactivity
that forbids the use of many reaction conditions during the
SPS sequence.
To overcome this drawback a tether that is stable during
SPS steps but becomes reactive after selective activation is
used (Scheme 1, path D). An example of such a strategy is the
safety-catch linker of Kenner et al.,[6] which is unreactive
towards nucleophiles as such, but becomes electrophilic upon
activation with diazomethane. Other linkers such as the REM
or hydrazide linkers were recently developed based on the
same principle.[7] Although they allow efficient cleavage, they
are highly specific and can not be used generally.
To the best of our knowledge, no strategy so far reported for
the safety-catch linkers enables concomitant formation of a
carbon ± carbon bond and functionalization within the cleav-
age step. During the course of our study on the SPS of
2551.
Traceless, Solid-Phase Synthesis of
Biarylmethane Structures through
Pd-Catalyzed Release of Supported
Benzylsulfonium Salts**
Â
Â
Cecile Vanier, Franz Lorge, Alain Wagner,* and
Charles Mioskowski*
Solid-phase synthesis (SPS) has attracted much attention
from the scientific community during the past decade,
particularly by pharmaceutical companies in their race to
speed up drug discovery. Solid-phase chemistry evolved from
peptide chemistry and gradually became a field on its own in
chemistry.[1] Multi-step processes were automated in a pep-
tide-like fashion, and gave birth to the so-called high-
throughput synthesis (HTS).
Â
[*] A. Wagner, C. Mioskowski, C. Vanier, F. Lorge
Á
Laboratoire de Synthese Bio-organique
Â
Universite Louis Pasteur de Strasbourg
Â
Â
UMR 7514 associee au CNRS, Faculte de Pharmacie
74, route du Rhin - B. P. 24, 67401 Illkirch cedex (France)
Fax : (‡33)3-88-67-88-91
E-mail: Wagner@bioorga.u-strasbg.fr,
Mioskowski@bioorga.u-strasbg.fr
Ã
Ã
[**] We thank Rhone Poulenc Rorer and Rhone Poulenc Agro for
financial support.
Angew. Chem. Int. Ed. 2000, 39, No. 9
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