Tetravalent tellurium ligands

Article abstract of DOI:10.1002/(SICI)1521-3773(19990215)38:4<512::AID-ANIE512>3.0.CO;2-R

Oxidative addition of TeCl₄ to Vaska's complex gave the trichlorotelluronium complex [IrCl₂-(TeCl₃)(CO)(PPh₃)₂] (structure depicted), which contains a rare example of a structurally characterized tetravalent tellurium ligand. The coordination at the Te(IV) center is - in full agreement with the VSEPR model - distorted trigonal bipyramidal.

Full text of DOI:10.1002/(SICI)1521-3773(19990215)38:4<512::AID-ANIE512>3.0.CO;2-R

COMMUNICATIONS
[16] It is interesting to note that a doubling of the signals in both the 1H and
13C spectra was observed in the NMR spectra of the diphosphate
compounds. This result was found to be concentration and substrate
dependent, and is thought to reflect slow rotation about the vinyl-
ogous carbamate bonds. The doubling of signals was especially
prevalent in the farnesyl derivative 2, and was observed, although to a
less degree (ca. 10 ± 15%), in the intermediates that lead up to the
farnesyl diphosphate derivative (5b and 6b). The doubling of the
NMR signals however, was not observed for the geranyl intermediates
(5a and 6a).
sulfines, sulfur diimides, and iminooxosulfuranes,[4] however
such compounds based on tellurium are either transient or
ˆ
oligomeric in nature. Complexes of the SF3 and Se( O)Cl
ligands have been previously reported from the oxidative
[5]
ˆ
addition of SF4 or O SeCl2 to [IrCl(CO)(PEt3)2] or [IrCl-
(CO)(PPh3)2],[6] respectively. A Lewis base adduct of TeCl4
with the pentacarbonyl manganate anion has also been
described very recently.[5b] Herein we report the first mono-
nuclear transition metal complexes ligated by the tetravalent
trichlorotelluronium group. These result from the reactions of
[17] K. Alexandrov, E. Rostkova, A. J. Scheidig, R. S. Goody, D. Owen, H.
Waldmann, unpublished results.
[18] Standard prenylation assay: 50 ml of the assay contained: 120 pmol
Rab 7, 120 pmol REP-1, 120 pmol RabGGTase, and 2.4 nmol of either
1 or 2. Buffer: 20mm Hepes pH 7.2, 20mm NaCl, 5mm 2-sulfanyl-
ethanol (BME), 1mm NP-40. The mixture was incubated at 378C for
20 minutes and the reaction stopped by diluting the samples with cold
H2O and precipitating the protein with 10% trichloroacetic acid. The
protein pellet was washed with cold acetone and re-suspended in SDS-
PAGE loading buffer. Proteins were resolved on the 15% SDS-PAGE
gel and the prenylated proteins were visualized with a Fluor 100
(BioRad) fluorescence scanner.
[19] I. Simon, M. Zerial, R. S. Goody, J. Biol. Chem. 1996, 271, 20470.
[20] F. Shen, M. C. Seabra, J. Biol. Chem. 1996, 271, 3692.
[21] For the expression and purification of REP-1, see K. Alexandrov, I.
Simon, A. Iakovenko, B. Holz, R. S. Goody, A. Scheidig FEBS Lett.
1998, 425, 460. RabGGTase baculoviral expression vectors pVL-
RabGGTalpha and pVL-RabGGTbeta were obtained from the
American Type Culture Collection (order numbers 87154 and 87155,
respectively). Baculoviruses were generated and RabGGTase was
expressed and purified as described previously: F. P. Cremers, S. A.
Armstrong, M. C. Seabra, M. C. Brown, J. L. Goldstein J. Biol. Chem.
1994, 269, 2111.
ˆ
[IrCl(CO)(PPh3)2] or [Ru(CH CH2)Cl(CA)(PPh3)2] (A ˆ O,
S) with tellurium tetrachloride.
We encountered the first trichlorotelluronium ligand in the
product of the reaction of [Ru(CH CH2)Cl(CO)(PPh3)2][7] with
ˆ
TeCl4. In addition to polyvinylchloride, a bright yellow complex
formulated as [Ru(TeCl3)Cl(CO)(PPh3)2] (1) is obtained in
37% yield after recrystallization (Scheme 1). If the prepara-
tion is carried out at room temperature a 1:1 mixture of cis/
trans-bis(phosphane) isomers results; however, at 508C the
trans-bis(phosphane) arrangement is formed exclusively. The
ˆ
same reaction with [Ru(CH CH2)Cl(CS)(PPh3)2] however
provides only the isomer of [RuCl(TeCl3)(CS)(PPh3)2] (2)
with trans-coordinated phosphanes. It is noteworthy that
whilst the TeCl3 ligand in 1 rotates freely at room temperature
(singlet 31P resonance), an apparently static structure is
adopted for 2 (31PA31PB system, trans-2J(AB) ˆ 335 Hz). This
is consistent with the enhancement of a (presumably weak) p-
dative component to the Te ± Ru interaction to the more p-
acidic but isosteric ruthenium center in 2. The subsequent
chemistry of complexes 1 and 2 has so far proven disappoint-
ing in that all attempts to introduce phosphanes, isocyanides,
or even CO(!) as a sixth ligand (and thereby coordinative
saturation) at ruthenium resulted in deposition of elemental
tellurium. Similar deposition of tellurium occurs on treatment
with amines or alcohols.
Tetravalent Tellurium Ligands
Paul J. Dyson, Anthony F. Hill,* Alexander G. Hulkes,
Andrew J. P. White, and David J. Williams
The comparatively sparse chemistry of tellurium-donor
ligands typically involves the chalcogen being formally in the
divalent state, that is, telluroethers and tellurolates. In recent
times, a substantial group of compounds involving ªnakedº
(i.e., substituent-free) tellurium has emerged,[1] heralded by
the unsurpassed elegance of the complex [Te{Mn(CO)2(h-
C5H5)}3] discovered by Herberhold et. al.[2] Clearly, oxidation
states are however of limited use in describing such com-
pounds. Well-defined ligands based on dative tellurium in
higher oxidation states are however unknown, although
Whitmire and Eveland have recently reported the Zintl
cluster [Fe2(CO)6(h2:m2,m2-Te4)(m-TeCl2)], wherein the
ªTeCl2º bridge might be described as based on either di- or
tetravalent tellurium.[3] Tetravalent sulfur ligands are of
course well known in the form of sulfoxides, sulfur dioxide,
Scheme 1. Reagents and conditions (258C unless otherwise indicated, L ˆ
PPh3): a) [Ru(CO)2L3], C6H6; b) [IrCl(CO)L2], THF; c) CO, CH2Cl2;
ˆ
ˆ
d) [Ru(CH CH2)Cl(CO)(PPh3)2], C6H6, 508C; e) [Ru(CH CH2)Cl(CO)-
ˆ
(PPh3)2], C6H6; f) [Ru(CH CH2)Cl(CS)(PPh3)2], C6H6; g) CDCl3, seven
[*] Dr. A. F. Hill, Dr. P. J. Dyson, A. G. Hulkes, Dr. A. J. P. White,
Prof. D. J. Williams
days.
Department of Chemistry
This apparent lack of synthetic utility, coupled with our
failure to obtain crystallographic grade crystals of 1 or 2, led
us to explore alternative examples of this ligand. As noted
above, the complexes [IrCl(CO)(PR3)2] (R ˆ Et, Ph) oxida-
Imperial College of Science, Technology and Medicine
South Kensington, London SW7 2AY (UK)
Fax: (‡44)171-5945804
E-mail: a.hill@ic.ac.uk
512
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1433-7851/99/3804-0512 $ 17.50+.50/0
Angew. Chem. Int. Ed. 1999, 38, No. 4

COMMUNICATIONS
tively add tetravalent halides of sulfur and selenium. Accord-
ingly the reaction of Vaskaꢁs complex with TeCl4 was
investigated: one major product [IrCl2(TeCl3)(CO)(PPh3)2]
(3) can be isolated (52%), in addition to small amounts of
[IrCl3(CO)(PPh3)2] and [IrHCl2(CO)(PPh3)2]. The formula-
tion of the orange compound follows from spectroscopic data
(see Experimental Section) and was confirmed by a crystallo-
graphic study (Figure 1).[8] The geometry at the iridium center
(CO)2(PPh3)2] is obtained, whilst in THF the all-trans isomer
is obtained. It seems reasonable that these reactions fail to
provide trichlorotelluronium complexes because in each case
one or more ligands can be liberated, which, as shown in the
case of 1, are capable of reducing the intermediate tetravalent
tellurium species. This problem is clearly obviated in the case
of 3.
Experimental Section
ˆ
trans-1: [Ru(CH CH2)Cl(CO)(PPh3)2] (0.25 g, 0.35 mmol) was added to a
solution of TeCl4 (0.10 g, 0.37 mmol) in benzene (35 mL) which was held at
508C. The resulting yellow solution was stirred for 15 min, filtered,
concentrated to 10 mL, and the crude product isolated by precipitation
with diethyl ether (30 mL). The precipitate was recrystallised three times
from a mixture of dichloromethane and diethyl ether. Yield 0.12 g(37%).
1
1
IR (CH2Cl2): nÄ ˆ 1972 cm (CO); (Nujol): nÄ ˆ1972 (CO), 333, 302 cm
(TeCl/RuCl); 31P NMR (CDCl3, 258C): d ˆ 27.4; FAB-MS: m/z: 1411
‡
‡
‡
[Ru2Cl3(CO)2(PPh3)4] , 1185 [M‡PPh3] , 717 [M TeCl3‡CO] , 689
‡
[M TeCl3] ; m.p. 174 ± 1768C(decomp); elemental analysis calcd for
C37H30Cl4OP2RuTe (%): C 48.1, H 3.3%; found: C 48.5, H 3.3.
cis-1 (spectroscopically observed when the above procedure was carried
1
out at room temperature) IR Nujol: nÄ ˆ 1961 [nÄ(CO)] cm
;
31P NMR
(CDCl3, 258C): d ˆ 30.4, 45.9 (AB, J(AB) ˆ 19.7 Hz). The cis isomer
converts to the trans isomer slowly on standing in solution.
Figure 1. Molecular Structure of 3. Phenyl groups simplified for clarity.
3: [IrCl(CO)(PPh3)2] (0.20 g, 0.26 mmol) in THF (15 mL) was treated with
TeCl4 (0.070g, 0.26 mmol). The resulting orange/yellow solution was stirred
for 25 min and then diluted with diethyl ether (20 cm3). The filtered
solution was then further diluted with hexane (10 mL) and then concen-
trated under reduced pressure to provide yellow crystals of the bis(thf)
is essentially octahedral with cis interligand angles in the
range 82.5(5) ± 100.70(8)8. The geometry of the ªIrCl2(CO)-
(PPh3)2º unit is generally unremarkable other than to note
that the two cis Ir± Cl bond lengths (Ir± Cl(1) 2.414(3), Ir±
Cl(2) 2.372(3) Š) reflect a lesser trans influence for the
carbonyl than the trichlorotelluronium ligand (14s). The
ligand of interest is the ªTeCl3º group and it is reassuring that
the geometry at tellurium is entirely as expected based on
VSEPR considerations. Thus a virtual trigonal bipyramid is
apparent with the two bulkiest substituents (iridium and a
lone pair of electrons) occupying equatorial sites; the two
ªaxialº chlorides (Te ± Cl(4) 2.609(6), Te ± Cl(5) 2.429(6) Š)[9]
are folded away from the iridium center (Cl(4)-Te-Cl(5)
163.1(2)8). The ªequatorialº Te ± Cl(3) bond length at
2.322(4) Š is substantially shorter than those to the axial
chlorides. The plane containing Ir, P(1), P(2), and Te is steeply
inclined (738) to that defined by Ir, Te, Cl(4), and Cl(5). If any
substantial p-component contributed to the Ir± Te interac-
tion, a value of 0 or 908 might be expected. The iridium ±
tellurium bond length of 2.656(1) Š is significantly longer
(41s) than that found in the only other structurally charac-
terized mononuclear complex containing an Ir± Te bond,
[Ir(Te-2,4,6-tBu3C6H2)(CO)(PPh3)2] (2.615(1) Š).[10]
Although the TeCl3 ligand is unprecedented in transition
metal chemistry, the structural features of 3 are entirely as
expected. This begs the question of generality for the
synthetic approach. Preliminary studies do not however bode
well. In the other low-valent systems so far investigated, TeCl4
serves ultimately as a mild chlorinating agent rather than
simply as an electrophile: [Fe(CO)5] and [Fe(CO)3(PPh3)2]
react with TeCl4 to cleanly provide (albeit conveniently)
[FeCl2(CO)4] and cis,cis,trans-[FeCl2(CO)2(PPh3)2]. The quan-
titative reaction of [Ru(CO)2(PPh3)3] with TeCl4 is solvent
dependent: in benzene, the product cis,cis,trans-[RuCl2-
1
solvate. Yield 0.16 g (52%). IR (Nujol): nÄ ˆ 2090 (CO), 345, 297, 271 cm
(TeCl/IrCl); 31P NMR (CDCl3, 258C): d ˆ 20.5; FAB-MS (3-nitrobenzyl
‡
‡
alcohol (nba) matrix): m/z: 1246 [M‡2nba 3HCl] , 815 [M TeCl3] ,
‡
‡
787 [M PPh3] , 780 [M TeCl4] , 752 [M PPh3 HCl] ‡ , 715 [M
‡
PPh3 2HCl] ; elemental analysis calcd for C37H30Cl5IrOP2Te ´ 2C4H8O
(%): C 45.3, H 3.88; found: C 45.70, H 4.00. The complex was also
characterised crystallographically.[8]
Received: July 22, 1998
Revised version: November 12, 1998 [Z12194IE]
German version: Angew. Chem. 1999, 111, 573 ± 575
Keywords: iridium ´ oxidative addition ´ tellurium
[1] a) K. H. Whitmire, Adv. Organomet. Chem. 1998, 42, 1; b) P. Mathur,
Adv. Organomet. Chem. 1997, 41, 243; c) W. A. Herrmann, Angew.
Chem. 1986, 98, 57; Angew. Chem. Int. Ed. Engl. 1986, 25, 56.
[2] M. Herberhold, D. Reiner, D. Neuge, Angew. Chem. 1983, 95, 46;
Angew. Chem. Int. Ed. Engl. 1983, 22, 59; Angew. Chem. Suppl. 1983,
10.
[3] J. R. Eveland, K. H. Whitmire, Angew. Chem. 1996, 95, 736; Angew.
Chem. Int. Ed. Engl. 1996, 35, 741.
[4] A. F. Hill, Adv. Organomet. Chem. 1994, 36, 159.
[5] a) R. W. Cockman, E. A. V. Ebsworth, J. H. Holloway, J. Am. Chem.
Soc. 1987, 109, 2194. A preliminary report has suggested on the basis of
19F and 31P NMR data that the reaction of [RhCl(CO)(PEt3)2] with
TeF4 provides [RhCl(TeF3)(CO)(PEt3)2][TeF5]: E. A. V. Ebsworth,
J. H. Holloway, P. G. Watson, J. Chem. Soc. Chem. Commun. 1991,
1443; b) W. F. Liaw, S. J. Chiou, G. H. Lee, S. M. Peng, Inorg. Chem.
1998, 37, 1131.
[6] J. Cartwright, A. F. Hill, Polyhedron 1995, 15, 157.
[7] J. C. Cannadine, A. F. Hill, A. J. P. White, D. J. Williams, J. D. E. T.
Wilton-Ely, Organometallics 1996, 15, 5409.
[8] Crystal data for 3: C37H30Cl5IrOP2Te ´ C4H8O, Mr ˆ 1121.7, triclinic,
Å
space group P1 (no. 2), a ˆ 12.345(1), b ˆ 12.820(1), c ˆ 15.147(2) Š,
a ˆ 95.62(1) b ˆ 96.18(1), g ˆ 99.76(1)8 Vˆ 2332.1(4) Š3, Z ˆ 2,
1calcd ˆ 1.60 gcm 3, m(CuKa) ˆ 139 cm 1, F(000) ˆ 1088. A yellow prism
Angew. Chem. Int. Ed. 1999, 38, No. 4
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1433-7851/99/3804-0513 $ 17.50+.50/0
513

COMMUNICATIONS
of dimensions 0.28 Â 0.13 Â 0.07 mm was used.
A total of 6403
independent reflections were measured on a Siemens P4/PC diffrac-
tometer with graphite-monochromated CuKa radiation using w scans.
The structure was solved by the heavy atom (Patterson) method and
all the major occupancy non-hydrogen atoms were refined anisotropi-
cally with absorption corrected (lamina [100]) data using full-matrix
least-squares based on F 2 to give R1 ˆ 0.071, wR2 ˆ 0.190 for 5193
independent observed reflections (jFo j> 4s(jFo j ), 2q ꢀ 1208) and 443
parameters. Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publica-
tion no. CCDC-102341. 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).
4-heterocyclohexanone carbonyl group with the active-site
cysteine nucleophile of the enzyme with reversible formation
of a hemithioacetal adduct.[5] In our current studies we are
interested in developing catalysts of amide hydrolysis, and we
reasoned that the amide substrates 5 ± 7 could be anchored
reversibly to a 4-heterocyclohexanone catalyst to form similar
hemithioacetal adducts. Hydrolysis of the amide could then
occur through a series of reactions that mimic the mechanism
used by serine proteases to catalyze hydrolysis of peptides, as
discussed below. These reactions serve as a model for
hydrolysis of peptides specifically on the C-terminal side of
cysteine residues.
[9] An examination of contacts does not reveal any obvious reason for
this difference in bond lengths. There is however an intermolecular
contact between Cl(5) and its symmetry-related counterpart (3.51 Š).
[10] P. J. Bonasia, J. Arnold, J. Organomet. Chem. 1993, 449, 147; Ir± Te
bond lengths in the range 2.626(1) ± 2.643(1) Š are observed in the
cubane [Ir4(m-Te)4(h-C5Me5)4]: S. Schulz, M. Andruh, T. Pape, T.
Heinze, H. W. Roesky, L. Häming, A. Kuhn, R. Herbst-Irmer,
Organometallics, 1994, 13, 4004.
We have monitored the hydrolysis of 5 ± 7 catalyzed by
1
4-heterocyclohexanones by H or 19F NMR spectroscopy, or
reverse-phase HPLC.[6] The reactions were performed under
pseudo-first-order conditions, and they showed an exponen-
tial decrease in the substrate concentration as a function of
time. Table 1 shows the observed rate constants for several
Hydrolysis of Amides Catalyzed by
4-Heterocyclohexanones: Small Molecule
Mimics of Serine Proteases**
Mousumi Ghosh, Jeffrey L. Conroy, and
Christopher T. Seto*
Table 1. Observed rate constants for hydrolysis of amides catalyzed by
4-heterocyclohexanones.[a]
1
[b]
Entry
Catalyst
Substrate
kobs [s
]
krel
One of the long-standing problems in bioorganic chemistry
is the design of catalysts that hydrolyze amide bonds under
mild conditions.[1, 2] Amides are stable species; the half-life for
peptide hydrolysis under neutral conditions at 258C has been
estimated to be seven years.[3] However, nature has been able
to develop four different classes of proteases that are capable
of sequence-specific hydrolysis of peptides with tremendous
rate accelerations. Therefore, the design of artificial catalysts
that begin to approach the activity and specificity of protein-
based catalysts is a fascinating and challenging problem. Here
we report that the cyclohexanone 1 and the 4-heterocyclo-
hexanones 2 ± 4 are efficient catalysts for the base-promoted
hydrolysis of amides.
8
8
8
8
4
4
8
4
8
7
1
2
3
4
5
6
7
8
9
none
1
5
5
5
5
5
6
6
7
7
8
1.5 Â 10
2.5 Â 10
5.9 Â 10
3.7 Â 10
2.2 Â 10
1.5 Â 10
1.5 Â 10
1.2 Â 10
3.1 Â 10
1.0 Â 10
2
4
2
2
3[c]
4
14700
10000
4
none
4
none
4[c]
3900
10
[a] All reactions were performed at 258C with 20mm substrate, 200mm
NaOD, and 600mm catalyst (where present) D2O/CD3OD (4/1) unless
otherwise specified. [b] Rate constant relative to the background reaction
(no catalyst) with the same substrate. [c] Reaction was performed in D2O/
CD3OD (1/1) because of low solubility of the catalyst or substrate in
aqueous solution.
We have shown previously that 4-heterocyclohexanones
can be used to synthesize inhibitors of cysteine proteases.[4]
These compounds inhibit the protease by reaction of the
reactions with a variety of substrates and catalysts. The most
efficient catalysis that we have measured is shown in entry 5.
In this reaction the hydrolysis of 5 is accelerated by more than
four orders of magnitude relative to the background reaction
when it is carried out in the presence of 600 mm tetrahydro-
pyranone (THP, 4).
[*] Prof. Dr. C. T. Seto, M. Ghosh, J. L. Conroy
Department of Chemistry
Brown University
324 Brook Street, Box H, Providence, RI 02912 (USA)
Fax: (‡1)401-863-2594
E-mail: christopher_seto@brown.edu
The efficiency of the hydrolysis reaction is highly depend-
ent on the heteroatom in the 4-heterocyclohexanone catalyst
(compare entries 2 ± 5, Table 1). The reactivity of the carbonyl
group in the catalyst is controlled by a through-space electro-
static repulsion between the dipoles of the ketone and the
heteroatom. We have demonstrated previously that the
equilibrium constant for addition of a thiol to 4-heterocyclo-
[**] This work was supported by the U.S. Army Medical Research and
Material Command (DAMD17-96-1-6161, Career Development
Award to C.T.S.). J.L.C. was supported by a GAANN Fellowship
from the U.S. Department of Education and a University Fellowship
from Brown University.
Supporting information for this article is available on the WWW
under http://www.wiley-vch.de/home/angewandte/ or from the au-
thor.
514
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1433-7851/99/3804-0514 $ 17.50+.50/0
Angew. Chem. Int. Ed. 1999, 38, No. 4