Patent Grant
6844442
This invention relates to a general method for preparing metal carbene complexes. These complexes may be used, inter alia, to catalyze olefin metathesis reactions, olefin ring opening metathesis polymerization reactions, alkyne metathesis or diolefin cyclization.
Alkylidene ligands, such as CH2, CHR, or CR2, form M═C double bonds and their metal compounds are often called metal carbene complexes. The chemistry of late-transition-metal (i.e. groups VIII, IX and X of the periodic table) carbene complexes has recently received much attention, primarily due to the high catalytic activity of phosphine ruthenium carbene complexes in olefin metathesis. The most useful ruthenium carbene in these series is Grubbs' catalyst, (PCy3)2Cl2Ru═CHPh, bearing a benzylidene unit (Schwab P. et al., Angew. Chem. Int. Ed. Engl. 1995, 34, 2039; Schwab P. et al., J. Am. Chem. Soc. 1996, 118, 100, U.S. Pat. No. 5,831,108). Being highly active and remarkably tolerant to common functional groups, this compound found broad applications in both organic and polymer chemistry.
There are several synthetic approaches towards alkylidene complexes, with the ones utilizing the corresponding diazoalkane being the most popular and most general (Schwab P. et al., J. Am. Chem. Soc. 1996, 118, 100). However, the instability of diazo compounds and the safety issues involved in handling them seriously limit this method. From safety considerations it is also difficult to use such diazo compounds in industry.
Another recent approach, involving the reaction of precursors to unstable Ru(0) complexes with alkyl dihalides ((a) Belderrain, T. R.; Grubbs, R. H. Organometallics 1997, 16, 4001. (b) Olivan, M.; Caulton, K. G. Inorg. Chem. 1999, 38, 566) is limited by the difficult synthesis of the unstable Ru(COD)(COT) precursor.
In view of the above, it is desired to provide a new method for the preparation of metal carbene complexes which is general, synthetically simple and safe.
Thus, the present invention describes a new method for the preparation of metal carbene complexes by using sulfur ylides as carbenoid precursors. Such ylides are extensively used in organic chemistry. The new synthetic route is synthetically simple and safe and can be applied to complexes of different metals and different ligands. Moreover, it can be used for the synthesis of new carbenes, which are difficult to obtain by known methods.
The metal carbene complexes are powerful catalysts in organic synthesis and may be used, inter alia, to catalyze olefin metathesis reactions, olefin ring opening metathesis polymerization reactions, alkyne metathesis, diolefin cyclization and olefin cyclopropanation.
According to a first of its aspects, the present invention provides a process for preparing a metal carbene complex of the formula (I)
wherein
Examples of preferable metal complexes are shown in the following Scheme 1.
According to a preferred embodiment, in the above metal carbene of formula (I) M is ruthenium or osmium. In such case the metal carbene has the general formula:
including isomers thereof, wherein
The nucleophilic carbene has the following general formula:
wherein
Alternatively, the metal carbene has the general formula:
including isomers thereof, wherein
The above nucleophilic carbene has the general formula:
wherein
According to another embodiment, in the above metal carbene of formula (I) M is rhodium or iridium. In such case the metal carbene has the general formula:
including isomers thereof, wherein
According to a first of its aspects, the present invention provides a general method for the preparation of metal carbene complexes. The general pathway is presented in Scheme 2.
A specific example of the process of the present invention is shown in Scheme 3 below. According to this scheme, benzyldiphenylsulfonium tetrafluoroborate 1, the precursor of the corresponding ylide compound, is prepared by a one-pot reaction between diphenylsulfide and benzyl bromide in the presence of AgBF4 (Franzen, V.; Schmidt, H. J.; Mertz, C. Ber., 1961, 94, 2942). Deprotonation of this sulfonium salt by base, results in the formation of the benzyl ylide 2, that readily reacts with the appropriate metal complex to give the metal carbene complex LaXbM═CHPh.
In another example, at least one of the phenyl groups in 1, bound to the sulfur, may be linked to an insoluble polymeric unit, for example polystyrene or a non-organic polymer such as silica. In such cases after the reaction is complete, the diphenyl sulfide linked to the insoluble polymer unit is separated by filtration from the metal carbene complex LaXbM═CHPh and re-used.
More specifically, when the sulfonium salt 1 is reacted with 1 equiv. of KN(SiMe3)2 at −30° C. in toluene, immediate formation of a yellow solution and precipitation of KBF4 takes place (Scheme 4). After filtration of KBF4, the formed sulfur ylide 2 is reacted with a complex 3a or 3b under a nitrogen atmosphere and at −30° C. resulting in clean conversion to the Rh-benzylidene complex 4a or 4b, respectively. The Rh(I) benzylidene complexes are not stable at room temperature and were characterized by multinuclear NMR spectroscopy at −40° C. The carbene protons in the 1H NMR spectrum are characterized by low-field signals (e.g. between 17 and 20 ppm), due to coupling with the Rh center. The carbenoid carbons also give rise to extremely low field signals in 13C NMR spectrum, between 270 and 350 ppm.
(In the Scheme above, iPr denotes an isopropyl radical; tBu denotes a tert-butyl radical)
The above compounds of formulae 3a, 3b, 4a and 4b are new and present a further aspect of the invention.
Stable, well-known metal carbenes can also easily and cleanly be prepared by the sulfur ylide approach described in the present invention. An example is the preparation of the synthetically very useful Grubbs' catalyst, (PCy3)2Cl2Ru═CHPh (5) (Cy denotes a cyclohexyl radical). The reaction of (PPh3)3RuCl2 in CH2Cl2 with the freshly prepared sulfur ylide 2 in THF at −30° C. and concomitant substitution of the PPh3 ligands by tricyclohexylphosphine at room temperature results, after the workup, in the Ru-benzylidene complex 5 in 98% yield (Scheme 5).
The process of the present invention is not limited to rhodium and ruthenium carbenes, see for example Werner's hydrido-osmium carbene 6 (Werner H. et al., Organometallics, 1997, 16, 2236) shown in Scheme 5. According to this scheme, ylide 2 is added to the osmium complex [OsHCl(CO)(PiPr3)2] (Esteruelas, M. A.; Werner, H. J. Organomet. Chem. 1986, 303, 22)1 in toluene at −30° C., resulting in an immediate color change to orange. Stirring for additional 30 min. at room temperature and workup results in quantitative formation of the benzylidene complex 6, as evident from its spectroscopic data compared to the literature.
The process of the present invention can be applied also to the synthesis of unknown carbenes, which are difficult to obtain by methods known in the art. For example, the carbene complexes trans-[RhCl(═CRR′)(PiPr3)2] have been prepared in the literature by an indirect route with the aid of SbR3 ligands, which were subsequently substituted by the bulky triisopropylphosphine ligands. However, attempts to prepare similar monosubstituted carbene trans-[RhCl(═CHPh)(PiPr3)2] by use of phenyldiazomethane didn't lead to the desired results. Remarkably, this complex may be synthesized by the new process of the invention and without the aid of stibine ligands (see Scheme 6).
Thus, the monosubstituted carbene trans-[RhCl(═CHPh)(PiPr3)2] is prepared as follows: bis-(triisopropylphosphine)rhodium chloride dimer 7 reacts with one equiv. of the sulfur ylide 2 at −30° C. in toluene, followed by selective formation of the Rh benzylidene complex 8 (Scheme 6).
Compound 8 is moderately stable and decomposes at room temperature within 3-4 days.
The present invention is now described by the following non-limiting examples.
All experiments below were performed under an inert nitrogen atmosphere.
A toluene solution (3 ml) of KN(SiMe3)2 (27 mg, 0.133 mmol) was added dropwise to a stirred suspension of [Ph2SCH2Ph]BF4 (48 mg, 0.132 mmol) in 2 ml of toluene at −30° C. The resulting yellow solution was filtered into a toluene solution of 3 (60 mg, 0.132 mmol) precooled to −30° C. A color change from brown to dark green-brown took place upon warming up of the mixture to room temperature. 31P{1H} NMR revealed formation of complex 4a in almost quantitative yield. Complex 4a is stable at temperatures below −30° C. and was spectroscopically characterized at −40° C.
Characterization of 4a
(toluene-d8) 31P{1H} NMR 71.90 (d, 1JRhP=165.0 Hz). 1H NMR 19.75 (d, 2JRhH=2.7 Hz, 1H, Rh═CHPh), 8.18 (d, JHH=7.1 Hz, 2H, Ar—H), 7.32 (d, JHH=8.1 Hz, 2H, Ar—H), 7.16 (m, 4H, Ar—H), 3.29 (vt, JHH=4.2 Hz, 4H, Ar—CH2-P), 1.70 (m, 4H, CH(CH3)2), 0.91 (m, 24H, CH(CH3)2).
Selected 13C{1H} NMR signals: 340.80 (m, Rh═CHPh), 182.60 (dt, JRhC=19.4 Hz, JPC=10.0 Hz, Cipso).
To a stirred suspension of [Ph2SCH2Ph]BF4 (48 mg, 0.132 mmol) in 2 ml of toluene was added a solution of KN(SiMe3)2 (27 mg, 0.133 mmol) in 3 ml of toluene at −30° C. The resulting yellow solution of 2 was filtered into a cold (−30° C.) toluene solution of 3b (63 mg, 0.132 mmol). The reaction mixture was warmed to the room temperature and an almost quantitative conversion to complex 4a was observed by 31P{1H} NMR. Compound 4b was not stable at room temperature and was characterized at −40° C.
Characterization of 4b
(toluene-d8) 31P{1H} NMR 92.72 (d, 1JRhP=218.23 Hz). 1H NMR: 17.21 (d, 2JRhH=7.8 Hz, 1H, Rh═CHPh), 8.37 (d, JHH=7.6 Hz, 2H, Ar—H), 7.75 (m, 1H, Ar—H), 7.53 (d, 1H, J=7.3 Hz Ar—H), 7.12 (m, 1H, Ar—H), 6.63 (bs, 1H, Ar—H) 3.99 (s, 2H, Ar—CH2—N), 3.63 (bd, 2H, JPH=8.4 Hz, Ar—CH2—P), 3.03 (m, 2H, N—CH2—CH3), 2.92 (m, 2H, N—CH2—CH3), 2.84 (m, 6H, N—CH2—CH3), 2.39 (s, 3H, Ar—CH3), 2.19 (s, 3H, Ar—CH3), 1.23 (d, 18H, JPH=12.6 Hz, C(CH3)3).
Selected 13C{1H} NMR signals: 283.51 (m, Rh═CHPh), 186.15 (dd, JRhC=18.6 Hz, JPC=9.4 Hz, Cipso), 32.41 (d, JPC=16.3 Hz, P—C(CH3)3).
[Ph2SCH2Ph]BF4 (53 mg, 0.146 mmole) was dissolved in THF (3 ml) and cooled to −30° C. A solution of KN(SiMe3)2 (35 mg, 0.146 mmole) in THF (1 ml) was added, resulting in a rapid change of color to yellow. The yellow solution was added, at −30° C., to a solution of Ru(PPh3)3Cl2 (138 mg, 0.144 mmole) in CH2Cl2 (5 ml). The mixture was kept at −30° C. for an additional 30 min. A solution of tricyclohexylphosphine (88 mg, 0.310 mmol) in CH2Cl2 (5 ml) was then added and the mixture was warmed up to room temperature and stirred for 2 hrs. The solvent was removed under vacuum and the residue was washed with methanol (3×10 ml) to remove the residual phosphine, sulfide and silyl by products. The remaining solid was dried under high vacuum to give the clean Grubss' carbene 5 (130 mg, 0.141 mmol) in 98% yield as evident from its spectral data compared to the literature.
A toluene solution (3 ml) of KN(SiMe3)2 (27 mg, 0.133 mmol) was added dropwise to a suspension of [Ph2SCH2Ph]BF4 (48 mg, 0.132 mmol) in 2 ml of toluene at −30° C. The resulting yellow solution was filtered into a cold (−30° C.) toluene solution of [OsHCl(CO)(PiPr3)2] (75 mg, 0.132 mmol). After the reaction mixture was stirred for 30 min., the solvent and volatile products were removed under high vacuum. The product was extracted from dry residue with ether (3×4 ml) and solvent was evaporated resulting in compound 6 as an orange solid.
Complex 8 was prepared analogously to complexes 4, using 30 mg (0.033 mmol) of dimer 7, 24 mg (0.066 mmol) of [Ph2SCH2Ph]BF4 and 14 mg (0.066 mmol) of KN(SiMe3)2.
Characterization of 8 (toluene-d8) 31P{1H} NMR 32.10 (d, 1JRhP=167.4 Hz). 1 NMR: 20.17 (dt, 2JRhH=3.2 Hz, 3JPH=6.1 Hz, 1H, Rh═CHPh), 8.12 (d, JHH=7.2 Hz, 1H, Ar—H), 7.30-6.92 (m, 4H, Ar—H), 2.21 (m, 6H, CH(CH3)2), 1.83 (m, 36H, CH(CH3)2). 13C NMR: 317.86 (m, Rh═CHPh), 25.53 (vt, CH(CH3)2), 20.34 (s, CH(CH3)2).
(This complex was previously reported by Schwab, P.; Grubbs, R. H, Ziller, J. W. J. Am. Chem. Soc. 1996, 118, 100)
(Ph2S+CH2CH═CH2)BF4−(10 mg, 0.032 mmol) was suspended in THF (3 ml) and cooled to −35° C. A solution of potassium bis(trimethylsilyl)amide (7 mg, 0.035 mmol) in THF (2 ml) was added to the suspension of the sulfonium salt, followed by rapid color change to yellow. The yellow solution was filtered through cotton directly into a solution at −35° C., of tris(triphenylphosphine)ruthenium dichloride (30 mg, 0.031 mmol) in THF (5 ml). A solution of tricyclohexylphosphine (18 mg, 0.064 mmol) in THF (2 ml) precooled to −35° C. was then added, and the mixture was kept for 2 h at −35° C. and then warmed to room temperature and kept at room temperature for 20 min. The solvent was removed under vacuum and the residue was extracted with pentane. The pentane extract was filtered and evaporated resulting in a red solid.
31P{1H} NMR in C6D6 (singlet at 37.9 ppm) and 1H NMR in C6D6 (doublet at 17.9 ppm, J=10.3 Hz) spectra of this solid indicated that the expected allyl carbene ruthenium complex was formed, in addition to impurities of PPh3 and PCy3.
| Number | Date | Country | Kind |
|---|---|---|---|
| 142610 | Apr 2001 | IL | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCTIL02/00304 | 4/15/2002 | WO | 00 | 4/28/2004 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO0208369 | 10/24/2002 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 5831108 | Grubbs et al. | Nov 1998 | A |
| 5912376 | Van Der Schaaf et al. | Jun 1999 | A |
| 6504041 | Grubbs et al. | Jan 2003 | B2 |
| 6515084 | Grubbs et al. | Feb 2003 | B2 |
| 6610626 | Grubbs et al. | Aug 2003 | B2 |
| 6613910 | Grubbs et al. | Sep 2003 | B2 |
| 6620955 | Pederson et al. | Sep 2003 | B1 |
| Number | Date | Country | |
|---|---|---|---|
| 20040176626 A1 | Sep 2004 | US |
