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Organometallics 2009, 28, 1286–1288
PNNP Macrocycles: A New Class of Ligands for Asymmetric Catalysis Marco Ranocchiari and Antonio Mezzetti* Department of Chemistry and Applied Biosciences, ETH Zu¨rich, CH-8093 Zu¨rich, Switzerland ReceiVed January 14, 2009 Summary: We report the first examples of enantiomerically pure P2N2 macrocycles containing either a diimino (1a) or diamino donor set, as well as their ruthenium(II) dichloro complexes. Unexpectedly, the diimino deriVatiVe 2a is a more efficient catalyst in the transfer hydrogenation of acetophenone than its diamino analogue. Macrocyclic ligands are of enormous interest not only because of the role played by porphyrins in (bio)chemistry1 but also because their complexes are particularly robust and, hence, suitable for application in homogeneous catalysis under harsh conditions.2 In sharp contrast to the large amount of N4 macrocyclic ligands,3 only a few species containing a P4 donor set have been prepared,4 and P2N2 ligands are even rarer.4-8 Furthermore, none of the latter ligands are either chiral or have been prepared as a single enantiomer. Thus, the meso macrocycle A has been prepared as a nickel(II) complex in a template synthesis (Chart 1).5 An analogous protocol, followed by demetalation with cyanide, gave meso-B, which features secondary amine units,6 whereas its tertiary amino analogue C is obtained by a metal-free pathway.7 Finally, Fryzuk has reported macrocycle D with alternating disilylamido donors and phenylphosphine units, which is to small to accommodate a metal ion and hence gives cis complexes of Zr(IV), Hf(IV), Y(III), and the lanthanides.8 To the best of our knowledge, PNNP macrocycles have never been used in homogeneous catalysis, even though macrocyclic ligands are known to increase the stability of the corresponding complexes. Open-chain chiral ligands with a P2N2 donor set have found application in the asymmetric transfer hydrogenation with * To whom correspondence should be addressed. E-mail: mezzetti@ inorg.chem.ethz.ch. (1) See, for instance: Kadish, K. M.; Smith, K. M.; Guilard, R. The Porphyrin Handbook; Academic Press: New York, 2000; Vol. 11. (2) Montanari, F.; Casella, L. Metalloporphyrin-Catalyzed Oxidations; Kluwer: Dordrecht, The Netherlands, 1994. (3) Bradshaw, J. S.; Krakowiak, K. E.; Izatt, R. M.; Aza-crown Macrocycles; Wiley: New York, 1993. (4) Caminade, A. M.; Majoral, J. P. Chem. ReV. 1994, 94, 1183. (5) (a) Scanlon, L. G.; Tsao, Y. Y.; Toman, K.; Cummings, S. C.; Toman, K.; Meek, D. W. J. Am. Chem. Soc. 1980, 102, 6849. (b) Scanlon, L. G.; Tsao, Y. Y.; Toman, K.; Cummings, S. C.; Meek, D. W. Inorg. Chem. 1982, 21, 1215. (6) Ansell, C. W. A.; Cooper, M. K.; Dancey, K. P.; Duckworth, P. A.; Henrick, K.; McPartlin, M.; Tasker, P. A. J. Chem. Soc., Chem. Commun. 1985, 439. (7) (a) Kyba, E. P.; Davies, R. E.; Hudson, C. W.; John, A. M.; Brown, S. B.; McPhaul, M. J.; Liu, L. K.; Glover, A. C. J. Am. Chem. Soc. 1981, 103, 3868. See also: (b) Kyba, E. P.; John, A. M.; Brown, S. B.; Hudson, C. W.; McPhaul, M. J.; Harding, A.; Larsen, K.; Niedzwiecki; Davies, R. E. J. Am. Chem. Soc. 1980, 102, 139. (8) (a) Fryzuk, M. D.; Love, J. B.; Rettig, S. J. Chem. Commun. 1996, 2783. (b) Fryzuk, M. D.; Love, J. B.; Rettig, S. J. Organometallics 1998, 17, 846. (c) Fryzuk, M. D.; Jafarpour, L.; Kerton, F. M.; Love, J. B.; Patrick, B. O.; Rettig, S. J. Organometallics 2001, 20, 1387. (d) Fryzuk, M. D.; Corkin, J. R.; Patrick, B. O. Can. J. Chem. 2003, 81, 1376.
Chart 1
ruthenium(II)9 and iron(II),10 as well as in catalytic reactions involving C-C11-13 and C-heteroatom14 bond formation. We have recently shown that linear PNNP ligands are flexible and can adopt a trans- or a cis-β configuration,11,13,14 which can lower enantioselection in some catalytic reactions, such as olefin cyclopropanation.11 Therefore, we decided to develop macrocyclic PNNP ligands to restrict the flexibility and impart additional robustness to the catalysts. We report here the first examples of a class of enantiomerically pure P2N2 macrocyclic ligands containing a diimino, (RP,SP,SC,SC)-1a, or diamino donor set, (RP,SP,SC,SC)-1b. Deprotonation of 1,2-bis(phenylphosphino)ethane (3) with t BuOK in the presence of 18-crown-6,15 followed by treatment with 2-(2-fluorophenyl)-1,3-dioxolane, gave 4 as a 1:1 mixture of the meso and rac stereoisomers, which were deprotected to 5 with aqueous HCl (Scheme 1). A preliminary study with a diastereoisomeric mixture of 5 showed that only (R,S)-5 forms (9) (a) Gao, J. X.; Ikariya, T.; Noyori, R. Organometallics 1996, 15, 1087. (b) Gao, J. X.; Zhang, H.; Yi, X. D.; Xu, P. P.; Tang, C. L.; Wan, H. L.; Tsai, K. R.; Ikariya, T. Chirality 2000, 12, 383. For related, nonenantioselective reactions, see: (c) Haque, F. N.; Lough, A. J.; Morris, R. H. Inorg. Chim. Acta 2008, 361, 3149. (d) Li, T.; Bergner, I.; Haque, F. N.; Zimmer-De Iuliis, M.; Song, D.; Morris, R. H. Organometallics 2007, 26, 5940. (10) (a) Sui-Seng, C.; Freutel, F.; Lough, A. J.; Morris, R. H. Angew. Chem., Int. Ed. 2008, 47, 940. (b) Mikhailine, A.; Lough, A. J.; Morris, R. H. J. Am. Chem. Soc. 2009, 131, 1394. (11) (a) Bachmann, S.; Furler, M.; Mezzetti, A. Organometallics 2001, 20, 2102. (b) Bonaccorsi, C.; Bachmann, S.; Mezzetti, A. Tetrahedron: Asymmetry 2003, 14, 845. (c) Bonaccorsi, C.; Mezzetti, A. Organometallics 2005, 24, 4953. (12) Guo, R. W.; Morris, R. H.; Song, D. J. Am. Chem. Soc. 2005, 127, 516. (13) (a) Althaus, M.; Bonaccorsi, C.; Mezzetti, A.; Santoro, F. Organometallics 2006, 25, 3108. (b) Santoro, F.; Althaus, M.; Bonaccorsi, C.; Gischig, S.; Mezzetti, A. Organometallics 2008, 27, 3866. (14) (a) Stoop, R. M.; Bachmann, S.; Valentini, M.; Mezzetti, A. Organometallics 2000, 19, 4117. (b) Toullec, P. Y.; Bonaccorsi, C.; Mezzetti, A.; Togni, A. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5810. (c) Althaus, M.; Becker, C.; Togni, A.; Mezzetti, A. Organometallics 2007, 26, 5902.
10.1021/om900028w CCC: $40.75 2009 American Chemical Society Publication on Web 02/12/2009
Communications
Organometallics, Vol. 28, No. 5, 2009 1287 Scheme 1
Figure 1. ORTEP drawing of 1b. Selected distances (Å): P(1) · · · N(2), 4.523(2); P(2) · · · N(1), 4.786(2); N(1)-H · · · N(2), 2.861(3). Selected angle (°): N(1)-H · · · N(2), 118.3(15).
a macrocylic product with (S,S)-1,2-cyclohexanediamine, whereas rac-5 gives oligo- or polymeric products. Therefore, (R,S)- and rac-4 were separated by several recrystallizations from ethanol to give pure (R,S)-4 in 42% yield (based on rac- + meso-3) as a white solid, which was quantitatively transformed into (R,S)5.16 The diphosphine (R,S)-5 was treated with (S,S)-1,2cyclohexanediamine in ethanol to give the 14-membered macrocycle (RP,SP,SC,SC)-1a as a white solid in 81% yield.17 The overall yield of (RP,SP,SC,SC)-1a is 34% based on rac- + meso-3. Preliminary molecular modeling calculations, which will be reported in full elsewhere, suggest that only the intermediate containing (R,S)-5 can assume the appropriate conformation to induce cyclization. It has been previously shown by conformational analysis that the cis stereochemistry of P,P′-diphenyl1,2-diphospha moieties (that is, with opposite absolute configuration at phosphorus) is pivotal for the metal-free ring closure of 11- and 14-membered tetraheteramacrocycles,7 and the same stereochemical effect has been observed in the template synthesis of A and B.5,6 Macrocycle 1a, however, is enantiomerically pure, despite the R,S (meso) configuration of the P atoms, by virtue of the stereogenic (S,S)-cyclohexanediamine, which reduces the symmetry to C1, as indicated by the AX pattern observed in the 31P NMR spectrum for the diastereotopic, inequivalent P atoms. Reduction of 1a with an excess of NaBH4
(15) The crown ether is required to shift the equilibrium completely toward the diphosphide and to make it more “naked” and thus more reactive toward aromatic nucleophilic substitution. Without crown ether, the deprotonation of 3 by tBuOK is not quantitative and the formation of 4 is much slower (3 days instead of overnight). The deprotonation of PHPh2 with tBuOK (without the addition of the crown ether) has been previously reported, see: Cooper, G. R.; Hassan, F.; Shaw, B. L.; Thornton-Pett, M. J. Chem. Soc., Chem. Commun. 1985, 614. (16) As confirmed by an X-ray study (see the Supporting Information). 31 P NMR (101.3 MHz, CDCl3): δ-26.6 (s, 2P, meso). The signal of rac-4 appears at δ-26.8 (s). (17) Synthesis of (RP,SP,SC,SC)-1a: (S,S)-diaminocyclohexane (0.080 g, 0.70 mmol) was added to a solution of (R,S)-5 (0.320 g, 0.70 mmol) in ethanol (70 mL). When it was stirred overnight, the yellow solution turned colorless, and a white precipitate formed. The solution was concentrated, and the resulting white solid was filtered off and dried overnight under vacuum at 100 °C. Yield: 0.303 g, 81%. 31P NMR (121.5 MHz, C6D6): δ-22.9 (d, 1P, JP,P′) 46 Hz),-25.1 (d, 1P, JP,P′ ) 46 Hz). Anal. Calcd for the monooxide C34H34N2OP2: C, 74.44; H, 6.25; N, 5.11. Found: C, 74.88; H, 6.66; N, 5.00. [R]D20 ) +31.4 ( 0.1° (c ) 1.0, CHCl3).
gave the diamino macrocycle (RP,SP,S,S)-1b.18 Its X-ray structure19 shows a macrocyclic ring with a diameter of 4.26 Å (as the average trans P · · · N distance). The equatorial arrangement of the exocyclic phenyls and the hydrogen bond between the amino groups account for the conformation of the ring (Figure 1). The ligand (RP,SP,SC,SC)-1a reacts with [RuCl2(p-cymene)]2 in refluxing toluene to give trans-[RuCl2(1a)] (2a) (Scheme 1),20 whose X-ray structure21 shows that ruthenium(II) fits in the macrocycle cavity, but with remarkably short Ru-P distances (Figure 2). The comparison between 3a and the corresponding open-chain PNNP dichloro complex9a dramatically shows the effect of the macrocycle on the P-Ru-P bite angle, which (18) Synthesis of (RP,SP,S,S)-1b: NaBH4 (0.465 g, 12.3 mmol) was added to (RP,SP,S,S)-1a (0.655 g, 1.23 mmol) suspended in EtOH (60 mL). The slurry was refluxed overnight, and then the solvent was evaporated. Extraction of the white solid with dichloromethane (3 × 20 mL) and evaporation of the yellowish solution gave (RP,SP,SC,SC)-1b as a colorless crystalline solid that was recrystallized from dichlorometane/hexane. Yield: 0.398 g, 62%. 31P NMR (121 MHz, C6D6): δ-30.3 (d, JP,P′ ) 49.5 Hz, 1P),-31.2 (d, JP,P′ ) 49.5 Hz, 1P). Anal. Calcd for C34H38N2P2: C, 76.10; H, 7.14; N, 5.22. Found: C, 75.09; H, 7.12; N, 5.08. [R]D20 ) +49.0 ( 0.1° (c ) 1.0, CHCl3). (19) Crystal data for (RP,SP,S,S)-1b: C34H38N2P2, monoclinic, P21, a ) 9.2787(17) Å, b ) 11.947(2) Å, c ) 13.284(2) Å, β ) 92.332(4)°, V ) 1471.3(5) Å3, Z ) 2, T ) 200 K, Dc ) 1.211 Mg/m3, µ ) 0.173 mm-1 (Mo KR, graphite monochromated), λ ) 0.710 73 Å, F(000) ) 572, 15 381 data collected at 200 K on a Bruker AXS SMART APEX platform in the θ range 1.53-28.30°, 7134 independent reflections (Rint ) 0.0397), R1 ) 0.0421 (for 5626 reflections with I > 2σ(I)) and wR2 ) 0.0724 (all data), GOF ) 0.885, Flack x parameter )-0.06(5), maximum and minimum difference peaks +0.46 and-0.23 e Å-3, largest and mean ∆/σ ) 0.001 and 0.000. (20) Synthesis of 2a: (RP,SP,S,S)-1a (0.364 g, 0.68 mmol) and [RuCl2(pcymene)]2 (0.210 g, 0.34 mmol) were refluxed overnight in toluene (40 mL). The resulting deep red solution was evaporated, and the red residue was chromatographed on a short column (alumina, activity IV, toluene/ dichloromethane (1/1) as eluent). Recrystallization from dichloromethane/ hexane gave pure (RP,SP,S,S)-trans-[RuCl2(1a)] (2a). Yield: 0.407 g, 85%. 31 P NMR (121.5 MHz, CDCl3): δ 91.3 (d, 1P, JP,P′) 5.0 Hz), 90.3 (d, 1P, JP,P′) 5.0 Hz). Anal. Calcd for C34H34N2P2Cl2Ru: C, 57.96; H, 4.86; N, 3.98. Found: C, 57.32; H, 4.91; N, 3.90. (21) Crystal data for 2a: C68H68Cl4N4P4Ru2, monoclinic, P21, a ) 17.0214(10) Å, b ) 10.1901(6) Å, c ) 18.4792(11) Å, β ) 105.4230(10)°, V ) 3089.8(3) Å3, Z ) 2, T ) 200 K, Dc ) 1.515 Mg/m3, µ ) 0.811 mm-1 (Mo KR, graphite monochromated), λ ) 0.710 73 Å, F(000) ) 1440, 72 940 data collected at 200 K on a Bruker AXS SMART APEX platform in the θ range 1.14-28.39°, 15 463 independent reflections (Rint ) 0.0514), R1 ) 0.0398 (for 14 666 reflections with I > 2σ(I)) and wR2 ) 0.0975 (all data), GOF ) 1.089, Flack x parameter ) 0.03(2), maximum and minimum difference peaks +1.63 and-1.12 e Å-3, largest and mean ∆/σ )-0.002 and 0.000. The asymmetric unit contains two crystallographically independent complex molecules with indistinguishable metrical parameters.
1288 Organometallics, Vol. 28, No. 5, 2009
Communications Scheme 2
Figure 2. ORTEP drawing of 2a. Selected distances (Å): Ru(1)-P(1), 2.204(1); Ru(1)-P(2), 2.213(1); Ru(1)-N(1), 2.065(3); Ru(1)-N(2), 2.071(3); Ru(1)-Cl(1), 2.413(1); Ru(1)-Cl(2), 2.419(1).
shrinks from 99.52(6)° to 85.07(4)°, and on the average Ru-P distances. The latter contract significantly from 2.295(2) and 2.288(2) Å in the open-chain complex to 2.204(1) and 2.213(1) Å in 2a as a consequence of the additional chelate ring between the phosphine donors. We attribute the slight displacement of ruthenium from the PNNP plane (by 0.161(1) Å) to the bis(axial) conformation of the phenyl rings imposed by the ring, which distorts 1a away from the regular “stepped” conformation found in the complexes of its acyclic, C2-symmetric PNNP analogues.9a The diamino analogue trans-[RuCl2(1b)] (2b) was isolated in 20% yield by refluxing (RP,SP,SC,SC)-1b and [RuCl2(C6H6)]2 in DMF, followed by column chromatography.22 The 31P and 1H NMR spectra of the crude reaction mixture indicate that further products are formed along with trans-2b, which explains the low yield of trans-2b.23 (22) Synthesis of 2b: (RP,SP,S,S)-1b (0.061 g, 0.11 mmol) and [RuCl2(C6H6)]2 (0.028 g, 0.057 mmol) were heated at 110 °C in DMF (1 mL). After the solvent was evaporated, the crude product was purified on a short column (alumina, activity IV, toluene as eluent). Yield: 0.015 g, 20%. 31P NMR (121.5 MHz, C6D6): δ 91.7 (d, 1P, JP,P′ ) 6.3 Hz), 89.2 (d, 1P, JP,P′ ) 6.3 Hz). Yield: 20%. MS (ESI): calcd for C34H38Cl2N2P2Ru (M+) 708.09, found m/z 708.1. (23) In addition to trans-2b, we observed an AX pattern at δ 87.6 (d, 1P, JP,P′ ) 25.6 Hz) and 70.9 (d, 1P, JP,P′ ) 25.6 Hz) (CDCl3, 121 MHz), which we attribute to a cis-β isomer formed in 20% yield, as well as several minor AX patterns that cannot be assigned. None of these products are eluted under the conditions used.
For the sake of comparison with the analogous open-chain PNNP complexes,9a both 2a and 2b were tested in the transfer hydrogenation of acetophenone (Scheme 2).24 The diamino catalyst 2b gives 1-phenylethanol with 96% yield and 11% ee after 36 h of reaction time, whereas the diimino analogue 2a gives a substantially quantitative yield of 1-phenylethanol after a shorter reaction time (8 h) with modest, but improved, enantioselectivity (30% ee). These results are surprisingly in contrast with those obtained with the open-chain ruthenium(II) PNNP complexes, for which the diamino complex is by far more active and enantioselective than the diimino derivative.9a In conclusion, we prepared the first chiral macrocyclic PNNP ligands 1a and 1b by a straightforward, high-yielding, and nontemplate synthesis. This protocol gives access to a new family of highly modular, enantiomerically pure, P-containing macrocycles as ligands for asymmetric catalysis. Preliminary tests indicate that the corresponding ruthenium(II) complexes, and in particular the diimino analogue 2a, catalyze the transfer hydrogenation of acetophenone. To the best of our knowledge, this is the first catalytic application of complexes derived from macrocycles containing phosphorus donors. As the pseudo meso stereochemical relationship between the P atoms is probably responsible for the low enantioselectivity observed, our next goal is to prepare C2-symmetric P2N2 macrocycles and to test them in catalysis. Preliminary results indicate that a possible strategy to enforce the cyclization of C2 diastereoisomer is to control the conformation of the open-chain intermediate by changing the number of C atoms in the N-N or P-P bridge.
Acknowledgment. We thank Mr. Pietro Butti and Mr. Raphael Aardoom for the X-ray structures. Supporting Information Available: Text, figures, a table, and CIF files giving detailed experimental procedures and crystal data for (RP,SP,SC,SC)-1b, (RP,SP,SC,SC)-2a, and (R,S)-4. This material is available free of charge via the Internet at http://pubs.acs.org. OM900028W (24) The reactions were carried out using a 0.1 M solution of acetophenone (152 mg, 1.0 mmol) in 2-propanol. The substrate:Ru:(CH3)3COK ratio was varied between 100:1:0.5 and 100:1:2 (see the Supporting Information). Yield and ee were determined by chiral GC analysis.
