Can a Butadiene-Based Architecture Compete with its Biaryl

To whom correspondence should be addressed. ... tropos class of ligand. rac-Me-CATPHOS can be resolved by fractional crystallization of the diastereoi...
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Organometallics 2009, 28, 888–895

Can a Butadiene-Based Architecture Compete with its Biaryl Counterpart in Asymmetric Catalysis? Enantiopure Me-CATPHOS, a Remarkably Efficient Ligand for Asymmetric Hydrogenation Simon Doherty,* Catherine H. Smyth,* Anthony Harriman, Ross W. Harrington, and William Clegg School of Chemistry, Newcastle UniVersity, Newcastle upon Tyne, NE1 7RU, U.K.

The double Diels-Alder cycloaddition between 9-methylanthracene and 1,4-bis(diphenylphosphinoyl)buta-1,3-diyne affords the oxide of the atropos diphosphine, Me-CATPHOS, which has an unusual bicyclic buta-1,3-diene-based architecture. Quantum chemical methods using DTF reveal that the barrier to atropinterconversion in Me-CATPHOS is 130 kJ mol-1, while the corresponding barrier for its unsubstituted counterpart is only 23 kJ mol-1, entirely consistent with the former being an atropos diphosphine while the latter belongs to the tropos class of ligand. rac-Me-CATPHOS can be resolved by fractional crystallization of the diastereoisomeric complexes formed with (2R,3R)-(-)-2,3-O-dibenzoyltartaric acid and reduction of the resulting enantiopure oxide, accomplished by silane reduction in xylene at 130 °C, to afford an operationally straightforward, three-step synthesis of an entirely new class of atropos buta-1,3-diene-based diphosphine. Rhodium complexes of enantiopure Me-CATPHOS catalyze the asymmetric hydrogenation of a range of dehydroamino acid derivatives, in some cases giving ee’s in excess of 99% and in all cases showing a significant enhancement compared with its BINAP counterpart. Gratifyingly, Rh/(S)-Me-CATPHOS outperforms all existing catalysts for the asymmetric hydrogenation of (E)-β-dehydroamino phosphonates, many of which are based on markedly more expensive biaryl- and ferrocenyl-based diphosphines. Surprisingly, in the case of the dehydroamino acid substrates, (S)-MeCATPHOS provides product of opposite absolute stereochemistry to that obtained with (S)-BINAP, despite both ligands having an Sax configuration, whereas (S)-Me-CATPHOS exerts (S)-BINAP-like stereoinduction for the hydrogenation of β-enamidophosphonates; both ligands afford product with the same absolute configuration. Introduction Atropos biaryl diphosphines have played a pivotal role in the development of asymmetric catalysis1 and as a result rightfully belong to the privileged class of ligand/structure.2 However, even though BINAP has this privileged status and is an excellent ligand for a host of transition metal-catalyzed reactions,3 it is not superior for all transformations and is often substrate-specific.4 In such cases the steric and electronic properties have to be modified in order to identify an optimum catalyst, which can involve a nontrivial multistep de noVo synthesis.5 The dramatic effect of the biaryl architecture on catalyst performance has been reported by Keay and co-workers for the rhodium-catalyzed asymmetric hydrogenation of dehydroamino acids.6,7 While cationic Rh/(S)-BINAP is a poor catalyst for the asymmetric hydrogenation of 2-acetamidoacrylic acid derivatives and gave ee’s ranging between 14.8% and 33.8%, the use of 3,3′-disubstituted BINAP resulted in a marked enhancement in enantioselectivity, with ee’s reaching 99%. However, this level of enhancement was restricted to unhindered * To whom correspondence should be addressed. E-mail: [email protected]. (1) (a) Shimizu, H.; Nagasaki, I.; Sayo, N.; Saito, T. In Phosphorus Ligands in Asymmetric Catalysis; Bo¨rner, A., Ed.; Wiley-VCH: Weinheim, 2008; p 207. (b) Li, Y.-M.; Yu, W.-Y.; Chan, A. S. C. In Phosphorus Ligands in Asymmetric Catalysis; Bo¨rner, A., Ed.; Wiley-VCH: Weinheim, 2008; p 260. (c) Li, Y.-M.; Yan, M.; Chan, A. S. C. In Phosphorus Ligands in Asymmetric Catalysis; Bo¨rner, A., Ed.; Wiley-VCH: Weinheim, 2008; p 284. (d) Seyden-Penne, J. Chiral Auxillaries and Ligands in Asymmetric Catalysis; Wiley: New York, 1995. (2) Yoon, T. P.; Jacobsen, E. N. Science 2003, 299, 1691.

alkenes, as a more hindered substrate gave markedly lower enantioselectivities, emphasizing the substrate-specific nature of the catalysts and the need for further modification. Group 9 metal catalyzed reductive C-C coupling,8 cycloisomerization,9 and cycloaddition10 provide further recent examples of trans(3) Selected examples. Asymmetric 1,4-additions:(a) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829. (b) Hayashi, T. Pure Appl. Chem. 2004, 76, 465. (c) Enantioselective cycloadditions:(d) Tanaka, K. Synlett 2007, 1977. (e) Shibata, T.; Tsuchikama, K. Org. Biomol. Chem. 2008, 6, 1317. Asymmetric hydrogenation of ketones: (f) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 41. (g) Noyori, R. Angew. Chem. Int. Ed 2002, 41, 2008. Asymmetric Pauson-Khand-type reactions: (h) Kim, D. E.; Choi, C.; Kim, I. S.; Jeulin, S.; Ratovelomanana-Vidal, V.; Geneˆt, J.-P.; Jeong, N. AdV. Synth. Catal. 2007, 249, 1999. Lewis acid-catalyzed reactions of enolates: (i) Sodeoka, M.; Hamashima, Y. Pure Appl. Chem. 2006, 78, 477. (j) Sodeoka, M.; Hamashima, Y. Bull. Chem. Soc. Jpn. 2005, 78, 941. Cycloisomerizations and related transformations: (k) Fairlamb, I. J. S. Angew. Chem., Int. Ed. 2004, 43, 1048. (l) Michelet, V.; Toullec, P. Y.; Geneˆt, J.-P. Angew. Chem., Int. Ed. 2008, 47, 4268. (m) Chianese, A. R.; Lee, S. J.; Gagne´, M. R. Angew. Chem. Int. Ed 2007, 46, 4042. (n) Brummond, K. M.; McCabe, J. M. In Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.; Wiley-VCH: Weinheim, 2005; p 151. (4) Shimizu, H.; Nagasaki, I.; Saito, T. Tetrahedron 2005, 61, 5405. (5) (a) Berthod, M.; Mignani, G.; Woodward, G.; Lemaire, M. Chem. ReV. 2005, 105, 1801. (b) Kumobayashi, H.; Miura, T.; Sayo, N.; Saito, T.; Zhang, X. Synlett 2001, 1055. (6) For relevant examples see:(a) Hopkins, M. J.; Dalrymple, S. A.; Parvez, M.; Keay, B. A. Org. Lett. 2005, 7, 3765. (b) Wu, S.; He, M.; Zhang, X. Tetrahedron: Asymmetry 2004, 15, 2177. (7) 3,3′-Disubstituted biaryl diphosphines also show enhanced enantioselectivities for the asymmetric hydrogenation of cyclic enamides compared with MeO-BINAP:(a) Tang, W.; Chi, Y.; Zhang, X. Org. Lett. 2002, 4, 1695. (9) (a) Michelet, V.; Toullex, P. Y.; Geneˆt, J.-P. Angew. Chem., Int. Ed. 2008, 47, 4268. (b) Fairlamb, I. J. S. Angew. Chem., Int. Ed. 2004, 43, 1048.

10.1021/om801145v CCC: $40.75  2009 American Chemical Society Publication on Web 01/15/2009

Enantiopure Me-CATPHOS

formations that exhibit a marked dependence of catalyst performance on the biaryl diphosphine. Even though BINAP is commercially available and inexpensive, the need to modify the basic architecture can increase the cost quite substantially, and thus there is considerable interest in developing alternative diphosphines that are easy to prepare, effective over a range of reactions and substrates, modular in nature, and costeffective.11-13 Herein we report an operationally straightforward three-step synthesis-resolution of a new atropos buta-1,3-dienebased diphosphine, Me-CATPHOS, that forms a highly efficient catalyst for the asymmetric hydrogenation of dehydroamino acid derivatives. A comparison has shown that a catalyst based on Me-CATPHOS is markedly more efficient and robust than that formed from biaryl diphosphines including BINAP and its 3,3′modified derivatives.

Organometallics, Vol. 28, No. 3, 2009 889 Scheme 1.a

a Conditions: (i) heat 200 °C, (ii) (2R,3R)-(-)-2,3-O-dibenzoyltartaric acid, CHCl3/EtOAc, fractional crystallization, (iii) HSiCl3, NBu3, xylenes, 130 °C, (iv) HSiCl3, P(OEt)3, THF/toluene, 40 °C.

Results and Discussion Synthesis and Computational Studies. Recently, we reported that the buta-1,3-diene-based bicyclic diphosphine CATPHOS (R ) H), prepared via a double Diels-Alder cycloaddition between 1,4-bis(diphenylphosphino)buta-1,3-diyne and anthracene, is a highly efficient ligand for the palladiumcatalyzed amination of aryl bromides.14 Following this we had cause to investigate the corresponding Diels-Alder reaction with 9-methylanthracene and found that cycloaddition occurred with high regioselectivity to afford the C2-symmetric adduct rac-1b as the sole product, in which the more bulky methyl-substituted bridgehead carbon atoms are attached to C2 and C3 of the 1,3butadiene tether (Scheme 1). The high regioselectivity obtained in this reaction can be accounted for by considering the possible steric interactions between the 9-methyl substituent and the diphenylphosphinoyl groups in the transition state for cycloaddition. Since the buta-1,3-diene axis in CATPHOS (R ) H) is unhindered by substitution, in much the same way as the biaryl (8) (a) Skucas, E.; Ngai, M. Y.; Komanduri, V.; Krische, M. J. Acc. Chem. Res. 2007, 40, 1394. (b) Ngai, M. Y.; Kong, J. R.; Krische, M. J. J. Org. Chem. 2007, 129, 1063. For specific examples: (c) Skucas, E.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 12678. (d) Bower, J. F.; Skucas, E.; Patman, R. L.; Krische, M. J. J. Am. Chem. Soc. 2007, 129, 15134. (10) (a) Tanaka, K. Synlett 2007, 1977. (b) Shibata, T.; Tsuchikama, K. Org. Biomol. Chem. 2008, 6, 1317. (11) For the use of rhodium-catalyzed [2+2+2] cycloaddition to prepare biaryl mono- and diphosphines see:(a) Nishida, G.; Noguchi, K.; Hirano, M.; Tanaka, K. Angew. Chem., Int. Ed. 2008, 47, 3410. (b) Nishida, G.; Noguchi, K.; Hirano, M.; Tanaka, K. Angew. Chem., Int. Ed. 2007, 46, 3951. (c) Kondoh, A.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2007, 129, 6996. (d) Doherty, S.; Knight, J. G.; Smyth, C. H.; Harrington, R. W.; Clegg, W. Org. Lett. 2007, 9, 4925. (12) For the synthesis of biaryl monophosphines via Diels-Alder cycloaddition see:(a) Ashburn, B. O.; Carter, R. G. Angew. Chem., Int. Ed. 2006, 45, 6737. (b) Ashburn, B. O.; Carter, R. G. J. Am. Chem. Soc. 2007, 129, 9109. (13) For the diastereoselective synthesis of chiral biaryl diphosphines see:(a) Qui, L.; Chan, S.; Au-Yeung, T. T.-L.; Ji, J.-X.; Guo, R.; Pai, C.C.; Zhou, Z.; Li, X.; Fan, Q.-H.; Chan, A. S. C. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5815. (b) Qui, L.; Kwong, Y.; Wu, J.; Lam, W. H.; Chan, S.; Yu, W.-Y.; Li, Y.-M.; Guo, R.; Zhou, Z.; Chan, A. S. C. J. Am. Chem. Soc. 2006, 128, 5955. (14) (a) Doherty, S.; Knight, J. G.; Smyth, C. H.; Harrington, R. W.; Clegg, W. Organometallics 2008, 27, 1679. (b) Li, M.-X.; Li, L.-J.; Wang, Y.-M.; Meng, J.-B. Chin. J. Chem. 2000, 18, 373.

axis in BIPHEP,15 it belongs to the tropos class of diphosphine;16,17 that is, resolution of the axial chiral conformers is not possible due to rapid interconversion through a planar transition state.18 Pursuing this analogy further, we reasoned that the introduction of methyl groups onto the bridgehead carbon atoms attached to C2 and C3 of the buta-1,3-diene tether (R ) Me) would restrict rotation about the C(sp2)-C(sp2) single bond such that it would be possible to resolve the axially chiral conformations, in much the same manner that 6,6′-substitution in 1,1′-bis(diphenylphosphino)biphenyl renders biaryl diphosphines atropos.4,19 Thus, the process of atropinterconversion in CATPHOS and MeCATPHOS was examined by quantum chemical methods, using DFT with the BP86 functional and having the solute dispersed in a reservoir of chloroform molecules. Figure 1 shows that the energy-minimized geometry computed for 2b has a connecting dihedral angle (φ) of 95.1° and that there is a significant barrier to complete rotation in either direction (EB ) 130 kJ mol-1), which is far too high to pass at ambient temperature. Replacing both methyl groups with hydrogen atoms lowers the barriers for rotation in both directions, the minimum energy corresponding to φ ) 94.2°, although there is a fairly wide plateau, and the resultant barrier is only 23 kJ mol-1. Such a modest barrier is easily surmounted at ambient temperature. This study clearly (15) (a) Ogasawara, M.; Yoshida, K.; Hayashi, T. Organometallics 2000, 19, 1567. (b) Tudor, M. D.; Becker, J. J.; White, P. S.; Gagne´, M. R. Organometallics 2000, 19, 4376. (16) Rotation about the biaryl axis in BIPHEP is too fast to resolve the enantiomeric conformations (∆Gq ) 22.1 ( 1 kcal mol-1, 125 °C). Desponds, O.; Schlosser, M. Tetrahedron Lett. 1996, 37, 47. (17) For insightful and authoritative reviews on tropos ligands and their applications in catalysis see:(a) Mikami, K.; Aikawa, K.; Yusa, Y.; Jodry, J. J.; Yamanaka, M. Synlett 2002, 1561. (b) Walsh, P. J.; Lurain, A. E.; Balsells, J. Chem. ReV. 2003, 103, 3297. (c) Otero, I.; Bo¨rner, A. In Phosphorus Ligands in Asymmetric Catalysis; Bo¨rner, A., Ed.; Wiley-VCH: Weinheim, 2008; p 307. (18) Atropisomers are physically separable species when they have a half-life of at least 1000 s (16.7 min), at a given temperature. Bringmann, G.; Price Mortimer, A. J.; Keller, P. A.; Gresser, M. J.; Garner, J.; Breuning, M. Angew. Chem., Int. Ed. 2005, 44, 5384. (19) (a) Schmid, R.; Foricher, J.; Cereghetti, M.; Scho¨nholzer, P. HelV. Chim. Acta 1991, 74, 370. (b) Cereghetti, M.; Foricher, J.; Heiser, B.; Schmid, R. Eur. Patent 398,132, 1990; Chem. Abstr. 1991, 114, 247526. (c) Schmid, R.; Broger, E. A.; Cereghetti, M.; Crameri, Y.; Foricher, J.; Lalonde, M.; Mu¨ller, R. K.; Scalone, M.; Schoettel, G.; Zutter, U. Pure Appl. Chem. 1996, 68, 131.

890 Organometallics, Vol. 28, No. 3, 2009

Figure 1. Computed barriers to rotation around the connecting C-C bond for 2b (black curve) and 2a (gray curve) in a reservoir of chloroform molecules.

Doherty et al.

Figure 2. One of the two independent molecules of (R)-(+)-MeCATPHOS (R-2b) in the asymmetric unit of the crystal structure, illustrating the absolute stereochemistry about the buta-1,3-diene axis. Hydrogen atoms have been omitted for clarity; displacement ellipsoids here and in Figure 3 are drawn at the 40% probability level. The second molecule is essentially identical.

supports our reasoning above that Me-CATPHOS will be atropisomeric, while its unsubstituted counterpart will belong to the tropos class of diphosphine. Resolution, Characterization, and the Catalyst Precursor. Having established Me-CATPHOS to be atropos in nature, optical resolution of the racemic oxide was carried out using (2R,3R)-(-)-2,3-O-dibenzoyltartaric acid, (-)-DBTA, as resolving agent. Following a procedure outlined by Noyori,20 the diastereomerically pure complex of (S)-(+)-1b and (-)DBTA was obtained in 68% yield after only two crystallizations (Scheme 1). The (R)-(-)-enantiomer was obtained in 79% yield by recovering the remaining phosphine oxide and performing the corresponding resolution with (+)-DBTA. The enantiopurity of (R)- and (S)-1b was firmly established by HPLC analysis and comparison with a racemic sample. In contrast to the reduction of CATPHOS dioxide, which had to be conducted under mild conditions to avoid the formation of undesired byproduct,14 reduction of 1b required heating at 130 °C for 3 days in xylenes with a mixture of chlorosilane and tributylamine and gave (R)-2b in good yield.21 Reoxidation of samples of (R)- and (S)-2b and analysis by hplc revealed that the stereochemical integrity of the 1,3-butadiene tether had remained intact during reduction. The identity of (R)-2b and its absolute configuration were unequivocally established by a single-crystal X-ray study; the structure of one of the two crystallographically independent molecules in the asymmetric unit is shown in Figure 2, and the other is very similar, with the same absolute configuration. With the intention of using enantiopure Me-CATPHOS as a surrogate for biaryl diphosphines in rhodium-catalyzed asymmetric hydrogenations, the cationic precatalyst [{(R)-2}Rh(cycloocta-1,5-diene)][BF4] (3) was prepared by reaction of (R)2b with [Rh(cycloocta-1,5-diene)2][BF4] in CH2Cl2, isolated, and characterized by a single-crystal X-ray study; the molecular structure is shown in Figure 3. The rhodium atom has a distorted square-planar geometry, coordinated by the two phosphorus atoms in (R)-2b and the two double bonds in cycloocta-1,5diene, C(60)-C(61) and C(62)-C(65). The angle between the

Figure 3. Molecular structure of the [Rh{(R)-2}(cycloocta-1,5diene)]+ cation in 3, illustrating the spatial arrange of P-Ph rings and the absolute stereochemistry about the buta-1,3-diene axis. Hydrogen atoms have been omitted for clarity.

(20) (a) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayahsi, H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629. (b) Mashima, K.; Kusano, K.; Sato, N.; Matsumura, Y.; Nozaki, K.; Kumobayashi, H.; Sayo, N.; Hori, Y.; Ishizaki, T.; Akutagawa, S.; Takaya, H. J. Org. Chem. 1994, 59, 3064. (21) (R)-Me-CATPHOS is commercially available in >99% ee from Strem Chemical Co., Catalogue number 15-0443.

(22) (a) Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 7932. (b) Toriumi, K.; Ito, T.; Takaya, H.; Souchi, T.; Noyori, R. Acta Crystallogr. Sect. B 1982, 38, 807. (23) (a) Magistrato, A.; Merlin, M.; Pregosin, P. S.; Rothlisberger, U. Organometallics 2000, 19, 3591. (b) Schmid, R.; Cereghetti, M.; Heiser, B.; Scho¨nholzer, P.; Hansen, H.-J. HelV. Chim. Acta 1988, 71, 897.

P(1)-Rh(1)-P(2) plane and the plane defined by the rhodium atom and the midpoints of the two double bonds in cycloocta1,5-diene is 33.4°. The spatial arrangement of P-Ph rings in 3 clearly resembles that in [Rh{(R)-BINAP}(norbornadiene)][ClO4]22 and [Rh{(R)-BIPHEMP}(norbornadiene)][BF4]23 in that the two equatorial rings project into the P-Rh-P in-plane coordination sites, while the two axial rings expose their edges toward the rhodium and are orientated away from the coordination plane. In this regard, the asymmetric environment created by the alternating edge-face arrangement of P-Ph rings in 3 appears to resemble that in its (R)-BINAP counterpart, and as such, it would be reasonable to expect a catalyst based on (R)2b to exert (R)-BINAP-like stereocontrol (Vide infra). The dihedral angle of 73.2° between the two mean planes containing the double bonds and bridgehead carbon atoms of the two halves of the ligand (labeled in Figure 3), which measures the twist

Enantiopure Me-CATPHOS

Organometallics, Vol. 28, No. 3, 2009 891

about the C(2)-C(3) bond, is comparable to that of 71.8° in [Rh{(R)-biphemp}(norbornadiene)][ClO4],23 while the natural bite angle of 93.13(4)° is slightly larger than that reported for related complexes of biaryl diphosphines such as BINAP (91.82(5)°),22 BIPHEMP (90.5(1)°),23 MeO-BIPHEP (88.07(6)°),24 and H8-BINAP, (90.6(1)°).25 The pseudoaxial P-Ph rings also lie close and parallel to the endoaryl ring of the anthracene-derived tether, in much the same manner as the corresponding P-Ph rings in complexes of biaryl diphosphines orient parallel to the biaryl fragment. There is a considerable distortion away from C2-symmetry and an ideal alternating edgeface arrangement of P-Ph rings, as evidenced, for example, by the difference in dihedral angles between the pairs of rings attached to each P atom, 63.1° and 77.6°, as can be seen in Figure 3. Asymmetric Hydrogenation. On the basis of the biaryl-like nature of 2b we chose to evaluate its performance against BINAP, as this was considered to be a close structural analogue, and identified the rhodium-catalyzed asymmetric hydrogenation of dehydroamino acid derivatives and related substrates as suitable benchmark reactions for our comparison.26 Preliminary studies focused on the hydrogenation of methyl-2-acetamidoacrylate 4 using 1 mol % catalyst generated from [Rh(cycloocta-1,5-diene)2][BF4] and either (S)-2b or (R)-BINAP,27 under 1 atm of hydrogen at room temperature. Table 1 reveals that (S)-2b is an excellent ligand for the rhodium-catalyzed hydrogenation of methyl 2-acetamidoacrylate, giving the desired N-acetylalanine methyl ester 5 in near-quantitative isolated yield and greater than 99% ee. In stark contrast, while complete conversion was also obtained with its BINAP and MeO-BIPHEP

counterparts under the same conditions, the ee’s of 33% and 25%, respectively, are both very poor.6 The Rh/(S)-2 catalyst gave complete conversion and greater than 99% ee across the range of solvents examined, whereas its BINAP counterpart showed a marked solvent effect; the highest ee of 45% achieved in THF was significantly lower than that obtained with (S)-2b and slightly lower than that of 67% reported by Noyori for the hydrogenation of N-acetamidoacrylic acid.28 Gratifyingly, the Rh/(S)-2b system also performed well at 0.1 mol % loading and gave complete conversion to 5 within 16 h, again with >99% ee (entry 2). A catalyst based on (S)-2b is also more active and robust than its BINAP counterpart, as evidenced from (i) conversions obtained after 15 min (entries 3 and 6) and (ii) reactions conducted with catalyst generated in air using solvent that had been neither degassed nor predried; Rh/(S)-2b showed no loss in enantioselectivity and only a minor reduction in isolated yield (entry 4), whereas no conversion was obtained with Rh/(R)-BINAP under the same conditions (entry 7). The absolute stereochemistry of the product generated with Rh/(S)2b has been determined to be S, by comparison of the sign of the optical rotation with that reported in the literature,29 and corresponds to that obtained with (R)-BINAP; that is, (S)-2b exerts (R)-BINAP-like stereocontrol. This is both unexpected and difficult to rationalize at this stage, particularly since we have described (S)-2b as a biaryl-like diphosphine, based on the close similarity of the skewed seven-membered chelate ring as well as the spatial arrangement of P-Ph rings in 3 with related complexes of its enantiomeric BINAP counterpart (Vide supra). In addition, while BINAP is generally a much less effective ligand for the hydrogenation of dehydroamino acid derivatives than electron-rich systems based on DUPHOS,30 BisP*,31 and phosphite-phosphoroamidites,32 high ee’s have been obtained with catalysts based on 3,3′-modified MeO-BIPHEP and BINAP.6,7 In this regard, enantiopure 2b is a potential alterative to biaryl-diphosphines since it outperforms 3,3′-modified BINAP derivatives and can be prepared in three operationally straightforward steps. Hydrogenation of (Z)-methyl-2-acetamidocinnamate (6a), as a sterically more demanding dehydroamino acid, further demonstrated the marked enhancement in performance of (S)-2b compared with BINAP, as Rh/(S)-2b gave N-acetylphenylalanine methyl ester (7a) in excellent yield and 82% ee in dichloromethane, which was considerably better than the 37% ee obtained with its (R)-BINAP counterpart under the same conditions (Table 2). While Keay has also obtained a low ee for the same hydrogenation with catalyst generated in situ from [Rh(cycloocta-1,5-diene)2]OTf and (S)-BINAP, early studies by Noyori showed that the isolated solvento complex [Rh{(S)BINAP}(MeOH)2]ClO4 gave N-acetylphenylalanine in 84% ee. The poor ee obtained with catalyst generated in situ is most likely due to the formation of a 9:1 mixture of [Rh{(S)BINAP}(MeOH)2]ClO4 and dimeric [Rh2{(S)-BINAP}2][ClO4]2, the latter of which is also a catalyst for the asymmetric hydrogenation of R-dehydroamino acids but gives the corre-

(24) Zhang, X.; Mashima, K.; Koyano, K.; Sayo, N.; Kumobayashi, H.; Akutagawa, S.; Takaya, H. J. Chem. Soc., Perkin Trans. 1 1994, 2309. (25) Svensson, G.; Albertsson, J.; Frejd, T.; Klingstedt, T. Acta Crystallogr. Sect. C 1986, 42, 1324. (26) (a) Tang, W.; Zhang, X. Chem. ReV. 2003, 103, 3029. (b) Zhang, W.; Chi, Y.; Zhang, X. Acc. Chem. Res. 2007, 40, 1278. (c) Geneˆt, J.-P. Acc. Chem. Res. 2003, 36, 908. (d) Geneˆt, J.-P. Pure Appl. Chem. 2002, 74, 77. (f) Blaser, H.-U.; Malan, C.; Pugin, B.; Spindler, F; Steiner, H.; Studer, M. AdV. Synth. Catal. 2003, 345, 103. (27) (S)-2 and (R)-BINAP were chosen for our comparison, as preliminary catalyst testing showed that they gave hydrogenation products with the same absolute configuration.

(28) (a) Miyashita, A.; Takaya, Y. H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932. (b) Miyashita, A.; Takaya, Y. H.; Souchi, T.; Noyori, R. Tetrahedron 1984, 40, 1245. (29) Boaz, N. W.; Debenham, S. D.; Mackenzie, E. B.; Large, S. E. Org. Lett. 2002, 4, 2421. (30) (a) Burk, M. J.; Feaster, J. E.; Nugent, W. A.; Harlow, R. L. J. Am. Chem. Soc. 1993, 115, 10125. (b) Burk, M. J.; Lee, R. R.; Martinez, J. P. J. Am. Chem. Soc. 1994, 116, 10847. (31) (a) Yamanoi, Y.; Imamoto, T. J. Org. Chem. 1999, 40, 4833. (b) Cre´py, K. V. L.; Imamoto, T. AdV. Synth. Catal. 2003, 345, 79. (32) (a) Die´guez, M.; Ruiz, A. ; Claver, C. Chem. Commun. 2001, 2702. (b) Die´guez, M.; Pamies, O.; Claver, C. Chem. ReV. 2004, 104, 3189.

Table 1. Asymmetric Hydrogenation of 4 Using Catalyst Generated from (S)-2b or (R)-BINAPa

entry

ligand

solvent

yield (%)b

ee (%)c

1 2d 3e 4f 5 6e 7f 8 9 10 11 12

(S)-2b (S)-2b (S)-2b (S)-2b (R)-BINAP (R)-BINAP (R)-BINAP (S)-2b (R)-BINAP (S)-2b (R)-BINAP (S)-2b

CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 THF THF i-PrOH i-PrOH [emim][NTf2]

98 94 96 84 92 59 0 98 96 96 94 93

>99 >99 >99 >99 33 32 >99 45 >99 22 >99

a Reaction conditions: 1 mol % [Rh(cycloocta-1,5-diene)2][BF4], 1.1 mol % (S)-2b or (R)-BINAP, 4 (0.5 mmol), 1 atm H2, 5.0 mL of solvent, 1 h. b Isolated yields. c Determined by chiral GC using a Supelco Beta DEX column. d Reaction conducted with 0.1 mol % catalyst for 16 h. e Reaction stopped after 15 min. f Catalyst generated in air using undried solvent and reaction stopped after 15 min.

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Table 2. Asymmetric Hydrogenation of 6 Using Catalyst Generated from (S)-2b or (R)-BINAPa

entry

ligand

solvent

yield (%)b

ee (%)c

1 2d 3e 4 5 6 7 8 9 10

(S)-2 (S)-2 (S)-2 (R)-BINAP (S)-2 (R)-BINAP (S)-2 (R)-BINAP (S)-2 (R)-BINAP

CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 THF THF iPrOH iPrOH acetone acetone

94 84 44 92 77 75 26 76 81 72

82 92 94 37 80 47 71 25 77 38

a Reaction conditions: 1 mol % [Rh(cycloocta-1,5-diene)2][BF4], 1.1 mol % (S)-2b or (R)-BINAP, 6 (0.5 mmol), 1 atm H2, 5.0 mL of solvent, rt, 1 h. b Isolated yields. c Determined by chiral GC using a Supelco Beta DEX column. d Reaction conducted at 0 °C. e Reaction conducted at -20 °C.

Table 3. Asymmetric Hydrogenation of Methyl N-Acetylphenylalanine Derivatives 6b-e Using Catalyst Generated from (S)-2ba

entry d

1 2 3 4 5

R

7

yield (%)b

ee (%)c

4-Cl 4-Cl 4-Me 4-OMe 2-Cl

7b 7b 7c 7d 7e

88 89 84 90 77

78 87 91 64 88

a Reaction conditions: 1 mol % [Rh(cycloocta-1,5-diene)2][BF4], 1.1 mol % (S)-2b, 6b-e (0.5 mmol), 1 atm H2, 5.0 mL of CH2Cl2, 0 °C, 1 h. b Isolated yields. c Determined by chiral HPLC using a Daicel Chiralpak AD-H column. d Reaction conducted at room temperature.

sponding amino acids in very low ee. Reassuringly, the ee obtained with Rh/(S)-2b is also an improvement on that of 74% recently reported for a catalyst based on a 3,3′-diacetoxysubstituted BINAP.6a A small solvent effect was observed for this substrate, with dichloromethane giving the best ee; which improved from 82% at RT to 92% and 94% when conducted at 0 and -20 °C, respectively (entries 2, 3). The poor conversion obtained in 2-propanol is most likely due to low solubility of the catalyst in this solvent. The ee’s obtained with Rh/(R)BINAP were also solvent-dependent, but in all cases they were significantly lower than those obtained with Rh/(S)-Me-CATPHOS. The asymmetric hydrogenation of a limited range of dehydrophenylalanine derivatives 6b-e was also investigated using 1 mol % Rh/(S)-2b in dichloromethane at 0 °C and 1 atm H2, the results of which are listed in Table 3. Under these conditions high enantioselectivities (87-92%) and excellent conversions were obtained for each of the substrates tested, except for that with a 4-methoxy-substituted aryl ring, which gave 7d in excellent yield but only 64% ee. As for methyl 2-acetamidoacrylate, catalysts based on (S)-2b and (R)-BINAP gave 7a-e with the same absolute configuration, assigned as S by comparing the sign of the optical rotation with those reported in the literature.6b,30a,33 The absolute configurations of 7a-e (and 5) obtained with Rh/(S)-2b are the same as that obtained with catalyst generated from (R,R)-BICP34 as well as (S)-MeOBIPHEP substituted with phenyl groups at the 3,3′-positions.6b

Figure 4

As Rh/(S)-2b has the same spatial arrangement of axial and equatorial P-Ph rings as Rh/(R,R)-BICP and Rh/(S)-MeOBIPHEP, it is reasonable to rationalize the sense of asymmetric induction using the conventional quadrant diagram, in which the pseudoequatorial and -axial phenyl groups occupy alternating quadrants (Figure 4, gray and white).35 According to this model, the two equatorial phenyl rings of (S)-Me-CATPHOS provide effective shielding of the upper right and lower left quadrants, which determines the absolute stereochemistry of the product. However, if this model is correct for Rh/(S)-2b, it is then difficult to account for the absolute stereochemistry obtained with catalyst based on (R)-BINAP, since this model would necessarily predict product of opposite absolute stereochemistry. This implies that our description of (S)-2b exerting biaryl-like stereocontrol is perhaps oversimplified, and a more sophisticated model may be required to account for the sense of stereocontrol. Further studies are clearly required in order to understand the factors that effect stereocontrol in these hydrogenations. Perhaps some insight can be gleaned from the work of Keay, who noted that catalyst generated from 3,3′-acetoxy- and alkoxy-substituted BINAP ligands gave product of opposite absolute configuration to that obtained with BINAP, despite both having Sax configuration.6a While asymmetric hydrogenation of β-dehydroamino acid derivatives is often used as a model reaction to test the efficiency of new ligands and catalysts,36 hydrogenation of the β-dehydroamino phosphonates to access the corresponding β-amino phosphonates has only recently been reported.37 Gratifyingly, 1 mol % Rh/(S)-2b catalyzed the hydrogenation of (E)-dimethyl2-acetylamino-2-phenylvinylphosphonate (E-8a), in dichloromethane at 5 bar H2, giving complete conversion to the desired β-acetylaminophosphonate (9a) in 99% ee, the highest ee to be reported for this class of substrate (Table 4). As only a handful of catalysts efficiently hydrogenate (Z)-β-aminoacrylic acid derivatives,38 the hydrogenation of (Z)-8a was also investigated. Under the same conditions, Rh/(S)-2b gave 9a in good yield (33) The absolute stereochemistry of 7a has been determined to be S, by comparison of the sign of the optical rotation with that reported in the literature. (a) Navarre, L.; Martinez, R.; Geneˆt, J.-P.; Darses, S. J. Am. Chem. Soc. 2008, 130, 6159. (34) Zhu, G.; Cao, P.; Jiang, Q.; Zhang, X. J. Am. Chem. Soc. 1997, 119, 1799. (35) Knowles, W. S. Acc. Chem. Res. 1983, 16, 106. (36) For a recent reviews see:(a) Bruneau, C.; Renaud, J.-L.; Jerphagnon, T. Coord. Chem. ReV. 2008, 252, 532. (b) Ma, J.-A. Angew. Chem., Int. Ed. 2003, 42, 4290. (37) For a recent relevant review see: (a) Ma, J.-A. Chem. Soc. ReV. 2006, 35, 630. (b) Kadyrov, R.; Holz, J.; Scha¨ffner, B.; Zayas, O.; Almena, J.; Bo¨rner, A. Tetrahedron: Asymmetry 2008, 19, 1189. (38) For selected examples:(a) Chen, J.; Liu, Q.; Zhang, W.; Spinella, S.; Lei, A.; Zhang, X. Org. Lett. 2008, 10, 3033. (b) Zhang, Y.-J.; Kim, K.-Y.; Park, J.-H.; Song, C.-E.; Lee, K.; Lah, M.-S.; Lee, S.-g. AdV. Synth. Catal. 2005, 347, 563. (c) Zhou, Y.-G.; Tang, W.; Wang, W.-B.; Li, W.; Zhang, X. J. Am. Chem. Soc. 2002, 124, 4952. (d) Lee, S.-g.; Zhang, Y. J. Org. Lett. 2002, 4, 2429. (e) Tang, W.; Zhang, X. Org. Lett. 2002, 4, 4159. (f) Heller, D.; Holz, J.; Drexler, H.-J.; Lang, J.; Drauz, K.; Krimmer, H.P.; Bo¨rner, A. J. Org. Chem. 2001, 66, 6816. (g) You, J.; Drexler, H.-J.; Zhang, S.; Fischer, C.; Heller, D. Angew. Chem., Int. Ed. 2003, 42, 913. (h) Wu, H.-P.; Hoge, G. Org. Lett. 2004, 6, 3645.

Enantiopure Me-CATPHOS

Organometallics, Vol. 28, No. 3, 2009 893

Table 4. Asymmetric Hydrogenation of (E)- and (Z)-β-Enamidophosphonates Using Catalyst Generated from (S)-2b, (R)-BINAP, or (R)-(S)-JOSIPHOSa

entry

ligand

E/Z

R

yield (%)b

ee (%)c

1 2 3 4 5 6 7 8 9 10 11 12

(S)-2b (S)-2b (R)-(S)-JOSIPHOS (R)-(S)-JOSIPHOS (R)-BINAP (R)-BINAP (S)-2b (S)-2b (R)-(S)-JOSIPHOS (R)-(S)-JOSIPHOS (R)-BINAP (R)-BINAP

E Z E Z E Z E Z E Z E Z

H H H H H H 4-Me 4-Me 4-Me 4-Me 4-Me 4-Me

97 47 56 72 57 39 94 43 45 77 66 37

>99 24(+) 23(-) 98(+) 81(+) 5(-) >99 17(+) 18(-) >99 77(+) 4(-)

a Reaction conditions: 1 mol % [Rh(COD)2][BF4], 1 mol % (S)-2b, (R)-BINAP or (R)-(S)-JOSIPHOS, substrate (0.1765 mmol), 5 atm H2, 6.0 mL of CH2Cl2, rt, 32 h. b Isolated yields. c Determined by chiral HPLC using a Chiralcel OD-H column.

but only 24% ee, and with the opposite absolute stereochemistry of that obtained from the E-isomer. The disparate performance obtained with (E)- and (Z)-8a was further exemplified by a similar trend for their p-tolyl counterparts. In this case, Rh/(S)2b proved to be an exceptionally efficient catalyst for the hydrogenation of (E)-8b and again gave 9b in >99% ee but was a poor catalyst for (Z)-8b, as evidenced by the yield of 43% and ee of 17%. Even though Rh/(S)-2b efficiently catalyzes the hydrogenation of only (E)-8a,b, the ee’s obtained with this system are exceptional and significantly better than those reported with catalysts based on biaryl- and ferrocenyl-based phosphines such as JOSIPHOS, SYNPHOS, and BoPHOZ,37b which, although commercially available, are relatively expensive. However, in our hands (R)-(S)-JOSIPHOS is a complementary ligand to (S)-2 in that it forms a highly efficient catalyst for the asymmetric hydrogenation of (Z)-8a,b (Table 4), and thus together this pair of ligands provides a powerful protocol for effecting the highly enantioselective hydrogenation of both (E)- and (Z)-β-dehydroamino phosphonates. Finally, to complete the comparison, Rh/(S)-2b also outperformed its (R)-BINAP counterpart by a convincing margin, as evidenced by the ee’s of 81% and 7% obtained for the hydrogenation of (E)- and (Z)8a, respectively, and those of 77% and 4% for their p-tolyl counterparts. In contrast to the dehydroamino acids described above, Table 4 reveals that (S)-2b and (R)-BINAP deliver β-acetylaminophosphonate 9b with opposite absolute stereochemistry, for both the E- and Z-substrates; that is, (S)-2b exerts (S)-BINAP-like stereocontrol for this class of substrate, and the sense of asymmetric induction for both catalysts can be accounted for on the basis of the quadrant diagram. Even though the absolute ee’s obtained with the catalyst based on (S)-2b are markedly higher than its (R)-BINAP counterpart for the hydrogenation of R-dehydroamino acids as well as (E)β-dehydroamino phosphonates, it is clear that while one affords product with the same sense of enantioselection, the other provides product of opposite enantioselection, which is somewhat unexpected considering the close analogy between the biaryl-like nature of Me-CATPHOS and its enantiomeric BINAP counterpart. Although we cannot provide an explanation for the different sense of stereoinduction at this stage, we note that Imamoto has also reported that Rh/BisP* catalyzes the hydro-

genation of R- and β-dehydroamino acids with the opposite sense of enantioselection, which was attributed to different reactions pathways operating.39 Concluding Remarks. In summary, a new class of atropos enantiopure buta-1,3-diene-bridged diphosphine based on a bicyclic architecture has been prepared in an operationally practical and straightforward three-step procedure. This diphosphine forms a highly efficient catalyst for the asymmetric hydrogenation of dehydroamino acid derivatives and related substrates, giving ee’s in excess of 99% for selected substrates and in all cases outperforming its BINAP counterpart by a significant margin. In fact the ee’s obtained for the asymmetric hydrogenation (E)-β-dehydroamino phosphonates by Rh/(S)Me-CATPHOS are markedly better than those obtained with more expensive biaryl- and ferrocenyl-based catalysts and are in fact the highest to be reported for this class of substrate. Interestingly, the parallels between Me-CATPHOS and biaryl diphosphines do not appear to apply to all substrates since (S)2b exerts (S)-BINAP-like stereocontrol in the hydrogenation of β-enamidophosphonates but behaves in a (R)-BINAP-like manner in the hydrogenation of R-dehydroamino acid derivatives. However, the performance of Me-CATPHOS is encouraging and suggests that ligands based on this architecture may well be effective for a range of platinum group metal-catalyzed reactions. Moreover, since the biaryl motif is found in a host of important ligands, we anticipate that this new atropos bicyclic buta-1,3-diene-based architecture could find widespread use in asymmetric catalysis. In particular, research is well advanced in terms of preparing a library of related diphosphines based onsubstitutedanthracenesinordertodevelopastructure-efficiency relationship and to establish a rational basis for the efficacy of this new class of ligand.

Experimental Section Diels-Alder Reaction between 1,4-Bis(diphenylphosphinoyl)buta-1,3-diyne and 9-Methylanthracene. 1,4-Bis(diphenylphosphinoyl)buta-1,3-diyne (0.50 g, 1.11 mmol) and 9-methylanthracene (0.47 g, 2.44 mmol) were mixed in a flask and heated to 220 °C using a Wood’s metal bath. The temperature was then lowered to 200 °C and the mixture heated for a further 20 min until the mixture turned solid. The product was purified by column chromatography eluting with CH2Cl2/ethyl acetate (1:0 then 3:1) to afford 1 as a white solid in 88% yield (0.815 g). 31P{1H} NMR (202.5 MHz, CDCl3, δ): 25.6 (s, P(O)Ph2). 1H NMR (500.0 MHz, CDCl3, δ): 7.86 (dd, J ) 10.7, 8.3 Hz, 4H, C6H5 o-H), 7.61 (m, 2H, C6H5 p-H), 7.55 (m, 4H, C6H5 m-H), 7.49 (dd, J ) 12.8, 8.1 Hz, 4H, C6H5 o-H), 7.25 (m, 2H, C6H5 p-H), 7.16-7.11 (m, 6H, C6H4, C6H5 m-H), 7.08-7.04 (m, 4H, C6H4), 6.98 (t, J ) 7.3 Hz, 2H, C6H4), 6.93 (t, J ) 7.0 Hz, 2H, C6H4), 6.86 (t, J ) 7.3 Hz, 2H, C6H4), 6.82 (d, J ) 7.2 Hz, 2H, C6H4), 6.72 (d, J ) 7.1 Hz, 2H, C6H4), 4.88 (d, J ) 9.6 Hz, 2H, bridgehead CH), 1.29 (s, 6H, CH3). 13 C{1H} NMR (125.8 MHz, CDCl3, δ): 163.2 (m, CdCP), 148.0 (C6H4 Q), 147.5 (C6H4 Q), 145.9 (C6H4 Q), 143.2 (C6H4 Q), 137.2 (d, J ) 102 Hz, CdCP), 133.1 (d, J ) 11.5 Hz, C6H5 o-C), 132.8 (d, J ) 8.9 Hz, C6H5 o-C), 132.11 (d, J ) 107 Hz, C6H5 Q), 132.0 (d, J ) 103 Hz, C6H5 Q), 131.6 (d, J ) 2.8 Hz, C6H5 p-C), 131.2 (d, J ) 2.7 Hz, C6H5 p-C), 128.0 (d, J ) 11.4 Hz, C6H5 m-C), 127.9 (d, J ) 12.7 Hz, C6H5 m-C), 124.5 (C6H4), 124.4 (C6H4), 124.3 (C6H4), 124.2 (C6H4), 122.8 (C6H4), 122.6 (C6H4), 121.5 (C6H4), 120.9 (C6H4), 55.5 (dd, J ) 9.8, 1.4 Hz, bridgehead Q), 53.6 (d, J ) 12.1 Hz, bridgehead CH), 13.5 (CH3). LRMS (ESI+): m/z 835 [M + H]+. HRMS (ESI+): exact mass calcd for C58H45O2P2 (39) Yasutake, M.; Gridnev, I. D.; Higashi, N.; Imamoto, T. Org. Lett. 2001, 3, 1701.

894 Organometallics, Vol. 28, No. 3, 2009 [M + H]+ requires m/z 835.2895, found m/z 835.2921. Anal. Calcd for C58H44O2P2: C, 83.44; H, 5.31. Found: C, 83.76; H, 5.98. Resolution of rac-9,9′-Dimethyl-9,9′,10,10′-tetrahydro9,10,9′,10′-biethenobianthracene-11,11′-bis(diphenylphosphinoyl)12,12′-diyl (1). rac-1 (0.933 g, 1.119 mmol) was dissolved in warm chloroform (45 mL). A solution of (-)-DBTA (0.400 g, 1.119 mmol) in ethyl acetate (30 mL) was added and the solution refluxed for 10 min. The solution was allowed to stand at room temperature overnight, the resulting white solid was isolated and dried (filtrate retained for recovery of R-enantiomer), and the optical rotation was recorded, [R]D ) +26.0 (c 0.5, acetone). The product was recrystallized by dissolving the solid in warm chloroform (ca. 25 mL), adding ethyl acetate (ca. 10 mL) and heating the mixture at reflux for ca. 10 min. After standing at room temperature overnight the resulting white solid was isolated, washed with hexane, and dried. The optical rotation was measured once again, and the value +26.8 (c 0.5, acetone) was very close to the value from the first crystallization. The optically pure white solid was dissolved in dichloromethane (35 mL), and 20% aqueous NaOH (30 mL) was added. The organic layer was removed and the aqueous layer extracted with dichloromethane (2 × 15 mL). The combined organics were washed with aqueous NaOH (20 mL), water (2 × 15 mL), and brine (2 × 15 mL) and dried over MgSO4. The solvent was removed in Vacuo to afford (S)-1 as an analytically pure white solid in 68% yield (0.32 g). The combined mother liquors from the crystallizations were treated with NaOH as above, and then the resolution was repeated using (+)-DBTA to obtain enantiopure (R)-1 in 79% yield (0.37 g). The optical purity of the phosphine oxide enantiomers was confirmed by HPLC analysis (Chiralpak AD-H, hexane/ethanol (90:10, 0.8 mL/min), retention times: (R)enantiomer 5.5 min, (S)-enantiomer 7.4 min; [R]D ) +55.6 (S), -55.6 (R) (c 0.5, CH2Cl2)). Reduction of (R)- and (S)-9,9′-Dimethyl-9,9′,10,10′-tetrahydro-9,10,9′,10′-biethenobianthracene-11,11′-bis(diphenylphosphinoyl)-12,12′-diyl (1). A flame-dried pressure vessel was charged with enantiopure oxide (0.300 g, 0.360 mmol), xylenes (25 mL), and tri-n-butylamine (1.7 mL, 7.19 mmol). Trichlorosilane (1.45 mL, 14.39 mmol) was added slowly, the flask sealed, and the mixture heated at 130 °C for 72 h. After cooling to 0 °C, the reaction mixture was diluted with dichloromethane (20 mL), and then ice (10 g) followed by 20% aqueous NaOH (30 mL) were added slowly. After stirring vigorously at room temperature for 1 h, the organic layer was removed and the aqueous phase extracted with dichloromethane (3 × 20 mL). The organic fractions were combined, washed with saturated NaHCO3, water, and brine (2 × 10 mL each), dried over MgSO4, and filtered, and the solvent was removed in Vacuo. The crude product was washed with hexane (5 × 15 mL) to remove excess tri-n-butylamine and then purified by column chromatography eluting with hexane/dichloromethane (2:1) to afford enantiopure 2 as a spectroscopically pure white solid in 85% yield (0.245 g). X-ray quality crystals of (R)-2 were obtained by slow diffusion of a chloroform solution layered with methanol at room temperature. [R]D ) -98.6 (S), +98.6 (R) (c 1.0, CH2Cl2). 31P{1H} NMR (202.5 MHz, CDCl3, δ): -14.3. 1H NMR (500.0 MHz, CDCl3, δ): 7.40 (m, 2H, C6H5 p-H), 7.35 (t, J ) 7.4 Hz, 4H, C6H5 m-H), 7.28 (t, J ) 6.7 Hz, 4H, C6H5 o-H), 7.24 (d, J ) 8.0 Hz, 2H, C6H4), 7.17 (m, 4H, C6H4 and C6H5 p-H), 7.13 (t, J ) 7.5 Hz, 4H, C6H5 m-H), 7.03 (m, 4H, C6H4), 6.96 (m, 4H, C6H5 o-H), 6.80 (t, J ) 7.2 Hz, 2H, C6H4), 6.72 (t, J ) 7.4 Hz, 2H, C6H4), 6.56 (d, J ) 7.0 Hz, 2H, C6H4), 6.45 (d, J ) 7.4 Hz, 2H, C6H4), 4.96 (s, 2H, bridgehead CH), 1.33 (s, 6H, CH3). 13C{1H} NMR (125.8 MHz, CDCl3, δ): 164.0 (m, C ) CP), 148.1 (C6H4 Q), 146.6 (C6H4 Q), 146.5 (C6H4 Q), 146.4 (C6H4 Q), 143.0 (m, C6H5 Q), 138.0 (m, C6H5 Q), 136.9 (m, CdCP), 134.6 (m, C6H5 o-C), 132.6 (m, C6H5 o-C), 128.6 (C6H5 p-C), 128.2 (m, C6H5 m-C), 127.9 (m, C6H5 m-C), 127.4 (C6H5 p-C), 124.4 (C6H4), 124.3 (C6H4), 123.8 (C6H4), 123.7 (C6H4), 123.1 (C6H4), 122.7 (C6H4), 121.3 (C6H4), 120.6 (C6H4),

Doherty et al. 55.0 (bridgehead Q), 54.8 (t, J ) 4.0 Hz, bridgehead CH), 14.0 (CH3). LRMS (EI+): m/z 802 [M]+. HRMS (EI+): exact mass calcd for C58H44P2 [M]+ requires m/z 802.291829, found m/z 802.293823. Anal. Calcd for C58H44P2: C, 86.76; H, 5.52. Found: C, 86.94; H, 5.71. [{(R)-2}Rh(cycloocta-1,5-diene)][BF4] (3). To a solution of [Rh(cycloocta-1,5-diene)2][BF4] (0.1 g, 0.246 mmol) in dichloromethane (10 mL) was added a solution of (R)-2 (0.197 g, 0.246 mmol) in dichloromethane (10 mL). After stirring for 1 h, the solvent was removed under reduced pressure and the resulting brickred solid triturated with hexane (2 × 5 mL) and diethyl ether (2 × 5 mL). Crystallization by slow diffusion of a chloroform solution layered with hexane at room temperature gave 3 in 87% yield (0.235 g). [R]D ) -39.1 (S), +39.1 (R) (c 1.0, CH2Cl2). 31P{1H} NMR (202.5 MHz, CDCl3, δ): 18.7 (d, JRh-P ) 151 Hz). 1H NMR (500.0 MHz, CDCl3, δ): 7.61 (m, 6H, C6H5), 7.51 (t, J ) 7.3 Hz, 2H, C6H5), 7.33 (br, 4H, C6H5), 7.25 (m, 6H, C6H5), 7.20 (d, J ) 7.4 Hz, 2H, C6H4), 7.16 (br, 4H, C6H4), 7.02 (t, J ) 7.5 Hz, 2H, C6H4), 6.98 (t, J ) 7.4 Hz, 2H, C6H4), 6.91 (t, J ) 7.4 Hz, 2H, C6H4), 6.79 (d, J ) 7.2 Hz, 2H, C6H4), 6.67 (t, J ) 7.6 Hz, 2H, C6H4), 6.08 (d, J ) 7.5 Hz, 2H, C6H5), 5.26 (m, 2H, bridgehead CH), 4.40 (br, 2H, C8H12), 4.02 (br, 2H, C8H12), 2.62 (m, 2H, C8H12), 2.40 (m, 2H, C8H12), 1.89 (m, 2H, C8H12), 1.79 (m, 2H, C8H12), 1.28 (s, 6H, CH3). LRMS (ESI+): m/z 1013 [M]+. HRMS (ESI+): exact mass calcd for C68H56P2P2Rh [M]+ requires m/z 1013.29122, found m/z 1013.2913. Anal. Calcd for C66H56BF4P2Rh.2CHCl3: C, 60.97; H, 4.36. Found: C, 61.12; H, 4.74. General Procedure for the Rhodium-Catalyzed Hydrogenation of Methyl Dehydroaminophenylalanine Derivatives. A flame-dried Schlenk flask was charged with [Rh(cycloocta-1,5diene)2][BF4] (2.0 mg, 0.005 mmol), (S)-2 (4.4 mg, 0.0055 mmol), and CH2Cl2 (3.0 mL), and the resulting orange solution was stirred for 15 min. The olefin substrate (0.50 mmol) was added followed by additional CH2Cl2 (2.0 mL). The flask was purged five times with hydrogen and the reaction left to stir under an atmosphere of hydrogen for 1 h, after which time the solution was passed through a silica plug and the solvent removed in Vacuo to leave a pale orange oil. The pure product was isolated after purification by column chromatography, eluting with hexane/CH2Cl2. The known products were characterized by 1H NMR spectroscopy, the ee’s were determined by either chiral GC or hplc, and the absolute configuration was assigned by comparison of the sign of the optical rotation with that reported in the literature.6b,29,30a,33 General Procedure for the Rhodium-Catalyzed Hydrogenation of (E)- and (Z)-β-N-acetylamino Vinylphosphonates. A flame-dried Schlenk flask was charged with [Rh(cycloocta-1,5diene)2][BF4] (3.6 mg, 0.008825 mmol), (S)-2 (7.1 mg, 0.008825 mmol), and CH2Cl2 (5.0 mL), and the resulting orange solution stirred for 15 min. The substrate (0.1765 mmol) was added followed by additional CH2Cl2 (3.0 mL), and the resulting solution was transferred to a 50 mL Parr stainless steel benchtop reactor. The vessel was pressurized to 5 atm with hydrogen and left to stand for 10 s before releasing the gas through an outlet valve. After this sequence had been repeated six times the reactor was pressurized to ca. 5 atm and the solution stirred vigorously at 20-22 °C for 16 h. After releasing the pressure the mixture was diluted with dichloromethane and extracted from the reactor, and the solvent was removed to leave a pale orange oil. The pure product was isolated after purification by column chromatography eluting with CHCl3/MeOH (96:4). Details of the Calculations. All quantum chemical calculations were performed with the TURBOMOLE suite of programs,40 using a valence triple-ζ basis including one set of polarization functions.41 The DFT calculations were made with the BP86 functional (40) Ahlichs, R.; Ba¨r, M.; Ha¨ser, M.; Horn, H.; Ko¨lmel, C. Chem. Phys. Lett. 1989, 162, 165. (41) Scha¨fer, A.; Horn, H.; Ahlrichs, R. J. Chem. Phys. 1992, 97, 2571.

Enantiopure Me-CATPHOS (exchange functional B8842 and correlation functional P8643). The resolution-of-identity algorithm was used for the two-electron integrals employing the corresponding auxiliary basis sets.44 The COSMO solvation model,45 implemented in TURBOMOLE, was used for all calculations made in the condensed phase. The VMD program package46 was used for graphical representation of the computed structures. Structures were optimized without any symmetry restrictions. Molecular mechanics calculations used for generating starting structures were made with SPARTAN.47 X-ray Crystallography. A summary of crystal data and information on the data collections and structure determinations is given in Table S1. Data were measured on an Oxford Diffraction Gemini A Ultra diffractometer with Cu KR radiation (λ ) 1.54178 Å) for 2 and Mo KR radiation (λ ) 0.71073 Å) for 3, both at 150 K.48 Further details are in the deposited CIF. The structures were solved (42) Becke, A. D. Phys. ReV. 1988, A38, 3098. (43) Perdew, J. P. Phys. ReV. 1986, B34, 8822. (44) Weigend, F.; Ha¨ser, M. Theor. Chem. Acc. 1997, 97, 331. (45) Klamt, A.; Schu¨rmann, G. J. Chem. Soc., Perkin Trans. 1993, 2, 799. (46) Humpfrey, W.; Dalke, A.; Schulten, K. J. Mol. Graphics 1996, 14, 33. (47) SPARTAN ‘06; version 1.1.2; Wavefunction Inc., 18401 Von Karman Avenue, Suite 370 Irvine, CA 92612, USA. (48) CrysAlisPro; Oxford Diffraction Ltd.: Abingdon, Oxfordshire, UK, 2008.

Organometallics, Vol. 28, No. 3, 2009 895 by direct methods and refined on all unique F2 values,49 including unambiguous determination of the absolute configuration through the refined Flack parameter.50 Disorder was modeled for chloroform solvent molecules in the structure of 3.

Acknowledgment. We thank Professor Steven H. Bergens for his helpful and incisive discussions that were instrumental to the success of this project and Dr. Fred Hancock (Johnson Matthey) for lending his expertise during the resolution. We gratefully acknowledge the EPSRC for funding (CHS, Newcastle University) and Johnson Matthey for generous loans of rhodium salts. Supporting Information Available: Full details of experimental procedures and characterization data for all new compounds, details of catalyst testing, chiral HPLC and GC analysis of the products, and for compounds (R)-2 and 3 details of crystal data, structure solution and refinement, atomic coordinates, bond distances, bond angles, and anisotropic displacement parameters in CIF format. This material is available free of charge via the Internet at http://pubs.acs.org. OM801145V (49) SHELXTL. Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112. (50) Flack, H. D. Acta Crystallogr., Sect. A 1983, 39, 876.