Synthesis of Biaryl Diphosphines via a Stepwise Regioselective

Organometallics 2009, 28, 5273–5276 DOI: 10.1021/om9004862

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Synthesis of Biaryl Diphosphines via a Stepwise Regioselective Double Diels-Alder Cycloaddition-Elimination Sequence: Efficient Ligands for the Palladium-Catalyzed Amination of Aromatic Bromides Simon Doherty,* Catherine H. Smyth,* Ross W. Harrington, and William Clegg School of Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne NE1 7RU, U.K. Received June 9, 2009 Summary: Tropos and atropos biaryl diphosphines have been prepared in a stepwise, highly regioselective double DielsAlder cycloaddition-elimination sequence between 1,4-bis(diphenylphosphinoyl)buta-1,3-diyne and various 1,3-dienes; the unsymmetrical phosphine 2,60 -bis(diphenylphosphino)-20 methoxy-1,10 -biphenyl prepared using this approach forms an efficient catalyst for the amination of a range of aromatic bromides, giving conversions that rival those obtained with its BIPHEP counterpart.

Mono- and bidentate biaryl-based phosphines have evolved into an exceptionally important class of ligand as a result of their application in a host of important transitionmetal-catalyzed carbon-carbon and carbon-heteroatom bond-forming reactions.1 However, the synthesis of these phosphines is often a nontrivial multistep process;2 two common approaches involve construction of the biaryl architecture via Ullmann coupling of a phosphonate-based aryl halide3a,b and introduction of the phosphino groups via a palladium- or nickel-catalyzed coupling between a preformed biaryl ditriflate and the corresponding secondary phosphine.3c Even though these approaches are now wellestablished, the demand for more efficient, cost-effective, and modular methods has led to a number of recent innovative developments in the synthesis of this class of ligand. In this regard, we have reported that rhodium-catalyzed [2 þ 2 þ 2] cycloaddition between a phosphine-substituted

1,3-butadiyne and a selection of 1,n-tethered diynes affords highly substituted biaryl diphosphines,4a and an asymmetric version of this reaction was subsequently applied to the synthesis of axially chiral biaryl phosphines and phosphonates with exceptionally high enantioselectivity.4b,c Rhodium-catalyzed [2 þ 2 þ 2] cycloaddition between oxides and sulfides of 1-alkynylphosphines and 1,n-tethered diynes has also been used to prepare bulky biaryl monophosphines5 as well as tetra-ortho-substituted axial chiral biaryl monophosphines6 and P-stereogenic monoaryl phosphines,7 the latter via rhodium-catalyzed desymmetrization of dialkynylphosphine oxides. Tetra-ortho-substituted biaryl monophosphines have also been prepared via a Diels-Alder cycloaddition extrusion sequence between 1-alkynylphosphine oxides and oxygenated 1,3-dienes;8 palladium complexes of these phosphines are highly efficient catalysts for C-C and C-N coupling.9 We have now demonstrated that the corresponding double Diels-Alder cycloaddition-extrusion between 1,4-bis(diphenylphosphinoyl)buta-1,3-diyne and 1,3-dienes occurs in a stepwise, and highly regioselective, manner to afford symmetrical and unsymmetrical tropos and atropos biaryl diphosphine oxides, an approach that will complement existing methodologies and provide access to a host of new biaryl-based ligands. By analogy with the Diels-Alder approach developed by Carter,8 we reasoned that the corresponding cycloadditionextrusion between 1,4-bis(diphenylphosphinoyl)buta-1,3diyne (1) and 1-methoxy-1,3-cyclohexadiene would afford the oxide of MeO-BIPHEP (4) (Scheme 1).10 Gratifyingly, this approach proved successful, and thermolysis of a mixture of 1 and 1-methoxy-1,3-cyclohexadiene at 150 °C for 20 h in a sealed vessel resulted in a highly regioselective double cycloaddition-extrusion to afford 4 as the sole product; its identity was established by comparison of the spectroscopic properties with those reported in the literature

*To whom correspondence should be addressed. E-mail: simon. [email protected] (S.D.). (1) (a) Shimizu, H.; Nagasaki, I.; Sayo, N.; Saito, T. In Phosphorus Ligands in Asymmetric Catalysis; B€orner, A., Ed.; Wiley-VCH: Weinheim. Germany, 2008; p 207 (b) Li, Y.-M.; Yu, W.-Y.; Chan, A. S. C. Phosphorus Ligands in Asymmetric Catalysis; Borner, A. ,Ed.; Wiley-VCH: Weinheim, Germany, 2008; p 260. (c) Seyden-Penne, J. Chiral Auxiliaries and Ligands in Asymmetric Catalysis: Wiley: New York, 1995. (d) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley: New York, 1994. Biaryl monophosphines: (e) Surry, D. S.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 6339 and references therein. (f) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461. (2) (a) Shimizu, H.; Nagasaki, I.; Saito, T. Tetrahedron 2005, 61, 5405. (b) Berhod, M.; Mignani, G.; Woodward, G.; Lemaire, M. Chem. Rev. 2005, 105, 1801. (3) (a) Foricher, J.; Heiser, B.; Schmid, R. (Hoffmann-La Roche AG) PCT Int. Appl. WO 9216535. (b) Cai, D.; Payack, J. F.; Bender, D. R.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. Org. Synth. 1998, 76, 6. (c) Ager, D. J.; East, M. B.; Esienstadt, A.; Laneman, S. A. Chem. Commun. 1997, 2369. (4) (a) Doherty, S.; Knight, J. G.; Smyth, C. H.; Harrington, R. W.; Clegg, W. Org. Lett. 2007, 9, 4925. (b) Doherty, S.; Smyth, C. H.; Harrington, R. W.; Clegg, W. Organometallics 2008, 27, 4837. (c) Nishida, G.; Ogaki, S.; Yusa, Y.; Yokozawa, T.; Noguchi, K.; Tanaka, K. Org. Lett. 2008, 10, 2849.

(5) Kondoh, A.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2007, 129, 6996. (6) Nishida, G.; Noguchi, K.; Hirano, M.; Tanaka, K. Angew. Chem., Int. Ed. 2007, 46, 3951. (7) Nishida, G.; Noguchi, K.; Hirano, M.; Tanaka, K. Angew. Chem., Int. Ed. 2008, 47, 3410. (8) For the synthesis of racemic biaryl monophosphines via DielsAlder 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. (9) For the synthesis of related diphosphines via Diels-Alder cycloaddition see: (a) Doherty, S.; Knight, K. J.; Smyth, C. H.; Harrington, R. W.; Clegg, W. Organometallics 2008, 27, 1679. (b) Doherty, S.; Smyth, C. H.; Harrington, R. W.; Clegg, W. Organometallics 2009, 28, 888. (10) Schmid, R.; Foricher, J.; Cereghetti, M.; Sch€ onholzer, P. Helv. Chim. Acta 1991, 74, 370.

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Doherty et al. Scheme 1a

a

Legend: (i) 150 °C, 20 h, no solvent; (ii) microwave, toluene, 300 W.

and confirmed by a single-crystal X-ray study.11 The high regioselectivity can be accounted for by considering the possible steric interactions between the 1-methoxy substituent and the diphenylphosphino groups in the transition state for cycloaddition. As microwave heating has been shown to reduce reaction times quite significantly compared with the same reaction conducted under conventional heating,12 a toluene solution of 1 and 1-methoxy-1,3-cyclohexadiene was heated with a microwave power of 300 W from room temperature to 200 °C for 10 min, cooled to room temperature. and analyzed by 31P NMR spectroscopy; this sequence was repeated until all the starting material had been consumed. Near-quantitative formation of 4 was obtained after only five 10 min bursts of microwave irradiation; the yields obtained under thermal and microwave heating were comparable. Monitoring of the reaction progress revealed that the cycloaddition-extrusion occurs in a stepwise manner to initially give the monoadduct 3, which undergoes a subsequent slower cycloaddition-extrusion to afford 4. Intermediate 3 was isolated, characterized by spectroscopic and analytical methods, and shown to react with 1-methoxy-1,3-cyclohexadiene

to afford 4 as the sole product. The 31P NMR spectrum of 3 contains two distinct well-separated signals at δ 29.4 and 8.5 characteristic of the biarylphosphine oxide and the alkynylphosphine oxide fragments, respectively. The identity of 3 was unequivocally established by a single-crystal X-ray study, and a perspective view of the molecular structure is shown in Figure 1. The C(7)-C(8) bond length of 1.2006(19) A˚ is close to that expected for a carbon-carbon triple bond and is similar to those found in related monocycloaddition adducts generated from 1 and substituted cyclopentadiene13 and anthracene14 derivatives. The P(2)-C(7)-C(8) and C(6)-C(7)-C(8) bond angles of 173.89(13) and 173.82(14)°, respectively, also lie within the range of 172.25-177.21° for the corresponding angles in these monoadducts. Here it is worth noting that the alkynylphosphine oxide adduct 3 could be used as a template for the synthesis of unsymmetrical atropos biaryl diphosphines, either by performing a second cycloaddition-extrusion with a different 1,3-diene or by conducting a metal-catalyzed asymmetric [2 þ 2 þ 2] cycloaddition with a 1,n-diyne or an ynenitrile; the latter would provide direct access to new nonracemic biaryl diphosphines for use in asymmetric catalysis. In the case of the former strategy, 3 undergoes a microwave-assisted cycloadditionelimination with 1-methoxy-1,3-butadiene in toluene to afford 2,60 -bis(diphenylphosphinoyl)-20 -methoxy-1,10 -biphenyl (5), which was reduced to the corresponding phosphine, 6, by heating with an excess of trichlorosilane and Bu3N in xylenes at 130 °C for 5 h (Scheme 1).15 In this regard, the synthesis of dissymmetric atropos biaryl diphosphines has only recently been investigated; the first modular synthesis of this class of diphosphine was reported by Leroux and Mettler and relied on a highly regioselective halogen/metal exchange of a common polybrominated biaryl precursor, but required the use of a dummy substituent to avoid undesired cyclization to the “9-phosphafluorene”.16 Our stepwise cycloadditionextrusion approach complements the Leroux synthesis, and together these two strategies will provide access to a host of

(11) Full details of the X-ray analysis of 4 are provided in the Supporting Information. (12) (a) Roberts, B. A.; Strauss, C. R. Acc. Chem. Res. 2005, 38, 653. (b) Larhed, M.; Moberg, C.; Hallberg, A. Acc. Chem. Res. 2002, 35, 717. (c) Lidstr€ om, P.; Tierney, J.; Wathey, B.; Westman, J. Tetrahedron 2001, 57, 9225. (d) Kappe, C. O. Angew. Chem., Int. Ed. 2004, 46, 6250. (e) Polshettiwar, V.; Varma, R. S. Acc. Chem. Res. 2008, 41, 629. (f) Leadbeater, N.; Shoemaker, K. M. Organometallics 2008, 27, 1254.

(13) Huang, Y.-D.; Yu, H.-T.; Meng, J.-B.; Wang, Y.-M. Chin. J. Struct. Chem. 2002, 149, 21. (14) Huang, Y.-D.; Yu, H.-T.; Meng, J.-B.; Metsuura, T.; Wang, Y.-M. J. Mol. Struct. 2002, 610, 247. (15) (a) Zhang, Z.; Qian, H.; Longmire, J.; Zhang, X. J. Org. Chem. 2000, 65, 6223. (b) Gorobets, E.; Wheatley, B. M. M.; Hopkins, J. M.; McDonald, R.; Keay, B. A. Tetrahedron Lett. 2005, 46, 3843. (16) (a) Leroux, F. R.; Mettler, H. Adv. Synth. Catal. 2007, 349, 323. (b) Leroux, F. R.; Mettler, H. Syn. Lett. 2006, 766.

Figure 1. Molecular structure of cycloaddition adduct 3. Hydrogen atoms and the water molecule of crystallization have been omitted for clarity. Ellipsoids are at the 40% probability level.

Note

Figure 2. Molecular structure of [{2,60 -bis(diphenylphosphino)20 -methoxy-1,10 -biphenyl}PdCl2] (7) showing the conformation of the twist of the biaryl axis. Hydrogen atoms and solvent molecules have been omitted for clarity. Ellipsoids are at the 40% probability level. Scheme 2

new atropos C1-symmetric biaryl diphosphines. With the intention of evaluating the efficiency of 6 in the palladiumcatalyzed amination of aryl halides (vide infra), we also investigated its platinum group metal coordination chemistry. Dropwise addition of a dichloromethane solution of 6 into a dichloromethane solution of [(cycloocta-1,5-diene)PdCl2] resulted in near-quantitative formation of [{2,60 -bis(diphenylphosphino)-20 -methoxy-1,10 -biphenyl}PdCl2] (7). X-ray-quality crystals of 7 were grown by slow diffusion of n-hexane into a dichloromethane solution at room temperature; a perspective view of the molecular structure is shown in Figure 2. The coordination around palladium is somewhat twisted from regular square planar, with a dihedral angle of 21.7° between the PdP2 and PdCl2 planes, and the natural bite angle of 93.31(3)° is comparable to those of 92.24(4) and 92.69(8)° in [(BIPHEP)PdCl2]17 and [(BINAP)PdCl2],18 respectively. The dihedral angle of 80.2° between the leastsquares planes of the two aromatic rings of the biaryl fragment is slightly larger than those of 70.3 and 71.8° found in [(MeOBIPHEP)Pd{(R)-(þ)-N,N,dimethyl-R-methylbenzylamineC,N}]19 and [(BINAP)PdCl2],18 respectively, giving a more nearly perpendicular arrangement. The four phenyl rings of the diphenylphosphino groups are arranged in the familiar alternating edge-face arrangement. By analogy, the Diels-Alder cycloaddition between 1 and 1-methoxy-1,3-butadiene under microwave heating resulted in elimination of methanol to afford 1,10 -bis(diphenylphosphinoyl)biphenyl (9) in good yield.20 Not surprisingly, this (17) Ogasawara, M.; Yoshida, K.; Hayashi, T. Organometallics 2000, 19, 1567. (18) Ozawa, F.; Kubo, A.; Matsumoto, Y.; Hayashi, T.; Nishioka, E.; Yanagi, K.; Moriguchi, K. Organometallics 1993, 12, 4188. (19) Schmid, R.; Foricher, J.; Cereghetti, M.; Sch€ onholzer, P. Helv. Chim. Acta 1991, 74, 370. (20) (a) Desponds, O.; Schlosser, M. J. Organomet. Chem. 1996, 507, 257. (b) Vehara, A.; Bailar, J. C. J. Organomet. Chem. 1982, 239, 1.

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Figure 3. Molecular structure of cycloaddition adduct 12, confirming the E stereochemistry of the alkene fragment. Hydrogen atoms and the water molecule of crystallization have been omitted for clarity. Ellipsoids are at the 40% probability level. Scheme 3

transformation also occurs in a stepwise manner in that 1 undergoes an initial rapid Diels-Alder cycloaddition-extrusion sequence to give 8, which undergoes a slower second cycloaddition-extrusion to afford 9 (Scheme 2). Moreover, microwave-assisted heating of a toluene solution containing 8 and 1-methoxy-1,3-cyclohexadiene results in regioselective cycloaddition with elimination of ethylene to afford 5 as the sole product in excellent yield after eight 10 min bursts each of 300 W. By direct analogy with the studies described above, we reasoned that monoadduct 10, the product of a single cycloaddition between 1 and 1,3-pentadiene, would eliminate hydrogen to afford 11, which would undergo a second cycloaddition-elimination sequence to give the oxide of BIPHEMP.21 Surprisingly, though, microwave heating of a toluene solution of 1 and 1,3-pentadiene at 300 W/200 °C resulted in a single rapid cycloaddition with immediate hydrogen transfer to the triple bond of the remaining alkynylphosphine oxide to afford 12, as the sole product (Scheme 3). The identity of 12 was initially based on a number of distinctive features in the 31P and 1H NMR spectra as well as a molecular ion peak corresponding to [M þ H]þ at m/z 519 in the electrospray mass spectrum. Even though the presence of two signals at δ 32.6 and 24.5 in the 31 P NMR spectrum of 12 provided clear evidence that double cycloaddition had not occurred, both resonances appear close to the region expected for a biaryl diphosphine oxide, which suggested that both triple bonds had reacted. A double (21) (a) Schmid, R.; Cereghetti, M.; Heiser, B.; Sch€ onholzer, P.; Hansen, H.-J. Helv. Chim. Acta 1988, 71, 897. (b) Cereghetti, M.; Schmid, R.; Sch€onholzer, P.; Rageot, A. Tetrahedron Lett. 1996, 30, 5343.

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Table 1. Comparative Study of the Palladium-Catalyzed Arylation of Aniline and n-Hexylamine using Catalyst Generated from Pd2(dba)3 and either 6 or BIPHEPa

entry

phosphine

aryl bromide

R0

time (h)

yield (%)b

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

6 BIPHEP 6 BIPHEP 6 BIPHEP 6 BIPHEP 6 BIPHEP 6 BIPHEP

4-MeC6H4 4-MeC6H4 4-CNC6H4 4-CNC6H4 3,5-Me2-C6H3 3,5-Me2-C6H3 4-MeOC6H4 4-MeOC6H4 4-CNC6H4 4-CNC6H4 4-t-BuC6H4 4-t-BuC6H4

C6H5 C6H5 C6H5 C6H5 C6H5 C6H5 C6H5 C6H5 n-Hex n-Hex n-Hex n-Hex

8 8 3 3 3 3 6 6 5 5 7 7

89 82 91 93 87 76 79 73 69 75 92 88

a Reaction conditions: 1.0 mmol of Ar-Br, 1.1 mmol of amine, 0.134 g (1.4 equiv) of NaO-t-Bu, 0.5 mol % of Pd2(dba)3, 1.5 mol % of 6 or BIPHEP, 1.5 mL of toluene, 80 °C. b Isolated yield. Average of three runs.

of doublets at δ 6.69 coupled to a multiplet at δ 7.30, each of intensity 1H and with a 3JHH value of 17.9 Hz, are characteristic of an aryl-substituted trans alkene. The identity of 12 was conclusively established by a single-crystal X-ray study; a perspective view of the molecular structure is shown in Figure 3. The structure clearly shows that 12 contains an arylphosphine oxide, derived from cycloaddition to one of the triple bonds of 1, and an aryl-substituted trans vinylphosphine oxide, arising from stereoselective hydrogen transfer across the adjacent triple bond in the intermediate cyclohexadiene adduct 10. The C(1)-C(2) bond length of 1.326(2) A˚ is close to that expected for a C(sp2)-C(sp2) double bond (1.34 A˚) and is similar to that of 1.339 A˚ in an unoxidized vinyldiphenylphosphine22 (where the double bond has a Z configuration) and that of 1.334 A˚ for all three E-configuration substituents of tris(styryl)phosphine oxide, which has exact crystallographic 3-fold rotation symmetry.23 Evidence for intermediate 10 was initially obtained by monitoring the thermal reaction between 1 and 1,3-pentadiene by 31P NMR spectroscopy, which showed the appearance of two resonances at δ 28.3 and 8.2, associated with the biarylphosphine oxide and alkynylphosphine oxide fragments, respectively, as well as electrospray mass spectrometry, which showed the presence of a molecular ion peak at m/z 519 corresponding to [M þ H]þ. Intermediate 10 was eventually isolated in high yield after heating the reaction mixture at 100 °C for 16 h. Microwave heating of a toluene solution containing 10 at 200 °C using an initial microwave power of 300 W resulted in near-quantitative conversion to 12 after five cycles each of 10 min. In stark contrast, thermolysis of a toluene solution of 10 using conventional heating methods resulted in hydrogen elimination to afford 11 as the major product together with a minor amount (ca. 15%) of hydrogen transfer adduct 12; the spectroscopic (22) Taillefer, M.; Cristau, H. J.; Fruchier, A.; Vicente, V. J. Organomet. Chem. 2001, 624, 307. (23) Bushuk, B. A.; Bushuk, S. B.; Cherepennikova, N. F.; Douglas, W. E.; Fukin, G. K.; Grigoviev, I. S.; Klapshina, L. G.; van der Lee, A.; Semenov, V. V. Mendeleev Commun. 2004, 109.

properties of 11 are similar to those of 3 and 8 (Scheme 3). Thus, conventional heating methods allows for the selective synthesis of the desired monadduct in good yield. Since palladium(0) complexes of biaryldiphosphines have been shown to be effective catalysts for the amination of aryl bromides with primary amines,24 this transformation was deemed to be an appropriate benchmark with which to undertake a comparative study between 6 and BIPHEP. Our preliminary evaluation focused on the amination of a range of aryl bromides with aniline and n-hexylamine using Pd2(dba)3/(phosphine) (1 mol % Pd) in toluene at 80 °C with sodium tert-butoxide as base; full details are given in Table 1. Gratifyingly, both amines coupled with a range of electron-poor and electron-rich aryl bromides; the former gave good conversions as expected, while good conversions could also be achieved with the latter more challenging substrates after sufficiently long reaction times. Although this comparison has been limited to a restricted range of substrate combinations, in the majority of cases Pd(0)/6 either competed with or outperformed its BIPHEP counterpart. In conclusion, this note describes the use of a regioselective stepwise double Diels-Alder cycloaddition-elimination sequence to prepare symmetrical and unsymmetrical biaryl diphosphines. In this regard, it will be straightforward to diversify the library of available biaryldiphosphines, since the steric and electronic properties can be modified through the phosphino groups of the butadiyne-bridged diphosphine, which is prepared from the dilithiobutadiyne and an appropriate chlorophosphine, while the substitution pattern of the biaryl architecture can varied through a judicious choice of diene, which is either commercially available or can be prepared from commercially available reagents. The stepwise manner of this approach could also lend itself to the selective synthesis of a much broader range of monosubstituted pseudo-C2-symmetric atropos biaryl diphosphines, while an asymmetric [2 þ 2 þ 2] cycloaddition between a monoadduct and a 1,n-diyne will provide access to new chiral C1-symmetric biaryl-differentiated diphosphines; precedent suggests this could occur in exceptionally high ee.4b,4c Preliminary catalyst testing using the arylation of primary amines as a benchmark reaction for comparison showed that Pd(0)/6 rivals its BIPHEP counterpart for the majority of substrate combinations. The use of Diels-Alder cycloaddition and extrusion to construct biaryl diphosphines provides a complementary approach to existing methodologies and is likely to find applications across the broader areas of ligand synthesis and catalysis.

Acknowledgment. We gratefully acknowledge the EPSRC for a studentship (C.H.S.) and an equipment grant (W.C.) and Johnson Matthey for generous loans of palladium salts. Supporting Information Available: Text, a figure, and a table giving full details of experimental procedures, characterization data for all new compounds, and details of catalyst testing and CIF files for compounds 3, 4, 7, and 12 giving details of crystal data, structure solution and refinement, atomic coordinates, bond distances, bond angles, and anisotropic displacement parameters. This material is available free of charge via the Internet at http://pubs.acs.org. (24) (a) Wolfe, J. P.; Wagaw, S.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 7215. (b) Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144.