Indian Patents. 270761:TETRAPHOSPHORUS LIGANDS FOR CATALYTIC HYDROFORMYLATION AND RELATED REACTIONS

Title of Invention	TETRAPHOSPHORUS LIGANDS FOR CATALYTIC HYDROFORMYLATION AND RELATED REACTIONS
Abstract	Tetraphosphorous ligands are combined with transition metal salts to form catalysts for use in hydroformylation, isomerization-hydroformylation, hydrocarboxylation, hydrocyan-ation isomerization-formylation, hydroaminomethylation and similar related reactions.

Full Text	TETRAPHOSPHORUS LIGANDS FOR CATALYTIC HYDROFORMYLATION AND RELATED REACTIONS Cross Reference to Related Application [001] This application claims the benefit of priority of Provisional Application No. 60/750,733 filed December 15, 2005, which is incorporated herein by reference. Field of the Invention [002] The present invention relates to new phosphorous ligands and their applications in hydroformylation and related reactions. More particularly, the present invention relates to transition metal complexes having chelating tetraphosphorus ligands with multichelating modes. Tetraphosphorus ligands with multichelating modes can enhance coordinating abilities for transition metals such as Rh and Ni, and thus enhance selectivities of catalytic reactions. The transition metal-tetraphosphorus complexes according to the present invention are useful as catalysts in hydroformylation, isomerization- hydroformylation, hydrocarboxylation, hydrocyanation, tandem reactions such as isomerization-formylation, and hydroaminomethylation. Background of the Invention [003] Hydroformylation, discovered by Roelen in 1938, has been the largest homogeneous catalytic process in industry. More than 15 billion pounds of aldehydes and alcohols per year have been produced based on Fe, Zn, Mn, Co, Cu, Ag, Ni, Pt, Pd, Rh, Ru and Ir based catalysts. In these processes, achieving high selectivity to linear products is extremely important for commercial application. Despite the extensive investigation by both academic and industrial groups such as BASF, Dow, Shell and Eastman, among others, there still remain fundamental and practical problems regarding selectivity. New concepts for controlling selectivities are very important in catalytic reactions. Highly efficient selective catalysts will allow some bulky chemicals to be produced in an environmentally sound manner under milder conditions. [004] Cobalt catalysts (e.g., HCo(CO)4) dominated industrial hydroformylation until rhodium catalysts (e.g., HRh(CO)2(PPh3)3 ) were introduced in earlier 1970's. In 2004, it is estimated that approximately 75% of all hydroformylation processes were based on rhodium triarylphosphine catalysts. Achieving high regioselectivity to linear aldehydes is critical for hydroformylation and related reactions. The resulting aldehydes are converted to alcohols, carboxylic acids or other derivatives, which are used as plasticizers, detergents, surfactants, solvents, lubricants and chemical intermediates. [005] Scheme 1 below shows the dissociation of a Rh catalyzed hydroformylation catalyst. [006] The successful commercialization of HRh(CO)(PPh3)2 technology has been based on the key discovery of Pruett at Union Carbide and Booth at Union oil that the use of rhodium with excess phosphine ligand can lead to forming active, selective hydroformylation catalysts. The need for excess phosphines is due to the facile Rh-PPh3 dissociation in the catalytic system as illustrated by Scheme 1. Loss of PPh3 from HRh(CO)(PPh3)2 results in more active, but less regioselective hydroformylation catalysts B and C. In the commercial process, up to an 820 fold excess of PPh3 to Rh is used to assure high lineanbranch selectivity ratio, i.e., up to 17:1, for the hydroformylation of 1-hexene. Commercial hydroformylation of propylene has been run with a 400 fold excess of PPh3 to Rh with a lineanbranch selectivity ratio of 8-9:1 being achieved. [007] Rh/PPh3 catalyzed hydroformylation is the key for making all oxo alcohols. Propylene is the largest single alkene hydroformylated to produce butylaldehyde, which can be hydrogenated to produce butanol, or dimerized by an aldol condensation and then hydrogenated to form 2-ethyl-1-hexanol, the largest single product produced by hydroformylation (over 5 billion lbs a year). 2-ethyl-1-hexanol is usually reacted with phthalic anhydride to produce dialkyl phthalic esters that are used as plasticizers to keep polyvinyl chloride plastics soft and flexible. [008] In the hydroformylation process, it is critical to get cheaper feed stocks for starting materials. For example, internal higher alkenes (SHOP alkenes) such as 3-octenes are desirable for converting the alkenes to linear aldehydes. Direct use of raffinate II (a mixture of n-butenes/butanes) and 1-butene and 2-butene mixtures are useful for hydroformylation. For hydroformylation of n-alkenes, it is important to obtain high linear selectivity. Hydroformylation of allylic alcohol and subsequent reduction can lead to 1, 4 butenol. Functionalized internal alkenes can be used as alternative routes to bifunctional building blocks for polymers. Hydroformylation of methyl-3-pentenoate leads to making starting materials for polyamides and polyesters. In the tandem-isomerization and - hydroformylation processes, high isomerization rates combined with high selectivity towards terminal aldehydes are desirable with minimized undesirable hydrogenation reactions and minimiun isomerization towards conjugated compounds. [009] To overcome the need of using large excess of phosphines in the hydroformylation processes and achieve high regioselectivity, a new generation of transition metal catalysts were developed using bisphosphine ligands. -For example: Bisbi by Eastman Chemical; Xantphos by Prof. Leeuwen (University of Amsterdam), Bernhard Breit, Ace. Chem. Res. 2003, 36, 264-275, Bernhard Breit,'~WoIfgang Seiche, Synthesis 2001, 1, 1-36); and UC-44 by Union Carbide. These ligands are illustrated below. By using these ligands, a typical 400 fold excess of PPh3 has been reduced to a 5 fold excess of chelating phosphines. This new generation of chelating phosphines has led to high linear branched ratios as well as to higher catalytic activities. For example, a linear to branch ratio of 70-120:1 for hydroformylation of 1-hexene has been observed. Casey and van Leeuwen proposed that part of regioselectivity in the Rh-catalyzed hydroformylation is due to metal bisphosphine bite angle around 120 degree is formed, i.e., "the Bite angle hypothesis" as illustrated below. [0010] Despite that a number of chiral bisphosphorus ligands being-used as catalysts for hydroformylation and related reactions, the highly selective, active phosphorus ligands for . hydroformylation still remain an area of strong research interest. However, because of the dissociation of phosphines from the Rh-CO coordination, is a problem for achieving high regioselectivity, that is high linear to branch ratios of the products produced. Developing families of phosphorus ligands with multi-chelating coordination modes is attractive. The tetraphosphorous ligands of the present invention, because of their coordinating abilities through multi-chelating coordination modes, lead to highly regioselective transition in metal- ligand catalyzed hydroformylation and related reactions to provide high linear to branch ratios than those previously obtained. Also, the symmetric nature of these ligands allows these ligands to be prepared easily. Summary of the Invention [0011] In the present invention, we introduce a variety of tetraphosphorus ligands (Type A) with multi-chelating coordination modes as illustrated. below to enhance coordination abilities: where M is a metal selected from the group consisting of Fe, Zn, Mn, Co, Cu, Ag, Ni, Pt, Pd, Rh, Ru and Ir; X is selected from the group consisting of O, NH, NR and CH2; Y is selected from the group consisting of Ar, OAr and pyrrole; R is an organic group and Ar is an aryl group. Type A ligand is a tetraphosphorous ligand of the present invention. Type B ligand is a bisphosphorous ligand. As illustrated below, the tetraphosphorus ligand (Type A) has at least four chelating coordination modes to enhance coordination abilities whereas the bisphosphorus ligand (Type B) has a single mode, namely, P1-M-P2. Compared with normal bisphosphorus ligands (Type B), the multi-chelating tetraphosphorus ligands (Type A) of the present invention enhance the coordinating abilities of ligands without major change of electronic properties of ligands. Detailed Description of the Invention [0012] The present invention is directed to tetraphosphorous ligands having multi- chelating coordination modes to used as catalysts for hydroformylation and related reactions. The transition metal catalysts prepared using the tetraphosphorous ligands of the present invention are highly active and regioselective. The tetraphosphorous ligands of the present invention have the following generic structure: wherein i, j, k, 1, m and n are, independently, H, R, Ar, substituted Ar, OR, OAr, COOEt, halide, SO2R, SO3H, SO2NHR, POR2, POAr2 or NR2, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; X1-X4 are, independently, R, Ar, OR, OAr, pyrrole or substituted pyrrole, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; and Y1, Y'1, Y2, Y'2, Y3, Y'3, Y4, Y'4, are, independently, R, Ar, OR, OAr, pyrrole or substituted pyrrole, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl, or where R, Ar, OR, OAr, pyrrole and substituted pyrrole are linked with a carbon to carbon bond, CH2, NH, NR and O. The substituted groups would include, for example, methyl, ethyl, t-butyl and phenyl. [0013] The following illustrates a first embodiment of the invention: wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; and a, b c, d, i, j, k, l, m and n are, independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H, POR2, halide or two of a, b, c, d, i, j, k, I, m and n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. [0014] A second embodiment of the invention is illustrated below: wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl; and Ar is an aryl; and a, b, c, d, e, f, i, j, k, I, m and n are, independently, H, alkyl, aryl, substituted alkyl, substituted, aryl, OR, OAr, SiR3, COOR, SO3R, SO3H, POR2, halide or two of a, b, c, d, e, f, i, j, k, 1, m and n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. [0015] A third embodiment of the invention is illustrated below: wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; and a, b, c, d, e, i, j, k, l, m and n are, independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H, POR2, halide, NR2, or two of a, b, c, d, e, i, j, k, 1, m and n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. [0016] A fourth embodiment of the invention is illustrated below: wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; Y is a carbon-carbon bond, O, CH2, NH or NR, where R is an alkyl, substituted alkyl, aryl or substituted aryl; and a to n are, independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H, POR2, halide, NR2, or two of a to n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. [0017] A fifth embodiment of the invention is illustrated below: wherein X is O, CH2, NH, NR, NSO2R,or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; and a, b, c, d, e, i, j, k, 1, m and n are, independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, CQOR, SO3R, SO3H, POR2, halide, NR2, or two of a, b, c, d, e, i, j, k, 1, m and n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. [0018] A sixth embodiment of the invention is illustrated below: wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; and a to n are, independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H, POR2, halide, NR2, or two of a to n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. When d and e are not hydrogen, enantiomers of these ligands can prepared for asymmetric catalytic reactions. [0019] Examples of the tetraphosphorus ligands of the present invention (LI to L91) are illustrated below: [0020] In a hydroformylation or related reaction, the transition metal- tetraphosphorous ligand complex is prepared by mixing a transition metal salt with the ligand. Hie transition metal salt is a salt of a transition metal selected from the group consisting of Fe, Zn, Mn, Co, Cu, Ag, Ni, Pt, Pd, Rh, Ru and Ir. Examples of the transition metal salts are FeX3> Fe(OTf)3, Fe(OAc)3, Mn(0Ac)3, Mn(OTf)3) MnX3, Zn(OTf>2, Co(OAc)zs AgX, Ag(OTf), Ag(OTf)2) AgOAc, PtCl2l HaPtCU, Pd2(DBA)3, Pd(OAc)2s PdCl2(RCN)2, (Pd(allyl)Cl)2, Pd(PR3)4, (Rh(NBD)2)X, (Rh(NBD)Cl)2, (Rh(COD)Cl)2, (Rh(COD)2)X, Rh(acac)(CO)2, Rh(ethylene)2(acac), (Rh(ethylene)2Cl)2, RhCl(PPh3)3, Rh(CO)2Cl2, RuH(CO)2(PPh3)2, Ru(Ar)X2, Ru(Ar)X2(PPh3)3, Ru(COD)(COT), Ru(COD)(COT)X, RuX2(cymen), Ru(COD)n, RuCfe(COD), (Ru(COD)2)X, RuX2(PN), RuCl2(=CHR)(PR'3)2, Ru(ArH)Cl2, Ru(COD)(methallyl)2, (Ir(NBD)2Cl)2, (Ir(NBD)2)X, (Ir(COD)2Cl)2, (Ir(COD)2)X, CuX (NCCH3)4, Cu(OTf), Cu(OTf)2, Cu(Ar)X, CuX, Ni(acac)2, NiX2, (Ni(allyl)X)2, Ni(COD)2j MoO2(acac)2, Ti(OiPr)4, VO(acac)2 and MeReO3, wherein each R and R' is independently selected from the group'consisting of alkyl or aryl; Ar is an aryl group group; X is a counteranion, such as BF4, CIO4, OTf, SbF6, CF3SO3, B(C6H3(CF3)2)4, Cl,Br or I; OTf is OSO2CF3; DBA is PhCH=CHCOCH=CHPh, NDB is norbornadiene; COD is cyclooctodiene and COT is cyclooctotriene; The mixture is placed in an autoclave that is purged with nitrogen and subsequently charged with CO and H2. Synthesis of the Tetraphosphate.Ligand [0021] All reactions and manipulations in the example set forth below were performed in a nitrogen-filled glovebox or using standard Schlenk techniques. THF and toluene were dried and distilled from sodium-benzophenone ketyl under nitrogen. Methylene "chloride was distilled from CaH2. Methanol was distilled from Mg under nitrogen. Column chromatography was performed using EM silica gel 60 (230-400 mesh). 1H, 13C and 31P NMR were recorded on Bruker WP-200, AM-300, and AMX-360 spectrometers. Chemical shifts were reported in ppm down field from tetramethylsilane with the solvent resonance as the internal standard. MS spectra were recorded on a KRATOS mass spectrometer MS 9/50 for LR-EI and HR-EI. GC analysis was carried on Helwett-Packard 6890 gas chromatography using chiral capillary columns. HPLC analysis was carried on WatersTM 600 chromatography. [0022] The following procedure was used to synthesize ligand having the structure L1. To a solution of chlorodipyrrolyphosphine (4.4 mmol, 0.87g) in THF (10 mL) was added dropwise triethylamine 1mL and a solution of tetraol (1 mmol, 0.218 g) in THF (5 mL) at room temperature. Tetraol was synthesized according to Lindsten, G.; Wennerstroem, O.; Isaksson, R., J. Org. Chetn. 1987, 52, 547-54, and chlorodipyrrolyphosphine was prepared according van der Slot, S. C; Duran, J.; Luten, J.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Organometallics 2002, 21, 3873-3883. TriethyIamine-HCl salts were formed immediately after the addition. The reaction mixture was stirred for 6h at room temperature. The triethylamine-HCl salts were then filtered off and the solvent was removed under vacuum. The crude product was purified by flash chromatography on basic aluminum oxide eluted with hexane/EtOAc/NEt3 (6:1:0.01) to produce ligand L1 (0.31 g, 36%) as a air-stable colorless solid. 1H NMR (300 Hz, CDCl2) δ 7.23 (t, 2H, J= 8.3 Hz), 6.68 (m, 20H), 6.21 (m, 16H); 13C NMR (90 Hz, CDCl2) δ 152.86 (d, J= 12.2Hzl3l.0, 121.4(d, J= 16.8Hz), 118.1, 115.3(d, J= 13.7 Hz ), 112.7; 31P NMR (146Hz, CDCl2) δ 107.3. HRMS (ES+) calcd. for C44H39N8O4P4 [MH+] 867.2045, found 867.2021. Typical Hydroformylation Process [0023] To a 2 mL vial with a magnetic stirring bar was charged the tetraphosphprus ligand L1 prepared in the previous example (3 µmol, 2.6 mg) and Rh(acac)(CO)2 (1 µmol, 0.1 mL of 10 mM solution in toluene). The mixture was stirred for 5 min. Then 2-octene (10 mmol, 1.56 mL) was added followed by decane (0.01 mL) as internal standard. The reaction mixture was transferred to an autoclave. The autoclave was purged with nitrogen for three times and subsequently charged with CO (5 bar) and H2 (5 bar). The autoclave was then heated to 100°C (oil bath). After 12h, the autoclave was cooled in icy water and the pressure was carefully released in a well ventilated hood. The reaction mixture was immediately analyzed by GC. [0024] The remarkable regioselectivities using a multi-chelating tetraphosphorus ligand LI for hydroformylation of styrene, 1-octene and 1-hexene are demonstrated in Table 1. Normally, styrene is a difficult substrate for achieving more than 2:1 ratio of linear to branched products when compared to bisphosphorous ligands of the prior art such as xantphos and UC-44. As shown in Table 1, the new tetraphosphorus ligands (Type A) such as LI is more selective hydroformylation ligand than the prior art bisphosphorous ligand (Type B). The reaction conditions included 0.1 mol%- Rh(CO)2(acac) and ligand, reaction temperature 80° C for 1 hour at 20 atm of CO and H2. These results indicate that tetraphosphorus ligands with multi-chelating coordination can be used to increase coordinating abilities of bisphosphine ligands. The regioselectivity with Type A is the highest reported to date. The results of hydroformylation of 2-hexene and 2-octene using the tetraphosphorus iigand (Type A) vs bisphosphorus Iigand (Type B) to produce an aldehyde are summarized below in Table 2. In Tables 2 to 11 which follow, "n:i" is the ratio of linear aldehyde to branched aldehyde and "TOF" is turnover frequency (turnover per catalyst per hour). The tetraphosphorus ligands of the present invention produce higher "n:i" ratios than bisphosphorus ligands. The hydroformylation conditions were S/C = 10000, [Rh] is 0.69 mM (for 2-hexene) and 0.57 mM (for 2-octene), Ligand/Rh ratio is 3:1, reaction temperature is 100°C, CO/H2 is 5/5 atm, toluene is the solvent, and decane is the internal standard. [0025] Table 3 below shows the results of hydroformylation of 1-hexene and 1-octene using the tetraphosphorus ligand (Type A) vs bisphosphorus ligand (Type B) to produce an aldehyde by a hydroformylation reaction: The reaction conditions: S/C = 10000, Rh concentation is 0.2mM, Ligand/Rh ratio is 3:1, temperature is 80°C, CO/H2 is 10/10 atm, toluene is the solvent, and decane is the internal standard. [0026] The hydroformylation reaction is highly dependent on the reaction conditions. Typical reaction conditions are S/C=10000, ligand metal ratio of about 3, transition metal. concentration of about 0.2 to 0.7mM, reaction temperature is 100°C,and the reaction time is 12h. To optimize the reaction conditions, the following experiments have been carried out with tetraphosphorus ligand (LI). As evidenced by the "n:i" ratios in Tables 2 and 3, there a substantial and significant improvement in the amount of linear aldehyde produced using a tetraphosphorus ligand of the present invention as opposed to using a bisphosphorus ligand. Ligand to Metal Ratio [0027] The hydroformylation was first carried out with different ligand to metal ratios. As shown in Table 4, increasing the ligand metal ratio slightly decreased the reaction rate. On the other hand, the ligand to metal ratio significantly affects the regioselectivity. At lower ratios, low regioselectivity were observed. A minimum ligand to metal ratio of 2 is essential to achieve high regioselectivity, which allows the tetraphosphorus ligand to be coordinated in a multi-coordination mode. Further increasing the ligand to metal ratio did not significantly improve the regioselectivity. The reaction conditions: substrate is 2-octene, S/C=10000, Rh concentation is 0.57 mM, temperature is 100°C, CO/H2 is 10/10 atm, reaction time is 1h, toluene is the solvent, and. decane is the internal standard. The results in Table 4 show that presence of two of free phosphorus ligands with the tetraphosphorus ligand is important for achieving high regioselectivity (n:i goes from 2.92 to 17.7). Table 5 below shows similar results with 2- hexene as the substrate. . Reaction conditions: substrate is 2-hexene, S/C= 10000, Rh concentation is 0.69mM, reaction temperature is 100°C, CO/H2 is10/10 atm, reaction time is lh, toluene is the solvent, and decane is the internal standard. The results in Table 5 show that presence of two of free phosphorus ligands with the tetraphosphorus ligand is important for achieving high regioselectivity (n:i goes from 12.7 to 42). Temperature [0028] The reaction temperature also plays a key role in hydroformylation. As shown in Tables 6 and 7 below, at low temperature, though high regioselectivity was observed, the reaction rate was low. To facilitate the olefin isomerization and hydroformylation, high temperature (100°C) is preferred to achieve high reaction rate as well as acceptable regioselectivity. Reaction conditions: substrate is 2-octene, S/C=10000, Rh concentation is 0.57mM, Ligand/Rh ratio is 3:1, CO/H2 is 10/10 atm, reaction time is 1h, toluene is the solvent, and decane is the internal standard. Reaction conditions: substrate is 2-hexene, S/C=10000, Rh concentation is 0.69mM, Ligand/Rh ratio is 3:1, CO/H2 is 10/10 atm, reaction time is lh, toluene is the solvent, and decane is the internal standard. Pressure [0029] The CO/H2 total pressure also influences the reaction. At high pressure, both reaction rate and regioselectivity were low. Lowering the pressure generally results in higher reaction rate and regioselectivity. Decreasing the CO/H2 pressure from 10/10 atm to 5/5 atm did not change the reaction rate very much, but the regioselectivity improved further. The results from the hydroformylation of 2-octene and 2-hexene are shown in Tables 8 and 9. Reaction. conditions: substrate is 2-octene, S/C= 10000, Rh concentation is 0.57mM, Ligand/Rh ratio is 3:1, reaction temperature is 100°C, reaction time is lh, toluene is the solvent, and decane is the internal standard. Reaction conditions: substrate is 2-hexene, S/C=10000, Rh concentation is 0.69mM, Ligand/Rh ratio is 3:1, reaction temperature is 100°C, reaction time is lh, toluene is the solvent, and decane is the internal standard. Reaction time [0030] The reaction time also affects the hydroformylation selectivity. As shown in . Tables 10 and 11 below, the longer the reaction time, the lower the regioselectivity. Further an increase in the reaction time from 12h to 18h only slightly improved the turnover number (TON), i.e. turnover per catalyst, at the expense of decreased regioselectivity. Reaction conditions: substrate is 2-octene, S/C= 10000, Rh concentation is 0.57mM, Ligand/Rh ratio is 3:1, reaction temperature is. 100°C, CO/H2 is 5/5 atm, toluene is. the solvent, and decane is the internal standard. Reaction conditions: substrate is 2-hexene, S/C=10000, Rh concentation is 0.69mM, Ligand/Rh ratio is 3:1, reaction temperature is 100°C, CO/H2 is 5/5 atm, toluene is the solvent, and decane is the internal standard. [0031] While this invention has been described with reference to several preferred embodiments, it is contemplated that various alterations and modifications thereof will become apparent to those skilled in the art upon a reading of the preceding detailed description. It is therefore intended that the following appended claims be interpreted as including all such alterations and modifications as fall within the true spirit and scope of this invention. AMENDED CLAIMS received by the International Bureau on 03 December 2007 (03.12.07); claim 1 amended, remaining claims unchanged. 1. A phosphorous ligand having the following formula: wherein i, j, k, 1, m and n are, independently, H, R, Ar, substituted Ar, OR, OAr, COOEt, halide, SO2R, SO3H, SO2NHR, POR2, POAr2 or NR2, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; X1-X4 are, independently, O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; and Y1, Y'1, Y2, Y'2, Y3, Y'3, Y4, Y'4, are, independently, R, Ar, OR, OAr, pyrrole or substituted pyrrole, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl, or where R, Ar, OR, OAr, pyrrole and substituted pyrrole are linked with a carbon to carbon bond, CH2, NH, NR or O. 2. The phosphorous ligand according to claim 1, wherein the ligand has the following structure: wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; and a, b c d, i, j, k, 1, m and n are, independently, H, alky], aryl, substituted alkyl. substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H, POR2, halide or two of a, b, c, d, i, j, k, 1, m and n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. 3. The phosphorous ligand according to claim 1, wherein the ligand has the following structure: wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; and a, b, c, d, e, f, i, j, k, 1, m and n are, independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, COOR, SO3R, SO3H, POR2, halide or two of a, b, c, d, e, f, i, j, k, 1, m and n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. 4. The phosphorous ligand according to claim I, wherein the ligand has the following structure: wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl; and Ar is an aryl; and a, b, c, d, e, i, j, k, 1, m and n are, independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H, POR2, halide, NR2, or two of a, b, c, d, e, i, j, k, 1, m and n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. 5. The phosphorous ligand according to claim 1, wherein the ligand has the following structure: wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; Y is a carbon-carbon bond, O, CH2, NH or NR, where R is an alkyl, substituted alkyl, aryl or substituted aryl; and a to n are, independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H, POR2, halide, NR2, or two of a to n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. 6. The phosphorous ligand according to claim 1, wherein the ligand has the following structure: wherein X is O, CH2, NH, NR, NSO2R, or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; and a, b, c, d, e, i, j, k, l, m and n are, independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H, POR2, halide, NR2, or two of a, b, c, d, e, i, j, k, l, m and n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. 7. The phosphorous ligand according to claim 1, wherein the ligand has the following structure: wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl; and a to n are, independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H, POR2, halide, NR2, or two of a to n can be a cyclic fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. 8. The phosphorous ligand according to claim 1, wherein the ligand has the following structure: 9. A catalyst comprising a ligand in claims 1 to 8 and a transition metal salt, wherein the metal of said metal salt is selected from the group consisting of: Fe, Zn, Mn, Co, Cu, Ag, Ni, Pt, Pd, Rh, Ru and Ir. 10. The catalyst of claim 9, wherein said transition metal salt is selected from the group consisting of FeX3, Fe(OTf)3, Fe(OAc)3, Mn(OAc)3, Mn(OTf)3, MnX3, Zn(OTf)2, Co(OAc)2, AgX, Ag(OTf), Ag(OTf)2, AgOAc, PtCl2, H2PtCl4, Pd2(DBA)3, Pd(OAc)2, PdCl2(RCN)2, (Pd(allyl)Cl)2, Pd(PR3)4, (Rh(NBD)2)X, (Rh(NBD)Cl)2, (Rh(COD)Cl)2, (RhCCOD)2)X, Rh(acac)(CO)2, Rh(ethylene)2(acac), (Rh(ethylene)2Cl)2, RhCl(PPh3)3, Rh(CO)2Cl2, RuH(CO)2(PPh3)2, Ru(Ar)X2, Ru(Ar)X2(PPh3)3, Ru(COD)(COT), Ru(COD)(COT)X, RuX2(cymen), Ru(COD)n, RuCl2(COD), (Ru(COD)2)X, RuX2(PN), RuCl2(=CHR)(PR'3)2, Ru(ArH)Cl2, Ru(COD)(methallyl)2, (Ir(NBD)2Cl)2, (Ir(NBD)2)X, (Ir(COD)2Cl)2, (Ir(COD)2)X, CuX (NCCH3)4, Cu(OTf), Cu(OTf)2, Cu(Ar)X, CuX, Ni(acac)2, NiX2, (Ni(allyl)X)2, Ni(COD)2, MoO2(acac)2, Ti(OiPr)4, VO(acac)2 and MeReO3, wherein each R and R' is independently selected from the group consisting of: alkyl or aryl; Ar is an aryl group group; and X is a counteranion, such as BF4, ClO4, OTf, SbF6, CF3SO3:, B(C6H3(CF3)2)4, Cl, Br or I; OTf is OSO2CF3; DBA is PhCH=CHCOCH=CHPh, NDB is norbornadiene; COD is cyclooctodiene; and COT is cyclooctotriene. 11. The catalyst according to claim 10, wherein the transition metal salt is selected from the group consisting of (Rh(COD)Cl)2, (Rh(COD)2)X, Rh(acac)(CO)2, and RuH(CP)2(PPh3)2. 12. A method of using the catalyst of claim 10, wherein the catalyst is the catalyst in a reaction selected from the group consisting of hydroformylation, isomerization- hydroformylation, hydro-carboxylation, hydrocyanation, isomerization-formylation, and hydroaminomethylation reactions of alkenes. 13. The method of claim 12, wherein the reaction is a hydroformylation reaction. 14. A method of using the catalyst in a hydroformylation reaction, the catalyst comprising a ligand of claim 8 and a transition metal salt selected from the group consisting of (Rh(COD)Cl)2, (Rh(COD)2)X, Rh(acac)(CO)2, and RuH(COMPPh3)2. Tetraphosphorous ligands are combined with transition metal salts to form catalysts for use in hydroformylation, isomerization-hydroformylation, hydrocarboxylation, hydrocyan-ation isomerization-formylation, hydroaminomethylation and similar related reactions.

Full Text

TETRAPHOSPHORUS LIGANDS FOR CATALYTIC HYDROFORMYLATION
AND RELATED REACTIONS
Cross Reference to Related Application
[001] This application claims the benefit of priority of Provisional Application No.
60/750,733 filed December 15, 2005, which is incorporated herein by reference.
Field of the Invention
[002] The present invention relates to new phosphorous ligands and their
applications in hydroformylation and related reactions. More particularly, the present
invention relates to transition metal complexes having chelating tetraphosphorus ligands with
multichelating modes. Tetraphosphorus ligands with multichelating modes can enhance
coordinating abilities for transition metals such as Rh and Ni, and thus enhance selectivities
of catalytic reactions. The transition metal-tetraphosphorus complexes according to the
present invention are useful as catalysts in hydroformylation, isomerization-
hydroformylation, hydrocarboxylation, hydrocyanation, tandem reactions such as
isomerization-formylation, and hydroaminomethylation.
Background of the Invention
[003] Hydroformylation, discovered by Roelen in 1938, has been the largest
homogeneous catalytic process in industry. More than 15 billion pounds of aldehydes and
alcohols per year have been produced based on Fe, Zn, Mn, Co, Cu, Ag, Ni, Pt, Pd, Rh, Ru
and Ir based catalysts. In these processes, achieving high selectivity to linear products is
extremely important for commercial application. Despite the extensive investigation by both
academic and industrial groups such as BASF, Dow, Shell and Eastman, among others, there
still remain fundamental and practical problems regarding selectivity. New concepts for
controlling selectivities are very important in catalytic reactions. Highly efficient selective
catalysts will allow some bulky chemicals to be produced in an environmentally sound
manner under milder conditions.
[004] Cobalt catalysts (e.g., HCo(CO)4) dominated industrial hydroformylation until
rhodium catalysts (e.g., HRh(CO)2(PPh3)3 ) were introduced in earlier 1970's. In 2004, it is

estimated that approximately 75% of all hydroformylation processes were based on rhodium
triarylphosphine catalysts. Achieving high regioselectivity to linear aldehydes is critical for
hydroformylation and related reactions. The resulting aldehydes are converted to alcohols,
carboxylic acids or other derivatives, which are used as plasticizers, detergents, surfactants,
solvents, lubricants and chemical intermediates.
[005] Scheme 1 below shows the dissociation of a Rh catalyzed hydroformylation
catalyst.

[006] The successful commercialization of HRh(CO)(PPh3)2 technology has been
based on the key discovery of Pruett at Union Carbide and Booth at Union oil that the use of
rhodium with excess phosphine ligand can lead to forming active, selective hydroformylation
catalysts. The need for excess phosphines is due to the facile Rh-PPh3 dissociation in the
catalytic system as illustrated by Scheme 1. Loss of PPh3 from HRh(CO)(PPh3)2 results in
more active, but less regioselective hydroformylation catalysts B and C. In the commercial
process, up to an 820 fold excess of PPh3 to Rh is used to assure high lineanbranch selectivity
ratio, i.e., up to 17:1, for the hydroformylation of 1-hexene. Commercial hydroformylation
of propylene has been run with a 400 fold excess of PPh3 to Rh with a lineanbranch
selectivity ratio of 8-9:1 being achieved.
[007] Rh/PPh3 catalyzed hydroformylation is the key for making all oxo alcohols.
Propylene is the largest single alkene hydroformylated to produce butylaldehyde, which can
be hydrogenated to produce butanol, or dimerized by an aldol condensation and then
hydrogenated to form 2-ethyl-1-hexanol, the largest single product produced by
hydroformylation (over 5 billion lbs a year). 2-ethyl-1-hexanol is usually reacted with

phthalic anhydride to produce dialkyl phthalic esters that are used as plasticizers to keep
polyvinyl chloride plastics soft and flexible.
[008] In the hydroformylation process, it is critical to get cheaper feed stocks for
starting materials. For example, internal higher alkenes (SHOP alkenes) such as 3-octenes
are desirable for converting the alkenes to linear aldehydes. Direct use of raffinate II (a
mixture of n-butenes/butanes) and 1-butene and 2-butene mixtures are useful for
hydroformylation. For hydroformylation of n-alkenes, it is important to obtain high linear
selectivity. Hydroformylation of allylic alcohol and subsequent reduction can lead to 1, 4
butenol. Functionalized internal alkenes can be used as alternative routes to bifunctional
building blocks for polymers. Hydroformylation of methyl-3-pentenoate leads to making
starting materials for polyamides and polyesters. In the tandem-isomerization and -
hydroformylation processes, high isomerization rates combined with high selectivity towards
terminal aldehydes are desirable with minimized undesirable hydrogenation reactions and
minimiun isomerization towards conjugated compounds.
[009] To overcome the need of using large excess of phosphines in the
hydroformylation processes and achieve high regioselectivity, a new generation of transition
metal catalysts were developed using bisphosphine ligands. -For example: Bisbi by Eastman
Chemical; Xantphos by Prof. Leeuwen (University of Amsterdam), Bernhard Breit, Ace.
Chem. Res. 2003, 36, 264-275, Bernhard Breit,'~WoIfgang Seiche, Synthesis 2001, 1, 1-36);
and UC-44 by Union Carbide. These ligands are illustrated below.

By using these ligands, a typical 400 fold excess of PPh3 has been reduced to a 5 fold excess
of chelating phosphines. This new generation of chelating phosphines has led to high
linear branched ratios as well as to higher catalytic activities. For example, a linear to branch

ratio of 70-120:1 for hydroformylation of 1-hexene has been observed. Casey and van
Leeuwen proposed that part of regioselectivity in the Rh-catalyzed hydroformylation is due to
metal bisphosphine bite angle around 120 degree is formed, i.e., "the Bite angle hypothesis"
as illustrated below.

[0010] Despite that a number of chiral bisphosphorus ligands being-used as catalysts
for hydroformylation and related reactions, the highly selective, active phosphorus ligands for .
hydroformylation still remain an area of strong research interest. However, because of the
dissociation of phosphines from the Rh-CO coordination, is a problem for achieving high
regioselectivity, that is high linear to branch ratios of the products produced. Developing
families of phosphorus ligands with multi-chelating coordination modes is attractive. The
tetraphosphorous ligands of the present invention, because of their coordinating abilities
through multi-chelating coordination modes, lead to highly regioselective transition in metal-
ligand catalyzed hydroformylation and related reactions to provide high linear to branch
ratios than those previously obtained. Also, the symmetric nature of these ligands allows
these ligands to be prepared easily.
Summary of the Invention
[0011] In the present invention, we introduce a variety of tetraphosphorus ligands
(Type A) with multi-chelating coordination modes as illustrated. below to enhance
coordination abilities:

where M is a metal selected from the group consisting of Fe, Zn, Mn, Co, Cu, Ag, Ni, Pt, Pd,
Rh, Ru and Ir; X is selected from the group consisting of O, NH, NR and CH2; Y is selected
from the group consisting of Ar, OAr and pyrrole; R is an organic group and Ar is an aryl
group. Type A ligand is a tetraphosphorous ligand of the present invention. Type B ligand is
a bisphosphorous ligand. As illustrated below, the tetraphosphorus ligand (Type A) has at
least four chelating coordination modes to enhance coordination abilities whereas the
bisphosphorus ligand (Type B) has a single mode, namely, P1-M-P2.

Compared with normal bisphosphorus ligands (Type B), the multi-chelating tetraphosphorus
ligands (Type A) of the present invention enhance the coordinating abilities of ligands
without major change of electronic properties of ligands.
Detailed Description of the Invention
[0012] The present invention is directed to tetraphosphorous ligands having multi-
chelating coordination modes to used as catalysts for hydroformylation and related reactions.
The transition metal catalysts prepared using the tetraphosphorous ligands of the present
invention are highly active and regioselective. The tetraphosphorous ligands of the present
invention have the following generic structure:

wherein i, j, k, 1, m and n are, independently, H, R, Ar, substituted Ar, OR, OAr, COOEt,
halide, SO2R, SO3H, SO2NHR, POR2, POAr2 or NR2, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; X1-X4 are, independently, R, Ar, OR, OAr, pyrrole
or substituted pyrrole, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is
an aryl; and Y1, Y'1, Y2, Y'2, Y3, Y'3, Y4, Y'4, are, independently, R, Ar, OR, OAr, pyrrole or
substituted pyrrole, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an
aryl, or where R, Ar, OR, OAr, pyrrole and substituted pyrrole are linked with a carbon to
carbon bond, CH2, NH, NR and O. The substituted groups would include, for example,
methyl, ethyl, t-butyl and phenyl.
[0013] The following illustrates a first embodiment of the invention:

wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; and a, b c, d, i, j, k, l, m and n are, independently, H,
alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H,
POR2, halide or two of a, b, c, d, i, j, k, I, m and n can be a cyclic fused ring or an extended
aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl.
[0014] A second embodiment of the invention is illustrated below:

wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl; and Ar is an aryl; and a, b, c, d, e, f, i, j, k, I, m and n are,
independently, H, alkyl, aryl, substituted alkyl, substituted, aryl, OR, OAr, SiR3, COOR,
SO3R, SO3H, POR2, halide or two of a, b, c, d, e, f, i, j, k, 1, m and n can be a cyclic fused
ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted
aryl and Ar is an aryl.
[0015] A third embodiment of the invention is illustrated below:

wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; and a, b, c, d, e, i, j, k, l, m and n are, independently,
H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H,
POR2, halide, NR2, or two of a, b, c, d, e, i, j, k, 1, m and n can be a cyclic fused ring or an

extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar
is an aryl.
[0016] A fourth embodiment of the invention is illustrated below:

wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; Y is a carbon-carbon bond, O, CH2, NH or NR,
where R is an alkyl, substituted alkyl, aryl or substituted aryl; and a to n are, independently,
H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H,
POR2, halide, NR2, or two of a to n can be a cyclic fused ring or an extended aromatic ring,
where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl.
[0017] A fifth embodiment of the invention is illustrated below:

wherein X is O, CH2, NH, NR, NSO2R,or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; and a, b, c, d, e, i, j, k, 1, m and n are, independently,
H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, CQOR, SO3R, SO3H,
POR2, halide, NR2, or two of a, b, c, d, e, i, j, k, 1, m and n can be a cyclic fused ring or an
extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar
is an aryl.
[0018] A sixth embodiment of the invention is illustrated below:

wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; and a to n are, independently, H, alkyl, aryl,
substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H, POR2, halide,
NR2, or two of a to n can be a cyclic fused ring or an extended aromatic ring, where R is an
alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl. When d and e are not
hydrogen, enantiomers of these ligands can prepared for asymmetric catalytic reactions.
[0019] Examples of the tetraphosphorus ligands of the present invention (LI to L91)
are illustrated below:

[0020] In a hydroformylation or related reaction, the transition metal-
tetraphosphorous ligand complex is prepared by mixing a transition metal salt with the
ligand. Hie transition metal salt is a salt of a transition metal selected from the group
consisting of Fe, Zn, Mn, Co, Cu, Ag, Ni, Pt, Pd, Rh, Ru and Ir. Examples of the transition
metal salts are FeX3> Fe(OTf)3, Fe(OAc)3, Mn(0Ac)3, Mn(OTf)3) MnX3, Zn(OTf>2,
Co(OAc)zs AgX, Ag(OTf), Ag(OTf)2) AgOAc, PtCl2l HaPtCU, Pd2(DBA)3, Pd(OAc)2s

PdCl2(RCN)2, (Pd(allyl)Cl)2, Pd(PR3)4, (Rh(NBD)2)X, (Rh(NBD)Cl)2, (Rh(COD)Cl)2,
(Rh(COD)2)X, Rh(acac)(CO)2, Rh(ethylene)2(acac), (Rh(ethylene)2Cl)2, RhCl(PPh3)3,
Rh(CO)2Cl2, RuH(CO)2(PPh3)2, Ru(Ar)X2, Ru(Ar)X2(PPh3)3, Ru(COD)(COT),
Ru(COD)(COT)X, RuX2(cymen), Ru(COD)n, RuCfe(COD), (Ru(COD)2)X, RuX2(PN),
RuCl2(=CHR)(PR'3)2, Ru(ArH)Cl2, Ru(COD)(methallyl)2, (Ir(NBD)2Cl)2, (Ir(NBD)2)X,
(Ir(COD)2Cl)2, (Ir(COD)2)X, CuX (NCCH3)4, Cu(OTf), Cu(OTf)2, Cu(Ar)X, CuX, Ni(acac)2,
NiX2, (Ni(allyl)X)2, Ni(COD)2j MoO2(acac)2, Ti(OiPr)4, VO(acac)2 and MeReO3, wherein
each R and R' is independently selected from the group'consisting of alkyl or aryl; Ar is an
aryl group group; X is a counteranion, such as BF4, CIO4, OTf, SbF6, CF3SO3,
B(C6H3(CF3)2)4, Cl,Br or I; OTf is OSO2CF3; DBA is PhCH=CHCOCH=CHPh, NDB is
norbornadiene; COD is cyclooctodiene and COT is cyclooctotriene; The mixture is placed in
an autoclave that is purged with nitrogen and subsequently charged with CO and H2.
Synthesis of the Tetraphosphate.Ligand
[0021] All reactions and manipulations in the example set forth below were
performed in a nitrogen-filled glovebox or using standard Schlenk techniques. THF and
toluene were dried and distilled from sodium-benzophenone ketyl under nitrogen. Methylene
"chloride was distilled from CaH2. Methanol was distilled from Mg under nitrogen. Column
chromatography was performed using EM silica gel 60 (230-400 mesh). 1H, 13C and 31P
NMR were recorded on Bruker WP-200, AM-300, and AMX-360 spectrometers. Chemical
shifts were reported in ppm down field from tetramethylsilane with the solvent resonance as
the internal standard. MS spectra were recorded on a KRATOS mass spectrometer MS 9/50
for LR-EI and HR-EI. GC analysis was carried on Helwett-Packard 6890 gas
chromatography using chiral capillary columns. HPLC analysis was carried on WatersTM
600 chromatography.
[0022] The following procedure was used to synthesize ligand having the structure
L1. To a solution of chlorodipyrrolyphosphine (4.4 mmol, 0.87g) in THF (10 mL) was added
dropwise triethylamine 1mL and a solution of tetraol (1 mmol, 0.218 g) in THF (5 mL) at
room temperature. Tetraol was synthesized according to Lindsten, G.; Wennerstroem, O.;
Isaksson, R., J. Org. Chetn. 1987, 52, 547-54, and chlorodipyrrolyphosphine was prepared
according van der Slot, S. C; Duran, J.; Luten, J.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.
Organometallics 2002, 21, 3873-3883. TriethyIamine-HCl salts were formed immediately
after the addition. The reaction mixture was stirred for 6h at room temperature. The

triethylamine-HCl salts were then filtered off and the solvent was removed under vacuum.
The crude product was purified by flash chromatography on basic aluminum oxide eluted
with hexane/EtOAc/NEt3 (6:1:0.01) to produce ligand L1 (0.31 g, 36%) as a air-stable
colorless solid. 1H NMR (300 Hz, CDCl2) δ 7.23 (t, 2H, J= 8.3 Hz), 6.68 (m, 20H), 6.21 (m,
16H); 13C NMR (90 Hz, CDCl2) δ 152.86 (d, J= 12.2Hzl3l.0, 121.4(d, J= 16.8Hz), 118.1,
115.3(d, J= 13.7 Hz ), 112.7; 31P NMR (146Hz, CDCl2) δ 107.3. HRMS (ES+) calcd. for
C44H39N8O4P4 [MH+] 867.2045, found 867.2021.
Typical Hydroformylation Process
[0023] To a 2 mL vial with a magnetic stirring bar was charged the tetraphosphprus
ligand L1 prepared in the previous example (3 µmol, 2.6 mg) and Rh(acac)(CO)2 (1 µmol,
0.1 mL of 10 mM solution in toluene). The mixture was stirred for 5 min. Then 2-octene (10
mmol, 1.56 mL) was added followed by decane (0.01 mL) as internal standard. The reaction
mixture was transferred to an autoclave. The autoclave was purged with nitrogen for three
times and subsequently charged with CO (5 bar) and H2 (5 bar). The autoclave was then
heated to 100°C (oil bath). After 12h, the autoclave was cooled in icy water and the pressure
was carefully released in a well ventilated hood. The reaction mixture was immediately
analyzed by GC.
[0024] The remarkable regioselectivities using a multi-chelating tetraphosphorus
ligand LI for hydroformylation of styrene, 1-octene and 1-hexene are demonstrated in Table
1. Normally, styrene is a difficult substrate for achieving more than 2:1 ratio of linear to
branched products when compared to bisphosphorous ligands of the prior art such as
xantphos and UC-44. As shown in Table 1, the new tetraphosphorus ligands (Type A) such
as LI is more selective hydroformylation ligand than the prior art bisphosphorous ligand
(Type B). The reaction conditions included 0.1 mol%- Rh(CO)2(acac) and ligand, reaction
temperature 80° C for 1 hour at 20 atm of CO and H2. These results indicate that
tetraphosphorus ligands with multi-chelating coordination can be used to increase
coordinating abilities of bisphosphine ligands. The regioselectivity with Type A is the
highest reported to date.

The results of hydroformylation of 2-hexene and 2-octene using the tetraphosphorus iigand
(Type A) vs bisphosphorus Iigand (Type B) to produce an aldehyde are summarized below in
Table 2. In Tables 2 to 11 which follow, "n:i" is the ratio of linear aldehyde to branched
aldehyde and "TOF" is turnover frequency (turnover per catalyst per hour). The
tetraphosphorus ligands of the present invention produce higher "n:i" ratios than
bisphosphorus ligands.

The hydroformylation conditions were S/C = 10000, [Rh] is 0.69 mM (for 2-hexene) and
0.57 mM (for 2-octene), Ligand/Rh ratio is 3:1, reaction temperature is 100°C, CO/H2 is 5/5
atm, toluene is the solvent, and decane is the internal standard.
[0025] Table 3 below shows the results of hydroformylation of 1-hexene and 1-octene
using the tetraphosphorus ligand (Type A) vs bisphosphorus ligand (Type B) to produce an
aldehyde by a hydroformylation reaction:

The reaction conditions: S/C = 10000, Rh concentation is 0.2mM, Ligand/Rh ratio is 3:1,
temperature is 80°C, CO/H2 is 10/10 atm, toluene is the solvent, and decane is the internal
standard.
[0026] The hydroformylation reaction is highly dependent on the reaction conditions.
Typical reaction conditions are S/C=10000, ligand metal ratio of about 3, transition metal.
concentration of about 0.2 to 0.7mM, reaction temperature is 100°C,and the reaction time is
12h. To optimize the reaction conditions, the following experiments have been carried out
with tetraphosphorus ligand (LI). As evidenced by the "n:i" ratios in Tables 2 and 3, there a
substantial and significant improvement in the amount of linear aldehyde produced using a
tetraphosphorus ligand of the present invention as opposed to using a bisphosphorus ligand.
Ligand to Metal Ratio
[0027] The hydroformylation was first carried out with different ligand to metal
ratios. As shown in Table 4, increasing the ligand metal ratio slightly decreased the reaction
rate. On the other hand, the ligand to metal ratio significantly affects the regioselectivity. At

lower ratios, low regioselectivity were observed. A minimum ligand to metal ratio of 2 is
essential to achieve high regioselectivity, which allows the tetraphosphorus ligand to be
coordinated in a multi-coordination mode. Further increasing the ligand to metal ratio did not
significantly improve the regioselectivity.

The reaction conditions: substrate is 2-octene, S/C=10000, Rh concentation is 0.57 mM,
temperature is 100°C, CO/H2 is 10/10 atm, reaction time is 1h, toluene is the solvent, and.
decane is the internal standard. The results in Table 4 show that presence of two of free
phosphorus ligands with the tetraphosphorus ligand is important for achieving high
regioselectivity (n:i goes from 2.92 to 17.7). Table 5 below shows similar results with 2-
hexene as the substrate. .

Reaction conditions: substrate is 2-hexene, S/C= 10000, Rh concentation is 0.69mM, reaction
temperature is 100°C, CO/H2 is10/10 atm, reaction time is lh, toluene is the solvent, and
decane is the internal standard. The results in Table 5 show that presence of two of free
phosphorus ligands with the tetraphosphorus ligand is important for achieving high
regioselectivity (n:i goes from 12.7 to 42).
Temperature

[0028] The reaction temperature also plays a key role in hydroformylation. As shown
in Tables 6 and 7 below, at low temperature, though high regioselectivity was observed, the
reaction rate was low. To facilitate the olefin isomerization and hydroformylation, high
temperature (100°C) is preferred to achieve high reaction rate as well as acceptable
regioselectivity.

Reaction conditions: substrate is 2-octene, S/C=10000, Rh concentation is 0.57mM,
Ligand/Rh ratio is 3:1, CO/H2 is 10/10 atm, reaction time is 1h, toluene is the solvent, and
decane is the internal standard.

Reaction conditions: substrate is 2-hexene, S/C=10000, Rh concentation is 0.69mM,
Ligand/Rh ratio is 3:1, CO/H2 is 10/10 atm, reaction time is lh, toluene is the solvent, and
decane is the internal standard.
Pressure
[0029] The CO/H2 total pressure also influences the reaction. At high pressure, both
reaction rate and regioselectivity were low. Lowering the pressure generally results in higher
reaction rate and regioselectivity. Decreasing the CO/H2 pressure from 10/10 atm to 5/5 atm

did not change the reaction rate very much, but the regioselectivity improved further. The
results from the hydroformylation of 2-octene and 2-hexene are shown in Tables 8 and 9.

Reaction. conditions: substrate is 2-octene, S/C= 10000, Rh concentation is 0.57mM,
Ligand/Rh ratio is 3:1, reaction temperature is 100°C, reaction time is lh, toluene is the
solvent, and decane is the internal standard.

Reaction conditions: substrate is 2-hexene, S/C=10000, Rh concentation is 0.69mM,
Ligand/Rh ratio is 3:1, reaction temperature is 100°C, reaction time is lh, toluene is the
solvent, and decane is the internal standard.
Reaction time
[0030] The reaction time also affects the hydroformylation selectivity. As shown in .
Tables 10 and 11 below, the longer the reaction time, the lower the regioselectivity. Further
an increase in the reaction time from 12h to 18h only slightly improved the turnover number
(TON), i.e. turnover per catalyst, at the expense of decreased regioselectivity.

Reaction conditions: substrate is 2-octene, S/C= 10000, Rh concentation is 0.57mM,
Ligand/Rh ratio is 3:1, reaction temperature is. 100°C, CO/H2 is 5/5 atm, toluene is. the
solvent, and decane is the internal standard.

Reaction conditions: substrate is 2-hexene, S/C=10000, Rh concentation is 0.69mM,
Ligand/Rh ratio is 3:1, reaction temperature is 100°C, CO/H2 is 5/5 atm, toluene is the
solvent, and decane is the internal standard.
[0031] While this invention has been described with reference to several preferred
embodiments, it is contemplated that various alterations and modifications thereof will
become apparent to those skilled in the art upon a reading of the preceding detailed
description. It is therefore intended that the following appended claims be interpreted as
including all such alterations and modifications as fall within the true spirit and scope of this
invention.

AMENDED CLAIMS
received by the International Bureau on 03 December 2007 (03.12.07);
claim 1 amended, remaining claims unchanged.
1. A phosphorous ligand having the following formula:

wherein i, j, k, 1, m and n are, independently, H, R, Ar, substituted Ar, OR, OAr, COOEt,
halide, SO2R, SO3H, SO2NHR, POR2, POAr2 or NR2, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; X1-X4 are, independently, O, CH2, NH, NR, NSO2R
or NSO2Ar, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl;
and Y1, Y'1, Y2, Y'2, Y3, Y'3, Y4, Y'4, are, independently, R, Ar, OR, OAr, pyrrole or
substituted pyrrole, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an
aryl, or where R, Ar, OR, OAr, pyrrole and substituted pyrrole are linked with a carbon to
carbon bond, CH2, NH, NR or O.
2. The phosphorous ligand according to claim 1, wherein the ligand has the
following structure:

wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; and a, b c d, i, j, k, 1, m and n are, independently, H,

alky], aryl, substituted alkyl. substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H,
POR2, halide or two of a, b, c, d, i, j, k, 1, m and n can be a cyclic fused ring or an extended
aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl.
3. The phosphorous ligand according to claim 1, wherein the ligand has the
following structure:

wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; and a, b, c, d, e, f, i, j, k, 1, m and n are,
independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, COOR,
SO3R, SO3H, POR2, halide or two of a, b, c, d, e, f, i, j, k, 1, m and n can be a cyclic fused
ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted
aryl and Ar is an aryl.
4. The phosphorous ligand according to claim I, wherein the ligand has the
following structure:

wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl; and Ar is an aryl; and a, b, c, d, e, i, j, k, 1, m and n are,
independently, H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR,
SO3R, SO3H, POR2, halide, NR2, or two of a, b, c, d, e, i, j, k, 1, m and n can be a cyclic
fused ring or an extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or
substituted aryl and Ar is an aryl.
5. The phosphorous ligand according to claim 1, wherein the ligand has the
following structure:

wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; Y is a carbon-carbon bond, O, CH2, NH or NR,
where R is an alkyl, substituted alkyl, aryl or substituted aryl; and a to n are, independently,
H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H,
POR2, halide, NR2, or two of a to n can be a cyclic fused ring or an extended aromatic ring,
where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl.
6. The phosphorous ligand according to claim 1, wherein the ligand has the
following structure:

wherein X is O, CH2, NH, NR, NSO2R, or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; and a, b, c, d, e, i, j, k, l, m and n are, independently,
H, alkyl, aryl, substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H,
POR2, halide, NR2, or two of a, b, c, d, e, i, j, k, l, m and n can be a cyclic fused ring or an
extended aromatic ring, where R is an alkyl, substituted alkyl, aryl or substituted aryl and Ar
is an aryl.
7. The phosphorous ligand according to claim 1, wherein the ligand has the
following structure:

wherein X is O, CH2, NH, NR, NSO2R or NSO2Ar, where R is an alkyl, substituted alkyl,
aryl or substituted aryl and Ar is an aryl; and a to n are, independently, H, alkyl, aryl,
substituted alkyl, substituted aryl, OR, OAr, SiR3, CF3, COOR, SO3R, SO3H, POR2, halide,
NR2, or two of a to n can be a cyclic fused ring or an extended aromatic ring, where R is an
alkyl, substituted alkyl, aryl or substituted aryl and Ar is an aryl.
8. The phosphorous ligand according to claim 1, wherein the ligand has the
following structure:

9. A catalyst comprising a ligand in claims 1 to 8 and a transition metal salt,
wherein the metal of said metal salt is selected from the group consisting of: Fe, Zn, Mn, Co,
Cu, Ag, Ni, Pt, Pd, Rh, Ru and Ir.

10. The catalyst of claim 9, wherein said transition metal salt is selected from the
group consisting of FeX3, Fe(OTf)3, Fe(OAc)3, Mn(OAc)3, Mn(OTf)3, MnX3, Zn(OTf)2,
Co(OAc)2, AgX, Ag(OTf), Ag(OTf)2, AgOAc, PtCl2, H2PtCl4, Pd2(DBA)3, Pd(OAc)2,
PdCl2(RCN)2, (Pd(allyl)Cl)2, Pd(PR3)4, (Rh(NBD)2)X, (Rh(NBD)Cl)2, (Rh(COD)Cl)2,
(RhCCOD)2)X, Rh(acac)(CO)2, Rh(ethylene)2(acac), (Rh(ethylene)2Cl)2, RhCl(PPh3)3,
Rh(CO)2Cl2, RuH(CO)2(PPh3)2, Ru(Ar)X2, Ru(Ar)X2(PPh3)3, Ru(COD)(COT),
Ru(COD)(COT)X, RuX2(cymen), Ru(COD)n, RuCl2(COD), (Ru(COD)2)X, RuX2(PN),
RuCl2(=CHR)(PR'3)2, Ru(ArH)Cl2, Ru(COD)(methallyl)2, (Ir(NBD)2Cl)2, (Ir(NBD)2)X,
(Ir(COD)2Cl)2, (Ir(COD)2)X, CuX (NCCH3)4, Cu(OTf), Cu(OTf)2, Cu(Ar)X, CuX, Ni(acac)2,
NiX2, (Ni(allyl)X)2, Ni(COD)2, MoO2(acac)2, Ti(OiPr)4, VO(acac)2 and MeReO3, wherein
each R and R' is independently selected from the group consisting of: alkyl or aryl; Ar is an
aryl group group; and X is a counteranion, such as BF4, ClO4, OTf, SbF6, CF3SO3:,
B(C6H3(CF3)2)4, Cl, Br or I; OTf is OSO2CF3; DBA is PhCH=CHCOCH=CHPh, NDB is
norbornadiene; COD is cyclooctodiene; and COT is cyclooctotriene.
11. The catalyst according to claim 10, wherein the transition metal salt is selected
from the group consisting of (Rh(COD)Cl)2, (Rh(COD)2)X, Rh(acac)(CO)2, and
RuH(CP)2(PPh3)2.
12. A method of using the catalyst of claim 10, wherein the catalyst is the catalyst
in a reaction selected from the group consisting of hydroformylation, isomerization-
hydroformylation, hydro-carboxylation, hydrocyanation, isomerization-formylation, and
hydroaminomethylation reactions of alkenes.
13. The method of claim 12, wherein the reaction is a hydroformylation reaction.
14. A method of using the catalyst in a hydroformylation reaction, the catalyst
comprising a ligand of claim 8 and a transition metal salt selected from the group consisting
of (Rh(COD)Cl)2, (Rh(COD)2)X, Rh(acac)(CO)2, and RuH(COMPPh3)2.

Tetraphosphorous ligands are combined with transition metal salts to form catalysts for use in hydroformylation, isomerization-hydroformylation,
hydrocarboxylation, hydrocyan-ation isomerization-formylation, hydroaminomethylation and similar
related reactions.

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Patent Number

270761

Indian Patent Application Number

2255/KOLNP/2008

PG Journal Number

04/2016

Publication Date

22-Jan-2016

Grant Date

18-Jan-2016

Date of Filing

04-Jun-2008

Name of Patentee

THE PENN STATE RESEARCH FOUNDATION

Applicant Address

304 OLD MAIN UNIVERSITY PARK, PA

Inventors:

#	Inventor's Name	Inventor's Address
1	ZHANG, XUMU	28 MEADOW LARK, PLAINSBORO, NJ 08356
2	YAN, YONGJUN	710 S.ATHERTON STREET,APT. 303, STATE COLLEGE,PA 16801, UNITED STATES OF AMERICA

PCT International Classification Number

C07F 9/572

PCT International Application Number

PCT/US2006/047766

PCT International Filing date

2006-12-15

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	60/750733	2005-12-15	U.S.A.