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The chemical, petroleum, and pharmaceutical industries have been taking steps to employ more “green” processes such as using water as a reaction medium.  Since many reactions are catalyzed by transition metal complexes, this change has necessitated the development of a library of water-soluble ligands.  Specifically, there is a need for a collection of phosphines with improved solubilities as well as with varied electronic, steric, and coordinating properties such as bifunctionality.  Bifunctional ligands containing P and N are of great interest because of their ability to impart hemilabile properties to their metal complexes.  To date, there is a very limited number of water-soluble P, N ligands.  Some of the few are 1,3,5-triaza-7-phosphaadamantane (PTA) and its derivatives including PTN(CH₃). Due to the rigid structure and spatial arrangement of the heteroatoms, PTA does not chelate.  PTN(CH₃), however, has been reported to bind in both k¹-P and k²-P,N modes.

One of the fundamental problems associated with derivatives of PTA is that they have limited water solubility (S₂₅^o = 3-14 g/L).  It was hypothesized that this problem could be alleviated by preparing related ligands that contain N for enhanced hydrogen bonding.  To probe this theory, amine and N-methyl imidazole derivatives were prepared.  Dimethylaniline-(1,3,5-triaza-7-phospha-tricyclo-[3.3.1.13,7]dec-6-yl)methanol (1, PZA-NH₂), 1-methylimidazole-(1,3,5-triaza-7-phosphatricyclo[3.3.1.1^3,7]dec-6-yl)methanol (2), and bis-1-methylimidazole-(1,3,5-triaza-7-phosphatricyclo[3.3.1.1^3,7]dec-6-yl)methanol (3) were produced by combining a THF slurry of PTA-Li with a solution of the p-dimethylaminobenzaldehyde, 1-methyl-2-imidazolecarboxaldehyde, and bis(N-methylimidazole-2-yl)ketone respectively at -80^oC (Scheme 1).  The resulting solutions were warmed to room temperature and quenched with H₂O.  Once isolated, compounds 1 - 3 were found to be air stable solids that slowly oxidized in solution after several days. This transformation was also readily accomplished by employing 35% H₂O₂.

Scheme 1.  The synthetic reactions which formed N containing upper-rim derivatives of PTA (1-3) and their oxides.

As was theorized, 1-3 exhibited increased water-solubilities with values of 38 g/L, 320 g/L, and 78 g/L respectively.  The lower solubility of 3 relative to 2 is believed to be a consequence of a polymeric network formation.  Phosphines 1-3 were also soluble in most common organic solvents.  However, it was dissolved that the RS/SR diastereomer of 1 was insoluble in CH₂Cl₂, and hence, this medium was employed to isolate the pure stereoisomer. 

In an effort to compare the coordination chemistry of 1-3 to the phenyl derivative of 1 (PZA), and the P,N chelate, PTN(CH₃), the ligands were allowed to combine with [(h⁶-p-cymene)RuCl₂]₂ (Scheme 2). 

Scheme 2.  The synthetic reactions which formed Ru complexes 7 - 11.

Room temperature CH₂Cl₂ solutions of PZA and PZA-NH₂ (1) reacted cleanly with the Ru dimer to form the neutral, three-legged piano stool compounds [(h⁶-p-cymene)Ru(PZA)Cl₂] (7) and [(h⁶-p-cymene)Ru(PZA-NH₂)Cl₂] (8) as evidenced by NMR, ESI-MS, and IR.  When a similar methodology was employed with the imidazole ligands,  2 and 3, intractable mixtures were obtained.  Peruzzini recently reported that pure [(h⁶- p-cymene)Ru(k²-PTN(Me))Cl]Cl (9) could be formed by refluxing the Ru synthon and P,N ligand in CHCl₃.  Therefore, 2 and 3 were heated with chloroform solutions of [(h⁶-p-cymene)RuCl₂]₂ to cleanly form [(h⁶-p-cymene)Ru(k²-PTA-CH(1-MeIm)OH)Cl]Cl (10) and [(h⁶-p-cymene)Ru(k²-PTA-C(1-MeIm)₂OH)Cl]Cl (11) (Scheme 2). The ¹H NMR spectra of 10 and 11 both contained four resonances for the p-cymene ring protons.  This indicated that the ring was coordinated to a RuL₁L₂L₃ moiety, and hence that the P,N ligands were binding in the k²-P,N mode. The ¹H and ¹³C data of the imidazole rings also indicated that the ligands were binding in the k²-P,N mode as the H⁴ resonance and the C⁴ signal were observed to dramatically shift downfield upon coordination to the metal center.  Interestingly, in 11, substantial chemical shifts of only one imidazole indicated that one of the rings had coordinated while the other ring was not attached.   Therefore, in this particular case, ligand 3 did not bind in a tridentate k³-P,N,N fashion. 

Ru complexes have a rich history as ketone hydrogenation catalysts.  Therefore, the abilities of 7-11 to catalytically reduce acetophenone with KOH/i-PrOH were examined under N₂ and H₂. In the presence of KOH, all metal compounds were active catalysts for the hydrogenation when ruthenium/substrate ratios of 1/500 were employed.  The k¹-P compounds 7 and 8 poorly catalyzed the reaction with respective conversions of only 3.8% and 6.8% (TOF = 6.3 and 11 hr^-1) after 3 hours at 80^oC.  The k²-P,N compounds 9 and 10, however, were quite effective at this transformation with >99% and 73% respective conversion (TOF = 165 and 121 hr^-1).   The initial rates of these catalyzed systems were even more impressive as the TOF values after 1 hour were 430 and 201 h^-1 respectively. Unfortunately, under these harsh conditions, the other P,N ligated compound (11) decomposed.  When the ruthenium/substrate ratio for 9 and 10 was increased to 1/100, the reaction was complete after only 1 hour with 9 and nearly complete after 3 hours with 10.  Compounds 7-10 showed no catalytic activity in the absence of base.  This indicated that the catalysis followed a transfer hydrogenation pathway in which i-PrOH was the hydride source.  The same reaction was also performed under a dihydrogen atmosphere of 30 bars at room temperature.  The Ru compounds that contained the monodentate PTA derivatives, 7 and 8, were again poor catalysts for the reduction.  The compounds with chelating P,N ligands, however, were quite efficient at this transformation.  The hydrogenation was complete after 4 hours in the presence of 10 (TOF = 63 h^-1) and 96% converted (TOF = 60 h^-1) when catalyzed by 9.

Through these studies, three new phosphines have been added to the library of water-soluble P,N ligands.  Of these two were shown to bind in the k²-P,N mode.  This is important as the hydrogenation studies reiterated the need for such a coordination mode in catalysis. More importantly, this work has forged a collaboration between my lab and that of Dr. Maurizio Peruzzini that will last into the foreseeable future.  At the present time, we are expanding the catalysis to involve the reduction of a,b-unsaturated ketones and plan to utilize new metals and new catalytic reactions in the years to come.