We aim to produce new water-soluble ligands for transition metal catalysts for phosphotriester hydrolysis.  Our most promising new class of ligands are the tris(triazolyl)borate ligands derived from sterically bulky triazoles.  For these studies, Patrick Fadden has optimized the synthesis of 3-t-butyl-5-methyl-1,2,4-triazole, which had previously been made in four steps with a 15% overall yield.[1]  Patrick has streamlined my group's procedure to make it more efficient: our two-step process now occurs in 38% overall yield and can be completed in less than one week.  We hope to publish this route soon.  Patrick has also worked on synthesizing 3,5-diisopropyl-1,2,4-triazole for use in ligands, but only the first step has been completed thus far.

Finith Jernigan and Kirsten Wells have been using 3-t-butyl-5-methyl-1,2,4-triazole to synthesize our ligand, potassium tris(3-t-butyl-5-methyl-1,2,4-triazolyl)borate (KTtz^tBu,Me).  They have improved upon the synthesis and purification of this ligand so that it is isolated in greater purity and higher yield (96%).  This ligand has been used to make new transition metal complexes that either elucidate the structure and electronics of this ligand or for studies towards enzyme mimics of the type Ttz^tBu,MeMOH.

Kirsten Wells has been working on new synthetic routes to Ttz^tBu,MeZnOH.  Her initial approach was to react Zn(ClO₄)₂•6H₂O with first KTtz^tBu,Me in a suitable solvent, followed by addition of a base.  However, when KOH is used in methanol, a mixture of products is seen in the NMR and ligand decomposition is likely.  When NMe₄OH•5H₂O is used in acetonitrile, the NMR, IR, and MS evidence suggests that we have partially decomposed the ligand and we have formed (Ttz^tBu,Me)Zn(3-t-butyl-5-methyl-1,2,4-triazolyl).  Other groups have also seen Tp ligands decompose to the corresponding pyrazole in the presences of zinc perchlorate.[2]  Kirsten next attempted a substitution reaction on (Ttz^tBu,Me)ZnCl.  However, when (Ttz^tBu,Me)ZnCl is treated with KOH the result is KTtz^tBu,Me (observed spectroscopically).  When (Ttz^tBu,Me)ZnCl is treated with NMe₄OH•5H₂O the result is [NMe₄][Ttz^tBu,Me] which was characterized by single crystal x-ray diffraction.  In both reactions, presumably Zn(OH)₂ and Zn(OH)Cl are formed as side products and provide a driving force for this chemistry. 

At this point I tried an alternate route to Ttz^tBu,MeZnOH.  KTtz^tBu,Me was treated with TlNO₃ in MeOH and water to produce TlTtz^tBu,Me in 59% yield.  Then, TlTtz^tBu,Me was treated with ZnEt₂ in THF to produce thallium metal precipitate and Ttz^tBu,MeZnEt.  Ttz^tBu,MeZnEt is a new complex and characterization is still ongoing, but the proposed composition is consistent with the ¹H and ¹³C-NMR spectra.  However, when water was added to an NMR tube containing Ttz^tBu,MeZnEt in C₆D₆, no change was observed in the 1H-NMR spectrum.  In fact the ethyl peaks in the ¹H-NMR fail to disappear after months, so it appears that the intended reaction to form Ttz^tBu,MeZnOH and ethane has not occured.  Despite this preliminary negative result, this new organometallic complex is publishable and interesting since it is the first alkyl complex of a Ttz ligand.

Similarly, Finith Jernigan has been investigating the reaction of Ttz^tBu,MeCoCl with MeMgCl in hopes of forming Ttz^tBu,MeCoMe, which would react with water to form Ttz^tBu,MeCoOH.  Unfortunately, the first reaction in this sequence has failed, but further investigation on this topic is needed before any conclusions can be drawn.

From the analysis of the crystal structures of zinc and cobalt complexes of the Ttz^tBu,Me ligand, we have learned that this ligand is sterically very similar to the Tp^tBu,Me ligand.  However, this does not mean that there are not important electronic differences, and it is not obvious whether the third nitrogen in the triazole ring will be electron donating or withdrawing.  Trisha Donahue has synthesized Ttz^tBu,MeCuCO in order to  investigate the electron donating ability of our new ligand.  She reacted KTtz^tBu,Me with CuCl in THF under an atmosphere of CO(g).  Recrystallization in THF and hexane yielded x-ray quality crystals; the structure contained a tetrahedral Cu atom coordinated to three nitrogen atoms from the Ttz^tBu,Me ligand and the C of CO.  This structure has also been confirmed by ¹H,¹³C-NMR, IR and MS.  Interestingly, the IR spectrum shows a CO stretch at 2080cm^-1 which indicates that the Ttz^tBu,Me ligand is a weaker electron donor than the Tp^tBu,Me ligand.  We are currently in the process of studying this complex electrochemically and we hope to publish a communication on this work shortly.

During the past year, Bryan Klebon has been working on the organic synthesis of other ligands.  He has spent most of his time attempting to make bis(3-t-butyl-5-methyl-pyrazolyl)propionate by two different retrosynthetic strategies.  Unfortunately, we have not been able to make this ligand consistently in high yield or purity.  More recently, Bryan has also worked on the synthesis of bis(3-t-butyl-5-methyl-1,2,4-triazolyl)acetate and this project is near completion.