Garner Research Group

Research in my group centers around the synthesis and analysis of chiral organic compounds. We are working to improve catalytic asymmetric processes by developing new chiral ligands for transition metal catalysts. The ligands we have developed fall into two broad categories:

Ligands related to 2,6-bis-hydrazinopyridine (BHP)

My lab was the first to develop a synthesis of BHP, which was complicated by several factors including its sensitivity to oxygen. We have a reliable procedure that provides analytically pure material in ~ 80% yield. BHP is useful in the preparation of 2,6-bis-pyrazolylpyridines, which are tridentate ligands. Traditional approaches to these ligands did not allow groups larger than methyl at the 5' positions. Using the BHP reaction with 1,3-diketones, we can make 2,6-bis-pyrazolylpyridines with groups as large as tert-butyl at the 5' positions (1). And unsymmetrical 1,3-diketones very selectively put the larger alkyl group at the 5' position. Garner Research 1

The tetraphenyl ligand had not been reported previously; we found that it readily forms metal complexes. Below are photos of a variety of transition metal chlorides in ethanol before and after addition of the tetraphenyl ligand. Note the significant color changes, indicative of metal complexation. We have developed a route to the related bis-indazolylpyridine ligands. And we identified a purely electronic effect on the regiochemistry of pyrazolylpyridine formation (see Tetrahedron Letters 2008, 49, 5766-69). This work has been funded by the Robert A. Welch Foundation. Garner Research 2

C2-Asymmetric phosphinine ligands

?Phosphinines (also known as phosphabenzenes) are relatively little studied ligands that have promise in hydroformylation catalysts. Very few chiral phosphinines have been reported, and (prior to our work) none that were C2-chiral. We recently reported the synthesis of the first such C2 ligand (3) from (+)-camphor. The synthesis necessarily proceeds through the corresponding pyrylium salt (2), only the third chiral pyrylium ever reported. The phosphinine is an air-stable and chromatographable crystalline solid. We are continuing the discovery and development of new pyryliums, phosphinines and related ligands. This work has been funded by the Petroleum Research Fund and the Robert A. Welch Foundation. Garner Research 3

New cyclodextrin derivatives to improve enantiomer separations by gas chromatography

Among chromatographic methods, capillary gas chromatography is rarely surpassed in terms of high separation power and sensitivity. Where applicable, capillary GC is the best method for determining very high enantiomeric purities. Most chiral GC stationary phases are based on cyclodextrin derivatives. Cyclodextrins are bucket-shaped molecules composed of six to eight D-glucose rings connected in a 1,4'-fashion. The upper rim is lined with secondary hydroxyl groups, and the bottom rim with primary hydroxyls. Garner Research 4

In order to be usable in gas chromatography, cyclodextrins need to be derivatized to eliminate the free OH groups. The primary hydroxyls are typically capped with TBS protecting groups, so most of the creativity occurs at the secondary hydroxyls. To date, the only types of derivatives tested in GC are very simple ethers (methyl, ethyl, etc.) or esters (acetate, propionate, etc.). I propose that a range of more effective stationary phases could be prepared by more sophisticated syntheses and/or novel derivatizations. We have an arrangement whereby compounds we produce are made into high-quality capillary columns by a collaborator. We have tested several such stationary phases and continue to make new ones.

Azulene-based materials for synthesis and analysis

Azulenes are fascinating intensely-colored relatively-polar hydrocarbons. We have a new project underway to make optically-active azulene derivatives, and hope to use them to advantage in synthesis and analysis. One reaction and the associated colors are shown below. Garner Research 5

Working in the Garner Group. The best reason to pursue graduate studies is that you love the sense of discovery that chemistry offers. I tend to stress careful lab technique, often necessary for the air-sensitive chemistry we do, but also important in many contexts. My students become very familiar with NMR (I teach our graduate course in Organic Spectroscopy) and capillary GC and GC-MS. We also do a lot of preparative liquid chromatography (including radial), and even some distillation (almost a lost art in modern organic chemistry). I do some lab work myself, which keeps me in touch with my students' needs and resources. I try hard to provide an excellent level of supplies (glassware, etc.) and specialized equipment to make lab-lif