Some of the areas in which we currently have active programs include:

Organometallic chemistry:

Further development of the chemistry of nickel-on-charcoal (Ni/C) is being pursued. Recent efforts have demonstrated that this material retains the vast majority of originally impregnated nickel within the matrix of the charcoal, where nickel atoms formally in solution (i.e.,not embedded into the solid support) appear to be mediating the catalysis observed (cf.'cartoon' below). This reagent holds promise for uses in several contexts where the cost of palladium is an issue, and where removal of soluble metal impurities is problematic. Studies involving this heterogeneous catalyst bearing nonracemic ligands, as well as its use under microwave-assisted conditions are ongoing. A related catalyst, nickel-on-graphite, is also being examined as a catalyst in selected C-C bond-forming processes.

We have recently disclosed a new benchmark method for effecting asymmetric hydrosilylations of aryl ketones using CuH chelated by the nonracemic Roche ligand 3,5-xyl-MeO-BIPHEP. Work in this area continues to further increase the substrate : ligand ratios beyond the 20,000:1 level already reported, as well as the ee's. Applications to other substrate types (e.g.,heteroaromatic ketones), as well as targeted intermediates in selected pharmaceuticals (e.g.,prozac) are underway.

Several targets are being synthesized using organometallic-based strategies. New routes to the especially important nutraceutical coenzyme Q₁₀ (CoQ₁₀), as well as antitumor agents related to all-trans-retinoic acid are of particular current interest.

AIDS-related research:

Construction of complex, highly functionalized biaryls is an especially challenging area of synthetic chemistry. The michellamines, and michellamine B in particular, are representative of natural products that posses axial chirality. The components of michellamine B, korupensamines A and B, which exist as diastereomers and are individually active as antimalarials, require new technology for their construction which brings the entire, fully functionalized naphthyl and tetrahydroisoquinoline units together in a highly stereocontrolled fashion. Our solution to the korupensamine A skeleton has focused on use of an internally positioned phosphine, which controls the directionality of biaryl formation in a Pd(0)-catalyzed Suzuki coupling. Ongoing work is aimed at providing an equally effective solution to the synthesis of korupensamine B.

Vancomycin biaryl:

Vancomycin ranks as one of the most important clinically useful antibiotics currently available. An especially challenging portion of this polycyclic heptapeptide is the biaryl A-B segment, which occurs naturally as its S-atropisomer. As alluded to above with respect to michellamine B, construction of this biaryl in a direct, stereocontrolled manner presents special problems for which as yet no solution exists. Our focus is on the use of both inter- and intra-molecular routes to this key subunit.

New BINOLs, NOBINs, and BINAPs:

The binaphthyl array has led to ligands such as BINOL, NOBIN, and BINAP, which are among the most heavily used in asymmetric synthesis. Enhancements in their effectiveness are oftentimes observed when substituents are present in the 3- and/or 3'-sites. We have developed modular routes to substituted "cyclo-BINOLs" and are further pursuing synthesis of related ligands in the "cyclo-NOBIN" and"cyclo-BINAP" series. Selected members from each, once realized, will be attached to a polystyrene backbone for use in heterogeneous catalysis.

Cyclopeptide Alkaloids:

These naturally-occuring, strained 14-membered ring systems may function as novel ion-sequestering agents and hence, as potential antibiotics. Our approach relies on the masking of the dipeptide unit in the form of an appropriately substituted oxazole, incorporated within a protected [3.3]-para-cyclophane as precursor. We are examining several approaches to this unsaturated cyclophane array, which upon mild acid hydrolysis, should cascade directly to the desired cyclic peptide.