Position title: Professor of Chemistry
Room 7112, Department of Chemistry
1101 University Avenue
Madison, WI 53706
B.S. 1973, University of Wisconsin-Eau Claire
Ph.D. 1978, University of Pittsburgh
PUBLICATIONS & AWARDS
Our primary research interests focus on synthetic organic chemistry, with an emphasis on the efficient synthesis of natural products (and analogues thereof) with potent biological activity. Development of synthetic methods and novel strategies in response to the demands of complex molecule construction are key elements of our approach to target-oriented synthesis. Exemplifying this is our ongoing exploitation of symmetry for simplification of synthetic sequences, with the accompanying need for methods to efficiently break symmetry. Recently completed syntheses of such diverse structural types as phorboxazole B, thromboxane B2, didemniserinolipid B, squamocin N, and dictyostatin illustrate common themes that have been developed in our group. Included among these themes are Pd(0)-mediated asymmetric double cycloetherification, ketalization/ring-closing metathesis, asymmetric double hetero Diels-Alder cycloaddition, and kinetically-controlled Meerwein-Ponndorf-Verley reduction.
A substantial portion of our current efforts are directed at developing Rh-catalyzed asymmetric hydroformylations (AHF) in tandem with compatible C-C and C-X bond forming reactions. We are pursuing this endeavor in collaboration with the Landis group, seeking to explore the possibility of using the chiral bis(diazaphospholane) [“BDP”] ligand/Rh(I) catalysts in complex molecule synthesis. The perfectly atom-economical AHF procedure delivers branched, chiral aldehydes in high enantiomeric excess from achiral alkenes, CO, and H2, with very low catalyst loadings. An illustrative example of the power of these tandem processes to facilitate complex natural product synthesis is shown in the scheme below, detailing a 4-step synthesis of the C1-C7 subunit of the methynolide antibiotics (see numbered structure of the natural product in 1st box). Beginning with the AHF of commercially available acrolein acetal, the branched aldehyde formed is directly reacted with the indicated E-crotyltrifluorborate to afford a stereotriad in a highly enantio- and diastereoselective manner. Acylation and Ru-catalyzed ring-closing metathesis provided the unsaturated d-lactone, which was reduced to the boxed C1-C7 subunit.