Kevin T. Sprott

Intramolecular cyclopropanation reactions en route to novel P-heterocycles

Abstract The first examples of intramolecular cyclopropanation reactions on a phosphonate template catalyzed by Rh 2 (OAc) 4 are described. These reactions proceed in excellent yield and give mixtures of the P-heterocycles cis - 2a-d and trans - 2a-d with moderate levels of diastereoselectivity. The diastereoselectivity of this tranformation is dependent upon the size of the alkyl group R contained in the alkyl α-diazodiallylphosphonoacetate starting materials 1a-d .

Ring-Closing Metathesis Strategies to P -heterocycles

A general approach to the synthesis of P -heterocycles using the ring-closing metathesis reaction is described. We have developed a new method utilizing phosphorus nuclei as suitable temporary tethers for the coupling of non-racemic allylic amines. This approach allows for the generation of symmetric and unsymmetric 1,4-diamines. Subsequent coupling of these 1,4-diamines with various nuclei produces an array of 7-membered heterocycles.

Ring-Opening Metathesis Polymerization Approach to Phosphorus-Containing Biooligomers

Naturally occurring biopolymers (peptides, oligonucleotides, and proteins) are, in theory, excellent drug candidates. However, their poor bioavailability profiles limit their use as potential therapeutic agents. In order to address this problem, the synthesis of diverse polymers consisting of unnatural subunits has emerged as a powerful means of constructing new scaffolds with potentially useful pharmaceutical properties. This approach has recently been applied in the synthesis of peptidosulfonamides,1 cyclic urea scaffolds,2 peptide nucleic acid-based (PNA) pseudopeptides,3,4 ethoxyformacetal oligomers,5 pyrrolin-4-onebased motifs as mimics of peptidal β-strands,6 and peptidomimetic oligomers with a phosphodiester backbone.7 Ring-opening metathesis polymerization (ROMP) strategies using the Grubbs benzylidene catalyst to an array of functionalized biopolymers containing phosphorus and sulfur are discussed. The synthesis of phosphorus and sulfur containing biooligomers utilizing maleimidebased monomers has been developed. Subsequent polymerizations were carried out with various monomer:catalyst ratios and the obtained biooligomers were characterized by MALDI-TOF analysis. A strategy employing both ring-closing metathesis (RCM) reactions and ROMP reactions to derive oligomeric sulfonamides as novel peptidomimetics has also been developed. In addition, our efforts toward the synthesis of cationic, amphiphilic polymers will be presented. These phosphonium contaning polymers show an intriguing reactivity difference between the first generation and second generation Grubbs metathesis catalysts.