SYNTHETIC EFFORTS TOWARDS INGENOL CROSS-CONJUGATED TRIENES AND THEIR APPLICATION TO RAPID INCREASES IN MOLECULAR COMPLEXITY
Synthesis of the ingenol skeleton using a Pauson-Khand reaction as the key step was investigated. Although the Pauson-Khand reaction failed to provide the highly strained ingenol skeleton, several relatively complex Pauson-Khand precursors were prepared in about ten steps. The scope and limitation of the Pauson-Khand reaction in accessing highly strained molecules were studied. A rhodium(I)-catalyzed allenic Alder-ene reaction was developed that provides cross-conjugated trienes in good yields. This method shows enticing functional group compatibility, and progress has been made to increase the stereoselectivity of the olefinic side chain via iridium(I) catalysis. A consecutive one-pot Alder-ene/[4+2]/[4+2] reaction has been developed to demonstrate the potential of the cross-conjugated triene for accessing polycyclic compounds. The reaction sequence is highly selective with the Alder-ene and the first Diels-Alder reaction only providing a single isomer and the intermolecular [4+2] cycloaddition giving two endo addition products resulting from addition of the dienophile to either face of the diene. The transformation is highly atom-efficient with all the atoms of the starting dialkynyl allenes and the dienophiles appearing in the products.
Advisor:Professor Billy Day; Professor Peter Wipf; Paul Floreancig; Professor Kay M. Brummond
School:University of Pittsburgh
School Location:USA - Pennsylvania
Source Type:Master's Thesis
Date of Publication:03/30/2006