Cyclization reactions in synthetic organic chemistry

The five areas of proposed research have a common thread. They are all aimed at making cyclic organic compounds. Cyclic molecules are extremely common in Nature, and the vast majority of organic molecules with interesting and beneficial biological activities contain at least one cyclic portion. 1. The first area of investigation is based on the Nazarov reaction. This work will build considerably on our groundbreaking research of the past four years in which we established that allenyl vinyl ketones are very useful substrates for cyclizations with additional bond formation in the same operation. The most exciting aspects of the new work will be the intramolecular trapping of Nazarov intermediates and the application of this process to the synthesis of natural products. 2. We have already been active in the second area, geminal acylation, for many years, but we are proposing an impressive demonstration of geminal acylation's synthetic potential by using the process for making all the rings of propellanes. Also, we are extending considerably geminal acylation's scope to the synthesis of 6-membered heterocycles in enantiomerically enriched/pure form. 3. We have developed procedures for effecting the Pauson-Khand cyclization with encumbered substrates. Our results will be exploited to synthesize a complex diterpene alkaloid, one of a family of biologically active compounds, but now our focus will shift to a different type of cyclization, one with little precedence, that is still to be achieved. 4. Two new areas of investigation will be opened. Cations derived from cyclic 1,3-dithia-compounds have been reported to cyclize. We will investigate this reaction to establish the synthetic scope and to gain insights into the mechanism. Some products may be transformed into chiral cyclopropanes/cyclopropanones. 5. The second new area involves a highly reactive species, cyclohexyne. Cyclizations of substituted cyclohexynes have never been explored. This cyclization will have great synthetic value when the reaction can be carried out with predictable regio- and stereoselectivity. All this research will serve as a rigorous training ground to educate graduate students who will become ideal candidates for positions in industry and academia.