The principal objective of the research proposed herein is the development of a new and general synthetic protocol for the preparation of a variety of medicinally important alkaloids and other nitrogen-containing natural products. A unified strategy for the synthesis of a diverse array of these materials would be attractive, as opposed to the more traditional approach involving a different strategy for each target. The target substructure, a pyrrolidine fused to another ring at the 2- and 3-positions, is widespread in nature. To prepare this subunit, the intramolecular cycloaddition of a 2-azaallyl anion onto an olefin is proposed. The flexibility of this method will be demonstrated through the synthesis of biomedically important nitrogen-containing compounds such as dendrobine, scandine, lycorine, and others, including some angiotension converting enzyme inhibitors. A concurrent goal is the investigation of the poorly understood chemistry of 2-azaallyl anions themselves. Model work has shown that the intramolecular cycloadditions of these species are feasible, but much work regarding their generation and the scope, stereochemistry, and regiochemistry of the cycloadditions must be addressed. Within the framework of natural products synthesis, these unexplored areas in the chemistry of these fascinating intermediates will be addressed.
