The goal of this research is the development of novel synthetic procedures which are highly efficient as well as highly regio-and stereoselective and which can be used for the synthesis of compounds that are either important medicinally or in the determination of the relationship between structure and biological activity. Most of the methods are to be based ultimately on reactions discovered in our laboratory which make use of the magnificently versatile properties of sulfur. We shall evaluate the scope and limitations of these methods and demonstrate their utility by applying them to the synthesis of natural products or to approaches to such syntheses. The following areas are to be developed: (A) one-pot preparations from commercial or otherwise readily available materials of usefully functionalized vinylecyclopropanes which are directly ring expandable to the 5- or 7- membered rings found in so many biologically active compounds. (B) A number of new ways to utilize the novel alkylidene- and allylidenecyclopropanes which can now be so easily prepared by our technology. These include the preparation of a variety of fused ring systems with the emphasis on hydrazulenes, a class of compounds many of which are active as antibiotics or as anticancer agents. Several approaches to natural product syntheses including the efficient preparation of a previously unsynthesized aromadendren sesquiterpene in optically active form are suggested. (C) New methods to control stereochemistry in our new allyl anion preparation, methods to easily produce alkylpotassiums and, from them, alkylpotassiums, and a variety of procedures for extending the utility of our method of allyl anion production, including the preparation by this method of allyl cuprates, stannanes, silanes and boranes. (D) Methods which should allow at will the ring expansion of 2- vinylcyclobutanones to either cyclopentenones or cyclohexenones. (E) A completely new method of producing carbocyclic rings involving the first examples of the 1,2-Wittig rearrangement of unstabilized Alpha-lithio cyclic ethers which we now have the almost unique ability to produce. (F) Methods to produce lithioenamines, which will be new and versatile synthetic intermediates.
