Development of novel catalytic syntheses of aziridines and [2]rotaxanes

Abstract

The first part of this dissertation introduces the accomplishment of an important methodological development towards the synthesis of Lewis acid-catalyzed aziridines. Aziridines, a class of three-membered nitrogen-containing heterocycles, have attracted a great interest to chemists owing to their ability to serve as versatile precursors for the synthesis of biologically-active compounds, including amino acids, amino alcohols and β-lactam antibiotics. Of the modern catalytic routes to aziridines, the Lewis acidcatalyzed reaction of diazoacetate with imines has been extensively studied, because the resulting aziridine-2-carboxylate ester is a convenient source of unnatural α- and β-amino acids. One problem that accompanies this route is the formation of β-amino-α,β- unsaturated ester (AUE) byproducts which thereby decreases the yield of the aziridine. We report the development of an alternative route to the Lewis acid-catalyzed aziridination that precludes the formation of the AUE byproducts. This pathway proceeds with excellent conversion of starting materials, high cis-selectivit, and the aziridine-2- carboxylate esters were formed in good to excellent yields. Variety of substrates were tested and a significant increase in product yield was observed for N-(paramethoxyphenyl)- protected aziridines, which are otherwise obtained in relatively low yield. In the second part of this dissertation we disclose a novel route for the synthesis of [2]rotaxanes, an interesting and useful supramolecular architecture. Rotaxanes have emerged as a special class of mechanically interlocked supramolecular assemblies due to their usefulness towards the development of molecular machines or molecular devices. Even though its chemistry has progressed over the years, until now there are only three general strategies for rotaxane synthesis, namely; threading-capping, clipping and slipping. In our efforts to develop routes to these supramolemolecular assemblies, we have uncovered a novel synthesis of a [2]rotaxane via the “insertion” of a [2]catenane into a di-stoppered axle. This complementary pathway proceeds with good to excellent yield of [2]rotaxanes. A report of the synthesis of the required starting materials along with studies on optimization of the reaction conditions are discussed in the second part of the dissertation.