The stereoselective synthesis of oxygen and nitrogen heterocycles

The development of new methodologies toward the synthesis of tetrahydrofurans, tetrahydropyrans and pyrrolidines are presented. Recently, a new method for the synthesis of tetrahydrofurans was developed in our laboratory. This approach involved a Lewis acid activated β-silyloxy aldehyde reacting with benzyldiazoacetate to afford tetrahydrofurans. This dissertation expands this methodology further to include tetrahydrofuran formation from epoxides. The epoxides were synthesized and treated with a Lewis acid to induce the rearrangement to the aldehyde in situ. The aldehyde was then treated with benzyldiazoacetate to generate the substituted tetrahydrofuran.; The second part of this dissertation discusses the stereoselective reaction of aldehydes with allylsilanes to synthesize tetrahydropyrans. Several different allylsilanes and β-silyloxy aldehydes were synthesized to investigate the scope and limitations of this formal [4+2] cycloaddition reaction. It was found that only one diastereomer was produced in the reaction of crotylsilane with aldehydes. The substituents in the product were found to possess a cis-trans-trans orientation about the ring with the hydroxyl group having a cis orientation to the silyl methylene substituent. It is well documented that the stereoselective reaction of allylsilanes with aldehydes proceeds via a syn-synclinal transition state. In the case of crotylsilane 50, we found that it proceeds through a syn-synclinal transition state also.; In an effort to exploit this methodology further, we sought to apply it to the synthesis of piperidines. However, the reaction of β-amido aldehydes with allylsilanes produced piperidines in low yield, though in high stereoselectivity. The β-amido aldehydes were then reacted with benzyldiazoacetate, in an analogous manner to the tetrahydrofuran synthesis, to generate pyrrolidines. The pyrrolidines possessed the same stereochemistry as the tetrahydrofurans previously synthesized in our laboratory: 4-alkyl substituted pyrrolidines possessed a cis-trans orientation of substituents about the ring, while 4-alkoxy pyrrolidines possessed a trans-trans orientation of substituents around the ring. Here, a new stereoselective synthesis for the formation of pyrrolidines is presented.