Thesis (M.S.)--Villanova University, 2010. / Chemistry Dept. Includes bibliographical references.

In the first part of this thesis, it is aimed to develope methods for the synthesis of trisubstituted pyrrrole derivatives. 2-Aminopyrrroles, alkoxy and sulfonyl substittitued pyrrole derivatives as well as pirolinones show interesting biological activities and are precursor of well know drugs. Although there is a number of methods for the synthesis of pyrroles, the synthesis of 2-aminopyrroles is limited to few works and is not widely known. Therefore, it is still an important goal in organic chemistry to improve methods for the synthesis of multifunctionalized pyrrole derivatives and pyrrolinones. Alkylation of &amp / #946 / -dicarbonyl compounds with bromoacetonitrile furnishes &amp / #945 / - cyanomethyl-&amp / #946 / -dicarbonyl compounds. The condensation reaction of &amp / #945 / - v cyanomethyl-&amp / #946 / -dicarbonyl compounds with amines catalyzed by p-TsOH affords the corresponding enamines and further base catalyzed cyclization furnishes 2- aminopyrroles in high yields, moreover, zinc perchlorate-catalyzed addition of amines, alcohols and thiols to the nitrile carbon of &amp / #945 / -cyanomethyl-&amp / #946 / -ketoesters followed by annulation gives the 5-alkoxy and 5-alkylsulfanylpyrrole-3-carboxylates in high yields. In the second part of the thesis, reactions of a broad range of acyl phosphonates with &amp / #945 / -bromo acetophenones at room temperature in the presence of different bases were described to afford two diastereomeric epoxy phosphonates in good yields and high diastereoselectivities. The diastereoselectivity of this reaction is easily controlled by changing the base. Accordingly, changing the base from Cs2CO3 to DBU changes the diatereomeric ratio (trans/cis) from 5/3 to 9/1. Furthermore, the treatment of trans isomer with DBU shows a complete conversion to the corresponding cis isomer. Additionally, these highly functionalized epoxyphosphonates are shown to be useful intermediates to give several reactions

<p>In the first part of this dissertation, the first asymmetric anti selective aldol addition of a ketone-derived donor that is independent of the structure of the ketone is described. This transformation is facilitated by the use of chiral N-amino cyclic carbamate (ACC) auxiliaries. Under certain conditions, this transformation not only exhibits near perfect anti selectivity and enantioselectivity but also does so via thermodynamic control. Simple manipulation of the reaction conditions allows for the <italic>O</italic>-benzylation of the prepared aldol products and the subsequent removal of the ACC auxiliary to give the &beta;-benzyloxy ketone. Both symmetric and asymmetric ketones can be utilized, and aldol products that would otherwise be difficult if not impossible to prepare via conventional methods are able to be prepared.</p><p>The second part of this dissertation describes the asymmetric total synthesis of (+)- and (-)-mefloquine hydrochloride, a potent antimalarial compound. The synthesis is based on an ACC-mediated asymmetric Darzens reaction between an &alpha;-chloro ketone and a quinoline-based aldehyde. This novel methodology gives a highly enantioenriched epoxide that can be further functionalized to prepare both enantiomers of the antimalarial drug.</p> / Dissertation