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dc.contributor.advisor Coltart, Don M en_US
dc.contributor.author Sauer, Scott J. en_US
dc.date.accessioned 2011-06-09T13:00:14Z
dc.date.available 2013-05-28T04:30:06Z
dc.date.issued 2011 en_US
dc.identifier.uri http://hdl.handle.net/10161/3952
dc.description Dissertation en_US
dc.description.abstract <p>The direct addition of enolizable aldehydes and sulfonyl imines to &alpha;-halo thioesters to produce &beta;-hydroxy/amino thioesters enabled by reductive soft enolization is reported. The transformation is operationally simple and efficient and has the unusual feature of giving high <italic>syn</italic>-selectivity, which is the opposite of that produced for the aldol addition with (thio)esters under conventional conditions. This method is tolerant to aldehydes and imines that not only contain acidic &alpha;-protons, but also towards electrophiles containing other acidic protons and base-sensitive functional groups. Moreover, excellent diastereoselectivity is achieved when a chiral non-racemic &alpha;-hydroxy aldehyde derivative is used. Using MgI<sub>2</sub> and Ph<sub>3</sub>P, this method gives a wide range of aldol and Mannich products in good yields with high <italic>syn</italic>-diastereoselectivity. The products obtained from the reductive aldol and Mannich reactions are synthetically important intermediates in both polyketide and &beta;-lactam synthesis, respectively, and can be readily derivatized to form many carbonyl derivatives through known manipulation of the thioester moiety.</p><p><p>Also, herein the asymmetric synthesis of (+)-mefloquine, a potent anti-malarial compound, is described. The synthesis is based on a key enantioselective Darzens reaction between a chiral &alpha;-chloro-N-amino cyclic carbamate (ACC) hydrazone and a quinoline-based aldehyde. This is a novel methodology developed by our lab, which gives a highly enantioenriched epoxide that can be further functionalized to give both enantiomers of mefloquine.</p> en_US
dc.subject Chemistry en_US
dc.subject Organic Chemistry en_US
dc.subject ACC en_US
dc.subject aldol en_US
dc.subject mannich en_US
dc.subject mefloquine en_US
dc.subject thioester en_US
dc.title Direct Carbon--Carbon Bond Formation Through Reductive Soft-Enolization of &alpha;-Halothioesters and The Total Synthesis of (+)-Mefloquine en_US
dc.type Dissertation en_US
dc.department Chemistry en_US
duke.embargo.months 24 en_US

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