The Anti Selective Aldol Addition of Ketones to Aldehydes Mediated by N-Amino Cyclic Carbamate Chiral Auxiliaries and Its Use in the Asymmetric Total Synthesis of (+)- and (-)-Mefloquine Hydrochloride

Coltart, Don M

Knight, John D

2012-09-04T13:15:48Z

2014-08-25T04:30:04Z

2012

Chemistry

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 O-benzylation of the prepared aldol products and the subsequent removal of the ACC auxiliary to give the β-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.

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 α-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.

https://hdl.handle.net/10161/5829

Organic chemistry

ACC

anti aldol

Darzens reaction

mefloquine

The Anti Selective Aldol Addition of Ketones to Aldehydes Mediated by N-Amino Cyclic Carbamate Chiral Auxiliaries and Its Use in the Asymmetric Total Synthesis of (+)- and (-)-Mefloquine Hydrochloride

Dissertation

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