Direct Carbon--Carbon Bond Formation Through Reductive Soft-Enolization of α-Halothioesters and The Total Synthesis of (+)-Mefloquine
| dc.contributor.advisor | Coltart, Don M | |
| dc.contributor.author | Sauer, Scott J. | |
| dc.date.accessioned | 2011-06-09T13:00:14Z | |
| dc.date.available | 2013-05-28T04:30:06Z | |
| dc.date.issued | 2011 | |
| dc.department | Chemistry | |
| dc.description.abstract | The direct addition of enolizable aldehydes and sulfonyl imines to α-halo thioesters to produce β-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 syn-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 α-protons, but also towards electrophiles containing other acidic protons and base-sensitive functional groups. Moreover, excellent diastereoselectivity is achieved when a chiral non-racemic α-hydroxy aldehyde derivative is used. Using MgI2 and Ph3P, this method gives a wide range of aldol and Mannich products in good yields with high syn-diastereoselectivity. The products obtained from the reductive aldol and Mannich reactions are synthetically important intermediates in both polyketide and β-lactam synthesis, respectively, and can be readily derivatized to form many carbonyl derivatives through known manipulation of the thioester moiety. 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 α-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. | |
| dc.identifier.uri | ||
| dc.subject | Chemistry | |
| dc.subject | Organic chemistry | |
| dc.subject | ACC | |
| dc.subject | aldol | |
| dc.subject | Mannich | |
| dc.subject | mefloquine | |
| dc.subject | Thioester | |
| dc.title | Direct Carbon--Carbon Bond Formation Through Reductive Soft-Enolization of α-Halothioesters and The Total Synthesis of (+)-Mefloquine | |
| dc.type | Dissertation | |
| duke.embargo.months | 24 |