Development of new syntheses and transformations of β-lactones : application to a concise total synthesis of (+)-brefeldin A /
A highly diastereoselective approach to cis-disubstituted β-lactones has been developed and involves a SnCl₄-mediated reaction between aldehydes and thiopyridyl ketene acetals. Results to date are most consistent with a stepwise [2 + 2] cycloaddition. Certain substrates and reaction conditions led...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2002.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=764786551&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | A highly diastereoselective approach to cis-disubstituted β-lactones has been developed and involves a SnCl₄-mediated reaction between aldehydes and thiopyridyl ketene acetals. Results to date are most consistent with a stepwise [2 + 2] cycloaddition. Certain substrates and reaction conditions led to two subsequent in situ transformations to deliver β-chloro carboxylic acids and a tetrahydrofuran. ¹³C KIE studies of Lewis acid-mediated [2 + 2] cycloadditions of ketenes and aldehydes were conducted, and divergent rate-limiting steps have been proposed for the formation of diastereomeric β-lactones. These results suggest that a broader range of mechanistic possibilities for stereoselectivity in multistep reactions should be considered. A diastereoselective, β-lactone-based route to functionalized cyclopentanes involving intramolecular allylsilane additions was studied and optimized. This transformation was then successfully applied to a concise total synthesis of (+)-brefeldin A and a few brefeldin analogs. The versatility of cross metathesis in the context of natural product synthesis was also demonstrated by highlighting the tolerance of a β-lactone, a β-ketophosphonate and a functionalized aldehyde. |
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| Item Description: | Vita. "Major Subject: Chemistry". |
| Physical Description: | xi, 267 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 202-220). |