A scalable protocol for the synthesis and use of neomenthyldiphenylphosphine.
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456565295-MIT.pdf
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Full printable version
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14.98 MB
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Checksum (MD5)
1f62703b6e9cde8db6e03b01437d86d2
Author(s)
Van Dyke, Aaron R. (Aaron Robert)
Advisor(s)
Timothy F. Jamison.
Date Issued
2009
Publisher
Massachusetts Institute of Technology
Abstract
A scalable and reproducible protocol has been developed for the preparation of (-)- neomenthyldiphenylphosphine ((-)-1) from inexpensive starting materials. This ligand was then utilized in the nickel-catalyzed reductive coupling of alkyne 3 and aldehyde 4 to afford allylic alcohol 5 in high yield and enantiomeric excess. Several important modifications were made to the initially communicated procedure in order to effectively translate this methodology from the millimole to decimole scale. Allylic alcohol 5 was then ozonolyzed to afford [beta]-hydroxy ketone 6 with complete preservation of enantiomeric purity. Chapter II. The endo-selective cyclization of alcohols onto epoxides provides a direct route for constructing the oxygen heterocycles found in ladder polyether natural products. Additionally strategies to transform multiple epoxides into multiple new rings have appealing parallels to the proposed biogenesis of these compounds. A continuing challenge is to overcome the inherent preference for the undesired smaller ring product over the larger ring product, processes termed exo and endo cyclization, respectively. Additionally, any method to address this problem should yield products that are themselves synthetically relevant intermediates. We discovered that a benzylidene acetal templated the cyclization of electronically unbiased epoxy alcohols, such as 75, affording products with significant synthetic utility. Critical for high endo-selectivity was the use of silicon-dioxide based promoters.
(cont.) Highlighting the template's utility, the newly formed product (76) was then transformed into a highly decorated THP template (84), corresponding to ring K of gymnocin A. In water, 84 underwent a waterpromoted cascade to construct three additional rings of gymnocin A. We have also achieved cascades of methylene acetal templates with electronically activated epoxides to construct the FG rings of gambierol. Use of these functionalized templates and the products derived from them sets the stage for the convergent total synthesis of ladder polyether natural products.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2009.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Vita.
Includes bibliographical references.
Subjects
Chemistry.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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