A scalable protocol for the synthesis and use of neomenthyldiphenylphosphine.

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Van Dyke, Aaron R. (Aaron Robert)

Advisor dc:contributor.advisor

• Timothy F. Jamison.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/49553

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/49553