Title

2-methylenetetrahydropyrans in the carbonyl-ene reaction: Studies toward the synthesis of spirastrellolide A

Date of Award

2009

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Advisor(s)

Nancy I. Totah

Keywords

Carbonyl-ene reaction, Spirastrellolide, Methylenetetrahydropyrans, Zinc chloride

Subject Categories

Chemistry | Organic Chemistry | Physical Sciences and Mathematics

Abstract

Catalyzed by ZnCl 2 , 2-methylenetetrahydropyran has been shown to readily undergo carbonyl-ene reactions with a variety of activated and unactivated aldehydes and ketones. In efforts to broaden the scope of the enol ether component of the reaction, substituted 2-methylenetetrahydropyrans were studied. Use of elelctron-rich exocyclic enol ethers provides higher yields in shorter reaction times. This new carbon-carbon bond forming reaction allows rapid access to tetrahydropyranyl ketides.

Isolated from the marine sponge Spirastrella coccinea , spirastrellolide A (SPA) is an example of a biologically active natural product that contains the tetrahydropyranyl ketide motif. Therefore, studies toward the synthesis of this natural product have been made employing carbonyl-ene reactions of 2-methylenetetrahydropyrans. In particular, the synthesis of [4.5]- and [5.5]-spiroketal model systems of SPA has been achieved through intramolecular cyclization of carbonyl-ene adducts. Cross-coupling of a [4.5]-spiroketal model system to the C40-C47 side chain has also been demonstrated. The synthesis of the C40-C47 fragment featured Wittig olefination to generate the Z -double bond.

In addition, progress has been made toward the synthesis of the C26-C47 segment of spirastrellolide A. Approach towards the DEF-spiroketal system exploited the exocyclic enol ether carbonyl-ene reaction in a bidirectional manner.

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