The Ester Enolate Claisen Rearrangement: I. Stereochemical Control Through Stereoselective Enolate Formation. II. Construction of the Prostanoid Skeleton

Author: Willard, Alvin Keith

Year: 1976

Degree: Dissertation (Ph.D.)

Advisor: Ireland, Robert E.

Committee Member: Unknown, Unknown

Option: Chemistry

DOI: 10.7907/FX8A-9T58

Abstract

Part I:

The [3,3]-sigmatropic rearrangement of a number of allylic esters 1, as the enolate anions of the corresponding silyl ketene acetals, produces the γ,δ-unsaturated acids 2 in 66 - 88% yield. The mild conditions allow rearrangement of acid sensitive and thermally labile esters. Rearrangement of ester 1g affords (E)-4-decenoic acid (2g) with greater than 99% stereoselectivity. (E)-Crotyl propanoate (12) leads to erythro-acid 14 when enolization is carried out in THF, but to the threo-acid 15 when the solvent is 23% HMPA-THF. Results with a variety of esters demonstrate that kinetic enolization with lithium diisopropylamide gives selective formation of the geometrical enolate H in THF and the isomeric enolate I in HMPA-THF. Similar results are obtained with 3-pentanone. (Scheme I)

Part II:

A convergent synthesis of the prostaglandin skeleton is described. The ester enolate modification of the aliphatic Claisen rearrangement is used to form the key C8-C12 bond. Rearrangement of ester 18 provides the lactone 29 which is converted to the prostanoid 30. Similarly, the lactone 52, a potential intermediate in the synthesis of 12-methyl PGA1, is obtained from ester 51. Preparation of ester 51 features Claisen rearrangement of ester 38, which leads to the dienoate 41 after desulfenylation. Model studies of reduction of γ,δ-epoxy-α-β-unsaturated esters to δ-hydroxy-β,γ-unsaturated esters are described. This reduction is accomplished with lithium in ammonia at -78° for conversion of epoxy ester 50 to ester 51. (Scheme II)

Scheme I:

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Scheme II:

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