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

Citation

Willard, Alvin Keith (1976) The Ester Enolate Claisen Rearrangement: I. Stereochemical Control Through Stereoselective Enolate Formation. II. Construction of the Prostanoid Skeleton. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/FX8A-9T58. https://resolver.caltech.edu/CaltechTHESIS:12042017-161832975

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:

Refer to pdf for formulas

Scheme II:

Refer to pdf for formulas

Thesis Files