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Title:Rearrangements of 1-Heterosubstituted Chrysanthemyl Aldehyde and Chrysanthemyl Amines
Author(s):Vancantfort, Christopher Kent
Department / Program:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Chemistry, Organic
Abstract:One theory concerning the mechanism for the conversion of presqualene pyrophosphate to squalene involves postulation of a new intermediate (known locally as protosqualene pyrophosphate) which is a ring expanded analog of presqualene pyrophosphate. There is no direct evidence for this discrete new intermediate but a successful synthesis of it would facilitate, via biosynthetic incorporation studies, determination of whether or not such an intermediate does exist. With this goal in mind, research was undertaken to ascertain the feasibility of protosqualene pyrophosphate synthesis.
The synthetic plan involved studying the possible ring expansion of the chrysanthemate system as a model for synthesis of protosqualene pyrophosphate from a presqualene derivative. Two different approaches to the rearrangement of the chrysanthemate system were studied. First, semi-pinacolic rearrangement of chrysanthemyl amines functionalized at C(,1) with electron-donor groups was examined. The necessary amines were prepared from the corresponding nitriles which were, in turn, formed by reaction of the alpha anion of chrysanthemyl nitrile with appropriate heteroatom-based electrophiles. Amines with either phenylthio or methoxyl substituents at C(,1) gave rise, upon deamination, to ring cleaved products possessing artemisyl or santolinyl skeletons. In the case of the methoxyl substituted amine some of the product (26%) was ring expanded.
Alkaline hydrolysis of the spiro-N-nitrosooxazolidone of the chrysanthemate system similarly produced predominantly ring cleaved product with a small amount of ring expanded product. Deamination of 1-methoxy dihydrochrysanthemyl amine afforded only ring expanded products. These results were interpreted as indication that cation-initiated semi-pinacolic ring expansion of the chrysanthemate system was thwarted by participation of the vinyl substituent of C(,3) in a fashion that led primarily to ring opened product. As a result, such a synthetic route to protosqualene pyrophosphate synthesis was not considered suitable.
The second approach to ring expansion was based upon anion-initiated rearrangement, specifically, semibenzilic type rearrangement. Thus, when 1-t-butyldimethylsiloxy chrysanthemyl aldehyde was reacted with a fluoride-based desilylation reagent the major product isolated was 2,2-dimethyl-3-(2-methyl-1-propenyl)-4-hydroxy cyclobutanone. The acyloin alkoxide intermediate in this rearrangement could be trapped as the acetate by addition of acetic anhydride to the desilylation solution. By this procedure, 2,2-dimethyl-3-(2-methyl-1-propenyl)-4-acetoxy cyclobutanone was prepared in 61% yield. The acetoxy group in this compound was reductively cleaved by a number of procedures including reaction with calcium-ammonia, lithium dimethylcuprate, and tri-n-butyltin hydride, to give 2,2-dimethyl-3-(2-methyl-1-propenyl) cyclobutanone. The latter method proved best (77% yield) for the conversion and represented a rather novel means of effecting such reduction. The tin hydride reduction of a variety of (alpha)-acetoxy ketones to the corresponding ketones in high yield suggested that this method might constitute the procedure of choice for accomplishing this transformation.
The results of the semibenzilic ring expansion of the chrysanthemate system indicate that a similarly derivatized presqualene compound might serve as a successful synthetic precursor to the proposed protosqualene intermediate.
Issue Date:1980
Description:135 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1980.
Other Identifier(s):(UMI)AAI8108693
Date Available in IDEALS:2014-12-13
Date Deposited:1980

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