I. Regiospecific synthesis of 2-allyloxy-2-cyclohexene-1-ones and -penten-1-ones. II. The use of the dimethyl(phenyl)silyl group as a latent hydroxyl in organic synthesis.

Abstract

2-Allyloxy-2-cyclohexen- and -penten-1-ones are synthetically valuable compounds. For example, they undergo a highly stereoselective organocuprate-induced anionic oxy-Claisen rearrangement which has great potential for applications to the synthesis of 1,3,5-trimethylated acyclic carbon chain compounds. A regiospecific synthesis of these 2-allyloxy-enones has been achieved highly efficiently in four steps starting from their readily accessible corresponding cyclohexenones and cyclopentenones in overall 40-60% and 30-40% yields, respectively, using allyl alcohols, propargyl alcohol, and 2-butyn-1-ol. The key step involving allyloxy anion addition at C-2 in 2,3-epoxy ketone oximes is followed by mild hydrolysis of an oxime group and dehydration to the 2-allyloxy enones. In the second part of the thesis, the use of the dimethyl(phenyl)silyl group as a latent hydroxyl is described as applied to the highly efficient synthesis of ($\pm$)-shikimic acid. The Diels-Alder reaction of (1$E$,3$E$)-dimethyl(phenyl)silyl-4-acetoxy-1,3-butadiene with methyl acrylate or 2-trimethylsilylethyl acrylate provides the corresponding cycloaddition adducts stereoselectively in good yield. These adducts, after cis-dihydroxylation and oxidative conversion of the dimethyl(phenyl)silyl group to a hydroxyl, have been converted into ($\pm$)-shikimic acid. In particular, the route employing 2-trimethylsilylethyl acrylate as a Diels-Alder dienophile provides free ($\pm$)-shikimic acid in 5 steps in 55.2% overall yield. The concept of the use of the dimethyl(phenyl)silyl group as a latent hydroxyl has been extended to elaborate a new d$\sp2$ acrylic ester equivalent by using 3-(dimethyl(phenyl)silyl) propionic acid. The construction of the $\alpha$-methylene-$\beta$-hydroxy ester moiety can be achieved by a 5-step sequence in 44-52% overall yield starting with 3-(dimethyl(phenyl)silyl) propionic acid and an appropriate aldehyde. A selective sulfonylation reaction on the primary alcohol of the $\beta$-$\beta\sp\prime$-dihydroxy ester is used to introduce the $\alpha$-methylene functionality. The new d$\sp2$ acrylic ester equivalent, 3-(dimethyl(phenyl)silyl) propionic acid, has been further applied to the study directed towards the total synthesis of conocandin, a biologically active C$\sb{18}$ fatty acid which contains the $\alpha$-methylene-$\beta$,$\gamma$-epoxy carboxylic acid moiety. Synthesis of (S)-($-$)-1,2-dihydroxy-8-methyl-7-tetradecene, the optically active key intermediate of the 15-carbon unit of conocandin, has been achieved starting from L-glutamic acid in 31% overall yield in 11 steps. The coupling of these two fragments should lead to the completion of the carbon backbone of conocandin, which could then be readily manipulated towards the synthesis of natural conocandin.