| The mechanism for the loss of stereospecificity in palladium-catalyzed dimethyl malonate substitution of the cis- and trans -isomers of several allylic esters under phase transfer catalysis was studied. Phase transfer catalysis was shown to be a convenient protocol since prior formation of the malonate anion was not required and the rate of the reaction dramatically increased. The loss of stereospecificity, responsible for the formation of the anomalous inversion product, was mainly due to isomerization of the pi-allyl intermediate via displacement of palladium by Pd(0). However isomerization of the starting material was also a minor contributing factor. The loss of stereospecificity could be inhibited by using a bidentate phosphine as a ligand.; A new approach for the synthesis of nucleoside analogues was investigated. The carbocyclic sugar framework was synthesized from a cyclopentenyl acetate derivative via palladium-catalyzed addition of isobutenylzinc, and conversion of the isobutenyl moiety to a hydroxymethyl group. Subsequent protecting group interconversion lacked chemoselectivity. An alternative route, involving palladium-catalyzed insertion of carbon monoxide into allylic carbonates and phosphates, produced only mixtures of allylic ethers and esters. Palladium-catalyzed coupling of the carbocyclic sugar with iodozinc pyrimidines failed to produce the desired product. Stannylpyrimidines coupled to cyclohexenyl carbonates, but did not react with cyclopentene derivatives.; N-Enoyl oxazolidinones tethered to alkynes were highly efficient substrates (relative to enoates) in nickel-catalyzed organozinc-mediated alkylative cyclizations. beta-Hydride elimination competed with reductive elimination, but was largely inhibited when organoaluminums were used. In organozinc-mediated cyclizations of chiral oxazolidinones, addition of Lewis acids or phosphine ligands was necessary to induce facial selectivity. Triphenylphosphine and titanium isopropoxide were found to be the best additives, with the opposite effect on the diastereomeric ratio. However, the best stereoselectivities were obtained with organoaluminums; (up to 80% de). In addition, N-enoyl oxazolidinones underwent uncatalyzed conjugate addition of organozincates, and the reaction was highly chemoselective with oxazolidinones tethered to alkynes. |
