Organ, Michael George2016-09-202016-09-202015-10-302016-09-20http://hdl.handle.net/10315/32194Part I: An efficient method for alkyl-alkyl Negishi cross-coupling reaction of unactivated primary alkyl halides with higher-order zincate species (synthesized from dialkylzinc and a non-coordinating halide salt in situ) using Pd-PEPPSI-IPent (Pyridine-Enhanced Pre-catalyst Preparation Stabilization and Initiation) pre-catalyst has been developed. The method requires no additive (such as LiX) or use of a polar co-solvent (such as THF/DMI) and reactions proceed in THF solvent alone. The transmetalating species in alkyl-alkyl Negishi cross-coupling has been identified and the catalytic cycle has been amended to include the formation of the higher-order zincate species. Subsequent investigation into diarylzinc as reagents in Negishi cross-coupling have shown they transmetalate directly without the use of halide additive in THF alone producing arylzinc halide as a resting state. Once the dielectric of the solvent becomes sufficiently polar, coupling resumes, and the aryl moiety transmetalates to palladium. The optimized protocol using Pd-PEPPSI-IPent allowed for the coupling of a variety of alkyl- and aryl- organozinc reagents providing the corresponding products in good to quantitative yields. Moreover, the developed protocol is generally applicable and tolerant of a variety of functional groups including esters, and nitriles. Part II: An improved and efficient method for the preparation of sterically demanding Pd PEPPSI-IPent, IPentCl, IHept, and IHeptCl pre-catalysts are presented and the results of optimization for the multi-gram synthesis of 2,6-disubstituted anilines is discussed.enAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.Inorganic chemistryElectronic Thesis or Dissertation2016-09-20Cross-couplingPalladiumZincateZincChemistryOrganic chemistryMethodologyIndustrial chemistryPd-PEPPSIPEPPSIPEPPSI catalystSynthesisOrganometallic chemistryOrganometallicInorganicInorganic chemistryScale-upProcess chemistryOptimizationNegishiNegishi Cross-couplingAlkyl-alkylBond formationNHCN-heterocyclic carbeneCarbeneMechanistic determinationReaction mechanismAryl-arylPd-PEPPSI-IPentPd-PEPPSI-IHeptPd-PEPPSI-IPrPd-PEPPSI-IPentClPd-PEPPSI-IHeptCl26-DI(4-HEPTYL)ANILINE6-DI(3-PENTYL)ANILINELarge-scale