Enantioselective Diamination of Alkenes, Hydroamination of 1,3-Dienes, and the Development of NHC Palladium Complexes
Ingalls, Erica L.
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Nitrogen containing heterocylces make up a vast majority of biologically relevant small molecules. Using transition metal catalysts to directly synthesize functionalized amine heterocycles is a valuable and efficient tool in chemical synthesis. Herein, the development of two palladium-catalyzed transformations are described; the enantioselective diamination of unactivated alkenes and the hydroamination of 1,3-dienes. Also, the synthesis and application of NHC-pyridine palladium catalysts for the hydroamination of protected aminoalkenes is discussed. An enantioselective Pd-catalyzed vicinal diamination of unactivated alkenes using N-fluorobenzenesulfonimide as both an oxidant and a source of nitrogen was achieved. Using either Ph-pybox or Ph-quinox ligands, this reaction produced differentially protected vicinal diamines in good yields and high enantioselectivities. Mechanistic experiments revealed that the high enantioselectivity arises from selective formation of only one of four possible diastereomeric aminopalladation products of the chiral Pd complex. This complex was shown to form through anti-aminopalladation. Finally, the aminopalladation complex was characterized by X-ray crystallography. A room temperature palladium-catalyzed hydroamination of amino-1,3-dienes was also developed. This transformation created homoallylic amines in high yields and high selectivity with intramolecular substrates. A variety of amine protecting groups and diene substitution patterns were tolerated. A palladium allyl complex was isolated and shown to be a viable intermediate, giving insight into the reaction mechanism. Synthesis of tridentate and bidentate pyridine or quinoline NHC Pd catalysts have been developed. Applications for these tridentate CNC-Pd compounds include a room temperature palladium-catalyzed intramolecular hydroamination of aminoalkenes. This reaction gave high conversions of carbamate protected aminoalkenes. Several chiral CNC-Pd complexes were attempted, but no enantioenriched hydroamination products were obtained. Both achiral and chiral bidentate NC ligands were synthesized along with several Pd complexes.
- Chemistry