Design, synthesis and radical addition reactions of chiral N-Acylhydrazones and their applications in chiral a-Branched amine and natural product

Abstract

Chiral a-branched amines are important components found within many diverse classes of biologically active natural products, designed pharmaceuticals and chiral building blocks. The study in the synthesis of chiral a-branched amines continues to be the focus of the methodology advancements due to their biological importance. In this dissertation, design and synthesis of novel chiral N-acylhydrazones and their applications in chiral a-branched amine and natural product synthesis are presented. Chiral N-acylhydrazones derived from N-aminooxazolidinone underwent intermolecular radical additions mediated by Bu3SnH. Simple secondary and tertiary radicals afforded N-acylhydrazine addition product in excellent stereocontrol in all cases in the presence of ZnCl2. Reduction of ketone acylhydrazones by Bu3SnH provided product hydrazines in high yield and moderate stereoselectivity. It was also found that Mn2(CO)10-mediated stereoselective intermolecular radical addition of different alkyl halides, including primary and difunctional alkyl iodides to different chiral hydrazones upon irradiation. Mn2(CO)10-mediated radical addition reactions tolerated additional functionality in either reactant, enabling hybrid radical-ionic annulation. Application of this methodology to natural product synthesis was demonstrated by an effective asymmetric synthesis of coniine and a synthetic approach to quinine.