Nickel-catalyzed cross-coupling reactions through C-O and C-N bond activation

Abstract

This dissertation focuses on nickel-catalyzed cross-couplings of amine and alcohols via C–N and C–O bond activation. Chapter 1 focuses on the development of a stereospecific, nickel-catalyzed Suzuki-Miyaura cross-coupling of allylic pivalates to deliver quaternary stereocenters. The enantioenriched allylic pivalates are prepared easily in high yield and high ee. The reaction uses an inexpensive nickel catalyst and air-stable reagents. Both the aryl boroxine and allylic pivalate include broad functional group tolerance including heteroatoms. ☐ Chapter 2 focuses on the development of a nickel-catalyzed Suzuki-Miyaura arylation of amino acid-derived pyridinium salts. This reaction uses a privileged class of widely available and inexpensive substrates, amino acid derivatives, to deliver -aryl esters. The products can be easily hydrolyzed to carboxylates to make propionic acid derivatives. Notably, this reaction tolerates a broad range of functional groups due to the mild conditions used. Finally, a one-pot procedure was developed that may be advantageous for parallel synthesis. ☐ Chapter 3 focuses on the development of a deaminative reductive cross-electrophile coupling of alkylpyridinium salts and aryl bromides. Using mild, neutral conditions, we were able to overcome limitations of our previous chemistry and provide a method with broad functional group tolerance, including 2 and 3 pyridyl groups, heteroaryls, and protic groups. This method uses primary, secondary, and one tertiary alkyl pyridinium salts to make a wide variety of exceptional products. ☐ Chapter 4 focuses on the development of a nickel-catalyzed synthesis of ketones from the reductive coupling of N-alkyl pyridinium salts with activated carboxylic acids. This reaction takes advantage of inexpensive abundant starting materials amines and carboxylic acids and makes a desirable ketone product. The catalyst systems used are commercially available and a broad, diverse group of products are made, including those from pharmaceutical intermediates.