Synthesis of Protected Amines from Azaallyl Anion and Azadiene Building Blocks
Paige Daniel, Ph.D. candidate
Steve Malcolmson, advisor
Thursday, November 15, 2018 - 11:00am to 1:00pm
Location: French Family Science Center 3232
Avery, Meg

Amines are ubiquitous in medicinal compounds and essential to human health. We have addressed some of the limitations of amine synthesis by significantly expanding the utility of 2-azaallyl anions and 2-azaallyl anion-like reagents in the production of imine-protected amines. We have advanced the methods, both transition metal-catalyzed and transition-metal free, by which chemists can synthesize 1,3-amino alcohols, a-trifluoromethyl amines anda-amino boronic esters. Amino alcohols are immensely important motifs in human health. They are found in many classes of bioactive compounds, including antibiotics, anti-HIV medicines, and antifungal agents, among others. Through the coupling of 2-azaallyl anions and substituted epoxides, the first intermolecular, stereoselective reactions that directly generate 1,3-amino alcohols bearing 3 contiguous stereogenic centers has been developed. Additionally, fluorine is known to enhance the pharmacology of compounds in several important ways, including improving pharmacokinetics, lipophilicity, cell permeability, and metabolic rates. A Pd-catalyzed fluoroarylation of difluoroazadienes has been developed to provide access to chiral a-trifluoromethyl amines. Furthermore, chiral α-amino boronates are found in medicinal compounds with great significance to human health, such as bortezomib and ixazomib,proteasome inhibitors used for treatment of cancer. To address these shortcomings, we have begun to develop a method for hydroboration of 2-azadienes to afford α-amino boronates.