Enantioselective synthesis of β-amino acid derivatives using amidine-based and bifunctional organocatalysts
Date of Award
Doctor of Philosophy (PhD)
Two new enantioselective methodologies have been developed that have important implications for the asymmetric synthesis of β-amino acids and their derivatives. First, chiral amidine-based catalyst (ABC) HBTM-2 catalyzed an asymmetric cyclocondensation between in situ activated fluoroacetic acid and N-sulfonyl aldimines to give α-fluoro-β-lactams in highly enantioenriched form, achieving modest to excellent diastereoselectivities. These reactive lactams can then be quenched with various alcohols and amines to deliver the α-fluoro-β-amino acid derivatives in moderate isolated yields. Secondly, bifunctional double hydrogen bond donor-amine organocatalysts enable the catalytic alcoholysis of various racemic N-carbalkoxy-3-substituted isoxazolidin-5-ones, resulting in their kinetic resolution. The enantioenriched unreacted isoxazolidinone and product (easily recyclable via a two-step transesterification-cyclization process) can undergo quantitative N-O bond cleavage by hydrogen to give β-amino acids in N-protected form. The fourth chapter of this dissertation, an extension of previous achievements in our group, describes the development of an organocatalyzed rearrangement of S-phenacyl thioesters that is mechanistically distinct from our previously published work. Additionally, more examples of asymmetric tandem rearrangements of S-aryl thioesters were demonstrated.
Chair and Committee
Vladimir B. Birman
Marcus Foston, Kevin Moeller, John-Stephen Taylor, Timothy Wencewicz,
Straub, Matthew Robert, "Enantioselective synthesis of β-amino acid derivatives using amidine-based and bifunctional organocatalysts" (2021). Arts & Sciences Electronic Theses and Dissertations. 2535.