Succinct Synthesis of β-Amino Acids via Chiral Isoxazolines

Abstract

beta-Amino acids are important synthetic targets due to their presence in a wide variety of natural products, pharmaceutical agents, and mimics of protein structural motifs. While beta-amino acids containing geminal substitution patterns have enormous potential for application in these contexts, synthetic challenges to the stereoselective preparation of this class of compound have thus far limited more complete studies. We present here a straightforward method employing chiral isoxazolines as key intermediates to access five different beta-amino acid structural types with excellent selectivity. Of particular note is the use of this approach to prepare highly substituted cis-beta-proline analogues. The ready access to these diversely substituted compounds is expected to facilitate future studies of the structure and function of this important class of molecules.

A Copper Catalyst with a Cinchona‐Alkaloid‐Based Sulfonamide Ligand for Asymmetric Radical Oxytrifluoromethylation of Alkenyl Oximes

“…In particular,c hiral CF 3 -containing isoxazolines with an a-tertiary stereocenter are important structural motifs in numerous biologically active compounds, [9] and also serve as important building blocks for the construction of valuable 1,3-aminoalcohols (Scheme 2a). [10] Recently,r adical oxytrifluoromethylation of alkenyl oximes was shown to provide efficient access to such back-Scheme 1. Copper catalysis for asymmetric radical 1,2-difunctionalization of alkenes.…”

Copper Nitrate Mediated Regioselective [2+2+1] Cyclization of Alkynes with Alkenes: A Cascade Approach to Δ2‐Isoxazolines

“…[6e] Furthermore,t hey can also be employed as efficient chiral ligands [7] and eminent building blocks in organic synthesis as the precursors of diverse key synthetic intermediates,s uch as b-amino acids, [8] b-hydroxy ketones, [9] b-hydroxy nitriles, [10] and g-amino alcohols. [11] Therefore,t he development of convenient methods for the synthesis of D 2 -isoxazoline scaffolds has invoked ever-growing synthetic efforts over the last decades.…”

Copper Nitrate Mediated Regioselective [2+2+1] Cyclization of Alkynes with Alkenes: A Cascade Approach to Δ2‐Isoxazolines

“…[2] Although copper nitrate has been disclosed as an effective direct nitration reagent for arenes [3] and ketones, [4] theu se of this simple and inexpensive reagent as an ew and versatile nitrogen and oxygen source to replace the traditionally required agents still remains both challenging and of great value. [6e] Furthermore,t hey can also be employed as efficient chiral ligands [7] and eminent building blocks in organic synthesis as the precursors of diverse key synthetic intermediates,s uch as b-amino acids, [8] b-hydroxy ketones, [9] b-hydroxy nitriles, [10] and g-amino alcohols. [6e] Furthermore,t hey can also be employed as efficient chiral ligands [7] and eminent building blocks in organic synthesis as the precursors of diverse key synthetic intermediates,s uch as b-amino acids, [8] b-hydroxy ketones, [9] b-hydroxy nitriles, [10] and g-amino alcohols.…”