RESUMEN
A simple protocol is outlined herein for rapid access to enantiopure unnatural amino acids (UAAs) from trivial glutamate and aspartate precursors. The method relies on Ag/Ni-electrocatalytic decarboxylative coupling and can be rapidly conducted in parallel (24 reactions at a time) to ascertain coupling viability followed by scale-up for the generation of useful quantities of UAAs for exploratory studies.
Asunto(s)
Aminoácidos , Aminoácidos/químicaRESUMEN
A useful protocol for achieving decarboxylative cross-coupling (DCC) of redox-active esters (RAE, isolated or generated in situ) and halo(hetero)arenes is reported. This pragmatically focused study employs a unique Ag-Ni electrocatalytic platform to overcome numerous limitations that have plagued this strategically powerful transformation. In its optimized form, coupling partners can be combined in a surprisingly simple way: open to the air, using technical-grade solvents, an inexpensive ligand and Ni source, and substoichiometric AgNO3, proceeding at room temperature with a simple commercial potentiostat. Most importantly, all of the results are placed into context by benchmarking with state-of-the-art methods. Applications are presented that simplify synthesis and rapidly enable access to challenging chemical space. Finally, adaptation to multiple scale regimes, ranging from parallel milligram-based synthesis to decagram recirculating flow is presented.
Asunto(s)
Ésteres , Catálisis , Ligandos , Oxidación-Reducción , SolventesRESUMEN
Pyridones are versatile building blocks in organic synthesis and a privileged motif in drug discovery. However, N-substituted 2-pyridones bearing an α-tertiary carbon, cyclopropyl, or heterocycle off of the pyridone nitrogen atom remain challenging to prepare. Herein, we describe the efficient synthesis of a large variety of N-substituted 2-pyridones from ethyl nitroacetate and readily available primary amine building blocks, which can be utilized on a large scale and in parallel medicinal chemistry applications.