Umpolung Flow Chemistry for the Synthesis of a 3-Oxo-3-spiro[benzofuran-2,4'-piperidine] Building Block.

An efficient and scalable route to -butyl 3-oxo-3-spiro[benzofuran-2,4'-piperidine]-1'-carboxylate, a central prochiral intermediate in the synthesis of SHP2 inhibitor (), was achieved. Preparation of the title compound from readily available 2-fluorobenzaldehyde included formation of a modified Katritzky benzotriazole hemiaminal, which, upon deprotonation by -butyllithium, participated in umpolung reactivity via 1,2-addition to -butyl 4-oxopiperidine-1-carboxylate (-Boc-4-piperidone). Most notably, this reaction was developed as a robust plug-flow process that could be executed on multiple kilograms without the need for pilot-scale reaction vessels operating at low cryogenic temperatures.

Syntheses of Square Planar Gallium Complexes and a Proton NMR Correlation Probing Metalloaromaticity.

Syntheses of square planar (SP) coordination complexes of gallium(III) are reported herein. Using the pyridine diimine ligand (PDI), we prepared both (PDI)GaH () and (PDI)GaCl (), which were spectroscopically and structurally characterized. Reduction of PDI using Na metal afforded "NaPDI", which reacts with in situ-prepared "GaHCl" or GaCl to afford the SP and .