Solvent-free Heck-Jeffery reactions under ball-milling conditions applied to the synthesis of unnatural amino acids precursors and Indoles

The syntheses of various amino- and hydroxy-substituted dehydrophenylalanine derivatives using the Heck-Jeffery protocol under non-solvent conditions in a ball mill are presented. The influences of electron-withdrawing groups and of the location of the heteroatom substituent relative to the halide are discussed. Suitably substituted ortho-amino dehydrophenylalanine derivatives undergo a cyclization-elimination reaction to the corresponding 2-substituted indoles.