Chemo-selective syntheses of -boc-protected amino ester analogs through Buchwald-Hartwig amination

The synthesis of N -protected amino esters is achieved via a chemo-selective Buchwald Hartwig cross-coupling reaction using PEPPSI-IPr Pd-catalyst. Nearly two dozen functionally and structurally diverse amino ester molecules are created by individually cross-coupling eight aryl halo esters and three different secondary amines. We observed that product formation is more facile in those heterocyclic esters where nitrogen is present ortho to the halo substituent in the heteroaromatic ring. Based on this observation, we propose a possible intermediate step in the cross-coupling cycle, where the nitrogen electron lone pair in the heterocycle may play an important role leading to a higher reaction yield. We showcased a library of amino ester molecules created through the BHA reaction. The product formation is more facile in the esters where nitrogen is present ortho to the halo substituent in the heteroaromatic ring.