Support influences in the Pd-catalyzed racemization and dynamic kinetic resolution of chiral benzylic amines

Abstract

The acid–base properties of the supports for Pd catalysts strongly affect their performance in racemization and dynamic kinetic resolution (DKR) of chiral benzylic amines. The need for a basic support was proven by comparing the racemization results obtained for Pd on silica, on LDH (layered double hydroxide) and on carbon. Pd on amine-functionalized silica proved to be more selective for the racemization of (S)-1-phenylethylamine than Pd on alkaline earth supports or Pd on LDH. The difference in selectivity between various Pd catalysts is determined by the rates of formation of the side products. The rate constants of side product formation processes were even higher in the case of Pd/SiO2 and Pd/C catalysts. The activity of the various catalysts for the rate determining amine dehydrogenation is similar when calculated per surface Pd atom. Combination of a Pd catalyst with Candida antarctica lipase B (Novozyme 435) for a one-pot DKR of 1-phenylethylamine gave the best results when Pd on 3-aminopropyl functionalized silica or Pd on 3-(1-piperazino)propyl functionalized silica were used as racemization catalysts, namely 93% yield of the corresponding (R)-amide, with 99% e.e.