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GPhos Ligand Enables Production of Chiral N ‐Arylamines in a Telescoped Transaminase‐Buchwald‐Hartwig Amination Cascade in the Presence of Excess Amine Donor
Author(s) -
Heckmann Christian M.,
Paradisi Francesca
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202103472
Subject(s) - amination , reductive amination , chemistry , amine gas treating , ligand (biochemistry) , cascade , combinatorial chemistry , aryl , transaminase , toluene , cascade reaction , organic chemistry , stereochemistry , catalysis , enzyme , biochemistry , chromatography , alkyl , receptor
The combination of biocatalysis and chemocatalysis can be more powerful than either technique alone. However, combining the two is challenging due to typically very different reaction conditions. Herein, chiral N ‐aryl amines, key features of many active pharmaceutical ingredients, are accessed in excellent enantioselectivity (typically>99.5 % ee ) by combining transaminases with the Buchwald‐Hartwig amination. By employing a bi‐phasic buffer‐toluene system as well as the ligand GPhos, the telescoped cascade proceeded with up to 89 % overall conversion in the presence of excess alanine. No coupling to alanine was observed.