GPhos Ligand Enables Production of Chiral N-Arylamines in a Telescoped Transaminase-Buchwald-Hartwig Amination Cascade in the Presence of Excess Amine Donor.
GPhos Ligand Enables Production of Chiral N-Arylamines in a Telescoped Transaminase-Buchwald-Hartwig Amination Cascade in the Presence of Excess Amine Donor.
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DOI：
10.1002/chem.202103472
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发表时间：
2021-12-01
影响因子：
4.3
通讯作者：
Paradisi, Francesca
中科院分区：
文献类型：
--
作者：
Heckmann, Christian M.;Paradisi, Francesca
生物催化和化学催化的结合可能比单独的技术更强大。然而，由于通常非常不同的反应条件，将两者组合是具有挑战性的。在本文中，手性N-芳基胺（许多活性药物成分的关键特征）通过将转氨酶与Buchwald-Hartwig胺化结合而以优异的对映体选择性（通常> 99.5%ee）获得。通过采用双相缓冲液-甲苯系统以及配体GPhos，在过量丙氨酸的存在下，该套叠级联以高达89%的总转化率进行。未观察到与丙氨酸的偶联。 手性N-芳基胺通过将转氨酶与Buchwald-Hartwig胺化（BHA）结合来获得，将前者的高对映选择性与钯的有效芳基化能力结合起来。配体GPhos是在过量丙氨酸存在下在两相水-甲苯体系中α-仲胺成功芳基化的关键，实现了高达89%的总转化率和> 99.5%ee。未观察到与丙氨酸的偶联。
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. Chiral N ‐arylamines were accessed by combining transaminases with the Buchwald‐Hartwig amination (BHA), combining the high enantioselectivity of the former with the efficient arylation ability of palladium. The ligand GPhos was key for the successful arylation of α‐secondary amines in a biphasic water‐toluene system in the presence of excess alanine, achieving overall conversions of up to 89 % with >99.5 % ee. No coupling to alanine was observed.
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