Synthesis of α,γ-Chiral Trifluoromethylated Amines through the Stereospecific Isomerization of α-Chiral Allylic Amines
作者:Víctor García-Vázquez、Pablo Martínez-Pardo、Alexandru Postole、A. Ken Inge、Belén Martín-Matute
DOI:10.1021/acs.orglett.2c01436
日期:2022.6.3
imine/enamine intermediates, leading to γ-trifluoromethylated aliphatic amines with two noncontiguous stereogenic centers, in excellent yields and high diastereo- and enantioselectivities. This approach has been used with primary amine substrates. This approach also provides a new synthetic pathway to chiral trifluoromethylated scaffolds, of importance in medicinal chemistry. Additionally, a gram-scale reaction
手性γ-支化脂肪胺存在于大量药物和天然产物中。然而,获取这些化合物的对映选择性方法很少,并且主要依赖于使用设计的手性过渡金属配合物。在此,我们将手性烯丙胺立体定向异构化的有机催化方法与手性亚胺/烯胺中间体的非对映选择性还原相结合,产生具有两个不连续立体中心的γ-三氟甲基化脂肪胺,具有优异的产率和高非对映选择性和对映选择性。该方法已用于伯胺底物。这种方法还提供了一种新的手性三氟甲基化支架的合成途径,这在药物化学中具有重要意义。此外,克级反应证明了该合成程序的适用性。