All-round catalytic and atroposelective strategy via dynamic kinetic resolution for N-/2-/3-arylindoles
Ahreum Kim, Chan-Hee Lee, Jayoung Song, Sang Kook Lee, Yongseok Kwon
Abstract
As the complexity of organic molecules utilized by mankind increases, the phenomenon of atropisomerism is more frequently encountered. While a variety of well-established methods enable the control of a stereogenic center, a catalytic method for controlling a stereogenic axis in one substrate is typically unavailable for controlling axial chirality in other substrates with a similar structure. Herein, we report o-amidobiaryl as a flexible platform for chiral phosphoric acid-catalyzed atroposelective dynamic kinetic resolution. To demonstrate our strategy, three distinct types of arylindoles were utilized and reacted intermolecularly with ketomalonate in the presence of chiral phosphoric acid. An investigation of 46 substrates having an aromatic ring in different positions yields the desired products with excellent enantioselectivities. Computational investigation into the origin of enantioselectivity highlights the importance of the NH group. Given the biological significance of indoles, antiproliferative effects have been investigated; our scaffold exhibits good efficacy in this regard.