Direct asymmetric N-propargylation of indoles and carbazoles catalyzed by lithium SPINOL phosphate

Catalytic asymmetric functionalization of the N–H groups of indoles and carbazoles constitutes an important but less developed class of reactions. Herein, we describe a propargylation protocol involving the use of a lithium SPINOL phosphate as the chiral catalyst and our recently developed C-alkynyl N,O-acetals as propargylating reagents. The direct asymmetric N-propargylation of indoles and carbazoles provides hitherto inaccessible N-functionalized products. Notably, the efficiency of the system allows reactions to be run at a very low catalyst loading (as low as 0.1 mol%). Mechanistic information about the titled reaction is also disclosed. This study represents an advance in the direct asymmetric functionalization of the N–H bonds of indoles and carbazoles, and additionally expands on the application of chiral alkali metal salts of chiral phosphoric acids in asymmetric catalysis. Asymmetric functionalization of N–H bonds constitutes an important but less developed class of reactions. Here, the authors report the asymmetric direct N-propargylation of indoles and carbazoles with a lithium SPINOL phosphate as the chiral catalyst and shed light on the reaction mechanism.