Cu(I)-Catalyzed Enantioselective Friedel–Crafts Alkylation of Indoles with 2-Aryl-N-sulfonylaziridines as Alkylating Agents

Abstract

A highly enantioselective Friedel-Crafts alkylation of indoles with N-sulfonylaziridines as alkylating agents has been developed by utilizing the complex of Cu(CH3CN)4BF4/(S)-Segphos as a catalyst. A range of optically active tryptamine derivatives are obtained in good to excellent yields and enantioselectivities (up to >99% ee) via a kinetic resolution process.

Catalytic Asymmetric [3 + 2] Annulation of Hantzsch Esters with Racemic N-Sulfonylaziridines

“…Decreasing the amount of aziridine to 2.0 equiv led to slightly lower yields and enantioselectivities, while increasing it to 2.5 equiv furnished comparable results (entries 7 and 8). Two experiments with enantioenriched ( S )- 2a and two BINAP ligands of opposite absolute configurations showed a match–mismatch effect similar to previous findings (entries 9 and 10). , Notably, in the absence of a ligand, poorer yield and diastereoselectivity were observed, together with the decomposition of the aziridine substrate (entry 11).…”

“…The catalytic asymmetric transformation of racemic aziridines has proven an efficient way to construct a range of chiral nitrogen-containing molecular architechtures . In particular, the combination of Cu­(I)/Ag­(I)-chiral diphosphine has demonstrated high efficacy in achieving enantiocontrol in the transformations of racemic 2-(hetero)­aryl aziridines via either kinetic resolution (KR) or dynamic kinetic asymmetric transformation (DyKAT) . As a continuation of our interest in this field, we report herein a novel Cu­(I)-catalyzed asymmetric [3 + 2] annulation of racemic aziridines with HEs, providing chiral pyrrolo­[2,3- b ]­tetrahydropyridine products containing multiple contiguous stereogenic centers in excellent yields and enantiopurities (Scheme c).…”

Synthesis of Chiral Vicinal Diamines by Silver(I)‐Catalyzed Enantioselective Aminolysis of N‐Tosylaziridines

“…Notably, such meso-aziridines are inert in previously described ring openings with indoles under chiral Cu I /diphosphine catalysis. [13] Six-membered cyclic aziridines worked particularly well in the reaction to furnish generally excellent yields and ee values (5 aa-ma), and both primary and secondary anilines were tolerated equally well. This reaction system also tolerates variations in the substituents positions of anilines better than previous aminolysis systems, in which 4-substituted anilines are usually required to achieve excellent enantioselectivity.…”

Nickel-Catalyzed Asymmetric Friedel–Crafts Propargylation of 3-Substituted Indoles with Propargylic Carbonates Bearing an Internal Alkyne Group

“…Thus, the catalytic asymmetric Friedel–Crafts alkylation of indoles has been well-explored in the past two decades, and various catalyst systems using transition-metal catalysts and organocatalysts have been established, enabling the straightforward access to a wide array of enantioenriched indole derivatives. While various electrophiles such as activated alkenes, activated ketones, N -protected imines, nitrones, strained ring systems, allylic alcohol derivatives, and others , have been employed in the catalytic asymmetric Friedel–Crafts alkylation of indoles, the use of propargylic alcohol derivatives remains rare despite that an alkyne group can be utilized for further derivatization in organic synthesis . In 2007, Nishibayashi and coworkers reported the first catalytic asymmetric Friedel–Crafts propargylation of indoles with propargylic alcohols as the electrophile using a chiral thiolate-bridged diruthenium complex, providing the corresponding β-propargylated indoles in good yields with high enantioselectivity (Scheme , eq 1) .…”