Lewis Acid Catalyzed Dynamic Kinetic Asymmetric Transformation of Racemic N-Sulfonylaziridines

Abstract

The first Lewis acid catalyzed stereoconvergent transformation of racemic 2-(hetero)aryl-N-sulfonylaziridines via C−N bond cleavage with nucleophiles is presented. This includes the [3 + 2] annulations with (hetero)aromatic aldehydes and 1,3-disubstituted indoles, asymmetric Friedel− Crafts type reaction with electron-rich (hetero)arenes, and asymmetric aminolysis with amines, providing facile access to chiral 1,3-isoxazolidines, pyrroloindolines, 2-(hetero)arylphenethylamines, and vicinal diamines. This method features a simple and cheaply available complex of Cu(I)− chiral BINAP catalyst, excellent yield and high diastereo-and enantioselectivities, and mild reaction conditions. A mechanism involving type I dynamic kinetic asymmetric transformations (DyKATs) of the racemic aziridines is proposed based on the results of control experiments.

Kinetic Resolution of Aziridines Enabled by N‐Heterocyclic Carbene/Copper Cooperative Catalysis: Carbene Dose‐Controlled Chemo‐Switchability

“…Thus, we hypothesized that fine‐tuning the proportions of copper, diphosphine ligand, and NHC would be able to leverage the racemization rate of electron‐rich aryl‐substituted aziridines so that either the KR or DyKAT of electron‐rich aryl‐substituted aziridines could be accessed (Figure 3). Indeed, the ratio of ternary catalysts had a considerable effect on the success of the KR, and premixing Cu(CH 3 CN) 4 PF 6 , diphosphine L2 , and NHC 4 c in a ratio of 1:2:2 enabled the generation of a hybrid NHC/diphosphine Cu I complex [21] and consumed the active Cu I diphosphine species responsible for the racemization of aziridines, [15] thereby enabling KR (Figure 3 a). As anticipated, in the presence of such an in situ‐generated hybrid copper complex, the KR of 2‐PMP‐substituted aziridine 2 l with enal 1 a successfully afforded desired product 3 al in 48 % yield, >95:5 d.r., 94 % ee , accompanied by the recovery of 2 l in 47 % yield with 96 % ee .…”

“…However, to date, NHC‐bound nucleophiles [16] have not been applied to stereoselectively open the aziridine ring [17] for manufacturing enantiomerically enriched N‐heterocyclic compounds. We envisioned that an NHC‐based homoenolate [18] could associate with copper complex‐activated styrenyl aziridines [13g, 15] to accomplish NHC/copper cooperatively catalyzed [8b,e,g] asymmetric [3+3] annulation, leading to KR‐produced enantioenriched spirooxindolyl lactams [19] and aziridines, [9] which have been both recognized as functional core units in numerous natural products and biologically active molecules (Figure 1 d,e). Herein, we report highly enantioselective KR of racemic aziridines via asymmetric [3+3] annulation with enals enabled by copper/NHC cooperative catalysis.…”

Enantioselective Dearomatization of Indoles by an Azoalkene‐Enabled (3+2) Reaction: Access to Pyrroloindolines

“…documented a Rh II ‐catalyzed formal (3+2) cycloaddition of 3 C3‐substituted indoles to 4‐aryl‐1‐sulfonyl‐1,2,3‐triazoles . Thereafter, the groups of Wang and Chai utilized aziridines as 1,3‐dioples for asymmetric dearomative (3+2) reactions of indoles, under the catalysis of Cu I and Mg II , respectively. To the best of our knowledge, a metal‐free approach for effective dearomatization of indoles allowing enantioselective synthesis of pyrroloindolines remains elusive .…”

Catalytic Asymmetric Transformations of Racemic Aziridines

“…Formation of azomethine ylide from D-A-type aziridines Scheme 12 Enantioconvergent transformations of racemic 2-(hetero)arylaziridines under Lewis acid catalysis enantioconvergent transformations under Lewis acid catalysis(Chai, 2018) …”