Enantioselective Synthesis of N−N Bisindole Atropisomers

Abstract

NÀ N Atropisomers are a common motif in natural products and represent a significant dimension for exploration in modern pharmaceutical and medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective synthesis of NÀ N bisindole atropisomers is unprecedented. Herein, the first enantioselective synthesis of NÀ N bisindole atropisomers via the palladium-catalyzed de novo construction of one indole skeleton is presented. A wide variety of NÀ N axially chiral bisindoles were generated in good yields with excellent enantioselectivities via a cascade condensation/N-arylation reaction. Structurally diverse indole-pyrrole, indolecarbazole, and non-biaryl-indole atropisomers possessing a chiral NÀ N axis were accessed using this protocol. Moreover, investigations using density functional theory (DFT) calculations provided insight into the reaction mechanism and enantiocontrol.

The Asymmetric Buchwald–Hartwig Amination Reaction

“…Recently, Liu and Li reported intramolecular Buchwald–Hartwig amination chemistry for constructing N , N ‐bisindole atropisomers (Scheme 22). [80] Firstly, enamines 72 were prepared in mostly excellent yields by condensing aryl bromides 70 with amino indoles 71 . Subsequent asymmetric amination was carried out with the assistance of Pd(OAc) 2 and ( S )‐DTBM‐SEGPHOS to afford N , N ‐bisindole atropisomers 73 with excellent selectivities.…”

Borane catalysis for epoxide (co)polymerization

“…In 2022, Liu, Li and co-workers focused on the impact of CO 2 pressure when using organic superbases to generate the initiating alkoxides species from alcohols in situ . 90 Thus, a specific type of phosphazene (C 3 N 3 -Py-P 3 , Scheme 4) was employed in conjunction with diol initiators and Et 3 B for the CHO/CO 2 copolymerization under various conditions. C 3 N 3 -Py-P 3 is characterized by a relatively weak basicity (p K a = 26.5 in acetonitrile) and a significant size (1.3 nm).…”

Stereodivergent Construction of Csp3−Csp3Bonds Bearing Vicinal Stereocenters by Synergistic Palladium and Phase‐Transfer Catalysis

“…Although anti products could be obtained with excellent enantio‐ and diastereoselectivities, syn selectivity was achieved only for a limited number of examples, and the diastereoselectivity was only moderate. Feng and co‐workers [12] disclosed an Ir/Eu bimetallic catalysis system for allylic alkylation of oxindoles, but this system also failed to realize stereodivergent synthesis. Recently, Chen et al [13] .…”