Enantioselective Aziridination of Unactivated Terminal Alkenes Using a Planar Chiral Rh(III) Indenyl Catalyst

Abstract

Chiral aziridines are important structural motifs found in natural products and various target molecules. They serve as versatile building blocks for the synthesis of chiral amines. While advances in catalyst design have enabled robust methods for enantioselective aziridination of activated olefins, simple and abundant alkyl-substituted olefins pose a significant challenge. In this work, we introduce a novel approach utilizing a planar chiral rhodium indenyl catalyst to facilitate the enantioselective aziridination of unactivated alkenes. This transformation exhibits a remarkable degree of functional group tolerance and displays excellent chemoselectivity favoring unactivated alkenes over their activated counterparts, delivering a wide range of enantioenriched high-value chiral aziridines. Computational studies unveil a stepwise aziridination mechanism in which alkene migratory insertion plays a central role. This process results in the formation of a strained four-membered metallacycle and serves as both the enantio-and rate-determining steps in the overall reaction.

[2.2]Benzoindenophane‐Based Chiral Indenyl Ligands: Design, Synthesis, and Applications in Asymmetric C−H Activation

“…[6] This catalyst was also effective for the enantioselective aziridination of unactivated terminal alkenes. [7] Very recently, Loginov et al developed a chiral indenyl rhodium catalyst II from (À )-α-pinene in 44 % yield over 4 steps, which could efficiently catalyze the asymmetric reaction of aryl hydroxamates with alkenes. [8] Notably, chiral resolution was not required in this case as rhodium coordinated selectively on the less sterically hindered side of indenyl ligand to give a single diastereomeric product.…”

Enantioselective Nitrene Transfer to Hydrocinnamyl Alcohols and Allylic Alcohols Enabled by Systematic Exploration of the Structure of Ion-Paired Rhodium Catalysts

“…An established approach for rhodium paddlewheels involves the replacement of the achiral carboxylate ligands with chiral variants, as demonstrated in early work on amination of benzylic C–H bonds from Hashimoto et al, Müller et al, Davies and Reddy, and Du Bois and Zalatan and followed by recent important intermolecular contributions from Dauban et al (Figure a, left) . Very recently, Miller et al have developed novel peptide-derived carboxylate ligands, which, through a well-defined hydrogen bonding network, form a chiral pocket in which benzylic C–H amination occurs (Figure a, center). − Applied to aziridination, chiral Rh carboxylate complexes have been recently showcased by Dauban and co-workers as being very effective on trisubstituted styrenes and terminal aliphatic alkenes. , Using a distinct approach, Rh(III) Cp* complexes have also been used productively in enantioselective allylic amination and aziridination reactions. Stereoinduction using chiral carboxylate complexes generally relies on repulsive interactions alone.…”