Halide Perovskite Induces Halogen/Hydrogen Atom Transfer (XAT/HAT) for Allylic C-H Amination

Abstract

Allylic C-H amination has emerged as a powerful tool to construct allylamines, common motifs in molecular therapeutics. Such reaction implies an oxidative path for C-H activation but furnishes reductive amines, inferring mild oxidants' inactivity for C-H oxidation but strong oxidants' detriment to products. Herein we report a heterogeneous catalytic approach that manipulates halogen-vacancies of perovskite photocatalyst and exploits halogenated-solvents (i.e. CH₂Cl₂, CH₂Br₂) as mild oxidants for selective C-H allyl amination with 19,376 turnovers. CsPbBr₃ nanocrystals induce cooperative hydrogen-atom-transfer (HAT, C-H oxidation, and halogen-vacancy CsPbBr_3-x formation) and halogen-atom-transfer (XAT, CsPbBr_3-x-induced solvent reduction) under a radical chain mechanism. Terminal/internal olefins are amenable to forge aromatic/aliphatic, cyclic/acyclic, secondary/tertiary allylamines (70 examples), including drugs or their derivatives.

Keywords: C−H amination; Halide perovskite; Halogen atom transfer; Hydrogen atom transfer; Photocatalyst.

Scheme 1

(A) Background, (B) Reaction design and (C) Reaction Scheme in this work.

Figure 1

Perovskite reactions. (A) Halogen‐vacancy formation in cyclohexene. (Red square: a vacancy with a delocalized surface radical) (B) Halogen‐rich perovskite re‐generation in CH₂Br₂. (C) Photocatalytic reaction optimization.

Figure 2

Reaction scope. (A) Olefin scope, (B) Amine scope and (C) Styrene‐scaffold and late‐stage C−H allylamination. * Olefin migration product observed. ^# Diastereomer detected, see Supporting Information, ^##  Trans and cis isomer detected, see Supporting Information for details. Reaction conditions: 1a (0.5 mmol), 1b (0.3 mmol), CsPbBr₃ NC (1 mg) in DBM (1 ml) under 456 nm Kessil LED illumination at an ambient atmosphere.

Figure 3

Mechanism. (A) Proposed reaction path, (B) Intermediate exploration (6 c–9 c experimental validation, details in S5), (Red square: a vacancy with a delocalized surface radical) and (C) Reaction comparison with traditional S_N2 reactions.