Palladium(0)/PAr₃‐Catalyzed Intermolecular Amination of C(sp³)H Bonds: Synthesis of β‐Amino Acids

Abstract

An intermolecular C(sp(3))-H amination using a Pd(0) /PAr3 catalyst was developed. The reaction begins with oxidative addition of R2 N-OBz to a Pd(0) /PAr3 catalyst and subsequent cleavage of a C(sp(3))-H bond by the generated Pd-NR2 intermediate. The catalytic cycle proceeds without the need for external oxidants in a similar manner to the extensively studied palladium(0)-catalyzed C-H arylation reactions. The electron-deficient triarylphosphine ligand is crucial for this C(sp(3))-H amination reaction to occur.

Ligand-Promoted meta-C–H Amination and Alkynylation

“…Based on our previous work concerning ortho -C–H amination using O -benzoyl hydroxylmorpholine as the aminating reagent, 12 we found that reaction of 1a with this aminating reagent in the presence of 10 mol% Pd(OAc) 2 , 20 mol% 3-acetylamino-2-hydroxy pyridine ligand ( L1 ), K 3 PO 4 (3.0 equiv.) and AgOAc (3.0 equiv.)…”

Intermolecular Amination of Unactivated C(sp3)−H Bonds with Cyclic Alkylamines: Formation of C(sp3)−N Bonds through Copper/Oxygen‐Mediated C(sp3)−H/N−H Activation

“…Amination of C(sp 2 )−H bonds by alkylamines was recently reported by Daugulis (Scheme a) . Due to lack of π‐bond coordinating character, C(sp 3 )−H activation for C(sp 3 )−N bond formation is challenging, and limited examples have been developed until now, exemplified by C(sp 3 )−H amidation by Che and C(sp 3 )−H aminations by Yu and Qin by using benzoyloxyamines as aminating reagents (Scheme b,c). Direct amination of unactivated C(sp 3 )−H bonds by alkylamines to construct C(sp 3 )−N bonds represents an unmet challenge and has never been reported, but offers a great advantage in that it saves extra steps for the preparation of benzoyloxyamines and simplifies the overall synthetic procedure.…”

Komplementäre Strategien für die dirigierte C(sp3)‐H‐Funktionalisierung: ein Vergleich von übergangsmetallkatalysierter Aktivierung, Wasserstoffatomtransfer und Carben‐ oder Nitrentransfer

“…Mit dem Hydroxylamin 139 als elektrophiler Stickstoffquelle liefert die intermolekulare C-H-Aminierung des Amids 138 das aminierte Produkt 140. [64] Wenn das Palladiumalkyl-Intermediat mit Selectfluor (141)a bgefangen wird, kann ein Fluoratom an der C-H-Bindung des Amids 127 eingebaut werden. [65] Mit B 2 pin 2 kann eine Borylierung vollzogen werden, wodurch das Amid 144 gebildet wird.…”