Pd^II‐Catalyzed Intermolecular Amination of Unactivated C(sp³)H Bonds

Abstract

Pd(II) -catalyzed intermolecular amination of unactivated C(sp(3) )-H bonds has been successfully developed for the first time. This method provides a new way to achieve the challenging intermolecular amination of unactivated C(sp(3) )-H bonds, producing a variety of unnatural β(2) -amino carboxylic acid analogues. This C(sp(3) )-H amination protocol is demonstrated with a broad substrate scope, good functional-group tolerance, and chemoselectivity. It is operated without use of phosphine ligand or external oxidant.

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

“…O -Benzoyl hydroxylamines were later applied to the Pd(II)-catalyzed C(sp 3 )–H amination of bidentate carboxylic acid-derived amides bearing α-hydrogen atoms. 212 …”

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.…”

“…In our continuing efforts to develop new C(sp 3 )−N bond‐formation reactions, we became interested in 8‐aminoquinoline (AQ)‐directed amination of β‐C(sp 3 )−H bonds of α,α‐disubstituted propionic amides by alkylamines as aminating agents. This transformation could produce a variety of unnatural β 2, 2 ‐amino acid analogues in a straightforward fashion if it was successful.…”

CH Bond Arylation of Diamondoids Catalyzed by Palladium(II) Acetate

“…[10,11] The development of catalytic methods for the functionalization of C sp 3 À H bonds [12] containing a metal substitution step (C À H activation) of an alkyl or cycloalkyl chain is nowadays extensively studied. Various transition metals, such as Cu, [13] Co, [14] Fe, [15] Ir, [16] Ni, [17] Pt, [18] Rh, [19] Ru, [20] and mainly Pd, [12e, 21] have been used in the reactions of alkanes, such as arylation, [22] alkylation, [23] alkenylation, [24] alkynylation [25] and oxidations to boron, [26] nitrogen, [27] oxygen, [28] sulphur [29] or halogen. [30] Several classes of directing groups were developed for regioselective, [21a, 31] diastereoselective [32] and even enantioselective [33] C À H activations of aliphatic systems using palladium catalysts.…”