Copper‐Catalyzed α‐Amination of Phosphonates and Phosphine Oxides: A Direct Approach to α‐Amino Phosphonic Acids and Derivatives

Abstract

A direct approach to important α-amino phosphonic acids and its derivatives has been developed by using copper-catalyzed electrophilic amination of α-phosphonate zincates with O-acyl hydroxylamines. This amination provides the first example of CN bond formation which directly introduces acyclic and cyclic amines to the α-position of phosphonates in one step. The reaction is readily promoted at room temperature with as little as 0.5 mol % of catalyst, and demonstrates high efficiency on a broad substrate scope.

An Umpolung Strategy for the Synthesis of β-Aminoketones via Copper-Catalyzed Electrophilic Amination of Cyclopropanols

“…We hypothesized that Cu(I) catalyst could be oxidized to Cu(III) by an O -benzoyl -N,-N -dialkylhydroxylamine 18 (cf. 2 , Figure 1C); the resulting Cu(III) species would promote a cyclopropanol ring opening reaction to generate copper-homoenolate 3 , which would undergo reductive elimination to form a C sp3 -N bond and regenerate the Cu(I) catalyst.…”

Copper-Catalyzed Electrophilic Amination of Heteroaromatic and Aromatic C−H Bonds via TMPZnCl•LiCl Mediated Metalation

“…We have recently developed a facile electrophilic C–H amination that can be achieved via organozinc intermediates derived from C–H bonds, 9 including a broad range of heteroaromatic and aryl substrates (Table 1). Such organozinc reagents can be generated in situ using the strong and non-nucleophilic base TMPZnCl•LiCl.…”

Transition Metal‐Free Synthesis of α‐Aminophosphine Oxides through C(sp3)−P Coupling of 2‐Azaallyls

“…[5] Their synthesis is generally limited by the harsh reaction conditions and the addition of toxic metal catalysts and stoichiometric quantities of oxidants. Representative studies by Wang [6] described a Cucatalyzed α-amination of phosphine oxides with obenzoylhydroxylamines via an organozinc intermediate, which showed a novel attractive protocol for αaminophosphine oxides in one step (Scheme 1b). Furthermore, an α-aminophosphonate cation equivalent reacted with organoboranes to yield α-aminophosphine oxides.…”