Synthesis of β‐Aryl‐α,β‐Dehydroaminophosphonates by Pd‐Catalyzed Fujiwara–Moritani C−C Coupling

β-aryl-N-acetyl-α,β-dehydroaminophosphonic esters can be synthesized through oxidative Fujiwara–Moritani C−C coupling of different arenes with diethyl α,β-dehydroaminophosphonate 1, process catalyzed by Pd²⁺ and assisted by Ag⁺. The reaction is regioselective to the E-isomer and tolerates the presence of both electrodonating and electronwithdrawing substituents.arylationC−H functionalizationdehydroaminophosphonic acidsFujiwara–Moritanipalladium catalysis

Abstract

The treatment of diethyl α,β-dehydroaminophosphonate 1 with various arenes (ArH=toluene 2 a, benzene 2 b, anisole 2 c, bromobenzene 2 d, chlorobenzene 2 e, benzyl alcohol 2 f, p-xylene 2 g) in acetic acid (AcOH) at 120 °C for 8 h in the presence of Pd(OAc)₂ (10 % mol, OAc=acetate) and AgOAc (3.4 equivalents) results in the formation of the corresponding β-aryl derivatives E-Ar(H)C=C(NHAc)P(O)(OEt)₂ 3 a–3 g. The reaction proceeds through double C−H activation (arene and alkene) and subsequent C−C oxidative coupling (Fujiwara–Moritani reaction), processes catalyzed by Pd and assisted by Ag. The obtained products 3 a–3 g are isosteric analogs of phenylalanine and are obtained with high selectivity. Thus, geometrical E-isomers have been obtained in all studied cases, however mixtures of ortho-/meta-/para-isomers are observed when the activated position in the starting arene 2 is considered.

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