Synthesis of enamines, enol ethers and related compounds by cross-coupling reactions

Abstract

For several decades, enamines and related compounds have been used as intermediates in organic synthesis and many methods are known for their preparation. Most of the synthetic protocols, however, require harsh reaction conditions. Recently, a new approach has emerged, inspired by the analogous arylation of amines catalysed by palladium or copper complexes (Buchwald-Hartwig reaction). Simultaneous and independent work from several research groups has led to the development of very powerful protocols for the preparation of enamines and their derivatives that require only readily available starting materials and proceed under very mild reaction conditions. Noteworthy is the fact that in less than five years an almost unknown reaction has reached such a high level of scope and generality that it is now very frequently applied in total syntheses of natural products.

Biarylphosphanliganden in der palladiumkatalysierten Aminierung

“…[130,131] Die erste Aminierung von Vinylhalogeniden dokumentierten Voskoboynikov und Beletskaya, die Azole und Phenothiazine als Nucleophile einsetzten. [132] Das beste System erfordert Lithiumazole und JohnPhos als Ligand für Palladium.…”

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

“…[130,131] The first amination of vinyl halides was documented by Voskoboynikov and Beletskaya using azoles and phenothiazines as nucleophiles. [132] The best system required lithium azoles and JohnPhos as ligand for palladium.…”

Ethers from esters; from exceptional transformation to synthetic method

“…32 Interestingly, we have successfully applied Pd-catalyzed O-alkylation of complex macrocyclic alcohols by allyl-tert-butylcarbonate. 33,34 Diaryl ethers, 9,35 aryl alkyl ethers 36 and enol ethers 37 can be synthesized by means of a palladium-catalyzed Buchwald-Hartwig reaction. Broad application of this metal-catalyzed coupling reaction has mainly been achieved by developing ever more effective ligands for the catalytic complexes, starting from dinitrogen ligands to mono-and bidentate phosphines, and -donor alkenes, dba (dibenzylideneacetone) in particular.…”