Palladium-Catalyzed Synthesis of N-Aryloxazolidinones from Aryl Chlorides

Abstract

An efficient method for intermolecular N-arylation of oxazolidinones using Pd(2)dba(3) and various phosphine ligands in the presence of a weak base is reported. The conditions allow the use of cheaper aryl chlorides containing functionalities such as enolizable ketones, amides, etc., which would be incompatible with other coupling methods. The coupling reaction can be used to prepare enantiopure N-aryl beta-amino alcohols. Depending on the stereoelectronic nature of the aryl chloride, careful choice of ligand was necessary for the success of these reactions. [reaction: see text]

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

“…[190] Dialkylbiaryl phosphine ligands generally gave a much faster reaction than processes with chelating ligands such as BINAP, Xantphos, DPEPhos or dppf, although the reaction is only efficient with electron-poor aryl chlorides.…”

Palladium‐Catalyzed CN and CO Coupling–A Practical Guide from an Industrial Vantage Point†

“…Further examples for the coupling of cyclic carbamates and ureas were provided by Ghosh [99] and Madar. [60] Madar used Pd 2 (dba) 3 in conjunction with BI-NAP and cesium carbonate as the base to couple cyclic ureas and carbamates with aryl bromides at 100 8C.…”

Applicability Aspects of Transition Metal‐Catalyzed Aromatic Amination Protocols in Medicinal Chemistry

“…The use of (biph)PA C H T U N G T R E N N U N G (t-Bu) 2 3a in this conversion (method C3) was in accordance to an effective amination of several chloroarenes (also nitro-substituted) with oxazolidinones, although it was stated that reactions proceeded quite sluggishly if substrates were equipped with an ortho substituent. [27] Eventually, a protocol based on Xantphos (4, Figure 1), a ligand highly effective for amination reactions of bromoarenes with weak N-nucleophiles, [28][29][30] proved to be most effective (method F1, 66 % isolated yield). Standard amination at the chlorine site in a second amination step now proceeded smoothly with K 3 PO 4 as base (entry 2, method C2, 82 %).…”

“…As there are only a few examples of amination reactions on chloroarenes with weak N-nucleophiles like amides, carbamates or N-heterocycles using Pd or Cu catalysis, [17,25,27,32] a less favorable amination sequence had to be chosen for the introduction of these amines in which divergence was already introduced within the first amination step at the 2-bromine site followed by introduction of N-methylpiperazine at the chlorine site (Table 3). For pyridazinone, the necessity of such a change in strategy was confirmed by its failed introduction into a 2-chloro-4-(N-methylpiperazin-1-yl)-nitrobenzene using ligand 3a (method C4).…”