New Insights into the Reaction Capabilities of Ionic Organic Bases in Cu‐Catalyzed Amination

Abstract

The application of ionic organic bases in the copper‐catalyzed amination reaction (Ullmann reaction) has been studied at room temperature, with sub‐mol‐% catalyst loadings, and with more challenging amines at elevated temperatures. The cation present in the base has been shown to have little effect on the reaction at standard catalyst and ancillary ligand loadings, whereas the choice of anion is crucial for good reactivity. A substrate scope carried out at room temperature with the best performing bases, TBAM and TBPM, showed both bases to be highly effective under these mild reaction conditions. Moreover, under sub‐mol % catalyst loadings and room temperature conditions, TBPM gave good to excellent yields for a number of different amines and functionalized aryl iodides (14 examples). However, reactions involving more challenging amines gave little or no yield. By using more forceful conditions (120 °C) moderate to excellent yields of cross‐coupled products containing more challenging amines was achievable using TBPM and to a lesser extent with TBAM. As part of this work a study on the stability of the organic bases at 120 °C was undertaken. TBAM is shown to decompose to give nBu3N and mono‐butylmalonate at higher temperatures, and this can be correlated to a decrease in performance in the coupling reaction. The phosphonium cations in TBPM did not undergo analogous reactivity but were shown instead to experience some degree of deprotonation at the α‐CH2 to generate phosphonium ylides. This however did not lead to a significantly degradation in the activity of the TBPM in the cross‐coupling reaction.

One‐Pot Transfer Hydrogenation Reductive Amination of Aldehydes and Ketones by Iridium Complexes “on Water”

“…There are many means to achieve this transformation. For example, the reduction of imines, [ 2 ] the reductive amination of aldehydes, [ 3 ] the borrowing hydrogenation of alcohols and amines, [ 4 ] the reduction of amides, [ 5 ] the coupling of halogenated hydrocarbons [ 6 ] and boric acids [ 7 ] to amines, and the addition of amines and alkynes, [ 8 ] etc.…”

The factors that govern the allosteric chemical sensing of polythiophene chemosensors: scope and limitation toward signal-amplification sensing

“…Tetrabutylammonium (TBA) and tetrabutylphosphonium isophthalates (TBP) were prepared according to the appropriate protocol. 34,35 Concentrations of the synthesized PTs are expressed as monomer unit throughout this work. All spectra were measured in a 1 cm cell in CHCl 3 at 25 C unless stated otherwise.…”

Tartramide Ligands for Copper‐Catalyzed N‐Arylation at Room Temperature

“…Room‐temperature Ullmann cross coupling was first reported by Shafir and Buchwald in 2006 employing CuI (5 mol%) and a β‐diketone ancillary ligand (20 mol%) for coupling of aryl iodides with aliphatic amines [11] . A small number of other room temperature studies subsequently followed with variations in ancillary ligand and substrate, however copper loadings remained in the 5–20 mol% range [12–15] . A switch from inorganic to organic base was shown by Fu and Liu to give improved room temperature reactivity, although 10 mol% CuI was still required [12] .…”

“…[11] A small number of other room temperature studies subsequently followed with variations in ancillary ligand and substrate, however copper loadings remained in the 5-20 mol% range. [12][13][14][15] A switch from inorganic to organic base was shown by Fu and Liu to give improved room temperature reactivity, although 10 mol% CuI was still required. [12] The use of organic bases also resulted in the formation of homogenous reaction mixtures, and this led us to use these as model systems for gaining improved kinetic and mechanistic data for copper catalyzed coupling processes.…”

“…[13] More recently, we further improved the protocol for these organic base systems to give good conversions with sub-mol% CuI loading at room temperature. [14] However, the cost and hydroscopic nature of organic bases is likely to hinder their widespread uptake. A drive to discover new systems that offer comparable performance with cheaper and more accessible inorganic bases has led to the work reported herein.…”