A Simple and Convenient Method for the Synthesis of N,N-Diaryl Tertiary Amines

Abstract

Direct preparation of tertiary amines in which two substituents are aromatic is described. In the presence of either the inorganic base sodium tert-butoxide or the sterically hindered organic base diisopropylethylamine, the alkylation of secondary diarylamines is achieved smoothly. In contrast to methods previously reported in the literature, this procedure is high-yielding and does not require the use of transition-metal catalysts or functional-group-intolerant hydride reductants.Amines are widely used in the chemical industry as basic intermediates in the preparation of fine chemicals and pharmaceuticals. 1,2 Since amines are common structural features of most naturally occurring biologically active compounds, they have been used in the design of chemotherapeutic approaches to a variety of diseases. 3 Thus, a great deal of sustained research interest in new synthetic approaches to amines has been generated. Specifically, the preparation of tertiary amines (NR 1 R 2 R 3 ) has been approached in a variety of ways, each with unique benefits and drawbacks. Buchwald 4 and Hartwig 5 have shown that the copper-or palladium-catalyzed N-arylation of a variety of amines using aryl halides is a powerful method for the synthesis of arylamines. However, the requirement of a transition-metal catalyst and often-poor yields of tertiary amines are undesirable aspects of this approach. The direct alkylation of secondary amines with alkyl halides is the most straightforward way for the synthesis of tertiary amines. However, formation of quarternary ammonium salts, together with mixtures of starting material and desired tertiary amine limits the general application of this method. 6 Reduction of amides using alkali metal or boron hydrides is another common procedure. However, the use of low functional group tolerant strong inorganic bases coupled with the air and moisture sensitivity of such hydrides complicates their general use. 7 Catalytic hydrogenation of primary and secondary amides to amines has been reported under conditions of high pressures and temperatures, but reductions of tertiary amides via hydrogenations has not been observed. 8 Over the last few years, metal-catalyzed reductions of amides employing silanes have been extensively investigated. Recently, Brookhart reported the use of an iridium pincer complex in the reduction of tertiary amides 9 (Scheme 1). However, the use of a precious metal catalyst and generation of stoichiometric siloxane by-products significantly limit the general use of this approach. Beller and co-workers recently reported an iron-catalyzed reduction procedure. 10 Whereas this method employs an earth-abundant transition metal, an important improvement, stoichiometric amounts of siScheme 1 Selected routes to reduction of amides to tertiary amines O N Ar Ar noble metal catalyst/silanes Brookhart/Beller Charette N H O OEt O EtO Me Me HNAr 2 DIPEA this work R O N Ar Ar R TMS R N Ar Ar R Br R OTf R N Ar Ar HNAr 2 , CsF (2.0 equiv ) Larock SYNTHESIS PSP 270 No Downloaded by: Flinders University of ...

Phosphorescent Thermal Chiroptical Switch Built through Highly Efficient Chiral Recognition and Amplification

“…The delicate design is shown in Scheme . Four aromatic compounds, namely, H1 to H4, tend to form conglomerate crystals with either P- or M-handed half-propeller or propeller chirality. − Bromo-naphthalimide conjugated with a chiral pendent (G1) behaves as a chiral seed, which was mixed with H1 to H4 in hot melting states. In the natural cooling process, homochiral crystals were obtained with excellent reproducibility.…”