Selective One-pot Synthesis of Symmetrical and Unsymmetrical Di- and Triarylamines with a Ligandless Copper Catalytic System

Transcription

1 This journal is The Royal Society of Chemistry 0 Selective One-pot Synthesis of Symmetrical and Unsymmetrical Di- and Triarylamines with a Ligandless Copper Catalytic System Anis Tlili [a], Florian Monnier* [a], Marc Taillefer [a] * [a] CRS, UMR, Institut Charles Gerhardt Montpellier AM Architectures Moléculaires et Matériaux anostructurés, Ecole ationale Supérieure de Chimie de Montpellier rue de l Ecole ormale, Montpellier Cedex, France Fax: (+) marc.taillefer@enscm.fr, florian.monnier@enscm.fr Supporting Information General Experimental Procedures All reactions were carried out in ml Schlenk tubes or in Carousel reaction stations RR00 Radley tubes, under a pure and dry nitrogen atmosphere. DMF was distilled and was stored on Å activated molecular sieves under a nitrogen atmosphere. Other solvents were distilled and stored under a nitrogen atmosphere. Lithium amide % (Alfa Aesar), Cesium carbonate % metals basis (Alfa Aesar), Potassium phosphate, anhydrous, % (Alfa Aesar), CuI.% metals basis (Aldrich) and all other solid materials were stored in the presence of P O in a bench-top desiccator under vacuum at room temperature and weighed in the air without further purification. Aryl iodide and aryl bromides were purchased from commercial sources. If solids, they were recrystallized in an appropriate solvent. [1] If liquids, they were distilled under vacuum and stored under an atmosphere of nitrogen. Column chromatography was performed with SDS 0 A C.C silica gel (-0 μm). Thin layer chromatography was carried out using Merck silica gel 0 F plates. All products were characterized by their MR, GC/MS spectra. MR spectra were recorded at 0 C on a Bruker AC 00 Mz or on a DRX-0 spectrometer working respectively at 00 Mz for 1, at 0 Mz for 1 C. Chemical shifts are reported in ppm/tms for 1 and { 1 } 1 C (δ.00 for CDCl signal). The first-order peak patterns are indicated as s (singulet), d (doublet), t (triplet), q (quadruplet). Complex non-first-order signals are indicated as m (multiplet). Gas chromatography - mass spectra (GC/MS) were recorded on an Agilent Technologies 0 instrument with an Agilent mass detector (EI) and a P-MS 0 m x 0. mm capillary apolar column (Stationary phase: % diphenyldimethylpolysiloxane film, 0. µm). GC/MS method: Initial temperature: C; Initial time: min; Ramp: C/min until 0 C then C/min; Final temperature: 0 C; Final time: min. RMS were recorded on a JEOL JMS-DX00 spectrometer ( kev, xenon) in a m-nitrobenzylalcohol matrix. Melting points were obtained on a Büchi B-0 melting point apparatus and are uncorrected. General Procedure for synthesis of biarylamines 1- (1 mmol scale) : (Conditions A, Scheme ). 1

2 This journal is The Royal Society of Chemistry 0 Protocol A: After standard cycles of evacuation and back-filling with dry and pure nitrogen, an oven-dried Radley tube (Carousel reaction stations RR00 ) or a Schlenk tube equipped with a magnetic stirring bar was charged with CuI (0.1 mmol), Li ( mmol), K PO (1 mmol) and the aryl halide (1 mmol). The tube was evacuated, back-filled with nitrogen. Then anhydrous and degassed DMF (.0 ml) was added under a stream of nitrogen by syringe at room temperature. The tube was sealed under a positive pressure of nitrogen, stirred and heated to C for h. After cooling to room temperature, ml of dichloromethane and μl of 1,- dimethoxybenzene (internal standard) were added. The filtrate is washed twice with water. Gathered aqueous phases were extracted with dichloromethane five times. Organic layers were gathered, dried over a SO, filtered and concentrated in vacuum to yield the crude product (a small sample of the crude was analyzed by gas chromatography). The obtained crude was purified by silica gel chromatography using heptanes as eluent. All products are known compounds (except products, and ) and characterized by comparison of their MR data with published information. The GC yields were determined by obtaining the correction factors using authentic samples of the expected products. Experimental procedures and characterization data Diphenylamine 1 1 Experimental procedure Following the general procedure Protocol A, iodobenzene (μl, 1.0 mmol) was coupled with Li to afford 0% yield desired product as a white solid (eluent: ethyl acetate/heptane =0/0). 1 Mp: - C 1 MR (00 Mz, CDCl ): δ.1-.1 (m,,,,, ),.-.01 (m,,,,, ),.-. (m,,, ),.1 (1, ). 1 C MR (0 Mz, CDCl ): δ 1.1 (C 1, ),. (C,,, ), 1.0 (C, ),. (C,,, ). GC/MS: rt = 1.0 min, M/Z = 1. RMS calculated for C (M+) Found: 10.0 bis(-(trifluoromethyl)phenyl)amine Experimental procedure Following the general procedure Protocol A, -Iodobenzotrifluoride (1μL, 1.0 mmol) was coupled with Li, in the presence of 0. mmol of DMEDA to afford % yield desired product as a white solid (eluent : ethyl acetate/heptane =0/0). 1 F C 1 1 CF Mp: - C 1 MR (00 Mz, CDCl ): δ.-. (d, J =. z,,,,, ),.0-. (d, J =. z,,,,, ),.0 (br s, 1, ). 1 C MR (0 Mz, CDCl ): δ. (C 1, ),. (q, J =. z,c 1,1 ),.0 (C, ),. (C,,,,,, ). GC/MS: rt = 1.0 min, M/Z = 0. RMS calculated for C 1 F (M+) Found: 0.01 bis(-fluorophenyl)amine

3 This journal is The Royal Society of Chemistry 0 Experimental procedure Following the general procedure Protocol A, -Fluoroiodobenzene (μl, 1.0 mmol) was coupled with Li to afford % yield desired product as a white solid (eluent: ethyl acetate/heptane =0/0). F 1 F Mp: -0 C 1 MR (00 Mz, CDCl ): δ.-. (m,,,,,,,,, ),. (br s, 1, ). 1 C MR (0 Mz, CDCl ): δ 1. (d, J C-F =. z, C, ), 1. (C 1, ),. (d, J C-F =. z,c,,, ),. (d, J C-F =. z, C,,, ). GC/MS: rt = 1. min, M/Z = 0. RMS calculated for C F (M+) 0.1. Found: 0.0 bis(-chlorophenyl)amine Experimental procedure Following the general procedure Protocol A, -Chloroiodobenzene ( mg, 1.0 mmol) was coupled with Li to afford % yield desired product as a white solid (eluent: ethyl acetate/heptane =0/0). 1 Mp: - C 1 MR (00 Mz, CDCl ): δ.-.0 (d, J =. z,,,,, ),.-. (d, J =. z,,,,, ),.(br s, 1, ). 1 C MR (0 Mz, CDCl ): δ 1. (C 1, ),. (C,,, ),. (C, ),. Cl Cl (C,,, ). GC/MS: rt = 0.0 min, M/Z =. RMS calculated for C Cl (M+).010. Found:.01. bis(-bromophenyl)amine Experimental procedure Following the general procedure Protocol A, -Bromoiodobenzene ( μl, 1.0 mmol) was coupled with Li to afford % yield desired product as a brown oil (eluent: ethyl acetate/heptane =0/0). Br 1 Br 1 MR (00 Mz, CDCl ): δ.-.1 (m,,, ),.0-.0 (d, J =. z,,, ), (m,,, ),.0-. (m,,, ),. (br s, 1, ). 1 C MR (0 Mz, CDCl ): δ.0 (C 1, ),. (C, ),. (C, ),. (C, ), 0. (C, ),. (C, ). GC/MS: rt =.01 min, M/Z =. RMS calculated for C Br (M+).10 Found:.1 bis(-methoxyphenyl)amine Experimental procedure Following the general procedure Protocol A, -Iodoanisole (μl, 1.0 mmol) was coupled with Li to afford % yield desired product as a brown oil (eluent: ethyl acetate/heptane=/0).

4 This journal is The Royal Society of Chemistry 0 MeO OMe 1 MR (00 Mz, CDCl ): δ.0-. (t, J =.0 z,,, ),.-. (m,,,,, ),.0-. (ddd, J = 0.,.,.0 z,,, ),. (br s, 1, ),.0 (s,, 1,1 ).. 1 C MR (0 Mz, CDCl ): δ 10. (C, ), 1.1 (C 1, ),.1 (C, ), 0. (C, ),. (C, ),. (C, ), 0. (C 1,1 ). GC/MS: rt = 1. min, M/Z =. RMS calculated for C 1 1 O (M+) 0.1 Found: 0. di-p-tolylamine Experimental procedure Following the general procedure Protocol A, -iodotoluene (1 mg, 1.0 mmol) was coupled with Li to afford % yield desired product as a white solid (eluent: ethyl acetate/heptane =0/0). 1 Mp: -1 C 1 MR (00 Mz, CDCl ): δ.-.00 (d, J = z,,,,, ),.-. (d, J = z,,,,, ),.(br s, 1, ). 1 C MR (0 Mz, CDCl ): δ 1.0 (C 1, ),.0 (C,,, ),. (C, ),. 1 1 (C,,, ). GC/MS: rt = 0. min, M/Z = 1. RMS calculated for C 1 1 (M+) 1. Found: 1. di-m-tolylamine Experimental procedure Following the general procedure Protocol A, -Iodotoluene (μl, 1.0 mmol) was coupled with Li to afford % yield desired product as a yellow oil (eluent: ethyl acetate/heptane =0/0) MR (00 Mz, CDCl ): δ.0-.0 (dd, J =., 1. z,,, ),.0-.1 (m,,,,, ),.-. (d, J =. z,,, ),. (br s, 1, ),. (s,, 1,1 ). 1 C MR (0 Mz, CDCl ): δ. (C 1, ), 1. (C, ),. (C, ), 0. (C, ). (C, ),.0 (C, ), 0. (C 1,1 ). GC/MS: rt = 0. min, M/Z = 1. RMS calculated for C 1 1 (M+) 1. Found: 1. bis(,-dimethylphenyl)amine Experimental procedure Following the general procedure Protocol A,,-Iodo-m-xylene (μl, 1.0 mmol) was coupled with Li to afford % yield desired product as a brown oil (eluent: ethyl acetate/heptane=/0) MR (00 Mz, CDCl ): δ. (m,,,,, ),.0 (m,,, ),.(br s, 1, ). 1 C MR (0 Mz, CDCl ): δ 1. (C 1, ), 1. (C,,, ),. (C, ),. (C,,, ), 1.(C,,, ). GC/MS: rt = 1. min, M/Z =. RMS calculated for C 1 0 (M+).1. Found:.1.

5 This journal is The Royal Society of Chemistry 0 bis(-methylpyridin--yl)amine Experimental procedure Following the general procedure Protocol A, -bromo--methylpyridine (μl, 1.0 mmol) was coupled with Li to afford % yield desired product as a yellow solid (eluent: ethyl acetate/heptane=0/0). 1 Mp: - C 1 MR (00 Mz, CDCl ): δ.-. (t, J =.0 z,,, ),.-.0 (d, J =.0 z,,, ),. (br s, 1, ),.-. (d, J =.0 z,,, ),. (s,, 1, 1 ). 1 C MR (0 Mz, CDCl ): δ 1. (C, ), 1. (C 1, ), 1.0 (C, ),. (C, ),. (C, ),. (C 1,1 ). GC/MS: rt = 1. min, M/Z = 00. RMS calculated for C 1 (M+) 00.. Found: 00. General Procedure for synthesis of symmetrical triarylamines -1 (1 mmol scale): (Conditions B, Scheme ). Protocol B: After standard cycles of evacuation and back-filling with dry and pure nitrogen, an oven-dried Radley tube (Carousel reaction stations RR00 ) or a Schlenk tube equipped with a magnetic stirring bar was charged with CuI (0.1 mmol), Li (0. mmol), K PO ( mmol) and the aryl halide (1 mmol). The tube was evacuated, back-filled with nitrogen. Then anhydrous and degassed DMF (.0 ml) was added under a stream of nitrogen by syringe at room temperature. The tube was sealed under a positive pressure of nitrogen, stirred and heated to C for h. After cooling to room temperature, ml of dichloromethane and μl of 1,- dimethoxybenzene (internal standard) were added. The filtrate is washed twice with water. Gathered aqueous phases were extracted with dichloromethane five times. Organic layers were gathered, dried over a SO, filtered and concentrated in vacuum to yield the crude product (a small sample of the crude was analyzed by gas chromatography).the obtained crude was purified by silica gel chromatography using heptanes as eluent heptanes. All products are known compounds (except products 1, 1, 1, 1, 1 and 1) and characterized by comparison of their MR data with published information. The GC yields were determined by obtaining the correction factors using authentic samples of the expected products. Triphenylamine Experimental procedure Following the general procedure Protocol B, iodobenzene (μl, 1.0 mmol) was coupled with Li to afford % yield desired product as a white solid (eluent: ethyl acetate/heptane =/0).

6 This journal is The Royal Society of Chemistry Mp: - C 1 MR (00 Mz, CDCl ): δ.1-.1 (t, J =. z,,,,,,1,1 ),.-.01 (d, J =. z,,,,,,1,1 ),.0-. (t, J =., z,,,,1 ). 1 C MR (0 Mz, CDCl ): δ 1.0 (C 1,,1 ),. (C,,,,1,1 ),. (C,,,,1,1 ),. (C,,1 ). GC/MS: rt =.00 min, M/Z =. RMS calculated for C 1 1 (M+).0. Found:.0 tris(-(trifluoromethyl)phenyl)amine Experimental procedure Following the general procedure Protocol A, -Iodobenzotrifluoride (1μL, 1.0 mmol) was coupled with Li, in the presence of 0. mmol of DMEDA, to afford % yield desired product as a white solid (eluent : ethyl acetate/heptane =0/0). 1 CF Mp : - C 1 MR (00 Mz, CDCl ): δ.-. (d, J =. z,,,,,,1,1 ),.1-.1 (d, 0 F C CF J =. z,,,,,,1,1 ). 1 C MR (0 Mz, CDCl ): δ 1. (C 1,,1 ),. (q, J C-F =. z,c 1,0,1 ),. (C,,,,,,,,1,1,1,1 ), 1. (C,,1 ). GC/MS: rt = 1.1 min, M/Z =. RMS calculated for C 1 1 Cl (M+).. Found:.. tris(-fluorophenyl)amine 1 Experimental procedure Following the general procedure Protocol B, -Fluoroiodobenzene ( μl, 1.0 mmol) was coupled with Li to afford % yield desired product as a white solid (eluent: ethyl acetate/heptane =/0). 1 1 F Mp : - C 1 MR (00 Mz, CDCl ): δ.-. (m,,,,,,,,,,1,1,1,1 ). 1 C MR (0 Mz, CDCl ): δ 1. (d, J C-F =. z,c,,1 ), 1.0 (d, J C-F =.0 z C 1,,1 ),.(d, J C-F =. z, C,,,,1,1 ),.1 (d, J C-F = z C,,,,1,1 ). GC/MS: rt = 1. min, M/Z =. RMS calculated for C 1 1 Cl (M+) Found: F F tris(-chlorophenyl)amine 1 Experimental procedure Following the general procedure Protocol B, -Cloroiodobenzene ( mg, 1.0 mmol) was coupled with Li to afford % yield desired product as a white solid (eluent : heptane).

7 This journal is The Royal Society of Chemistry 0 Cl 1 1 Cl Cl Mp: 1-1 C 1 MR (00 Mz, CDCl ): δ.1-. (d,, J =. z,,,,,1,1 ),.-. (d, J =. z,,,,,,1,1 ). 1 C MR (0 Mz, CDCl ): δ 1. (C 1,,1 ),. (C,,,,1,1 ),.(C,,1 ),. (C,,,,1,1 ). GC/MS: rt =. min, M/Z =. RMS calculated for C 1 1 Cl (M+).0. Found:.0. tri-p-tolylamine 1 Experimental procedure Following the general procedure Protocol B, -Iodotoluene ( mg, 1.0 mmol) was coupled with Li to afford % yield desired product as a white solid (eluent : ethyl acetate/heptane =0/0) Mp: - C 1 MR (00 Mz, CDCl ): δ.-. (m,,,,,,1,1 ),.-. (m,, 1 1 1,,,,1,1 ). 1 C MR (0 Mz, CDCl ): δ.1 (C 1,,1 ),. (C,,,,1,1 ),.(C,,1 ), (C,,,,1,1 ). GC/MS: rt =. min, M/Z =. RMS calculated for C 1 (M+).. Found:.11. tris(-methoxyphenyl)amine 1 Experimental procedure Following the general procedure Protocol B, -Iodoanisole ( μl, 1.0 mmol) was coupled with Li to afford % yield desired product as a brown oil (eluent : ethyl acetate/heptane = 0/0). MeO OMe 1 OMe 1 1 MR (00 Mz, CDCl ): δ.0-.0 (t, J =.0 z,,,,1 ),.-.1 (dd, J =, 1. z,,,,1 ),.-. (t, J =. z,,,,1 ),.-.1 (dd, J =,., z,,,,1 ). 1 C MR (0 Mz, CDCl ): δ 10. (C,,1 ), 1.1 (C 1,,1 ),.0 (C,,1 ),. (C,,1 ), 0. (C,,1 ).. (C,,1 ). GC/MS: rt =.1 min, M/Z =. RMS calculated for C 1 1 O (M+).1. Found:.1. Tri(pyridin--yl)amine 1 Experimental procedure Following the general procedure Protocol B, -Bromopyridine ( μl, 1.0 mmol) was coupled with Li to afford % yield desired product as a yellow solid (eluent: ethyl acetate/heptane =0/0).

8 This journal is The Royal Society of Chemistry Mp : 1- C 1 MR (00 Mz, CDCl ): δ.1 (br s,,,,1 ),.-. (m,,,,1 ), (m,,,,1 ),.-. (m,,,, ). 1 C MR (0 Mz, CDCl ): δ 1. (C 1,, ),. (C,,1 ),. (C,,1 ),. (C,, ). GC/MS: rt =.0 min, M/Z =. RMS calculated for C 1 (M+).0. Found:. tris(-methylpyridin--yl)amine 1 Experimental procedure Following the general procedure Protocol A ( mmol of K PO were used), -bromo--methylpyridine ( μl, 1.0 mmol) was coupled with Li to afford % yield desired product as a yellow oil (eluent: ethyl acetate/heptane =0/0 to 0/0) MR (00 Mz, CDCl ): δ.-.1 (t,, J =.0 z,,,,1 ),.-. (d,, J =.0 z,,,,,,,1 ),. (s,, 1, 1, 1 ). 1 C MR (0 Mz, CDCl ): δ 1. (C,,1 ), 1.0 (C 1,, ), 1. (C,,1 ),. (C,,1 ),. (C,, ),. (C 1,1,1 ). GC/MS: rt = 1. min, M/Z =. RMS calculated for C 1 1 (M+) 1.1. Found: 1.10 General Procedure for synthesis of unsymmetrical diarylamines 1-0 (1 mmol scale) : (Scheme ). Protocol C: After standard cycles of evacuation and back-filling with dry and pure nitrogen, an oven-dried Radley tube (Carousel reaction stations RR00 ) or a Schlenk tube equipped with a magnetic stirring bar was charged with CuI (0.1 mmol), Li ( mmol), K PO (1 mmol) and the first aryl halide RC I (1 mmol). The tube was evacuated, back-filled with nitrogen. Then anhydrous and degassed DMF (.0 ml) was added under a stream of nitrogen by syringe at room temperature. The tube was sealed under a positive pressure of nitrogen, stirred and heated to C. Then after h at C, the second aryl halide R C X (0. mmol) was added under a stream of nitrogen and the reaction was heated for an additional 1h at C. After cooling to room temperature, ml of dichloromethane and μl of 1,-dimethoxybenzene (internal standard) were added. The filtrate is washed twice with water. Gathered aqueous phases were extracted with dichloromethane five times. Organic layers were gathered, dried over a SO, filtered and concentrated in vacuum to yield the crude product (a small sample of the crude was analyzed by gas chromatography). The obtained crude was purified by silica gel chromatography using heptanes as eluent. All products are known compounds (except products 1, 0,,,, and 0) and characterized by comparison of their MR data with published information. The GC yields were determined by obtaining the correction factors using authentic samples of the expected products.

9 This journal is The Royal Society of Chemistry 0 -methyl--(-(trifluoromethyl)phenyl)aniline 1 Following the general procedure Protocol C, -Iodotoluene (1 mg, 1.0 mmol) was coupled with Li and - trifluoromethylidobenzene (μl, 0. mmol) to afford % yield desired product as a white solid (eluent : ethyl acetate/heptane =0/0) CF Mp : - C 1 MR (00 Mz, CDCl ): δ.-. (d, J =. z,,, ),.1-.1 (d, J =. z,,, ),.0-.0 (d, J =. z,,, ),.-. (d, J =. z,,, ),. (1, ),. (s,, 1 ). 1 C MR (0 Mz, CDCl ): δ 1. (C 1 ), 1. (C ), 1.0 (C ),.0 (C, ),. (C, ),. (q, J =. z,c 1 ), 1. (C ), 0. (C, ),. (C, ), 1.0 (C 1 ). GC/MS: rt = 1.0 min, M/Z = 1. RMS calculated for C 1 1 F (M+).00. Found:.1. -bromo--phenylaniline 0 Following the general procedure Protocol C, Iodobenzene ( μl, 1.0 mmol) was coupled with Li and - Bromo-Iodobenzene ( μl, 0. mmol) to afford % yield desired product as a colorless oil (eluent : ethyl acetate/heptane =0/0). 1 Br 1 MR (00 Mz, CDCl ): δ.0-. (m, 1,, ),.1 (br s, 1, ),.-.0 (m,,,, ),.-. (d, J =. z, 1, ),.-. (t, J =. z,, ),. (1, ). 1 C MR (0 Mz, CDCl ): δ 1. (C ), 1.1 (C 1 ),. (C ),. (C, ),.1 (C ),. (C ), 1.1 (C ),.0 (C ),. (C, ),. (C ). GC/MS: rt = 1. min, M/Z =. RMS calculated for C 1 Br (M+).00. Found:.00. -(phenylamino)benzonitrile 1 Following the general procedure Protocol C, Iodobenzene (μl, 1.0 mmol) was coupled with Li and - Iodobenzonitrile (10. mg, 0. mmol) to afford 1% yield desired product as a white solid (eluent : ethyl acetate/heptane =0/0). Mp : -0 C 1 MR (00 Mz, CDCl ): δ.0-. (d, J =. z,,, ),.-.1 (t, J =. z,,, ),.0-. (d, J =. z,,, ), (t, J =. z, 1, ),.-.1 (d, J =. z,,, ),. (1, ). 1 C MR (0 Mz, CDCl ): δ 1.0 (C 1 ), 1. (C ), 1. (C, ),. (C, ),.1 (C ), 1. (C, ),. (C ),.0 (C, ), 1. (C 1 ). GC/MS: rt =.0 min, M/Z = 1. RMS calculated for C 1 (M+) 1.0. Found: (-(phenylamino)phenyl)ethanone 1 Following the general procedure Protocol C, iodobenzene (μl, 1.0 mmol) was coupled with Li and - Iodoacetophenone (. mg, 0. mmol) to afford % yield desired product as a white solid (eluent: ethyl acetate/heptane =0/0).

10 This journal is The Royal Society of Chemistry O 1 Mp : - C 1 MR (00 Mz, CDCl ): δ.-.1 (d, J =. z,,, ),.-.0 (m,,, ),.1-.1 (m,,, ), (t, J =.0 z, 1, ),.-. (d, J =.0 z,,, ),.01 (1, ),. (s,, 1 ). 1 C MR (0 Mz, CDCl ): δ 11. (C 1 ), 1. (C 1 ),. (C ),. (C, ),. (C ),. (C, ),. (C ), 0. (C, ),. (C, ), 0. (C 1 ). GC/MS: rt =.0 min, M/Z =. RMS calculated for C 1 1 O (M+).. Found:.1. -fluoro--(p-tolyl)aniline Following the general procedure Protocol C, -Iodotoluene (1 mg, 1.0 mmol) was coupled with Li and - Fluoroiodobenzene (10. mg, 0. mmol) to afford % yield desired product as a colorless oil (eluent : ethyl acetate/heptane =0/0). 1 1 F 1 MR (00 Mz, CDCl ): δ.-. (d, J =. z,,, ),.1-.1 (d, J =. z,,, ),.0-.0 (d, J =. z,,, ),.-. (d, J =. z,,, ),. (1, ),. (s,, 1 ). 1 C MR (0 Mz, CDCl ): δ 1. (C 1 ), 1. (C ), 1.0 (C ),.0 (C, ),. (C, ), 1. (C ), 0. (C, ),. (C, ), 1.0 (C 1 ). GC/MS: rt = 1.0 min, M/Z = 01. RMS calculated for C 1 1 F (M+) 0.. Found: methoxy--(-(fluoro)phenyl)aniline Following the general procedure Protocol C, -Fluoroiodobenzene (μl, 1.0 mmol) was coupled with Li and -Iodoanisole (. μl, 0. mmol) to afford 1% yield desired product as a yellow solid (eluent : ethyl acetate/heptane =0/0). Mp : -0 C 1 MR (00 Mz, CDCl ): δ.0-.0 (t, J =. z, 1, ),.-.01 (m,,, ),.1-. (m,,, ),.-. (ddd, J = 0.,.0,.0 z, 1, ),.-. (t, J =.0 z, 1, ),.-. (ddd, J = 0.,.,.0 z, 1, ).1 (1, ),.0 (s,, 1 ). 1 C MR (0 Mz, CDCl ): δ 10. (C ), 1. (C ), 1. (C 1 ), 1. (C ),.1 (C ), 1. (d, J C-F =. z, C, ),. (d, J C-F =. z, C, ),. (C ),. (C ),. (C ),. (C 1 ). GC/MS: rt = 1.0 min, M/Z = 1. RMS calculated for C 1 1 OF (M+) Found: 1.0 -(p-tolylamino)benzonitrile Following the general procedure Protocol C, -Iodotoluene (1 mg, 1.0 mmol) was coupled with Li and - Iodobenzonitrile (10. mg, 0. mmol) to afford 1% yield desired product as a yelow solid (eluent : ethyl acetate/heptane =0/0) C Mp : - C 1 MR (00 Mz, CDCl ): δ.-. (d, J =. z,,, ),.0-. (d, J =. z,,, ),.-.00 (d, J =. z,,, ),.1-. (d, J =. z,,, ),. (1, ),. (s,, 1 ). 1 C MR (0 Mz, CDCl ): δ 1. (C 1 ), 1. (C ), 1.1 (C ), 1. (C, ),. (C, ),.1 (C, ), 1. (C ), 0.0 (C 1 ),. (C, ), 0.0 (C ), 1. (C ).

11 This journal is The Royal Society of Chemistry 0 GC/MS: rt =. min, M/Z = 0. RMS calculated for C 1 1 (M+) 0.. Found: 0.. -methoxy--(-(trifluoromethyl)phenyl)aniline Following the general procedure Protocol C, -Iodoanisole (μl, 1.0 mmol) was coupled with Li and - trifluoromethylidobenzene (μl, 0. mmol)to afford % yield desired product as a yellow solid (eluent : ethyl acetate/heptane =0/0). : 1 MeO 1 1 CF Mp : -0 C 1 MR (00 Mz, CDCl ): δ.-.0 (d, J =. z, 1, ),.-.1 (m,,, ),.-.00 (d, J =. z, 1, ),.0-. (m,,, ),.-. (m, 1, ),.0-. (m, 1, ). (1, ),.0 (s,, 1 ). 1 C MR (0 Mz, CDCl ): δ 10. (C ), 1. (C 1 ),. (C ),.1 (C ),.0 (C ),. (q, J =. z,c 1 ),. (C, ), 0. (C ),. (C, ),. (C ),. (C ),. (C 1 ). GC/MS: rt =. min, M/Z =. RMS calculated for C 1 1 F O (M+).01. Found:.0. -(-fluorophenyl)--methoxyaniline Following the general procedure Protocol C, -Iodoanisole (μl, 1.0 mmol) was coupled with Li and - Fluoroiodobenzene (0.μL, 0. mmol) to afford % yield desired product as a yellow solid (eluent : ethyl acetate/heptane =0/0). : ( 1 and 1 C MR spectra are the same as those for the product ) 1 1 MeO F -(p-tolylamino)benzonitrile Following the general procedure Protocol C, -Iodobenzonitrile ( mg, 1.0 mmol) was coupled with Li and -Iodotoluene (. mg, 0. mmol) to afford 1% yield desired product as a yelow solid (eluent : ethyl acetate/heptane =0/0). ( 1 and 1 C MR spectra are the same as those for the product ) 1 1 C 1 -methoxy--(-(trifluoromethyl)phenyl)aniline

12 This journal is The Royal Society of Chemistry 0 Following the general procedure Protocol C, -trifluoromethyliodobenzene (1 μl, 0. mmol) was coupled with Li and -Iodoanisole (. μl, 1.0 mmol) to afford % yield desired product as a yellow solid (eluent : ethyl acetate/heptane =0/0). ( 1 and 1 C MR spectra are the same as those for the product ) -(p-tolyl)pyridin--amine Following the general procedure Protocol C, -Iodotoluene (1 mg, 1.0 mmol) was coupled with Li and - Bromopyridine (μl, 0. mmol) to afford % yield desired product as a white solid (eluent : ethyl acetate/heptane =0/0). 1 Me Mp : 0- C 1 MR (00 Mz, CDCl ): δ. (brs, 1, ),.-.1 (t, J =., z, 1, ),.-.1 (d, J =. z,,, ),.0-.0 (d, J =. z,,, ),.-. (d, J =., 1, ),.1-. (t, J =. z,,, ),. (1, ),. (s,, C 1 ). 1 C MR (0 Mz, CDCl ): δ 1. (C ), 1. (C ), 1. (C ), 1. (C 1 ),. (C 1 ),. (C, ), 1. (C, ),. (C ),. (C ). GC/MS: rt = 1.0 min, M/Z = 1. RMS calculated for C 1 (M+) 1.. Found: 1.. -phenylpyridin--amine Following the general procedure Protocol C, iodobenzene (μl, 1.0 mmol) was coupled with Li and - Bromopyridine (μl, 0. mmol) to afford % yield desired product as a white solid (eluent: ethyl acetate/heptane =0/0). 1 Mp: - C 1 MR (00 Mz, CDCl ): δ.1-.1 (m, 1, ),.0-. (m, 1, ),.-. (m, 1, ),.-.00 (m,,, ),.-.1 (d, J =. z, 1, ),.-. (m, 1, ),. (1, ). 1 C MR (0 Mz, CDCl ): δ 1. (C ), 1. (C ),. (C 1 ), 1.0 (C ),. (C, ),.0 (C ), 0. (C, ),. (C ),. (C). GC/MS: rt = 1.0 min, M/Z = 1. RMS calculated for C (M+) Found: (-fluorophenyl)pyridin--amine Following the general procedure Protocol C, -Fluoroiodobenzne ( μl, 1.0 mmol) was coupled with Li and -Bromopyridine (μl, 0. mmol) to afford % yield desired product as a white solid (eluent : ethyl acetate/heptane =0/0).

13 This journal is The Royal Society of Chemistry 0 1 F Mp : - C 1 MR (00 Mz, CDCl ): δ.-. (m, 1, ),.-. (m, 1, ),.1-. (m,,, ),.-. (m,,, ),.-. (m,,, ),. (1, ). 1 C MR (0 Mz, CDCl ): δ 10.1 (C ), 1. (C ), 1. (C ), 1. (C ), 1. (C 1 ),. (d, J C-F =. z, C, ),. (d, J C-F =. z, C, ),.0 (C ),. (C). GC/MS: rt = 1.0 min, M/Z = 1. RMS calculated for C F (M+) 1.0. Found: (-(trifluoromethyl)phenyl)pyridin--amine 0 Following the general procedure Protocol C, 1-iodo--(trifluoromethyl)benzene (1 μl, 1.0 mmol) was coupled with Li and -Bromopyridine (μl, 0. mmol) to afford % yield desired product as a yelow oil (eluent : ethyl acetate/heptane =0/0). 1 CF 1 MR (00 Mz, CDCl ): δ. (m, 1, ),.-. (m,,,,,, ),.-. (m,,, ),. (1, ). 1 C MR (0 Mz, CDCl ): δ 1. (C ), 1. (C ), 1. (C 1 ), 1. (C ), 1. (C, ),. (q, J C-F =. z, C ),.1 (C, ),. (C ),. (C). GC/MS: rt = 1.0 min, M/Z =. RMS calculated for C F (M+).01. Found:.0. General Procedure for synthesis of triarylamine 1- (1 mmol scale) : Protocol D (Scheme ). Protocol D: After standard cycles of evacuation and back-filling with dry and pure nitrogen, an oven-dried Radley tube (Carousel reaction stations RR00 ) or a Schlenk tube equipped with a magnetic stirring bar was charged with CuI (0.1 mmol), Li ( mmol), K PO ( mmol) and the aryl halide R-C -I (1 mmol). The tube was evacuated, back-filled with nitrogen. Then anhydrous and degassed DMF (.0 ml) was added under a stream of nitrogen by syringe at room temperature. The tube was sealed under a positive pressure of nitrogen, stirred and heated to C. Then after h at C, R -C -Br (0. mmol) was added under a stream of nitrogen and the reaction was heated for an additional 1h at C. After cooling to room temperature, ml of dichloromethane and μl of 1,-dimethoxybenzene (internal standard) were added. The filtrate is washed twice with water. Gathered aqueous phases were extracted with dichloromethane five times. Organic layers were gathered, dried over a SO, filtered and concentrated in vacuum to yield the crude product (a small sample of the crude was analyzed by gas chromatography).the obtained crude was purified by silica gel chromatography using heptanes as eluent. -(pyridin--yl)--(p-tolyl)pyridin--amine 1 Experimental procedure Following the general procedure Protocol D, -Iodotoluene (1 mg, 1.0 mmol) was coupled with Li and - Bromopyridine (μl, 0. mmol) to afford % yield desired product as a white solid (eluent: heptanes to heptanes/ethyl acetate : 0/0). 1

14 This journal is The Royal Society of Chemistry Mp : - C 1 MR (00 Mz, CDCl ): δ.-, (m,,, ),.-. (m,,, ),.-.1 (m,, 1,1 ), (m,,, ), -0-. (m,,, ),.-. (m,,,1 ),.0 (s,, 1 ). 1 C MR (0 Mz, CDCl ): δ 11. (C 1, ), 1. (C, ),.0 (C ), 1. (C, ), 1. (C 1 ),. (C 1,1 ),.(C, ),. (C,1 ),.( C, ). GC/MS: rt = 0. min, M/Z = 1. RMS calculated for C 1 1 (M+).1. Found:.1. -(-fluorophenyl)--(pyridin--yl)pyridin--amine Experimental procedure Following the general procedure Protocol B, -Fluoroiodobenzene ( μl, 1.0 mmol) was coupled with Li and -Bromopyridine (μl, 0. mmol) to afford % yield desired product as a white solid (eluent : heptane). 1 F Mp : 0- C 1 MR (00 Mz, CDCl ):.-, (m,,, ),.-.0 (m,,, ),.0-. (m,, 1,1 ), (m,,, ), -0-. (m,,, ),.-. (m,,,1 ). 1 C MR (0 Mz, CDCl ): 10. (C 1, ), 1. (C ), 1. (C, ), 1. (C, ),. (d, J =. z, C 1,1 ),.1 (C, ),. (C, ),. (d, J =. z, C,1 ).. (C).GC/MS: rt = 0.0 min, M/Z =. RMS calculated for C 1 1 F (M+).. Found:.. -(-Chlorophenyl)--(pyridin--yl)pyridin--amine Experimental procedure Following the general procedure Protocol B, -Chloroiodobenzene ( mg, 1.0 mmol) was coupled with Li and -Bromopyridine (μl, 0. mmol) to afford % yield desired product as a white solid (eluent : heptane). 1 Cl Mp : -1 C 1 MR (00 Mz, CDCl ):.-, (m,,, ),.-. (m,,, ),.-. (d, J =. z,, 1,1 ),.0-.0 (m,,, ),.-. (m,,,,,1 ). 1 C MR (0 Mz, CDCl ): 1. (C 1, ), 1. (C ), 1. (C, ), 1.0 (C, ),. (C 1,1 ),. (C,1 ),. (C, ),. (d, C, ). GC/MS: rt =.0 min, M/Z = 1. RMS calculated for C 1 1 F (M+).00. Found:.00. -(pyridin--yl)--(-(trifluoromethyl)phenyl)pyridin--amine Experimental procedure Following the general procedure Protocol D, -trifluoromethyliodobenzene (1 μl, 1.0 mmol) was coupled with Li and -Bromopyridine (μl, 0. mmol) to afford % yield desired product as a yellow oil (eluent : heptanes/ethyl acetate : /). 1

15 This journal is The Royal Society of Chemistry CF MR (00 Mz, CDCl ): δ.-.0(m,,, ),.-.(m,,,,1,1 ),.1-.1 (d, J =.0 z,,,1 ),.-. (m,,,,, ). 1 C MR (0 Mz, CDCl ): δ 11. (C 1, ), 1. (C, ), 1. (C ), 1.0 (C, ),.. (C 1 ),. (q, J C-F =. z,c 1 ),.(C 1,1 ),. (C,1 ),.( C,,, ). GC/MS: rt = 0. min, M/Z = 1. RMS calculated for C 1 1 F (M+) 1.. Found: 1.. General Procedure for synthesis of unsymmetrical triarylamine (1 mmol scale) : Protocol E (table ). Protocol E: After standard cycles of evacuation and back-filling with dry and pure nitrogen, an oven-dried Radley tube (Carousel reaction stations RR00 ) or a Schlenk tube equipped with a magnetic stirring bar was charged with CuI (0.1 mmol), Li ( mmol), K PO ( mmol) and the Iodobenzene (1 mmol). The tube was evacuated, back-filled with nitrogen. Then anhydrous and degassed DMF (.0 ml) was added under a stream of nitrogen by syringe at room temperature. The tube was sealed under a positive pressure of nitrogen, stirred and heated to C. Then after h at C, -Iodobenzonitrile (0. mmol) and -Bromopyridine (0. mmol) werre added under a stream of nitrogen and the reaction was heated for an additional 1h at C. After cooling to room temperature, ml of dichloromethane and μl of 1,-dimethoxybenzene (internal standard) were added. The filtrate is washed twice with water. Gathered aqueous phases were extracted with dichloromethane for five times. Organic layers were gathered, dried over a SO, filtered and concentrated in vacuum to yield the crude product (a small sample of the crude was analyzed by gas chromatography).the obtained crude was purified by silica gel chromatography. -(phenyl(pyridin--yl)amino)benzonitrile Experimental procedure Following the general procedure Protocol E, Iodobenzene ( μl, 1.0 mmol), -Bromopyridine (, μl, 0. mmol) and -Iodobenzonitrile (10. mg, 0. mmol) was coupled with Li to afford 1% yield desired product as a white solid (eluent : ethyl acetate/heptane =0/0) C 1 Mp : - C 1 MR (00 Mz, CDCl ): δ. (br, 1, 1 ),.-. (m, 1, 1 ),.-. (d, J =. z,,, ),.1-. (t, J =. z,,, ),.1-.1 (m, 1, ),.0-. (dd, J =., 1, z,,,,,, ),.-. (d, J =. z,1, 1 ),.1-. (m, 1, 1 ). 1 C MR (0 Mz, CDCl ): δ 1.1 (C 1 ),.0 (C 1 ), 1. (C 1 ), 1. (C ), 1.1 (C 1 ), 1.1 (C, ),.0 (C, ),. (C, ),. (C ),.1 (C, ),. (C 1 ),. (C 1 ),. (C 1 ),.0 (C ). GC/MS: rt =. min, M/Z = 1. RMS calculated for C 1 1 (M+).. Found:. 1

16 This journal is The Royal Society of Chemistry 0 Below are given some selected 1 and 1 C MR spectra: Diphenylamine 1 1 1

17 This journal is The Royal Society of Chemistry 0 bis(-(trifluoromethyl)phenyl)amine 1 F C 1 1 CF 1

18 This journal is The Royal Society of Chemistry 0 bis(-fluorophenyl)amine 1 F F 1

19 This journal is The Royal Society of Chemistry 0 1 bis(-clorophenyl)amine Cl Cl 1

20 This journal is The Royal Society of Chemistry 0 bis(-methoxyphenyl)amine MeO 1 1 OMe 1 0

21 This journal is The Royal Society of Chemistry 0 di-p-tolylamine

22 This journal is The Royal Society of Chemistry 0 di-m-tolylamine 1 1 1

23 This journal is The Royal Society of Chemistry bis(,-dimethylphenyl)amine 1 1

24 This journal is The Royal Society of Chemistry 0 bis(-methylpyridin--yl)amine 1

25 This journal is The Royal Society of Chemistry Triphenylamine

26 This journal is The Royal Society of Chemistry 0 tris(-(trifluoromethyl)phenyl)amine 1 CF F C 1 CF

27 This journal is The Royal Society of Chemistry 0 Cl tris(-chlorophenyl)amine Cl Cl

28 This journal is The Royal Society of Chemistry 0 1 tri-p-tolylamine

29 This journal is The Royal Society of Chemistry OMe 1 tris(-methoxyphenyl)amine 1 MeO OMe 1

30 This journal is The Royal Society of Chemistry 0 tris(-methylpyridin--yl)amine

31 This journal is The Royal Society of Chemistry 0 -methyl--(-(trifluoromethyl)phenyl)aniline CF 1

32 This journal is The Royal Society of Chemistry 0 1 Br -bromo--phenylaniline 0

33 This journal is The Royal Society of Chemistry 0 -(phenylamino)benzonitrile 1

34 This journal is The Royal Society of Chemistry 0 1-(-(phenylamino)phenyl)ethanone 1 1 O 1

35 This journal is The Royal Society of Chemistry 0 -methoxy--(-(fluoro)phenyl)aniline 1 MeO 1 F

36 This journal is The Royal Society of Chemistry 0 -(p-tolylamino)benzonitrile C

37 This journal is The Royal Society of Chemistry 0 -methoxy--(-(trifluoromethyl)phenyl)aniline 1 MeO 1 1 CF

38 This journal is The Royal Society of Chemistry 0 1 -(p-tolyl)pyridin--amine Me

39 This journal is The Royal Society of Chemistry 0 1 -phenylpyridin--amine

40 This journal is The Royal Society of Chemistry 0 -(-fluorophenyl)pyridin--amine 1 F 0

41 This journal is The Royal Society of Chemistry 0 -(-(trifluoromethyl)phenyl)pyridin--amine 0 1 CF 1

42 This journal is The Royal Society of Chemistry 0 1 -(pyridin--yl)--(p-tolyl)pyridin--amine F

43 This journal is The Royal Society of Chemistry 0 -(-fluorophenyl)--(pyridin--yl)pyridin--amine

44 This journal is The Royal Society of Chemistry 0 -(-Chlorophenyl)--(pyridin--yl)pyridin--amine 1 Cl

45 This journal is The Royal Society of Chemistry 0 -(pyridin--yl)--(-(trifluoromethyl)phenyl)pyridin--amine 1 CF

46 This journal is The Royal Society of Chemistry 0 -(phenyl(pyridin--yl)amino)benzonitrile

47 This journal is The Royal Society of Chemistry 0 1 Kuwano, R.; Utsunomiya, M.; artwig, J. F. J. Org. Chem. 00,,. Changfeng Z.; Dongpeng Y.; Xiaofei J.; Lixue Z.; Jiang C., Synlett. 00, 1, 1. Surry, D. S.; Buchwald, S.L, J. Am. Chem. Soc, 00,,. Kataoka,.; Shelby, Q.; Stambuli, J. P.; artwig, J. F. J. Org. Chem. 00,,. Wolfe, J. P ; Buchwald, S.L. J. Org. Chem. 000,,. Shen, Q.; Ogata, T.; artwig; J. F. J. Am. Chem. Soc, 00,,.