PROCESS FOR THE PRODUCTION OF ARYLAMINES

Abstract

The invention relates to a process for producing compounds containing at least one arylamino group by means of a palladium-catalysed coupling reaction of an arylamino compound with an aryl compound, using LiOtBu as a base.

Claims

1. A process for preparing a secondary or tertiary arylamino compound by a palladium-catalyzed coupling reaction between a primary or secondary arylamino compound and an aryl compound, characterized in that the process is conducted in the presence of lithium tert-butoxide (LiOtBu) as base.

2. The process as claimed in claim 1, characterized in that the arylamino compound used is a compound of formula (1) ##STR00128## where the symbols used are as follows: R is the same or different at each instance and is an aromatic or heteroaromatic ring system which has 5 to 60 aromatic ring atoms and may be substituted in each case by one or more R.sup.1 radicals; R′ is the same or different and is R or is H or D; at the same time, it is possible for R and R′ to be joined to one another directly or via an R.sup.1 group and hence form a ring system together with the nitrogen atom to which they bind; R.sup.1 is the same or different at each instance and is selected from H, D, F, Cl, Br, I, B(OR.sup.2).sub.2, CHO, C(═O)R.sup.2, CR.sup.2═C(R.sup.2).sub.2, CN, C(═O)OR.sup.2, C(═O)N(R.sup.2).sub.2, Si(R.sup.2).sub.3, N(R.sup.2).sub.2, NO.sub.2, P(═O)(R.sup.2).sub.2, OSO.sub.2R.sup.2, OR.sup.2, S(═O)R.sup.2, S(═O).sub.2R.sup.2, a straight-chain alkyl, alkoxy or thioalkyl group having 1 to 20 carbon atoms or a branched or cyclic alkyl, alkoxy or thioalkyl group having 3 to 20 carbon atoms or an alkenyl or alkynyl group having 2 to 20 carbon atoms, where the abovementioned groups may each be substituted by one or more R.sup.2 radicals and where one or more CH.sub.2 groups in the abovementioned groups may be replaced by —R.sup.2C═CR.sup.2—, —C≡C—, Si(R.sup.2).sub.2, C═O, C═S, C═NR.sup.2, —C(═O)O—, —C(═O)NR.sup.2—, NR.sup.2, P(═O)(R.sup.2), —O—, —S—, SO or SO.sub.2 and where one or more hydrogen atoms in the abovementioned groups may be replaced by D, F, Cl, Br, I, CN or NO.sub.2, or an aromatic or heteroaromatic ring system which has 5 to 30 aromatic ring atoms and may be substituted in each case by one or more R.sup.2 radicals, or an aryl- or heteroaryloxy group which has 5 to 30 aromatic ring atoms and may be substituted by one or more R.sup.2 radicals; at the same time, it is possible for two or more R.sup.1 radicals to be joined to one another and hence form a ring; R.sup.2 is the same or different at each instance and is selected from H, D, F, Cl, Br, I, B(OR.sup.3).sub.2, CHO, C(═O)R.sup.3, CR.sup.3═C(R.sup.3).sub.2, CN, C(═O)OR.sup.3, C(═O)N(R.sup.3).sub.2, Si(R.sup.3).sub.3, N(R.sup.3).sub.2, NO.sub.2, P(═O)(R.sup.3).sub.2, OSO.sub.2R.sup.3, OR.sup.3, S(═O)R.sup.3, S(═O).sub.2R.sup.3, a straight-chain alkyl, alkoxy or thioalkyl group having 1 to 20 carbon atoms or a branched or cyclic alkyl, alkoxy or thioalkyl group having 3 to 20 carbon atoms or an alkenyl or alkynyl group having 2 to 20 carbon atoms, where the abovementioned groups may each be substituted by one or more R.sup.3 radicals and where one or more CH.sub.2 groups in the abovementioned groups may be replaced by —R.sup.3C═CR.sup.3—, —C≡C—, Si(R.sup.3).sub.2, C═O, C═S, C═NR.sup.3, —C(═O)O—, —C(═O)NR.sup.3—, NR.sup.3, P(═O)(R.sup.3), —O—, —S—, SO or SO.sub.2 and where one or more hydrogen atoms in the abovementioned groups may be replaced by D, F, Cl, Br, I, CN or NO.sub.2, or an aromatic or heteroaromatic ring system which has 5 to 30 aromatic ring atoms and may be substituted in each case by one or more R.sup.3 radicals, or an aryl- or heteroaryloxy group which has 5 to 30 aromatic ring atoms and may be substituted by one or more R.sup.3 radicals; at the same time, it is possible for two or more R.sup.2 radicals to be joined to one another and hence form a ring; R.sup.3 is the same or different at each instance and is H, D, F or an aliphatic, aromatic or heteroaromatic organic radical having 1 to 20 carbon atoms, in which one or more hydrogen atoms may also be replaced by D or F; at the same time, two or more R.sup.3 substituents may be joined to one another and hence may form a ring.

3. The process as claimed in claim 2, characterized in that the aryl compound used is a compound of formula (2)
Ar—(X).sub.n   Formula (2) where R.sup.1, R.sup.2 and R.sup.3 have the definitions detailed in claim 2 and the further symbols and indices used are as follows: Ar is an aromatic or heteroaromatic ring system which has 5 to 60 aromatic ring atoms and may be substituted by one or more R.sup.1 radicals; X is the same or different at each instance and is a leaving group; n is an integer from 1 to 10.

4. The process as claimed in claim 2, characterized in that R and R′, when R′ is not H or D, are the same or different at each instance and are selected from the group consisting of phenyl, biphenyl, terphenyl, quaterphenyl, fluorenyl, spirobifluorenyl, naphthyl, indolyl, benzofuranyl, benzothienyl, carbazolyl, dibenzofuranyl, dibenzothienyl, indenocarbazolyl, indolocarbazolyl, phenanthryl and triphenylenyl, each of which may be substituted by one or more R.sup.1 radicals.

5. The process as claimed in claim 3, characterized in that the aryl compound is substituted by a leaving group and the leaving group or the X group in the compound of the formula (2) is selected from the group consisting of optionally substituted alkylsulfonate, optionally substituted arylsulfonate, halide and diazonium.

6. The process as claimed in claim 5, characterized in that the aryl compound is substituted by a leaving group and the leaving group or the X group in the compound of the formula (2) is selected from the group consisting of triflate, phenylsulfonate and tosylate.

7. The process as claimed in claim 3, characterized in that the aromatic or heteroaromatic ring system in the aryl compound or the Ar group in the compound of the formula (2) is selected from the group consisting of phenyl, biphenyl, terphenyl, quaterphenyl, fluorenyl, spirobifluorenyl, naphthyl, indolyl, benzofuranyl, benzothienyl, carbazolyl, dibenzofuranyl, dibenzothienyl, indenocarbazolyl, indolocarbazolyl, phenanthenryl and triphenylenyl, each of which may be substituted by one or more R.sup.1 radicals.

8. The process as claimed in claim 1, characterized in that lithium tert-butoxide is used in an amount of 0.5 to 10 equivalents, based on the molar amount of aryl compound used.

9. The process as claimed in claim 1, characterized in that the catalyst used is PdCl.sub.2, Pd(OAc).sub.2, (CH.sub.3CN).sub.2PdCl.sub.2, bis(dibenzylideneacetone)dipalladium or tris(dibenzylideneacetone)dipalladium together with at least one ligand.

10. The process as claimed in claim 1, characterized in that the ligands used for the catalyst are phosphines, phosphites, amines, aminophosphines or N-heterocyclic carbenes.

11. The process as claimed in claim 10, characterized in that the phosphine is selected from the group consisting of dicyclohexylphosphino-2′,6′-dimethoxybiphenyl, dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl, di-tert-butyl(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine, dicyclohexyl(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine, trimethylphosphine, triethylphosphine, tripropylphosphine, triisopropylphosphine, tributylphosphine, tri-tert-butylphosphine, tricyclohexylphosphine, triphenylphosphine, di-tert-butylchlorophosphine, triphenylphosphine, tri(o-tolyl)phosphine, triisopropylphosphine, tricyclohexylphosphine, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), 1,2-bis(dimethylphosphino)ethane, 1,2-bis(diethylphosphino)ethane, 1,2-bis(dipropylphosphino)ethane, 1,2-bis(diisopropylphosphino)ethane, 1,2-bis(dibutylphosphino)ethane, 1,2-bis(dicyclohexylphosphino)ethane, 1,3-bis(dicyclohexylphosphino)propane, 1,3-bis(diisopropylphosphino)propane, 1,4-bis(diisopropylphosphino)butane, 2,4-bis(dicyclohexylphosphino)pentane, 1,1′-bis(diphenylphosphino)ferrocene, SPhos, PCy.sub.3, Cy-JohnPhos, CataCxium Pcy, APhos, XantPhos, dppf, XPhos and BrettPhos.

12. The process as claimed in claim 9, characterized in that the palladium compound and the phosphine ligand in the case of monophosphines are used in a Pd:phosphine ratio of 1:1 to 1:4, and in that the palladium compound and the phosphine ligand in the case of biphosphines are used in a Pd:phosphine ratio of 1:0.5 to 1:2.

13. The process as claimed in claim 1, characterized in that the process is conducted in one or more aprotic organic solvents.

14. The process as claimed in claim 1, characterized in that the process is conducted under inert gas atmosphere.

15. The use of LiOtBu as base in a palladium-catalyzed coupling reaction between an arylamino compound and an aryl compound.

16. The process as claimed in claim 1, characterized in that the process is conducted in one or more aprotic organic solvents selected from the group consisting of benzene, toluene, 1,2-xylene, 1,3-xylene, 1,4-xylene, mesitylene, tetrahydrofuran (THF), 1,4-dioxane, dimethoxyethane (dme) and bis(2-methoxyethyl) ether (diglyme).

Description

EXAMPLES

[0093] The syntheses which follow, unless stated otherwise, are conducted under a protective gas atmosphere in dried solvents. The solvents and reagents can be purchased, for example, from Sigma-ALDRICH or ABCR. The respective figures in square brackets or the numbers quoted for individual compounds relate to the CAS numbers of the compounds known from the literature.

Example 1

General Procedure

[0094] The triflate, the amine and the base are weighed out under an argon atmosphere in a glovebox. After catalyst and ligand have been added, the solvent is added and the vessel closed. The reaction vessel is discharged from the glovebox and stirred in an oil bath at internal temperature 110° C. for 16 h. After cooling to room temperature, a sample is taken and analyzed by HPLC.

Example 2

Variation of the Base

[0095] In the reaction that follows, Pd-iPr-cinnamyl-CI CX31 (CAS No. 884879-23-6) is used as catalyst. The base used is LiOtBu according to the present invention, or NaOtBu or KOtBu as comparison according to the prior art. The results are collated in table 1. The reaction with LiOtBu as base leads to a distinctly better yield compared to NaOtBu or KOtBu, and a good yield is still obtained even when the amount of catalyst is reduced.

##STR00098##

TABLE-US-00002 TABLE 1.sup.[a] Variation of the base with Pd-iPr-cinnamyl-CI CX31 as catalyst [Pd] Base Y.sub.1 Y.sub.2 Y.sub.3 Y.sub.4 Ex. [mol %] (200 mol %) [%] [%] [%] [%] 1 2 NaOtBu 0 12 58 25 (comp.) 2 2 KOtBu 0 28 1 52 (comp.) 3 2 LiOtBu 1 3 91 1 4 0.5 LiOtBu 11 17 40 30 .sup.[a]Reaction conditions: 0.44 mmol 8-(9-pheny1-9H-carbazol-3-yl)dibenzofuran-1-yl trifluoromethanesulfonate 1, 0.48 mmol bipheny1-4-y1-(9,9-dimethy1-9H-fluoren-4-yl)amine 2, 8 ml toluene, 110° C., 16 h. Area percent determined by HPLC.

Example 3

Use of a Different Catalyst System

[0096] In this example, the reaction from example 2 is conducted with a different catalyst system, with variation of the amount of catalyst and base. The catalyst used for this purpose is a system composed of Pd(OAc).sub.2 and SPhos (table 2).

TABLE-US-00003 TABLE 2 Optimization of the experimental parameters for the Pd(OAc).sub.2/SPhos/LiOtBu system..sup.[a] Pd(OAc).sub.2 SPhos LiOtBu Y.sub.1 Y.sub.2 Y.sub.3 Y.sub.4 Ex. [mol %] [mol %] [mol %] [%] [%] [%] [%] 1 1 2 220 2 6 82 8 2 1 2 150 8 3 75 8 3 1 2 110 25 3 57 12 4 0.5 1 220 2 8 74 14 5 1 1 220 2 6 83 5 6 1 1.5 220 1 8 82 6 7 2 4 200 0 3 94 0 8 2 4 250 0 3 95 0 9 2 4 300 0 3 95 0 .sup.[a]Reaction conditions: 0.44 mmol 8-(9-pheny1-9H-carbazol-3-yl)dibenzofuran-1-y1 trifluoromethanesulfonate 1, 0.48 mmol bipheny1-4-y1-(9,9-dimethy1-9H-fluoren-4-yl)amine 2, 8 ml toluene, 110° C., 16 h. Area percent determined by HPLC.

Example 4

Use of Different Ligands and Different Substrates

[0097] In this example, the reaction is conducted with different ligands and different substrates, with retention of Pd(OAc).sub.2 as palladium source and LiOtBu as base (tables 3 and 4).

a) Reaction of a Dibenzofuran Triflate With Bis(Para-Biphenyl)Amine

[0098] ##STR00099##

TABLE-US-00004 TABLE 3.sup.[a] Variation of the ligand Ex. Ligand Y.sub.5 [%] Y.sub.6 [%] Y.sub.7 [%] Y.sub.8 [%] 1 SPhos 0.02 0.69 96.4 — 4 mol % 2 XantPhos 0.09 4.79 71.3 — 2 mol % 3 CPhos 0.54 1.09 95.8 — 4 mol % 4 XPhos 0.32 0.76 96.9 — 4 mol % .sup.[a]Reaction conditions: 0.60 mmol 4-(9-phenyl-9H-carbazol-3-yl)dibenzofuran-1-yl trifluoromethanesulfonate 5, 0.60 mmol bis(biphenyl-4-yl)amine 6, 250 mol % LiOtBu, 2 mol % Pd(OAc).sub.2, 6.0 ml toluene, 110°C., 16 h. Area percent determined by HPLC.

b) Reaction of a Dibenzofuran Triflate With a Para-Biphenyl-4-Fluorenylamine

[0099] ##STR00100## ##STR00101##

TABLE-US-00005 TABLE 4.sup.[a] Variation of the ligands Ex. Y.sub.5 [%] Y.sub.2 [%] Y.sub.9 [%] Y.sub.8 [%] 1 SPhos 1.37 4.71 84.0 — 2 XPhos 0.75 2.98 87.5 — .sup.[a]Reaction conditions: 0.35 mmol 4-(9-phenyl-9H-carbazol-3-yl)dibenzofuran-1-yl trifluoromethanesulfonate 5, 0.39 mmol biphenyl-4-yl-(9, 9-dimethyl-9H-fluoren-4-yl)amine 2, 220 mol % LiOtBu, 2 mol % Pd(OAc).sub.2, 4 mol % ligand, 6.0 ml toluene, 110° C., 16 h. Area percent determined by HPLC.

Example 5

Use of Different Substrates

[0100] In this example, the reaction conditions from table 3, entry 4, and table 4, entry 2, are applied to different substrates (table 5). For this purpose, in this example, phenyl triflate is reacted with ortho-biphenyl(phenyl)amine as a sterically demanding secondary amine. The reaction with LiOtBu as base leads to a significantly better yield here compared to NaOtBu.

##STR00102##

TABLE-US-00006 TABLE 5.sup.[a] Ex. Base Y.sub.10 [%] Y.sub.11 [%] Y.sub.12 [%] Y.sub.13 [%] 1 LiOtBu 0 15.3 76.4 — 2 (comp.) NaOtBu 0 91.3 2.3 — .sup.[a]Reaction conditions: 0.86 mmol phenyl trifluoromethanesulfonate 10, 0.95 mmol biphenyl-2-yl(phenyl)amine 11, 220 mol % base, 2 mol % Pd(OAc).sub.2, 4 mol % XPhos, 5.7 ml toluene, 110° C., 16 h. Area percent determined by HPLC.

Example 6

Reaction of Phenyl Triflate With Carbazole

[0101] In this example, carbazole is used as a secondary amine, i.e. an amine in which the two aromatic groups are joined to one another (table 6). The reaction with LiOtBu as base leads to a distinctly better yield here compared to NaOtBu.

##STR00103##

TABLE-US-00007 TABLE 6.sup.[a] Ex. Base Y.sub.10 [%] Y.sub.14 [%] Y.sub.15 [%] Y.sub.13 [%] 1 LiOtBu 0 — 96.1 — 2 (comp.) NaOtBu 0 — 77.8 — .sup.[a]Reaction conditions: 0.86 mmol phenyl trifluoromethanesulfonate 10, 0.95 mmol carbazole 14, 220 mol % base, 2 mol % Pd(OAc).sub.2, 4 mol % XPhos, 5.7 ml toluene, 110° C., 16 h. Area percent determined by HPLC.

Example 7

Reaction of 1-Naphthyl Triflate With Secondary Amine

[0102] In this example, the aryl compound used is 1-naphthyl triflate, i.e. a compound having a fused aryl group (table 7). The reaction with LiOtBu as base leads to a significantly better yield here compared to NaOtBu.

##STR00104##

TABLE-US-00008 TABLE 7.sup.[a] Ex. Base Y.sub.16 [%] Y.sub.17 [%] Y.sub.18 [%] Y.sub.19 [%] 1 LiOtBu 0.5 3.2 94.1 0.2 2 (comp.) NaOtBu 0 32.4 8.5 46.9 .sup.[a]Reaction conditions: 0.70 mmol 1-naphthyl trifluoromethanesulfonate 16, 0.77 mmol diphenylamine 17, 220 mol % base, 2 mol % Pd(OAc).sub.2, 4 mol % XPhos, 5.7 ml toluene, 110° C., 16 h. Area percent determined by HPLC.

Example 8

Reaction of 1-Naphthyl Triflate With Sterically Demanding Secondary Amine

[0103] In this example, the aryl compound reacted is 1-naphthyl triflate, i.e. an aryl compound having a fused aryl group, with phenyl(ortho-biphenyl)amine as a sterically demanding secondary amine (table 8). The reaction with LiOtBu as base leads to a good yield here, whereas virtually no conversion to the tertiary amine at all is observed with NaOtBu as base.

##STR00105##

TABLE-US-00009 TABLE 8.sup.[a] Ex. Base Y.sub.16 [%] Y.sub.11 [%] Y.sub.20 [%] Y.sub.10 [%] 1 LiOtBu 19.9 21.4 51.6 0 2 (comp.) NaOtBu 0.1 55.9 0.4 35.6 .sup.[a]Reaction conditions: 0.70 mmol 1-naphthyl trifluoromethanesulfonate 16, 0.77 mmol biphenyl-2-yl(phenyl)amine 11, 220 mol % base, 2 mol % Pd(OAc).sub.2, 4 mol % XPhos, 5.7 ml toluene, 110° C., 16 h. Area percent determined by HPLC.

Example 9

Reaction of Sterically Demanding Triflate and Sterically Demanding Secondary Amine

[0104] In this example, ortho-biphenyl triflate as a sterically demanding aryl compound is reacted with phenyl(ortho-biphenyl)amine as a sterically demanding amine (table 9). The reaction with LiOtBu as base leads to a good yield here, whereas no conversion to the tertiary amine at all is observed with NaOtBu as base.

##STR00106##

TABLE-US-00010 TABLE 9.sup.[a]: Ex. Base Y.sub.21 [%] Y.sub.11 [%] Y.sub.22 [%] Y.sub.23 [%] 1 LiOtBu 3.3 29.9 21.2 2.5 2 (comp.) NaOtBu 0 63.6 0 33.7 .sup.[a]Reaction conditions: 0.65 mmol biphenyl-2-yl trifluoromethanesulfonate 21, 0.72 mmol biphenyl-2-yl(phenyl)amine 11, 220 mol % base, 2 mol % Pd(OAc).sub.2, 4 mol % XPhos, 5.7 ml toluene, 110° C., 16 h. Area percent determined by HPLC.

Example 10

Reaction of Sterically Demanding Triflate With Secondary Amine

[0105] In this example, ortho-biphenyl triflate as a sterically demanding aryl compound is reacted with diphenylamine as secondary amine (table 10). The reaction with LiOtBu as base leads to a very good yield here, whereas no conversion to the tertiary amine at all is observed with NaOtBu as base.

##STR00107##

TABLE-US-00011 TABLE 10.sup.[a] Ex. Base Y.sub.21 [%] Y.sub.17 [%] Y.sub.24 [%] Y.sub.23 [%] 1 LiOtBu 0 5.5 89.7 0.3 2 (comp.) NaOtBu 0 45.5 0 52.5 .sup.[a]Reaction conditions: 0.65 mmol biphenyl-2-yl trifluoromethanesulfonate 21, 0.72 mmol diphenylamine 17, 220 mol % base, 2 mol % Pd(OAc).sub.2, 4 mol % XPhos, 5.7 ml toluene, 110° C., 16 h. Area percent determined by HPLC.

Example 11

Reaction of Sterically Demanding 9-Phenyl-9H-Carbazol-4-yl Trifluoromethanesulfonate With Carbazole

[0106] In this example, a carbazolyl derivative substituted by triflate as leaving group in the 4 position, as sterically demanding aryl compound, is reacted with carbazole as secondary amine (table 11). The reaction with LiOtBu as base leads to a good yield here, whereas no conversion to the C—N-coupled product at all is observed with NaOtBu as base.

##STR00108##

TABLE-US-00012 TABLE 11.sup.[a] Ex. Base Y.sub.25 [%] Y.sub.14 [%] Y.sub.26 [%] Y.sub.27 [%] 1 LiOtBu 61.5 13.5 18.1 4.1 2 (comp.) NaOtBu 0 92.4 0 2.0 .sup.[a]Reaction conditions: 0.50 mmol 9-phenyl-9H-carbazol-4-yl trifluoromethanesulfonate 25, 0.55 mmol carbazole 14, 220 mol % base, 2 mol % Pd(OAc).sub.2, 4 mol % XPhos, 5.7 ml toluene, 110° C., 16 h. Area percent determined by HPLC.

Example 12

Reaction of Electron-Rich Triflate With Sterically Demanding Secondary Amine

[0107] In this example, para-methoxyphenyl triflate as aryl compound is reacted with para-biphenyl-(2,4-diphenylphenyl)amine as a sterically demanding secondary amine (table 12). The reaction with LiOtBu as base leads to a good yield here, whereas almost no conversion to the tertiary amine is observed with NaOtBu as base.

##STR00109##

TABLE-US-00013 TABLE 12.sup.[a] Ex. Base Y.sub.28 [%] Y.sub.29 [%] Y.sub.30 [%] Y.sub.31 [%] 1 LiOtBu 3.7 59.5 28.2 k.A. 2 (comp.) NaOtBu 0 95.3 <1.0 k.A. .sup.[a]Reaction conditions: 0.76 mmol 4-methoxyphenyl trifluoromethanesulfonate 28, 0.83 mmol 2, 4-diphenyl-N-(4-phenylphenyl)aniline 29, 220 mol % base, 2 mol % Pd(OAc).sub.2, 4 mol % XPhos, 5.7 ml toluene, 110° C., 16 h. Area percent determined by HPLC.

Example 13

Selectivity of the Reaction of Chloroaryl Triflate With Sterically Demanding Secondary Amine

[0108] In this example, the aryl compound used is para-chlorophenyl triflate, which has two potential leaving groups in the form of the chlorine group and the triflate group. This is reacted selectively at the triflate group with ortho-biphenyl(phenyl)amine as a sterically demanding amine. The reaction with LiOtBu as base leads to a good yield here, whereas almost no conversion to the tertiary amine is observed with NaOtBu as base.

##STR00110##

TABLE-US-00014 TABLE 13.sup.[a] Ex. Base Y.sub.32 [%] Y.sub.11 [%] Y.sub.33 [%] Y.sub.34 [%] 1 LiOtBu 1.7 20.3 71.3 — 2 (comp.) NaOtBu 1.5 85.6 5 — .sup.[a]Reaction conditions: 0.76 mmol 4-chlorophenyl trifluoromethanesulfonate 32, 0.84 mmol biphenyl-2-yl(phenyl)amine 11, 220 mol % base, 2 mol % Pd(OAc).sub.2, 4 mol % XPhos, 5.7 ml toluene, 110° C., 15 h. Area percent determined by HPLC.

Example 14

Reaction of Phenyl Triflate With a Primary Amine to Give a Secondary Amine

[0109] In this example, phenyl triflate is reacted with aniline as primary arylamino compound (table 14). The reaction with LiOtBu as base leads to a distinctly better yield here compared to NaOtBu.

##STR00111##

TABLE-US-00015 TABLE 14.sup.[a] Ex. Base Y.sub.10 [%] Y.sub.38 [%] Y.sub.17 [%] Y.sub.13 [%] 1 LiOtBu 0 1.2 98.8 — 2 (comp.) NaOtBu 0 17.2 82.8 — .sup.[a]Reaction conditions: 0.88 mmol phenyl trifluoromethanesulfonate 10, 0.97 mmol aniline 38, 220 mol % base, 2 mol % Pd(OAc).sub.2, 4 mol % XPhos, 5.7 ml toluene, 110° C., 15 h. Area percent determined by HPLC.

Example 15

Reaction of Phenylsulfonate With Sterically Demanding Secondary Amine

[0110] In this example, a phenylsulfonate is used as leaving group. For this purpose, para-tolyl phenylsulfonate is reacted with ortho-biphenyl(phenyl)amine as a sterically demanding secondary amine (table 15). The reaction with LiOtBu as base leads to a distinctly better yield here compared to NaOtBu.

##STR00112##

TABLE-US-00016 TABLE.sup.[a] Y.sub.39 Y.sub.11 Y.sub.40 Y.sub.41 Ex. Base [%] [%] [%] [%] 1 XPhos LiOtBu 7.4 52.4 32.7 — 2 XPhos NaOtBu 3.12 81.3 10.9 — (comp.) 3 BrettPhos LiOtBu 3.6 68.3 23.6 — 4 BrettPhos NaOtBu 0 92.4 4 — (comp.) .sup.[a]Reaction conditions: 0.81 mmol phenyl 4-methylbenzenesulfonate 39, 0.88 mmol bipheny1-2-yl(phenyl)amine 11, 220 mol % base, 2 mol % Pd(OAc).sub.2, 4 mol % ligand, 5.7 ml toluene, 110° C., 15 h. Area percent determined by HPLC.

Example 16

Conversion on a Larger Scale

[0111] ##STR00113##

[0112] In an autoclave, 98.0 g (172 mmol) of 8-(9-phenyl-9H-carbazol-3-yl)-dibenzofuran-1-yl trifluoromethanesulfonate 1, 76.1 g (189 mmol, 110 mol %) of (9,9-dimethyl-9H-fluoren-4-yl)(9,9-dimethyl-9H-fluoren-2-yl)amine 32 and 30.3 g (379 mmol, 220 mol %) of LiOtBu are weighed out and suspended in 1.90 l of anhydrous toluene. The mixture is degassed and flooded with nitrogen three times. In parallel, in a glovebox under an argon atmosphere, 0.78 g (3.49 mmol, 2.03 mol %) of Pd(OAc).sub.2 and 3.37 g (7.07 mmol, 4.11 mol %) of XPhos are weighed out, dissolved in 100 ml of anhydrous toluene and stirred for 1 h. Subsequently, the catalyst solution is added to the reactant solution against a nitrogen flow and the mixture is stirred at 110° C. for 16 h. After cooling to room temperature, a 3% N-acetylcysteine solution is added and the mixture is stirred for 30 min. After phase separation, the organic phase is filtered through basic alumina and then concentrated. A mixture of n-heptane and ethanol is added to the residue, and the crystallized solid is purified further by two hot extractions with n-heptane/toluene over basic alumina. Subsequently, the solid obtained is dissolved in THF and filtered through basic alumina. The filtrate is concentrated, and n-heptane is added. The solid obtained is finally sublimed under high vacuum. Yield: 85.2 g (105 mmol, 65.0%), purity >99.9% by HPLC.

Example 17

Bromine-Selective Suzuki Reaction

[0113] This example describes the preparation of the reactant for example 16 that has a triflate leaving group from a compound having both triflate and bromine as leaving groups. This involves selective conversion of the bromine group in the Suzuki coupling.

General Procedure

[0114] The reactant and the boronic acid are weighed out together with the catalyst and the ligand and dissolved in the solvent. The mixture is saturated with argon for 5 min and then stirred at the specified temperature for 16 h. After cooling to room temperature, a sample is taken and analyzed by HPLC or GC-MS. The results of the catalyst screening are collated in table 16.

##STR00114##

TABLE-US-00017 TABLE 16 Catalyst screening for the preparation of 102..sup.[a] Ex. Catalyst system (ratio) Y.sub.100 [%] Y.sub.102 [%] Y.sub.103 [%] 1 Pd(PPh.sub.3).sub.4 2 52 33 2 Pd.sub.2dba.sub.3/PPh.sub.3 (1:2) 2 52 31 3 Pd.sub.2dba.sub.3/P(o-Tol).sub.3 (1:2) 0 80 3 4 Pd.sub.2dba.sub.3/SPhos (1:2) 5 11 73 5 Pd.sub.2dba.sub.3/XPhos (1:2) 4 24 61 6 Pd.sub.2dba.sub.3/CMPhos (1:2) 18 6 5 7 Pd.sub.2dba.sub.3/PCy.sub.3 (1:2) 3 70 11 8 Pd.sub.2dba.sub.3/P(t-Bu).sub.3 (1:2) 3 7 1 9 Pd.sub.2dba.sub.3/CataCxium A (1:2) 0 74 9 10 Pd-PEPPSI-iPr 0 73 12 .sup.[a]Reaction conditions: 1.27 mmol 8-bromodibenzofuran-1-yl trifluoromethanesulfonate 100, 1.52 mmol 9-phenylcarbazol-3-ylboronic acid, 2.53 mmol potassium carbonate, 1 mol % [Pd], 5.75 ml toluene, 2.00 ml water, 90° C., 16 h. Area percent determined by HPLC. Boronic acid content cannot be determined owina to co-elution with toluene.

[0115] The experimental parameters for the Pd.sub.2dba.sub.3/P(o-Tol).sub.3 catalyst/ligand system are optimized further (table 17).

TABLE-US-00018 TABLE 17 Optimization of the experimental parameters for the system Pd.sub.2dba.sub.3/P(o-To1).sub.3 system for preparation of 102..sup.[a] mol % Pd.sub.2dba.sub.3/ K.sub.2CO.sub.3 101 T Y.sub.100 Y.sub.102 Y.sub.103 Ex. P(o-To1).sub.3 [mol %] [mol %] [° C.] [%] [%] [%] 1 0.25:1 200 120 80 0 78 0 2 0.25:1.5 200 120 80 0 79 0 3 0.5:2 200 110 80 0 83 0 4 0.5:2 120 110 80 0 83 0 5 0.5:2 120 100 70 2 83 0 6 0.5:2 120  80 70 5 79 0 7.sup.[b] 0.5:2 200 120 80 0 87 0 (78.sup.[c]) .sup.[a]Reaction conditions: 1.27 mmol 8-bromodibenzofuran-1-yl trifluoromethanesulfonate 100, 5.75 ml toluene, 2.00 ml water, 16 h. Area percent determined by HPLC. Boronic acid content could not be determined owing to co-elution with toluene. .sup.[b]Up-scaling reaction with 78 g 100. .sup.[c]Isolated yield.

[0116] Analogously to the reaction conditions in table 17, it is possible to prepare the following compounds:

TABLE-US-00019 Product content Reactant 1 Reactant 2 Product by GC-MS [00115] [00116] [00117] 81% [00118] [00119] [00120] 78% [00121] [00122] [00123] 95% [00124] [00125] [00126] 90%

Example 18

Triflate-Selective Suzuki Reaction

[0117] This example describes the preparation of reactants for the process of the invention that have a bromine leaving group from a compound having both triflate and bromine as leaving groups. This involves selective conversion of the triflate group in the Suzuki coupling.

##STR00127##

[0118] 20.0 g (49.2 mmol) of 8-bromodibenzofuran-1-yl trifluoromethanesulfonate, 14.8 g (51.6 mmol) of N-phenylcarbazole-3-boronic acid and 13.6 g (98.3 mmol) of potassium carbonate are suspended in 400 ml of toluene and 100 ml of water and inertized with argon for 20 min. After addition of 337 mg (0.37 mmol) of Pd.sub.2dba.sub.3 and 629 mg (1.47 mmol) of dppb, the mixture is heated to reflux for 48 h. After cooling to room temperature, the aqueous phase is separated off, and the organic phase is washed twice with water, dried over sodium sulfate and concentrated. The residue is crystallized from 500 ml of ethanol and is obtained in solid form. Yield: 22.0 g (45.1 mmol, 92%). Purity >98%.