Ligands and their preparation

Abstract

The present invention relates to secondary amines suitable for the preparation of ligands for organometallic complexes, their preparation and their use.

Claims

1. A method for preparing a secondary amine (P) comprising reacting a compound (E1) and a primary amine (E2), wherein E1 is a compound of formula (13), E2 is a compound of formula (14) and P is a compound of formula (15): ##STR00056## wherein X.sup.1 is C, X.sup.2 is N, X.sup.3 is C, and X.sup.4 is N, or X.sup.1 is N, X.sup.2 is C, X.sup.3 is C, and X.sup.4 is N, or X.sup.1 is C, X.sup.2 is N, X.sup.3 is N, and X.sup.4 is C, or X.sup.1 is C, X.sup.2 is C, X.sup.3 is N, and X.sup.4 is N, wherein C is a carbon atom and N is a nitrogen atom; V is a leaving group; R.sup.1 is, identically or differently on each occurrence, H, D, F, Cl, Br, I, N(R.sup.2).sub.2, CN, NO.sub.2, Si(R.sup.2).sub.3, B(OR.sup.2).sub.2, C(O)R.sup.2, P(O)(R.sup.2).sub.2, S(O)R.sup.2, S(O).sub.2R.sup.2, OSO.sub.2R.sup.2, B(R.sup.2).sub.2, a straight-chain alkyl, alkoxy, or thioalkoxy group having 1 to 40 C atoms or a straight-chain alkenyl or alkynyl group having 2 to 40 C atoms or a branched or cyclic alkyl, alkenyl, alkynyl, alkoxy, or thioalkoxy group having 3 to 40 C atoms, each of which are optionally substituted by one or more R.sup.2, wherein one or more non-adjacent CH.sub.2 groups are optionally replaced by R.sup.2CCR.sup.2, CC, Si(R.sup.2).sub.2, Ge(R.sup.2).sub.2, Sn(R.sup.2).sub.2, CO, CS, CSe, CNR.sup.2, P(O)(R.sup.2), SO, SO.sub.2, NR.sup.2, O, S, or CONR.sup.2 and wherein one or more H atoms are optionally replaced by D, F, Cl, Br, I, CN, or NO.sub.2, an aromatic or heteroaromatic ring system having 5 to 60 aromatic ring atoms optionally substituted by one or more R.sup.2, an aryloxy or heteroaryloxy group having 5 to 60 aromatic ring atoms optionally substituted by one or more R.sup.2, a diarylamino group, diheteroarylamino group, or arylheteroarylamino group having 10 to 40 aromatic ring atoms optionally substituted by one or more R.sup.2, or a combination of two or more of these groups; and wherein two or more R.sup.1 optionally define a mono- or polycyclic, aliphatic, aromatic, and/or benzo-fused ring system with one another; R.sup.2 is, identically or differently on each occurrence, H, D, F, Cl, Br, I, N(R.sup.3).sub.2, CN, NO.sub.2, Si(R.sup.3).sub.3, B(OR.sup.3).sub.2, C(O)R.sup.3, P(O)(R.sup.3).sub.2, S(O)R.sup.3, S(O).sub.2R.sup.3, OSO.sub.2R.sup.3, a straight-chain alkyl, alkoxy, or thioalkoxy group having 1 to 40 C atoms or a straight-chain alkenyl or alkynyl group having 2 to 40 C atoms or a branched or cyclic alkyl, alkenyl, alkynyl, alkoxy or thioalkoxy group having 3 to 40 C atoms, each of which are optionally substituted by one or more R.sup.3, wherein one or more non-adjacent CH.sub.2 groups are optionally replaced by R.sup.3CCR.sup.3, CC, Si(R.sup.3).sub.2, Ge(R.sup.3).sub.2, Sn(R.sup.3).sub.2, CO, CS, CSe, CNR.sup.3, P(O)(R.sup.3), SO, SO.sub.2, NR.sup.3, O, S, or CONR.sup.3 and wherein one or more H atoms are optionally replaced by D, F, Cl, Br, I, CN, or NO.sub.2, an aromatic or heteroaromatic ring system having 5 to 60 aromatic ring atoms optionally substituted by one or more radicals R.sup.3, an aryloxy or heteroaryloxy group having 5 to 60 aromatic ring atoms, optionally substituted by one or more R.sup.3, a diarylamino group, diheteroarylamino group, or arylheteroarylamino group having 10 to 40 aromatic ring atoms optionally substituted by one or more radicals R.sup.3, or a combination of two or more of these groups; and wherein two or more adjacent radicals R.sup.2 optionally define a mono- or polycyclic, aliphatic, or aromatic ring system with one another; and R.sup.3 is, identically or differently on each occurrence, H, D, F, or an aliphatic, aromatic, and/or heteroaromatic hydrocarbon radical having 1 to 20 C atoms, wherein one or more H atoms are optionally replaced by F; and wherein two or more substituents R.sup.3 optionally define a mono- or polycyclic, aliphatic, or aromatic ring system with one another.

2. The method of claim 1, wherein E1 is a compound of formula (34), E2 is a compound of formula (35), and P is a compound of formula (36): ##STR00057##

3. A method for preparing a compound for use as a ligand for metal complexes comprising reacting the compound P of claim 1 with a halide of formula R.sup.1-Hal to obtain a compound having the following formula: ##STR00058## wherein the reaction is a Buchwald reaction.

Description

WORKING EXAMPLES

(1) The following syntheses are, unless indicated otherwise, carried out under a protective-gas atmosphere in dried solvents. Compound (I) can be prepared in accordance with Chem. Commun., 2010, 46, 3958 and compound (II) can be prepared according to WO 2007/000339. Compound (IV) can be prepared according to WO 2011/021689. Compounds (VIII), (IX), (XVII), (XXIII), (XXIV), (XXV), (XXIX), (XXXI) and (XXXII) are commercially available. Compound (XXII) can be prepared according to Inorg. Chem. 2011, 50, 8261. Compounds (XXVI) and (XXVII) can be prepared according to Inorg. Chem. 2010, 49, 5107. Compound (XXVIII) can be prepared according to Eur. J. Org. Chem. 2011, 1280. Compound (XXX) can be prepared according to Chem. Mater. 2011, 23, 4487.

Example 1

Preparation of Compound (III)

Synthetic Procedure for the Preparation of Compound (III)

(2) ##STR00039##
Preparation of Compound (III)
7.2 g (30.6 mmol) of compound (I) and 5.2 g (30.6 mmol) of compound (II) are suspended in 200 mL of toluene under Ar atmosphere. 340 mg (0.61 mmol) of 1,1-bis-(diphenylphosphino)-ferrocene and 140 mg (0.61 mmol) of Pd(OAc).sub.2 are added to the flask and stirred vigorously under Ar atmosphere. Then 3.5 g (36.7 mmol) of sodium t-butoxide is added to the flask under Ar. The reaction mixture is stirred under reflux for 24 h. After cooling to room temperature, the organic phase is separated off, washed three times with 100 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 82 g (29.4 mmol), corresponding to 96% of theory.

Example 2

Preparation of Compound (VI)

Synthetic Procedure for the Preparation of Compound (VI)

(3) ##STR00040##
Preparation of Compound (V)
15.8 g (51.1 mmol) of compound (IV), 9.7 g (51.1 mmol) of copper iodide, 6.6 g (102.2 mmol) of sodium azide and 5.4 g (61.3 mmol) of N,N-dimethyl-ethane-1,2-diamine are stirred under reflux for 10 h in 300 mL of dimethylsulfoxide (DMSO). After cooling to room temperature, 200 mL of ethylacetate and 100 mL of a solution of saturated NH.sub.4Cl are added to the reaction mixture. The organic phase is separated off, washed three times with 300 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is recrystallised from toluene and finally dried under reduced pressure. The yield is 11.1 g (44.9 mmol), corresponding to 88% of theory.
Preparation of Compound (VI)
10.5 g (34.1 mmol) of compound (IV) and 8.4 g (34.1 mmol) of compound (V) are suspended in 400 mL of toluene under Ar atmosphere. 380 mg (0.68 mmol) of 1,1-bis-(diphenylphosphino)-ferrocene and 150 mg (0.68 mmol) of Pd(OAc).sub.2 are added to the flask and stirred vigorously under Ar atmosphere, Then 3.9 g (40.9 mmol) of sodium t-butoxide is added to the flask under Ar. The reaction mixture is stirred under reflux for 24 h. After cooling to room temperature, the organic phase is separated off, washed three times with 100 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 15.3 g (32.4 mmol), corresponding to 95% of theory.

Example 3

Preparation of Compound (VII)

Synthetic Procedure for the Preparation of Compound (VII)

(4) ##STR00041##
Preparation of Compound (VII)
10.5 g (34.1 mmol) of compound (IV) and 5.8 g (34.1 mmol) of compound (II) are suspended in 400 mL of toluene under Ar atmosphere. 380 mg (0.68 mmol) of 1,1-bis-(diphenylphosphino)-ferrocene and 150 mg (0.68 mmol) of Pd(OAc).sub.2 are added to the flask and stirred vigorously under Ar atmosphere. Then 3.9 g (40.9 mmol) of sodium t-butoxide is added to the flask under Ar. The reaction mixture is stirred under reflux for 24 h. After cooling, the organic phase is separated off, washed three times with 100 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 11.1 g (27.9 mmol), corresponding to 82% of theory.

Example 4

Preparation of Compound (XII)

Synthetic Procedure for the Preparation of Compound (XII)

(5) ##STR00042##
Preparation of Compound (X)
17.2 g (100.2 mmol) of compound (IX) and 20.5 g (120.2 mmol) of compound (VIII) and 16.8 g (120.2 mmol) of potassium carbonate are suspended in 600 mL of toluene and 200 mL of water. 1.1 g (1.0 mmol) of tetrakis(triphenylphosphine)palladium(0) are added to this suspension, and the reaction mixture is stirred under reflux for 16 h. After cooling, the organic phase is separated off, washed three times with 600 mL of water, dried over sodium sulfate and subsequently evaporated to dryness. The residue is purified by column chromatography using a mixture of ethylacetate/heptane (1:3). The yield is 21.6 g (87.2 mmol), corresponding to 86% of theory.
Preparation of Compound (XI)
21.6 g (87.2 mmol) of compound (X), 16.6 g (87.2 mmol) of copper iodide, 11.3 g (174.4 mmol) of sodium azide and 9.2 g (104.6 mmol) of N,N-dimethyl-ethane-1,2-diamine are stirred under reflux for 10 h in 500 mL of dimethylsulfoxide (DMSO). After cooling to room temperature, 200 mL of ethylacetate and 100 mL of a solution of saturated NH.sub.4Cl are added to the reaction mixture. The organic phase is separated off, washed three times with 300 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is recrystallised from toluene and finally dried under reduced pressure. The yield is 14.1 g (76.7 mmol), corresponding to 88% of theory.
Preparation of Compound (XII)
14.0 g (56.6 mmol) of compound (IV) and 10.4 g (56.6 mmol) of compound (XI) are suspended in 300 mL of toluene under Ar atmosphere. 620 mg (1.1 mmol) of 1,1-bis-(diphenylphosphino)-ferrocene and 250 mg (1.1 mmol) of Pd(OAc).sub.2 are added to the flask, stirred vigorously under Ar atmosphere then 6.5 g (68.0 mmol) of sodium t-butoxide is added to the flask under Ar. The reaction mixture is stirred under reflux for 24 h. After cooling to room temperature, the organic phase is separated off, washed three times with 200 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 18.3 g (52.1 mmol), corresponding to 92% of theory.

Example 5

Preparation of Compound (XIV)

Synthetic Procedure for the Preparation of Compound (XIV)

(6) ##STR00043##
Preparation of Compound (XIV)
6.8 g (21.1 mmol) of compound (III) and 3.3 g (21.1 mmol) of compound (XIII) are suspended in 120 mL of toluene under Ar atmosphere. 94 mg (0.42 mmol) of Pd(OAc).sub.2 are added to the flask and stirred under Ar atmosphere then 0.8 mL of a 1 M tri-tert-butylphosphine solution and 2.4 g (25.4 mmol) of sodium t-butoxide are added to the flask. The reaction mixture is stirred under reflux for 24 h. After cooling, the organic phase is separated off, washed three times with 60 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 8.0 g (20.0 mmol), corresponding to 95% of theory.

Comparative Example for Compound (XIV)

Routes Published

(7) 1) According to U.S. Pat. No. 7,442,792: 78% of overall yield

(8) ##STR00044##
2) According to Inorg. Chem. 2010, 49, 5107: 34% of overall yield

(9) ##STR00045##

Example 6

Preparation of Compound (XVI)

Synthetic Procedure for the Preparation of Compound (XVI)

(10) ##STR00046##
Preparation of Compound (XVI)
5.5 g (17.1 mmol) of compound (III) and 3.4 g (17.1 mmol) of compound (XIII) are suspended in 120 mL of toluene under Ar atmosphere. 76 mg (0.34 mmol) of Pd(OAc).sub.2 are added to the flask and stirred under Ar atmosphere then 0.7 mL of a 1 M tri-tert-butylphosphine solution and 2.0 g (20.5 mmol) of sodium t-butoxide are added to the flask under Argon. The reaction mixture is stirred under reflux for 24 h. After cooling to room temperature, the organic phase is separated off, washed three times with 60 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 6.8 g (15.4 mmol), corresponding to 90% of theory.

Comparative Example for Compound (XVI)

Route Published

(11) 1) According to U.S. Pat. No. 7,442,792: 52% of overall yield

(12) ##STR00047##

Example 7

Preparation of Compound (XVIII)

Synthetic Procedure for the Preparation of Compound (XVIII)

(13) ##STR00048##
Preparation of Compound (XVIII)
8.5 g (26.3 mmol) of compound (III) and 8.4 g (26.3 mmol) of compound (XVII) are suspended in 250 mL of toluene under Ar atmosphere. 118 mg (0.53 mmol) of Pd(OAc).sub.2 are added to the flask and stirred under Ar atmosphere then 1 mL of a 1 M tri-tert-butylphosphine solution and 3.0 g (31.5 mmol) of sodium t-butoxide are added to the flask under Argon. The reaction mixture is stirred under reflux for 24 h. After cooling to room temperature, the organic phase is separated off, washed three times with 60 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 13.7 g (24.2 mmol), corresponding to 92% of theory.

Comparative Example for Compound (XVIII)

Route Published

(14) 1) According to U.S. Pat. No. 7,442,792: 67% of overall yield

(15) ##STR00049##

Example 8

Preparation of Compound (XIX)

Synthetic Procedure for the Preparation of Compound (XIX)

(16) ##STR00050##
Preparation of Compound (XIX)
12.4 g (26.3 mmol) of compound (III) and 3.9 g (26.3 mmol) of compound (XIII) are suspended in 250 mL of toluene under Ar atmosphere. 118 mg (0.53 mmol) of Pd(OAc).sub.2 are added to the flask and stirred under Ar atmosphere then 1 mL of a 1 M tri-tert-butylphosphine solution and 3.0 g (31.5 mmol) of sodium t-butoxide are added to the flask under Argon. The reaction mixture is stirred under reflux for 24 h. After cooling to room temperature, the organic phase is separated off, washed three times with 60 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 13.1 g (23.7 mmol), corresponding to 90% of theory.

Comparative Example for Compound (XIX)

Route Published

(17) According to U.S. Pat. No. 7,442,792: 28% of overall yield

(18) ##STR00051##

Example 9

Preparation of Compound (XX)

Synthetic Procedure for the Preparation of Compound (XX)

(19) ##STR00052##
Preparation of Compound (XX)
9.2 g (23.2 mmol) of compound (VII) and 3.6 g (23.2 mmol) of compound (XIII) are suspended in 150 mL of toluene under Ar atmosphere. 104 mg (0.46 mmol) of Pd(OAc).sub.2 are added to the flask and stirred under Ar atmosphere then 0.9 mL of a 1 M tri-tert-butylphosphine solution and 2.7 g (27.9 mmol) of sodium t-butoxide are added to the flask under Argon. The reaction mixture is stirred under reflux for 24 h. After cooling to room temperature, the organic phase is separated off, washed three times with 60 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 10.4 g (21.8 mmol), corresponding to 94% of theory.

Comparative Example for Compound (XX)

Preparation of Comparative Compound (XX)

Synthetic Procedure for the Preparation of Compound (XX)

(20) ##STR00053##
Preparation of Compound (XX)
7.9 g (25.6 mmol) of compound (IV) and 6.3 g (25.6 mmol) of compound (XXII) are suspended in 200 mL of toluene under Ar atmosphere. 115 mg (0.51 mmol) of Pd(OAc).sub.2 are added to the flask and stirred under Ar atmosphere then 1.0 mL of a 1 M tri-tert-butylphosphine solution and 2.9 g (30.7 mmol) of sodium t-butoxide are added to the flask under Ar. The reaction mixture is stirred under reflux for 24 h. After cooling to room temperature, the organic phase is separated off, washed three times with 50 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 8.3 g (17.4 mmol), corresponding to 68% of theory.

Example 10

Preparation of Compound (XXI)

Synthetic Procedure for the Preparation of Compound (XXI)

(21) ##STR00054##
Preparation of Compound (XXI)
25.5 g (72.6 mmol) of compound (XII) and 3.2 g (72.6 mmol) of compound (XIII) are suspended in 300 mL of toluene under Ar atmosphere. 325 mg (1.45 mmol) of Pd(OAc).sub.2 are added to the flask and stirred under Ar atmosphere then 2.9 mL of a 1 M tri-tert-butylphosphine solution and 8.4 g (87.2 mmol) of sodium t-butoxide are added to the flask under Ar. The reaction mixture is stirred under reflux for 24 h. After cooling to room temperature, the organic phase is separated off, washed three times with 200 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 34.6 g (81.1 mmol), corresponding to 93% of theory.

Comparative Example for Compound (XXI)

Synthetic Procedure for the Preparation of Compound (XXI)

(22) ##STR00055##
Preparation of Compound (XXI)
16.9 g (68.2 mmol) of compound (X) and 3.2 g (34.1 mmol) of compound (XXIII) are suspended in 150 mL of toluene under Ar atmosphere. 380 mg (0.68 mmol) of Pd(OAc).sub.2 are added to the flask and stirred under Ar atmosphere then 1.4 mL of a 1 M tri-tert-butylphosphine solution and 7.9 g (82.1 mmol) of sodium t-butoxide are added to the flask under Ar. The reaction mixture is stirred under reflux for 24 h. After cooling to room temperature, the organic phase is separated off, washed three times with 50 mL of water, dried over magnesium sulfate, filtered and subsequently evaporated to dryness. The residue is purified by column chromatography on silica gel using a mixture of ethylacetate/heptane (1:2). The yield is 5.7 g (16.4 mmol), corresponding to 48% of theory.

(23) The following Tables 1 and 2 summarize the results.

(24) TABLE-US-00001 TABLE 1 Last step yield Yield Yield (according to the Compound (Prior art) present invention) (XIV) 91%.sup.(1) 95% 75%.sup.(2) (XVI) 58%.sup.(1) 90% (XVIII) 75%.sup.(1) 92% (XIX) 65%.sup.(1) 90% (XX) 68%.sup.(3) 94% (XXI) 48%.sup.(3) 93% .sup.(1)U.S. Pat. No. 7,442,792; .sup.(2)Inorg. Chem. 2010, 49, 5107; .sup.(3)Preparation of comparative compounds

(25) TABLE-US-00002 TABLE 2 Overall yield Overall Yield Overall Yield (according to the Compound (prior art) present invention) (XIV) 78%.sup.(1) 91% 33%.sup.(2) (XVI) 52%.sup.(1) 75% (XVIII) 68%.sup.(1) 88% (XIX) 28%.sup.(1) 75% (XX) 41%.sup.(3) 77% (XXI) 41%.sup.(3) 65% .sup.(1)U.S. Pat. No. 7,442,792; .sup.(2)Inorg. Chem. 2010, 49, 5107; .sup.(3)Preparation of comparative compound