Complexes

Abstract

A palladium(II) complex of formula (1) or a palladium(II) complex of formula (3). ##STR00001##
Also, processes for the preparation of the complexes, and their use in carbon-carbon and carbon-heteroatom coupling reactions.

Claims

1. A palladium(II) complex of formula (1): ##STR00105## wherein: Pd.sup. is a cationic palladium atom; R.sub.1 and R.sub.2 are, independently, an organic group having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are, independently, H or an organic group having 1-20 carbon atoms; or R.sub.1/R.sub.3 or R.sub.2/R.sub.3 forms a ring structure with the atoms to which they are attached and in this instance R.sub.4/R.sub.5, R.sub.5/R.sub.6, R.sub.7/R.sub.8, R.sub.8/R.sub.9, R.sub.9/R.sub.10 or R.sub.10/R.sub.11, independently, form a ring structure with the carbon atoms to which they are attached or R.sub.1, R.sub.2, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are as defined above; R.sub.12 is an organic group having 1-20 carbon atoms; m is 0, 1, 2, 3, 4 or 5; E is P or As; and X.sup. is a non-coordinated anionic ligand.

2. A palladium(II) complex according to claim 1, wherein E is P.

3. A palladium(II) complex according to claim 1, wherein R.sub.1 and R.sub.2 are, independently, substituted or unsubstituted straight-chain alkyl, substituted or unsubstituted branched-chain alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl wherein the heteroatoms of the substituted or unsubstituted heteroaryl are, independently, sulfur, nitrogen or oxygen.

4. A palladium(II) complex according to claim 1, wherein R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are, independently, H, substituted or unsubstituted straight-chain alkyl, substituted or unsubstituted branched-chain alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted N(alkyl).sub.2 (wherein the alkyl is the same or different and is, independently, a straight-chain or branched-chain alkyl), substituted or unsubstituted N(cycloalkyl).sub.2 (wherein the cycloalkyl is the same or different), substituted or unsubstituted N(aryl).sub.2 (wherein the aryl is the same or different), substituted or unsubstituted N(heteroaryl).sub.2 (wherein the heteroaryl is the same or different) or substituted or unsubstituted heterocycloalkyl.

5. A palladium(II) complex according to claim 4, wherein R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are H.

6. A palladium(II) complex according to claim 4, wherein R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are, independently, a straight-chain alkyl.

7. A palladium(II) complex according to claim 1, wherein two of R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are H, and the other two of R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are, independently, unsubstituted straight-chain alkyl, unsubstituted branched-chain alkyl, unsubstituted cycloalkyl, or unsubstituted alkoxy.

8. A palladium(II) complex according to claim 1, wherein R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are, independently, H, substituted or unsubstituted straight-chain alkyl, substituted or unsubstituted branched-chain alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted N(alkyl).sub.2 (wherein the alkyl is the same or different and is, independently, a straight-chain or branched-chain alkyl), substituted or unsubstituted N(cycloalkyl).sub.2 (wherein the cycloalkyl is the same or different), substituted or unsubstituted N(aryl).sub.2 (wherein the aryl is the same or different), substituted or unsubstituted N(heteroaryl).sub.2 (wherein the heteroaryl is the same or different) or substituted or unsubstituted heterocycloalkyl.

9. A palladium(II) complex according to claim 7, wherein R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are H.

10. A palladium(II) complex according to claim 7, wherein three of R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are H, and the other two of R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are, independently, unsubstituted straight-chain alkyl, unsubstituted branched-chain alkyl, unsubstituted cycloalkyl, unsubstituted alkoxy, unsubstituted N(alkyl).sub.2 (wherein the alkyl is the same or different and, independently, straight-chain or branched-chain alkyl), or unsubstituted N(aryl).sub.2 (wherein the aryl is the same or different).

11. A palladium(II) complex according to claim 7, wherein two of R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are H, and the other three of R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are, independently, unsubstituted straight-chain alkyl, unsubstituted branched-chain alkyl, unsubstituted cycloalkyl, unsubstituted alkoxy, unsubstituted N(alkyl).sub.2 (wherein the alkyl is the same or different and, independently, straight-chain or branched-chain alkyl) or unsubstituted N(aryl).sub.2 (wherein the aryl is the same or different).

12. A palladium(II) complex according to claim 1, wherein the ##STR00106## moiety is a monodentate tertiary phosphine ligand that is: ##STR00107## ##STR00108##

13. A palladium(II) complex according to claim 1, wherein each R.sub.12 is, independently, substituted or unsubstituted straight-chain alkyl, substituted or unsubstituted branched-chain alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl wherein the heteroatoms of the heteroaryl are, independently, sulfur, nitrogen or oxygen.

14. A palladium(II) complex according to claim 1, wherein X.sup. is triflate, tetrafluoroborate, hexafluoroantimonate, hexafluorophosphate, [B[3,5-(CF.sub.3).sub.2C.sub.6H.sub.3].sub.4].sup.or mesylate.

15. A palladium(II) complex according to claim 1, wherein the complex of formula (1) is: ##STR00109## ##STR00110## ##STR00111## ##STR00112## ##STR00113## ##STR00114## ##STR00115## ##STR00116## ##STR00117## ##STR00118## ##STR00119##

16. A palladium(II) complex of formula (3): ##STR00120## wherein: R.sub.1 and R.sub.2 are, independently, an organic group having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.12 is an organic group having 1-20 carbon atoms; R.sub.20, R.sub.21, R.sub.22, R.sub.23 and R.sub.24 are, independently, H or an organic group having 1-20 carbon atoms; or one or more pairs of R.sub.1/R.sub.20, R.sub.2/R.sub.20, R.sub.20/R.sub.21 or R.sub.22/R.sub.23, independently, form a ring structure with the atoms to which they are attached; m is 0, 1, 2, 3, 4 or 5; and X.sup. is a non-coordinated anionic ligand.

17. A palladium(II) complex according to claim 16, wherein R.sub.1 and R.sub.2 are, independently, substituted or unsubstituted straight-chain alkyl, substituted or unsubstituted branched-chain alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl wherein the heteroatoms of the heteroaryl are independently, sulfur, nitrogen or oxygen.

18. A palladium(II) complex according to claim 16, wherein each R.sub.12 is, independently, substituted or unsubstituted straight-chain alkyl, substituted or unsubstituted branched-chain alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl wherein the heteroatoms of the heteroaryl are, independently, sulfur, nitrogen or oxygen.

19. A palladium(II) complex according to claim 16, wherein X.sup. is triflate, tetrafluoroborate, hexafluoroantimonate, hexafluorophosphate, [B[3,5-(CF.sub.3).sub.2C.sub.6H.sub.3].sub.4].sup.or mesylate.

20. A palladium(II) complex according to claim 16, wherein R.sub.20 and R.sub.21 are, independently, H, substituted or unsubstituted straight-chain alkyl, substituted or unsubstituted branched-chain alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, substituted or unsubstituted N(alkyl).sub.2 (wherein the alkyl is the same or different and, independently, straight-chain or branched-chain alkyl), substituted or unsubstituted N(cycloalkyl).sub.2 (wherein the cycloalkyl is the same or different), substituted or unsubstituted N(aryl).sub.2 (wherein the aryl is the same or different), substituted or unsubstituted N(heteroaryl).sub.2 (wherein the heteroaryl is the same or different) or substituted or unsubstituted heterocycloalkyl.

21. A palladium(II) complex according to claim 20, wherein R.sub.20 and R.sub.21 are H.

22. A palladium(II) complex according to claim 16, wherein R.sub.22 and R.sub.24 are, independently, H, substituted or unsubstituted straight-chain alkyl, substituted or unsubstituted branched-chain alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted thioalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted N(alkyl).sub.2 (wherein the alkyl is the same or different and, independently, straight-chain or branched-chain alkyl), substituted or unsubstituted N(cycloalkyl).sub.2 (wherein the cycloalkyl is the same or different), substituted or unsubstituted N(aryl).sub.2 (wherein the aryl is the same or different), or substituted or unsubstituted N(heteroaryl).sub.2 (wherein the heteroaryl is the same or different).

23. A palladium(II) complex according to claim 16, wherein R.sub.23 is H, substituted or unsubstituted straight-chain alkyl, substituted or unsubstituted branched-chain alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, or substituted and unsubstituted heteroaryl.

24. A palladium(II) complex according to claim 16, wherein R.sub.22, R.sub.23 and R.sub.24 are phenyl.

25. A palladium(II) complex according to claim 16, wherein the complex of formula (3) is: ##STR00121## ##STR00122##

26. A process for preparing a complex of formula (1), the process comprising the steps of: (a) reacting a complex of formula (4) with a monodentate biaryl ligand of formula (5) to form a complex of formula (6) ##STR00123## and; (b) reacting the complex of formula (6) with a silver salt of formula (7) to form the complex of formula (1), ##STR00124## wherein: R.sub.1 and R.sub.2 are, independently, an organic group having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are, independently, H or an organic group having 1-20 carbon atoms; or one or more pairs selected from R.sub.1/R.sub.3, R.sub.2/R.sub.3, R.sub.3/R.sub.4, R.sub.4/R.sub.5, R.sub.5/R.sub.6, R.sub.7/R.sub.8, R.sub.8/R.sub.9, R.sub.9/R.sub.10 or R.sub.10/R.sub.11, independently, form a ring structure with the atoms to which they are attached; R.sub.12 is an organic group having 1-20 carbon atoms; m is 0, 1, 2, 3, 4 or 5; E is P or As; Y is a coordinating anionic ligand; and X.sup. is a non-coordinated anionic ligand.

27. A process for preparing a complex of formula (1) or a complex of formula (3), the process comprising the steps of: (a) reacting a complex of formula (4) with a silver salt of formula (7), ##STR00125## and; (b) reacting the product of step (a) with a monodentate biaryl ligand of formula (5) or a monodentate bi-heteroaryl tertiary phosphine ligand of formula (8) to form the complex of formula (1) or the complex of formula (3), ##STR00126## wherein: R.sub.1 and R.sub.2 are, independently, an organic group having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are, independently, H or an organic group having 1-20 carbon atoms; or one or more pairs selected from R.sub.1/R.sub.2, R.sub.2/R.sub.3, R.sub.3/R.sub.4, R.sub.4/R.sub.5, R.sub.5/R.sub.6, R.sub.7/R.sub.8, R.sub.8/R.sub.9, R.sub.9/R.sub.10 or R.sub.10/R.sub.11, independently, form a ring structure with the atoms to which they are attached; R.sub.12 is an organic group having 1-20 carbon atoms; R.sub.20, R.sub.21, R.sub.22, R.sub.23 and R.sub.24 are, independently, H or an organic group having 1-20 carbon atoms; or one or more pairs of R.sub.1/R.sub.20, R.sub.2/R.sub.20, R.sub.20/R.sub.21 or R.sub.22/R.sub.23, independently, form a ring structure with the atoms to which they are attached; m is 0, 1, 2, 3, 4 or 5; E is P or As; Y is a coordinating anionic ligand; and X.sup. is a non-coordinated anionic ligand.

28. A process for performing a carbon-carbon coupling reaction in the presence of a catalyst, the process comprising using a complex of formula (1) according to claim 1 or a complex of formula (3): ##STR00127## wherein: R.sub.1 and R.sub.2 are, independently, an organic group having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.12 is an organic group having 1-20 carbon atoms; R.sub.20, R.sub.21, R.sub.22, R.sub.23 and R.sub.24 are, independently, H or an organic group having 1-20 carbon atoms; or one or more pairs of R.sub.1/R.sub.20, R.sub.2/R.sub.20, R.sub.20/R.sub.21 or R.sub.22/R.sub.23 independently form a ring structure with the atoms to which they are attached; m is 0, 1, 2, 3, 4 or 5; and X.sup. is a non-coordinated anionic ligand.

29. A process for performing a carbon-heteroatom coupling reaction in the presence of a catalyst, the process comprising using a complex of formula (1) according to claim 1 or a complex of formula (3): ##STR00128## wherein: R.sub.1 and R.sub.2 are, independently, an organic group having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.12 is an organic group having 1-20 carbon atoms; R.sub.20, R.sub.21, R.sub.22, R.sub.23 and R.sub.24 are, independently, H or an organic group having 1-20 carbon atoms; or one or more pairs of R.sub.1/R.sub.20, R.sub.2/R.sub.20, R.sub.20/R.sub.21 or R.sub.22/R.sub.23, independently, form a ring structure with the atoms to which they are attached; m is 0, 1, 2, 3, 4 or 5; and X.sup. is a non-coordinated anionic ligand.

30. A palladium (II) complex according to claim 6, wherein R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are Me.

Description

(1) The invention will now be described by way of the following non-limiting examples and with reference to the following figures in which:

(2) FIG. 1 is a .sup.1H NMR spectrum of [(-crotyl)Pd(tBuXPhos)]OTf.

(3) FIG. 2 is a .sup.1H NMR spectrum of [(-cinnamyl)Pd(tBuXPhos)]OTf.

(4) FIG. 3 is a .sup.1H NMR spectrum of [(-crotyl)Pd(BrettPhos)]OTf.

(5) FIG. 4 is a .sup.13C NMR spectrum of [(-crotyl)Pd(BrettPhos)]OTf.

(6) FIG. 5 is a .sup.1H NMR spectrum of [(-cinnamyl)Pd(BrettPhos)]OTf.

(7) FIG. 6 is a .sup.13C NMR spectrum of [(-cinnamyl)Pd(BrettPhos)]OTf.

(8) FIG. 7 is a .sup.1H NMR spectrum of [(-crotyl)Pd(tBuBrettPhos)]OTf.

(9) FIG. 8 is a .sup.13C NMR spectrum of [(-crotyl)Pd(tBuBrettPhos)]OTf.

(10) FIG. 9 is a .sup.1H NMR spectrum of [(-cinnamyl)Pd(tBuBrettPhos)]OTf.

(11) FIG. 10 is a .sup.13C NMR spectrum of [(-cinnamyl)Pd(tBuBrettPhos)]OTf.

(12) FIG. 11 illustrates the gas chromatography (GC) conversion of the amination of 4-chloroanisole with n-BuNH.sub.2 with BrettPhos complexes.

EXAMPLES

(13) All solvents and reagents were purchased from commercial sources and used as received. All catalysts, ligands or precious metal precursors were obtained from Johnson Matthey Catalysis or Alfa Aesar. Flash chromatography was performed on a Teledyne ISCO CombiFlashRf using 12 g RediSepRf silica cartridges. .sup.31P, .sup.1H, .sup.19F and .sup.13C NMR spectra were recorded on a 400 MHz spectrometer, with chemical shifts reported relative to residual solvent as internal references (CDCl.sub.3: 7.26 ppm for .sup.1H NMR and 77.26 ppm for .sup.13C NMR, C.sub.6D.sub.6: 7.16 ppm for .sup.1H NMR and 128.06 ppm .sup.13C NMR, DMSO-d6: 2.50 ppm for .sup.1H NMR and 39.52 ppm for .sup.13C NMR, toluene-d8: 2.08 ppm for .sup.1H NMR and 20.43 ppm for .sup.13C NMR), unless otherwise stated, while .sup.31P{.sup.1H} NMR spectra were externally referenced to 85% H.sub.3PO.sub.4, and .sup.19F NMR spectra were externally referenced to CFCl.sub.3. The following abbreviations were used to explain the multiplicities: s=singlet, d=doublet, t=triplet, q=quartet, quint=quintet, sept=septet, m=multiplet, b=broad, app t=apparent triplet, app d=apparent doublet, br=broad. Elemental analyses were sent to Robertson Microlit Laboratories, Inc. All reactions were carried out in individual Schlenk flasks under a nitrogen atmosphere. The purity of the isolated products was >95% as determined by .sup.1H NMR, GC/MS or elemental analysis, unless otherwise noted.

(14) Crystallographic data were obtained at 120K on a APEX Bruker-AXS CCD X-ray diffractometer equipped with a monocap collimator. Structures were solved with SHELXTL software. These data was obtained from University of Delaware X-ray Crystallography Laboratory of the Department of Chemistry and Biochemistry.

(15) General Procedure for the Preparation of [Pd(Optionally Substituted (R.sub.12).sub.n-Allyl)(X)].sub.2 Complexes:

(16) Distilled H.sub.2O in a three-necked roundbottom flask is purged with nitrogen for 30 minutes. PdCl.sub.2 and KCl are subsequently added to the flask and the solution is stirred at room temperature for 1 h. Then, optionally substituted (R.sub.4).sub.n-allyl chloride is added and the resulting reaction mixture is stirred at room temperature overnight (18-20 hrs). The reaction is extracted with chloroform, and the aqueous layer washed with chloroform three times. The organic layers are combined, dried over MgSO.sub.4, filtered and concentrated in vacuo. The crude product is recrystallised from chloroform and methyl tert-butyl ether, and the resulting solid is isolated by filtration and dried in vacuo.

[Pd(-cinnamyl)Cl]2

(17) ##STR00056##

(18) PdCl.sub.2 (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol); cinnamyl chloride (1.39 mL, 9.99 mmol); H.sub.2O (83 mL). The dimer is obtained as a yellow solid.

[Pd(-1-crotyl)Cl]2

(19) ##STR00057##

(20) PdCl.sub.2 (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol); crotyl chloride (0.97 mL, 9.99 mmol); H.sub.2O (83 mL). The dimer is obtained as a yellow solid.

[Pd(-prenyl)Cl]2

(21) ##STR00058##

(22) PdCl.sub.2 (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol); 1-chloride-3-methyl-2-butene (1.13 mL, 9.99 mmol); H.sub.2O (83 mL). The dimer is obtained as a yellow solid.

[Pd(-methallyl)Cl]2

(23) ##STR00059##

(24) PdCl.sub.2 (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol); 3-chloride-2-methyl-1-propene (0.98 mL, 9.99 mmol); H.sub.2O (83 mL). The dimer is obtained as a yellow solid (269 mg, 41%).

Example 1 (According to the Invention)

[(-allyl)Pd(tBuBrettPhos)]OTf

(25) ##STR00060##

(26) A dry Schlenk flask is charged with 183 mg (0.50 mmol) of [(allyl)PdCl].sub.2 and 257 mg (1.0 mmol) of silver trifluoromethanesulfonate. A second dry Schlenk flask is fitted with a Schlenk frit and is charged with 485 mg (1.0 mmol) of tBuBrettPhos. The flasks are evacuated and backfilled with nitrogen. This evacuation/backfill cycle was repeated a total of three times. 10 mL of anhydrous THF is added to the first flask and the mixture is stirred for 30 min at room temperature (rt) while protecting from light. The mixture from flask one is then transferred via cannula through the Schlenk frit into the second flask to remove the AgCl. The frit is rinsed with an additional 10 mL of anhydrous THF. The mixture is stirred at room temperature for 2 hours, followed by the slow addition of 30 mL of hexanes to obtain a pale yellow precipitate. It is filtered, washed (210 mL of hexanes) and dried in vacuo to give 653 mg (0.84 mmol, 84%) of analytically pure (-allyl)Pd(tBuBrettPhos)OTf as a slightly yellow solid; .sup.1H NMR (400 MHz, CDCl.sub.3, ): 7.45 (d, J=1.8 Hz, 1H), 7.28 (d, J=1.7 Hz, 1H), 7.07 (dd, J=2.9 Hz, 9.0 Hz, 1H), 6.96 (dd, J=2.9 Hz, 8.9 Hz, 1H), 5.52 (sept, J=7.1 Hz, 1H), 4.39 (app d, J=6.3 Hz, 1H), 3.83 (s, 3H), 3.35 (dd, J=9.2 Hz, 13.9 Hz, 1H), 3.32 (s, 3H), 2.97 (sept, J=6.9 Hz, 1H), 2.78 (app d, J=12.4 Hz, 1H), 2.54 (sept, J=6.7 Hz, 1H), 2.30-1.12 (m, 2H), 1.45-1.27 (m, 24H), 1.24 (dd, J=6.9 Hz, 11.8 Hz, 6H), 0.87 (d, J=6.9 Hz, 3H), 0.70 (d, J=6.9 Hz, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3, ): 156.3, 154.6 (2 peaks), 154.5, 152.2, 151.5, 136.5, 136.2, 125.8, 125.7, 125.6, 125.4, 125.2, 122.6, 119.7, 119.6, 119.4, 116.2, 115.5 (2 peaks), 112.8 (2 peaks), 112.0 (2 peaks), 99.8, 99.5, 58.4 (2 peaks), 54.7, 54.6, 39.9, 39.8, 39.3, 39.1, 34.0, 32.1, 32.0, 31.9, 31.7, 31.6 (2 peaks), 25.7, 25.5, 24.6, 24.5, 24.2 [Observed complexity due to CF and CP coupling]; .sup.19F NMR (372 MHz, CDCl.sub.3, ): 77.9 (s, 3F); .sup.31P NMR (162 MHz, CDCl.sub.3, ): 86.2; Anal. calcd. for C.sub.35H.sub.54O.sub.5F.sub.3PSPd: C, 53.81; H, 6.97. Found C, 53.81; H, 7.10.

Example 2

(27) The following complexes are prepared using substantially the same procedure of Example 1.

[(-allyl)Pd(tBuXPhos)]OTf

(28) ##STR00061##

(29) [(allyl)PdCl].sub.2 (183 mg, 0.50 mmol); AgOTf (257 mg, 1.00 mmol); tBuXPhos (425 mg, 1.00 mmol); THF (10.0 mL); 2 h. Product obtained as a slightly yellow solid (708 mg, 98%); .sup.1H NMR (400 MHz, CDCl.sub.3, ): 7.92 (t, J=7.3 Hz, 1H), 7.59-7.47 (m, 3H), 7.42-7.40 (m, 1H), 6.79 (dd, J=3.2 Hz, 7.5 Hz, 1H), 5.72 (sept, J=7.2 Hz, 1H), 4.49 (d, J=6.7 Hz, 1H), 3.52 (dd, J=9.0 Hz, 14.0 Hz, 1H), 3.03 (quint, J=7.1 Hz, 1H), 2.93 (d, J=12.9 Hz, 1H), 2.67-2.62 (m, 1H), 2.50 (quint, J=7.1 Hz, 1H), 2.26 (quint, J=6.9 Hz, 1H), 1.49-1.40 (m, 9H), 1.40-1.28 (m, 21H), 0.96 (d, J=6.7 Hz, 3H), 0.88 (d, J=6.7 Hz, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3, ): 153.6, 152.7, 149.2, 146.0, 145.8, 135.1 (2 peaks), 134.9, 133.7, 133.6, 131.7, 131.6, 128.3, 128.2, 126.6, 126.2, 125.8, 122.6, 120.3 (2 peaks), 120.1 (2 peaks), 119.4, 116.2, 101.3, 101.1, 55.5, 38.3 (2 peaks), 38.2, 38.1, 33.9, 32.0, 31.7, 31.2, 31.1, 30.9, 30.8, 25.9, 25.4, 24.9, 24.5 (2 peaks), 24.1 [Observed complexity due to CF and CP coupling]; .sup.19F NMR (372 MHz, CDCl.sub.3, ): 78.1 (s, 3F); .sup.31P NMR (162 MHz, CDCl.sub.3, ): 70.1; Anal. calcd. for C.sub.33H.sub.50O.sub.3F.sub.3PSPd: C, 54.96; H, 6.99. Found C, 54.84; H, 7.13.

[(-crotyl)Pd(tBuXPhos)]OTf

(30) ##STR00062##

(31) [(crotyl)PdCl].sub.2 (197 mg, 0.50 mmol); AgOTf (257 mg, 1.00 mmol); tBuXPhos (425 mg, 1.00 mmol); 2-MeTHF (10.0 mL); 2 h. Product obtained as a slightly yellow solid (722 mg, 98%); The spectral properties are complicated due to the presence of isomers. .sup.1H NMR (400 MHz, CDCl.sub.3, ): Complex spectrum, see FIG. 1; .sup.13C NMR (100 MHz, CDCl.sub.3, ): 153.4, 152.3, 152.0, 146.4, 146.2, 146.0, 145.8, 144.1, 135.0, 134.9, 134.7, 134.4, 134.1, 133.7, 133.6, 133.3, 133.2, 131.5 (2 peaks), 131.4 (2 peaks), 128.1 (2 peaks), 128.0, 127.1, 126.1, 125.7, 124.6, 124.1, 122.9, 122.8, 122.5, 121.7, 121.4, 119.3, 112.9 (2 peaks), 48.3, 38.9, 38.8, 38.3, 38.1, 37.5, 37.3, 33.8, 33.5, 32.0, 31.9, 31.7, 31.6, 31.3, 31.1 (2 peaks), 31.0 (2 peaks), 30.7 (2 peaks), 26.2, 25.6, 25.5, 25.4, 25.1, 24.9, 24.3, 24.2, 24.0 (2 peaks), 23.7, 23.4, 22.8, 16.4 (2 peaks) [Observed complexity due to CF and CP coupling]; .sup.19F NMR (372 MHz, CDCl.sub.3, ): 77.9 (s, 3F); .sup.31P NMR (162 MHz, CDCl.sub.3, ): 72.2, 71.7, 66.7; Anal. calcd. for C.sub.34H.sub.52O.sub.3F.sub.3PSPd: C, 55.54; H, 7.13. Found C, 55.66; H, 6.99.

[(-cinnamyl)Pd(tBuXPhos)]OTf

(32) ##STR00063##

(33) [(cinnamyl)PdCl].sub.2 (259 mg, 0.50 mmol); AgOTf (257 mg, 1.00 mmol); tBuXPhos (425 mg, 1.00 mmol); 2-MeTHF (10.0 mL); 2 h. Product obtained as a yellow solid (725 mg, 91%); .sup.1H NMR (400 MHz, CDCl.sub.3, ): Complex spectrum, see FIG. 2; .sup.13C NMR (100 MHz, CDCl.sub.3, ): 153.1, 151.5, 146.8, 146.6, 135.4, 135.1, 135.0, 134.1, 133.6, 133.5, 131.5, 130.3 (2 peaks), 129.6 (2 peaks), 128.1, 128.0, 125.2, 123.3, 122.6, 119.4, 118.9, 116.2, 110.2, 39.3, 39.1, 32.1, 31.5, 31.3 (2 peaks), 31.0, 25.7, 25.5, 24.9, 24.8, 24.4, 22.6, 22.5, 14.1 [Observed complexity due to CF and CP coupling]; .sup.19F NMR (372 MHz, CDCl.sub.3, ): 78.6 (s, 3F); .sup.31P NMR (162 MHz, CDCl.sub.3, ): 76.0; Anal. calcd. for C.sub.39H.sub.54O.sub.3F.sub.3PSPd: C, 58.75; H, 6.83. Found C, 58.81; H, 6.76.

[(-allyl)Pd(Me4tBuXPhos)]OTf

(34) ##STR00064##

(35) [(allyl)PdCl].sub.2 (183 mg, 0.50 mmol); AgOTf (257 mg, 1.00 mmol); Me.sub.4tBuXPhos (481 mg, 1.00 mmol); THF (10.0 mL); 2 h. Product obtained as a pale yellow solid (727 mg, 94%), product contains a trace amount of residual THF (5 mol % as judged by .sup.1H NMR); .sup.1H NMR (400 MHz, CDCl.sub.3, ): 7.42 (s, 1H), 7.32 (s, 1H), 5.58 (sept, J=7.1 Hz, 1H), 4.53 (d, J=6.5 Hz, 1H), 3.31 (dd, J=9.5, 13.4 Hz, 1H), 3.00 (sept, J=7.3 Hz, 1H), 2.91 (d, J=12.8 Hz, 1H), 2.61 (sept, J=6.8 Hz, 1H), 2.60 (s, 3H), 2.31 (sept, J=6.6 Hz, 1H), 2.25 (s, 3H), 2.16-2.08 (m, 4H), 1.52-1.37 (m, 18H), 1.32 (d, J=7.0 Hz, 6H), 1.24 (t, J=7.6 Hz, 6H), 0.88 (d, J=6.8 Hz, 3H), 0.82 (s, 3H), 0.74 (d, J=6.6 Hz, 3H), peaks attributable to THF were observed at 3.76 and 1.85 ppm; .sup.13C NMR (100 MHz, CDCl.sub.3, ): 155.1, 154.6, 151.4, 143.3, 143.0, 141.5 (2 peaks), 139.2, 138.5, 138.4, 137.1, 137.0, 133.6, 133.4, 125.8, 125.6, 125.5, 122.6, 120.0, 119.9, 119.4, 116.2, 116.1, 98.3, 98.0, 62.7 (2 peaks), 40.9, 40.8, 40.1, 40.0, 34.0, 33.4 (2 peaks), 32.9 (2 peaks), 32.2, 32.0, 26.9, 26.3, 26.2, 24.8, 24.6, 24.3 (2 peaks), 18.7, 17.5, 17.3 [Observed complexity due to CF and CP coupling], peaks attributable to THF were observed at 67.9 and 25.6 ppm; .sup.19F NMR (372 MHz, CDCl.sub.3, ): 78.1 (s, 3F); .sup.31P NMR (162 MHz, CDCl.sub.3, ): 93.5; Anal. calcd. for C.sub.37H.sub.58O.sub.3F.sub.3PSPd: C, 57.17; H, 7.52. Found C, 57.19; H, 7.64.

[(-allyl)Pd(RockPhos)]OTf

(36) ##STR00065##

(37) [(allyl)PdCl].sub.2 (183 mg, 0.50 mmol); AgOTf (257 mg, 1.00 mmol); RockPhos (469 mg, 1.00 mmol); THF (10.0 mL); 2 h. Product obtained as a yellow solid (744 mg, 97%), product contains a trace amount of residual THF (8 mol % as judged by .sup.1H NMR); .sup.1H NMR (400 MHz, CDCl.sub.3, ): 7.44 (d, J=1.3 Hz, 1H), 7.37 (d, J=1.3 Hz, 1H), 7.32 (d, J=8.5 Hz, 1H), 7.01 (dd, J=2.2, 8.4 Hz, 1H), 5.57 (sept, J=6.9 Hz, 1H), 4.44 (d, J=6.6 Hz, 1H), 3.88 (s, 3H), 3.38 (dd, J=9.4, 13.7 Hz, 1H), 3.01 (sept, J=7.1 Hz, 1H), 2.86 (d, J=12.7 Hz, 1H), 2.63 (sept, J=6.7 Hz, 1H), 2.31 (sept, J=6.8 Hz, 1H), 2.23 (dt, J=2.3, 7.5 Hz, 1H), 1.45-1.20 (m, 30H) 1.08 (s, 3H), 0.97 (d, J=6.5 Hz, 3H), 0.84 (d, J=6.8 Hz, 3H), peaks attributable to THF were observed at 3.76 and 1.85 ppm; .sup.13C NMR (100 MHz, CDCl.sub.3, ): [Observed complexity due to CF and CP coupling], peaks attributable to THF were observed at 67.9 and 25.6 ppm; .sup.19F NMR (372 MHz, CDCl.sub.3, ): 78.2 (s, 3F); .sup.31P NMR (162 MHz, CDCl.sub.3, ): 84.8; Anal. calcd. for C.sub.35H.sub.54O.sub.4F.sub.3PSPd: C, 54.93; H, 7.11. Found C, 54.92; H, 7.25.

[(-allyl)Pd(BippyPhos)]OTf

(38) ##STR00066##

(39) [(allyl)PdCl].sub.2 (183 mg, 0.50 mmol); AgOTf (257 mg, 1.00 mmol); BippyPhos (507 mg, 1.00 mmol); THF (10.0 mL); 2 h. Product obtained as a pale yellow solid (786 mg, 91%), and is a MTBE solvate (MTBE/hexanes used to in the precipitation); .sup.1H NMR (400 MHz, CDCl.sub.3, ): (2 isomers present in 6:4 ratio) 8.15-8.05 (m, 1H), 7.49-7.08 (m, 15H), 7.71-7.60 (m, 1H), 6.10-5.79 (m, 1H), 4.52-4.29 (m, 2H), 4.06-3.96 (m, 0.4H), 3.85-3.75 (m, 0.6H), 3.37-3.30 (m, 0.4H), 3.02-2.92 (m, 0.6H), 0.91-0.50 (m, 18H), peaks attributable to MTBE were observed at 3.10 and 1.05 ppm; .sup.13C NMR (100 MHz, CDCl.sub.3, ): 156.4, 154.8, 150.5, 148.0, 146.3 (2 peaks), 146.1, 146.0, 141.9, 141.5, 137.7, 137.6, 131.2, 130.5, 130.3, 129.8, 129.7, 129.4 (2 peaks), 129.2, 129.1, 129.0, 128.9, 127.9, 127.7, 125.6, 125.2, 124.6, 122.6 (2 peaks), 122.4, 121.8 (2 peaks), 119.2, 116.0, 114.9, 104.0, 103.9, 93.4, 93.2, 90.1, 89.9, 57.8, 56.9, 36.4. 36.2, 36.1 (2 peaks), 36.0, 35.9, 35.8, 29.0 (2 peaks), 28.9 (2 peaks), 28.5 (2 peaks) [Observed complexity due to CF and CP coupling], peaks attributable to MTBE were observed at 72.5, 49.2 and 26.8 ppm; .sup.19F NMR (372 MHz, CDCl.sub.3, ): 80.0 (s, 3F); .sup.31P NMR (162 MHz, CDCl.sub.3, ): 50.4, 49.5; Anal. calcd. for C.sub.36H.sub.40N.sub.4O.sub.3F.sub.3PSPd.( C.sub.5H.sub.12O): C, 54.81; H, 5.61. Found C, 54.97; H, 5.70.

Example 3 (According to the Invention)

(40) General Procedure

(41) A dry Schlenk flask equipped with a Teflon-coated magnetic stir bar is charged with [(R-allyl)PdCl].sub.2 (0.50 mmol, 0.50 equiv) followed by AgOTf (257 mg, 1.00 mmol, 1.00 equiv). The flask is fitted with a rubber septum evacuated and backfilled with nitrogen. This evacuation/nitrogen backfill cycle is repeated two additional times. Solvent (10 mL THF or 2-MeTHF) is added and the reaction mixture is stirred at it for 30 min while protected from light. A second dry Schlenk flask is equipped with a magnetic stir bar, fitted with a Schlenk frit, and charged with the appropriate ligand (1.00 mmol, 1.00 equiv). The flask is fitted with a rubber septum and it is evacuated and backfilled with nitrogen. This evacuation/nitrogen backfill cycle is repeated two additional times. The solution from the first Schlenk flask is transferred via cannula through the Schlenk frit (to remove AgCl) and into the second Schlenk flask containing the ligand, rinsing with 5 mL of additional solvent (THF or 2-MeTHF). This mixture is stirred at it for 2 h. 30 mL of hexanes is then added to fully precipitate the product. The solid materials are then collected by suction filtration, washed with additional pentane (or hexanes), and dried in vacuo.

[(-allyl)Pd(BrettPhos)]OTf

(42) ##STR00067##

(43) The general procedure is followed using 183 mg (0.50 mmol) of [(allyl)PdCl].sub.2, 257 mg (1.00 mmol) of AgOTf, 537 mg (1.00 mmol) of BrettPhos in anhydrous THF to give 803 mg (0.94 mmol, 94%) of the title compound as a yellow solid. The material contains 3 wt % of THF.

(44) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 7.34 (s, 1H), 7.23 (s, 1H), 7.07-6.98 (m, 1H), 6.96-6.87 (m, 1H), 5.45 (sept, J=7.52 Hz, 1H), 4.14 (d, J=6.8 Hz, 1H), 3.84 (s, 3H), 3.42 (dd, J=8.2, 13.1 Hz, 1H), 3.29 (s, 3H), 2.90 (sept, J=8.2 Hz, 1H), 2.79-2.63 (m, 1H), 2.59 (d, J=13.2 Hz, 1H), 2.55-2.41 (m, 1H), 2.40-2.25 (m, 2H), 2.14 (sept, J=7.8 Hz, 1H), 1.98-1.82 (m, 2H), 1.81-0.93 (m, 29H), 0.92-0.66 (m, 7H).

(45) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 154.8 (2 peaks), 153.3, 151.4, 150.5, 135.0, 134.8, 125.6, 124.9, 124.8, 124.2, 123.9, 122.4, 119.5, 119.4, 119.3, 115.2, 113.7, 112.7 (2 peaks), 100.7, 100.5, 55.8, 54.7, 52.0, 38.5, 38.4, 38.3, 38.1, 33.7, 32.5, 31.5, 30.0, 27.2, 26.7, 26.6, 24.3, 24.0, 23.9, 23.8 [Observed complexity due to CP and CF coupling]; peaks attributable to THF are observed at 67.7 and 25.4.

(46) .sup.31P NMR (162 MHz, CDCl.sub.3, ): 51.4.

(47) .sup.19F NMR (376 MHz, CDCl.sub.3, ): 78.4 (s, 3F).

(48) Anal. Calcd. for C.sub.39H.sub.58F.sub.3O.sub.5PPdS: C, 56.21; H, 7.02. Found: C, 56.46; H, 7.05.

[(-crotyl)Pd(BrettPhos)]OTf

(49) ##STR00068##

(50) The general procedure is followed using 197 mg (0.50 mmol) of [(crotyl)PdCl].sub.2, 257 mg (1.00 mmol) of AgOTf, 537 mg (1.00 mmol) of BrettPhos in anhydrous THF to give 816 mg (0.96 mmol, 96%) of the title compound as a yellow solid. The material contains 2 wt % of THF.

(51) .sup.1H NMR (400 MHz, CDCl.sub.3, ): complex spectrumsee FIG. 3.

(52) .sup.13C NMR (100 MHz, CDCl.sub.3, ): complex spectrumsee FIG. 4.

(53) .sup.31P NMR (162 MHz, CDCl.sub.3, ): 54.0, 52.2, 45.7, 43.3.

(54) .sup.19F NMR (376 MHz, CDCl.sub.3, ): 78.2 (s, 3F).

(55) HRMS (ESI) m/z [M-OTf].sup.+ Calcd. for C.sub.39H.sub.60).sub.2PPd: 697.3366. Found: 697.3384.

[(-cinnamyl)Pd(BrettPhos)]OTf

(56) ##STR00069##

(57) The general procedure is followed using 259 mg (0.50 mmol) of [(cinnamyl)PdCl].sub.2, 257 mg (1.00 mmol) of AgOTf, 537 mg (1.00 mmol) of BrettPhos in anhydrous 2-MeTHF to give 884 mg (0.97 mmol, 97%) of the title compound as a yellow solid.

(58) .sup.1H NMR (400 MHz, CDCl.sub.3, ): complex spectrumsee FIG. 5.

(59) .sup.13C NMR (100 MHz, CDCl.sub.3, ): complex spectrumsee FIG. 6.

(60) .sup.31P NMR (162 MHz, CDCl.sub.3, ): 57.6, 39.5

(61) .sup.19F NMR (376 MHz, CDCl.sub.3, ): 78.1 (s, 3F).

(62) Anal. Calcd. for C.sub.45H.sub.62F.sub.3O.sub.5PPdS: C, 59.43; H, 6.87. Found: C, 59.26; H, 6.68.

[(-crotyl)Pd(tBuBrettPhos)]OTf

(63) ##STR00070##

(64) The general procedure is followed using 197 mg (0.50 mmol) of [(crotyl)PdCl].sub.2, 257 mg (1.00 mmol) of AgOTf, 485 mg (1.00 mmol) of tBuBrettPhos in anhydrous 2-MeTHF to give 784 mg (0.99 mmol, 99%) of the title compound as a light yellow solid.

(65) .sup.1H NMR (400 MHz, CDCl.sub.3, ): Complex spectrumsee FIG. 7.

(66) .sup.13C NMR (100 MHz, CDCl.sub.3, ): Complex spectrumsee FIG. 8.

(67) .sup.31P NMR (162 MHz, CDCl.sub.3, ): 90.1, 88.4, 83.9.

(68) .sup.19F NMR (376 MHz, CDCl.sub.3, ): 78.0 (s, 3F).

(69) Anal. Calcd. for C.sub.36H.sub.56F.sub.3O.sub.5PPdS: C, 54.37; H, 7.10. Found: C, 54.58; H, 7.01.

[(-cinnamyl)Pd(tBuBrettPhos)]OTf

(70) ##STR00071##

(71) The general procedure is followed using 259 mg (0.50 mmol) of [(cinnamyl)PdCl].sub.2, 257 mg (1.00 mmol) of AgOTf, 485 mg (1.00 mmol) of tBuBrettPhos in anhydrous 2-MeTHF to give 812 mg (0.95 mmol, 95%) of the title compound as a dark yellow solid.

(72) .sup.1H NMR (400 MHz, CDCl.sub.3, ): Complex spectrumsee FIG. 9.

(73) .sup.13C NMR (100 MHz, CDCl.sub.3, ): Complex spectrumsee FIG. 10.

(74) .sup.31P NMR (162 MHz, CDCl.sub.3, ): 94.5

(75) .sup.19F NMR (376 MHz, CDCl.sub.3, ): 77.9 (s, 3F).

(76) Anal. Calcd. for C.sub.41H.sub.58F.sub.3O.sub.5PPdS: C, 57.44; H, 6.82. Found: C, 57.04; H, 6.77.

[(-allyl)Pd(AdBrettPhos)]OTf

(77) ##STR00072##

(78) The general procedure is followed using 57.1 mg (0.156 mmol) of [(allyl)PdCl].sub.2, 80.2 mg (0.312 mmol) of AgOTf, 200 mg (0.312 mmol) of AdBrettPhos in anhydrous THF to give 265 mg (0.281 mmol, 90%) of the title compound as a tan solid. The product contained 2 wt % of THF.

(79) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 7.40 (s, 1H), 7.35 (s, 1H), 7.17 (dd, J=2.3 Hz, 8.7 Hz, 1H), 7.04 (app d, J=9.1 Hz, 1H), 5.60 (sept, J=6.8 Hz, 1H), 4.54 (d, J=6.2 Hz, 1H), 3.94 (s, 3H), 3.45-3.35 (m, 4H), 3.04 (quint, J=7.0 Hz, 1H), 2.85 (d, J=12.0 Hz, 1H), 2.63 (quint, J=6.3 Hz, 1H), 2.39-1.91 (m, 18H), 1.81-1.60 (m, 12H), 1.42-1.19 (m, 13H), 0.99-0.82 (m, 4H), 0.78 (d, J=6.7 Hz, 3H). Resonances attributable to THF are observed at 3.76 and 1.83 ppm.

(80) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 157.1, 154.8, 154.6, 152.6, 151.7, 151.5, 137.1, 136.8, 125.9, 125.3, 124.6, 124.4, 119.3 (2 peaks), 115.4, 112.9, 112.8, 112.0 (2 peaks), 100.2, 99.9, 58.1, 54.7, 45.6, 44.8, 44.7, 42.0, 36.3, 36.2, 34.4, 31.7, 29.2, 26.0, 25.6, 25.5, 24.9, 24.6, 24.3 (2 peaks).

(81) .sup.31P NMR (162 MHz, CDCl.sub.3, ): 88.9

(82) .sup.19F NMR (376 MHz, CDCl.sub.3, ): 77.9 (s, 3F).

Example 4 (According to the Invention)

(83) Amination with BrettPhos Complexes

(84) ##STR00073##

(85) A dry Schlenk tube, equipped with a Teflon-coated magnetic stir bar and fitted with a rubber septum, is charged with 5.1 mg (0.003 mmol, 0.3 mol %) of [(allyl)Pd(BrettPhos)]OTf and 231 mg (2.41 mmol, 1.2 equiv) of NaOtBu. The tube is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. n-Butylamine (238 L, 2.41 mmol, 1.2 equiv), n-dodecane (GC standard; 91 L, 0.40 mmol, 0.2 equiv), and 4-chloroanisole (250 L, 2.04 mmol, 1.0 equiv) are added followed by 2 mL of anhydrous THF. The tube is placed in a preheated (80 C.) oil bath and stirred vigorously. The tube is then sealed. Aliquots are removed at certain time intervals and analyzed by gas chromatography to monitor conversion.

(86) The experiment was repeated exchanging [(allyl)Pd(BrettPhos)]OTf for [(crotyl)Pd(BrettPhos)]OTf, [(cinnamyl)Pd(BrettPhos)]OTf and a BrettPhos 3.sup.rd generation Buchwald palladacycle (illustrated below).

(87) ##STR00074##

(88) FIG. 11 shows the inhibitory effect of carbazole on the reaction rate. The reaction in which carbazole is released (3.sup.rd generation palladacycle) proceeds significantly more slowly (full conversion in 2 hours) than reactions in which carbazole is not generated (i.e. using [(allyl)Pd(BrettPhos)]OTf, [(crotyl)Pd(BrettPhos)]OTf and [(cinnamyl)Pd(BrettPhos)]OTf). The reaction catalysed by [(crotyl)Pd(BrettPhos)]OTf with 0.3 mol % of carbazole added exhibits a significantly reduced reaction rate in which the conversion profile closely matches that of the reaction using the 3.sup.rd generation palladacycle. The use of [(cinnamyl)Pd(BrettPhos)]OTf results in full conversion in only 5 minutes.

Example 5 (According to the Invention)

Arylation of Tert-Butylacetate with 4-Chloroanisole

(89) TABLE-US-00001 Precatalyst Relative GC Conversion* 3rd Gen. tBuXPhos (comparative) 98% [(crotyl)Pd(tBuXPhos)]OTf 90% [(cinnamyl)Pd(tBuXPhos)]OTf 93% *Uncorrected GC ratio of Product/SM*100%

(90) A dry Schlenk tube, equipped with a Teflon-coated magnetic stir bar and fitted with a rubber septum, is charged with the precatalyst (0.01 mmol, 1 mol %) and the tube is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. 4-Chloroanisole (1.00 mmol, 1.0 equiv) and tert-butylacetate (1.5 mmol, 1.5 equiv) are added followed by LiHMDS solution, 1.0 M in toluene (3.0 mmol, 3.0 equiv). The contents are stirred vigorously at ambient temperature for 30 minutes. The reaction mixture is then quenched by the addition of 5 mL of sat. NH.sub.4Cl, and then diluted with 5 mL of EtOAc. An aliquot is removed and analyzed by gas chromatography.

(91) The most active of the [(R-allyl)Pd(tBuXPhos)]OTf precatalysts (R=cinnamyl) compares very well with the 3.sup.rd generation palladacycle precatalyst in the arylation of ester enolates (both >90% conversion after 30 min at rt).

Example 6 (According to the Invention)

Arylation of Benzamide with 1-Chloro-2,5-Dimethoxybenzene

(92) ##STR00078##

(93) A dry Schlenk tube is charged with 7.8 mg (0.015 mmol, 1.5 mol %) of [(allyl)Pd(tBuBrettPhos)]OTf, 145 mg (1.20 mmol, 1.20 equiv) of benzamide, and 297 mg (1.40 mmol, 1.40 equiv) of powdered K.sub.3PO.sub.4. The tube is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. 1-Chloro-2,5-dimethoxybenzene (143 L, 1.00 mmol, 1.00 equiv) is added followed by 2 mL of anhydrous t-BuOH. The tube is placed in a preheated (110 C.) oil bath and the contents are stirred vigorously. The tube is then sealed and aged in the oil bath for 90 min. The tube is then removed from the oil bath and the contents are allowed to cool to ambient temperature. The reaction mixture is diluted with 5 mL EtOAc and 5 mL of H.sub.2O. The organic phase is removed and the aqueous is extracted two additional times with 5 mL portions of EtOAc. The organic extracts are combined, dried (MgSO.sub.4), filtered, and concentrated in vacuo. The residue is chromatographed on silica gel with 10% EtOAc/hexanes as the eluent to give 252 mg (0.98 mmol, 98%) of the N-benzoyl-2,5-dimethoxyaniline as a light orange viscous oil.

(94) In Pd-catalyzed amidation, the [(allyl)Pd(tBuBrettPhos)]OTf precatalyst gives a higher yield than the originally reported water preactivation method of catalyst generation, and compares well with the 3.sup.rd generation palladacycle precatalyst, giving a nearly quantitative yield of the aryl amide product. At higher temperatures, the [(allyl)Pd(tBuBrettPhos)]OTf precatalyst quickly and efficiently forms the active catalyst. Additionally, the reaction can be run with a significantly reduced catalyst loading of 0.1 mol % of [(allyl)Pd(tBuBrettPhos)]OTf, and 100% conversion/98% isolated yield is still obtained with a 16 hour reaction time.

Example 7 (According to the Invention)

Arylation of Primary Amines Catalysed by [(-Crotyl)Pd(BrettPhos)]OTfa

(95) ##STR00079##

(96) N-butyl-4-methoxyaniline, N-([1,1-biphenyl]-2-yl)benzo[d][1,3]dioxol-5-amine and (R)-6-methoxy-N-(1-phenylethyl)pyridin-2-amine are formed with fast reaction times (5-10 min) using primary aliphatic (for N-butyl-4-methoxyaniline), aromatic (for N-([1,1-biphenyl]-2-yl)benzo[d][1,3]dioxol-5-amine), and optically active -chiral (for (R)-6-methoxy-N-(1-phenylethyl)pyridin-2-amine) amines at 0.3 mol % catalyst loading. Notably, (R)-6-methoxy-N-(1-phenylethyl)pyridin-2-amine is formed with high stereochemical fidelity (99% stereoretention), as erosion of enantiopurity of a-chiral amines in Buchwald-Hartwig amination reactions can be problematic. Heterocyclic substrates which contain more than one nitrogen atom can also be efficiently coupled in good-high yields using [(-crotyl)Pd(BrettPhos)]OTf (i.e. N-(pyridin-3-yl)pyrazin-2-amine, N-(2,5-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridin-4-amine and N-(2-(thiophen-2-yl)ethyl)pyrimidin-5-amine) using slightly modified conditions. The similar yields of N-butyl-4-methoxyaniline are observed using [(-crotyl)Pd(BrettPhos)]OTf and [(-cinnamyl)Pd(BrettPhos)]OTf (96%) demonstrate the interchangeability of these complexes.

(97) General Procedure for the Primary Amination Reactions

(98) An oven dried Schlenk tube equipped with a Teflon-coated magnetic stir bar is charged with [(-crotyl)Pd(BrettPhos)]OTf (0.3-1.2 mol % as indicated), BrettPhos (0.3-1.2 mol % as indicated), aryl chloride (1.00 mmol, if solid), and NaOt-Bu (1.20 mmol). The tube is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. Dodecane (GC standard, 0.20 mmol), the amine (1.20 mmol), aryl chloride (1.00 mmol, if liquid), and anhydrous THF (2 mL) are added sequentially via syringe. The tube is placed in a preheated oil bath and stirred for the indicated time. The tube is then removed from the oil bath and allowed to cool to room temperature. The reaction mixture is diluted with 10 mL of EtOAc and filtered through a pad of Celite. The solution is concentrated in vacuo and the residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf.

N-butyl-4-methoxyaniline

(99) ##STR00080##

(100) According to the general procedure, a mixture of 4-chloroanisole (123 L, 1.00 mmol), n-butylamine (119 L, 1.20 mmol), NaOtBu (115 mg, 1.20 mmol), [(-crotyl)Pd(BrettPhos)]OTf (2.5 mg, 0.003 mmol), BrettPhos (1.6 mg, 0.003 mmol), and 2 mL THF are stirred at 80 C. for 10 minutes. The crude material is chromatographed on silica gel with a gradient of 0-5% EtOAc/hexanes as the eluent to give 171 mg (0.96 mmol, 96%) of N-butyl-4-methoxyaniline as a colorless oil. The spectral properties match those previously reported (Shankaraiaha, N.; Markandeya, N.; Srinivasulu, V.; Sreekanth, K.; Reddy, C. S.; Santos, L. S.; Kamal, A. J. Org. Chem. 2011, 76, 7017).

N-([1,1-biphenyl]-2-yl)benzo[d][1,3]dioxol-5-amine

(101) ##STR00081##

(102) According to the general procedure, a mixture of 5-chloro-1,3-benzodioxole (117 L, 1.00 mmol), 2-aminobiphenyl (203 mg, 1.20 mmol), NaOtBu (115 mg, 1.20 mmol), [(-crotyl)Pd(BrettPhos)]OTf (2.5 mg, 0.003 mmol), BrettPhos (1.6 mg, 0.003 mmol), and 2 mL THF are stirred at 80 C. for 10 minutes. The crude material is chromatographed on silica gel with a gradient of 0-5% EtOAc/hexanes as the eluent to give 272 mg (0.94 mmol, 94%) of N-([1,1-biphenyl]-2-yl)benzo[d][1,3]dioxol-5-amine as a colorless oil.

(103) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 7.53-7.43 (m, 4H), 7.42-7.34 (m, 1H), 7.28-7.15 (m, 3H), 7.01-6.90 (m, 1H), 6.74 (d, J=8.6 Hz, 1H), 6.69 (d, J=2.3 Hz, 1H), 6.53 (dd, J=2.3 Hz, 8.3 Hz, 1H), 5.93 (s, 2H), 5.51 (s, 1H).

(104) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 148.3, 143.1, 141.9, 139.2, 137.7, 130.9, 130.3, 129.5, 129.1, 128.5, 127.6, 120.1, 115.8, 113.6, 108.7, 103.2, 101.2.

(105) Anal. Calcd. for C.sub.19H.sub.15NO.sub.2: C, 78.87; H, 5.23; N, 4.84. Found: C, 78.91; H, 5.29; N, 4.79.

(R)-6-methoxy-N-(1-phenylethyl)pyridin-2-amine

(106) ##STR00082##

(107) According to the general procedure, a mixture of 2-chloro-6-methoxypyridine (119 L, 1.00 mmol), (R)-(+)--methylbenzylamine (98% ee, 153 L, 1.20 mmol), NaOtBu (115 mg, 1.20 mmol), [(-cinnamyl)Pd(BrettPhos)]OTf (2.7 mg, 0.003 mmol), BrettPhos (1.6 mg, 0.003 mmol), and 1 mL THF are stirred at 80 C. for 5 minutes. The crude material is chromatographed on silica gel with a gradient of 0-5% EtOAc/hexanes as the eluent to give 223 mg (0.98 mmol, 98%) of (R)-6-methoxy-N-(1-phenylethyl)pyridin-2-amine as a colorless oil. [].sub.D.sup.25=38.2 (c. 1.03 CHCl.sub.3). The enantiomeric excess is measured to be 97% by chiral HPLC analysis (Chiracel OD-H column, 5% IPA/Hexanes, 1 mL/min, 254 nm). Racemic material is prepared in an identical experiment using racemic -methylbenzylamine.

(108) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 7.41-7.29 (m, 4H), 7.28-7.19 (m, 2H), 6.00 (d, J=8.0 Hz, 1H), 5.77 (d, J=8.1 Hz, 1H), 4.89-4.63 (m, 2H), 3.81 (s, 3H), 1.54 (d, J=7.2 Hz, 3H).

(109) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 163.6, 157.0, 145.2, 140.1, 128.7, 127.0, 126.0, 98.2, 97.9, 53.2, 52.1, 24.4.

(110) Anal. Calcd. for C.sub.14H.sub.16N.sub.2O: C, 73.66; H, 7.06. Found: C, 73.96; H, 6.97.

N-(pyridin-3-yl)pyrazin-2-amine

(111) ##STR00083##

(112) The general procedure is followed with the following modifications: A mixture of 3-chloropyridine (95 L, 1.00 mmol), 2-aminopyrazine (114 mg, 1.20 mmol), K.sub.2CO.sub.3 (194 mg, 1.40 mmol), [(-crotyl)Pd(BrettPhos)]OTf (2.5 mg, 0.003 mmol), BrettPhos (1.6 mg, 0.003 mmol), and 2 mL t-AmOH are stirred at 110 C. for 2 hours. The crude material is chromatographed on silica gel with a gradient of 0-5% MeOH/CH.sub.2Cl.sub.2 as the eluent to give 170 mg (0.99 mmol, 99%) of N-(pyridin-3-yl)pyrazin-2-amine as a white solid. The spectral properties match those previously reported (Fors, B. P.; Davis, N. R.; Buchwald, S. L. J. Am. Chem. Soc. 2009, 131, 5766).

N-(2,5-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridin-4-amine

(113) ##STR00084##

(114) An oven dried Schlenk tube equipped with a Teflon-coated magnetic stir bar is charged with [(-crotyl)Pd(BrettPhos)]OTf (8.5 mg, 1.2 mol), and 4-chloro-7-azaindole (153 mg, 1.00 mmol). The tube is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. 2,5-Dimethylaniline (150 L, 1.20 mmol) and 2.4 mL of LiHMDS solution in THF (2.4 mmol) are added sequentially via syringe. The tube is placed in a preheated oil bath (65 C.) and stirred for 4 hours. The tube is then removed from the oil bath and allowed to cool to room temperature, and 2 mL of 1M HCl (aq) is added followed by 15 mL EtOAc. The contents of the tube are then poured into a separatory funnel containing 20 mL of sat. NaHCO.sub.3. The aqueous is extracted with EtOAc (315 mL), and the combined extracts are washed with brine, dried over anhydrous MgSO.sub.4, concentrated in vacuo, and the residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf using a gradient of 0-10% MeOH/CH.sub.2Cl.sub.2 as the eluent to give 223 mg (0.94 mmol, 94%) of N-(2,5-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridin-4-amine as a light brown solid.

(115) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 12.2 (br, s, 1H), 8.10 (d, J=5.1 Hz, 1H), 7.37-7.11 (m, 3H), 6.99 (d, J=7.4 Hz, 1H), 6.42 (d, J=5.7 Hz, 1H), 6.38 (d, J=2.5 Hz, 1H), 6.08 (s, 1H), 2.36 (s, 3H), 2.27 (s, 3H).

(116) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 150.2, 145.7, 143.9, 138.3, 136.7, 131.0, 129.6, 126.1, 125.3, 122.4, 108.8, 99.3, 96.9, 21.1, 17.6.

(117) HRMS (ESI) m/z [M+H].sup.+ Calcd. for C.sub.15H.sub.16N.sub.3: 238.1344. Found: 238.1341.

N-(2-(thiophen-2-yl)ethyl)pyrimidin-5-amine

(118) ##STR00085##

(119) The general procedure was followed with the following modifications: A mixture of 5-bromopyrimidine (159 mg, 1.00 mmol), 2-thiophenemethylamine (140 L, 1.20 mmol), K.sub.2CO.sub.3 (194 mg, 1.40 mmol), [(-crotyl)Pd(BrettPhos)]OTf (10.2 mg, 0.012 mmol), BrettPhos (6.4 mg, 0.012 mmol), and 2 mL t-AmOH are stirred at 110 C. for 19 hours. The crude material is chromatographed on silica gel with a gradient of 25-75% EtOAc/hexanes as the eluent to give 152 mg (0.74 mmol, 74%) of N-(2-(thiophen-2-yl)ethyl)pyrimidin-5-amine as an off-white solid.

(120) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 8.60 (s, 1H), 8.10 (s, 2H), 7.19 (dd, J=1.2 Hz, 3.2 Hz, 1H), 6.97 (dd, J=7.4 Hz, 5.3 Hz, 1H), 6.89-6.83 (m, 1H), 3.89 (br s, 1H), 3.47 (q, J=6.5 Hz, 2H), 3.16 (app t, J=6.5 Hz, 2H).

(121) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 148.9, 141.5, 141.2, 140.7, 127.3, 125.8, 124.5, 44.4, 29.5.

(122) Anal. Calcd. for C.sub.10H.sub.11N.sub.3S: C, 58.51; H, 5.40; N, 20.47. Found: C, 58.28; H, 5.43; N, 20.42.

Example 8 (According to the Invention)

(123) ##STR00086## ##STR00087##

(124) The tBuBrettPhos-based catalyst [(-allyl)Pd(tBuBrettPhos)]OTf shows excellent reactivity in challenging CN cross-coupling reactions. The results are summarized in the table above. The arylation of primary amides are highly efficient giving aryl amide products generally with high yields using 1.0 mol % of [(-allyl)Pd(tBuBrettPhos)]OTf. The exception is the synthesis of N-(6-methoxypyridazin-3-yl)cyclopropanecarboxamide, which still gives the product in 68% yield. Notably, in the reaction to form N-(2,5-dimethoxyphenyl)benzamide, the catalyst loading could be lowered to 0.1 mol % with a longer reaction time without a deleterious effect on yield. Additionally, cyclic secondary amides as well as a cyclic oxazolidinone prove to be excellent substrates if the catalyst loading is increased to 1.5 mol %, as 1-(4-methoxyphenyl)pyrrolidin-2-one, 3-(4-(trifluoromethoxy)phenyl)oxazolidin-2-one and (S)-4-(4-benzyl-2-oxooxazolidin-3-yl)benzonitrile are all formed in 95% yields. With [(-allyl)Pd(tBuBrettPhos)]OTf, 2-aminothiazole is efficiently coupled with 4-bromoanisole to produce N-(4-methoxyphenyl)thiazol-2-amine in 85% yield in the absence of acetate.

(125) General Procedure for the Arylation Reactions of Primary Amides

(126) An oven dried Schlenk tube equipped with a Teflon-coated magnetic stir bar is charged with [(-allyl)Pd(tBuBrettPhos)]OTf (7.8 mg, 0.01 mmol, 1 mol %), aryl chloride (1.00 mmol, if solid), amide (1.20 mmol), and K.sub.3PO.sub.4 (297 mg, 1.40 mmol). The tube is capped with a rubber septum and is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. The aryl chloride (1.00 mmol, if liquid), and anhydrous tBuOH (2 mL) are added sequentially via syringe. The tube is placed in a preheated oil bath (110 C.), sealed, and stirred for 1.5 hours unless otherwise indicated. The tube is then removed from the oil bath and allowed to cool to room temperature. H.sub.2O (5 mL) was added, and the aqueous phase is extracted with EtOAc (35 mL). The organic extracts are combined, dried over anhydrous MgSO.sub.4, filtered, and concentrated in vacuo. The residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf.

N-(2,5-dimethoxyphenyl)benzamide

(127) ##STR00088##

(128) According to the general procedure, a mixture of 2-chloro-1,4-dimethoxybenzene (143 mL, 1.00 mmol), benzamide (145 mg, 1.20 mmol), K.sub.3PO.sub.4 (297 mg, 1.40 mmol), [(-allyl)Pd(tBuBrettPhos)]OTf (7.8 mg, 0.01 mmol), and 2 mL of anhydrous tBuOH are stirred at 110 C. for 1.5 hours. The crude material is chromatographed on silica gel with 10% EtOAc/hexanes as the eluent to give 252 mg (0.98 mmol, 96%) of N-(2,5-dimethoxyphenyl)benzamide as a near-colorless oil. The spectroscopic properties match those previously reported (Fors, B. P. Dooleweerdt, K.; Zeng, Q.; Buchwald, S. L. Tetrahedron 2009, 65, 6576).

(129) A similar experiment using 0.8 mg of [(p-allyl)Pd(tBuBrettPhos)]OTf (0.001 mmol, 0.1 mol %) and a 16 hour stir time gives 251 mg (0.98 mmol, 98%) of N-(2,5-dimethoxyphenyl)benzamide as a colorless oil.

N-(6-methoxypyridazin-3-yl)cyclopropanecarboxamide

(130) ##STR00089##

(131) According to the general procedure, a mixture of 3-chloro-6-methoxypyridazine (145 mg, 1.00 mmol), cyclopropanecarboxamide (102 mg, 1.20 mmol), K.sub.3PO.sub.4 (297 mg, 1.40 mmol), [(-allyl)Pd(tBuBrettPhos)]OTf (7.8 mg, 0.01 mmol), and 2 mL of anhydrous tBuOH are stirred at 110 C. for 2 hours. The crude material is chromatographed on silica gel with a gradient of 0-2.5% MeOH/CH.sub.2Cl.sub.2 as the eluent to give 132 mg (0.68 mmol, 68%) of N-(6-methoxypyridazin-3-yl)cyclopropanecarboxamide as a white solid.

(132) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 11.2 (br s, 1H), 8.54 (d, J=8.5 Hz, 1H), 7.02 (d, J=8.5 Hz, 1H), 3.98 (s, 3H), 2.57-2.46 (m, 1H), 1.14-1.06 (m, 2H), 0.93-0.84 (m, 2H).

(133) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 174.0, 162.4, 152.9, 123.8, 119.8, 54.4, 15.5, 8.79.

(134) Anal. Calcd. for C.sub.9H.sub.11N.sub.3O.sub.2: C, 55.95; H, 5.74; N, 21.75. Found: C, 56.18; H, 5.76; N, 21.70.

N-(quinolin-6-yl)acetamide

(135) ##STR00090##

(136) According to the general procedure, a mixture of 6-chloroquinoline (164 mg, 1.00 mmol), acetamide (71 mg, 1.20 mmol), K.sub.3PO.sub.4 (297 mg, 1.40 mmol), [(-allyl)Pd(tBuBrettPhos)]OTf (7.8 mg, 0.01 mmol), and 2 mL of anhydrous tBuOH are stirred at 110 C. for 1.5 hours. The crude material is chromatographed on silica gel with a gradient of 0-4% MeOH/CH.sub.2Cl.sub.2 as the eluent to give 132 mg (0.95 mmol, 95%) of N-(quinolin-6-yl)acetamide as a pale yellow solid.

(137) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 8.86-8.64 (m, 2H), 8.38 (s, 1H), 8.06 (d, J=7.7 Hz, 1H), 7.97 (d, J=9.5 Hz, 1H), 7.59 (dd, J=2.5 Hz, 9.1 Hz, 1H), 7.34 (dd, J=3.9 Hz, 8.6 Hz, 1H), 0.88 (s, 3H).

(138) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 169.3, 149.2, 145.4, 136.4, 136.2, 129.8, 129.0, 123.5, 121.7, 116.3, 24.7.

(139) Anal. Calcd. for C.sub.11H.sub.10N.sub.2O: C, 70.95; H, 5.41; N, 15.04. Found: C, 70.66; H, 5.51; N, 14.94.

N-(2-methylbenzo[d]thiazol-5-yl)-2-(pyridin-2-yl)acetamide

(140) ##STR00091##

(141) According to the general procedure, a mixture of 5-chloro-2-methylbenzothiazole (184 mg, 1.00 mmol), 2-(pyridine-2-yl)acetamide (143 mg, 1.20 mmol), K.sub.3PO.sub.4 (297 mg, 1.40 mmol), [(-allyl)Pd(tBuBrettPhos)]OTf (7.8 mg, 0.01 mmol), and 2 mL of anhydrous tBuOH are stirred at 110 C. for 1.5 hours. The crude material is chromatographed on silica gel with a gradient of 0-2% MeOH/CH.sub.2Cl.sub.2 as the eluent to give 279 mg (0.99 mmol, 99%) of N-(2-methylbenzo[d]thiazol-5-yl)-2-(pyridin-2-yl)acetamide as a pale yellow-green solid.

(142) .sup.1H NMR (400 MHz, DMSO-d.sub.6, ): 10.4 (br s, 1H), 8.51 (d, J=4.6 Hz, 1H), 8.32 (d, J=1.8 Hz, 1H), 7.91 (d, J=8.5 Hz, 1H), 7.76 (td, J=1.5 Hz, 7.4 Hz, 1H), 7.57 (dd, J=1.5 Hz, 8.5 Hz, 1H), 7.42 (d, J=7.5 Hz, 1H), 7.27 (dd, J=4.9 Hz, 7.4 Hz, 1H), 3.90 (s, 2H), 2.76 (s, 3H).

(143) .sup.13C NMR (100 MHz, DMSO-d.sub.6, ): 168.3, 167.9, 156.0, 153.5, 149.0, 137.6, 136.5, 129.5, 124.0, 121.9, 121.8, 117.0, 111.9, 45.9, 19.8.

(144) HRMS (ESI) m/z [M+H].sup.+ Calcd. for C.sub.15H.sub.14N.sub.3OS: 284.0858. Found: 284.0861.

N-(benzo[d][1,3]dioxol-5-yl)nicotinamide

(145) ##STR00092##

(146) According to the general procedure, a mixture of 6-chloroquinoline (164 mg, 1.00 mmol), acetamide (71 mg, 1.20 mmol), K.sub.3PO.sub.4 (297 mg, 1.40 mmol), [(-allyl)Pd(tBuBrettPhos)]OTf (7.8 mg, 0.01 mmol), and 2 mL of anhydrous tBuOH are stirred at 110 C. for 1.5 hours. The crude material is chromatographed on silica gel with a gradient of 0-4% MeOH/CH.sub.2Cl.sub.2 as the eluent to give 132 mg (0.95 mmol, 95%) of N-(benzo[d][1,3]dioxol-5-yl)nicotinamide as a pale yellow solid.

(147) .sup.1H NMR (400 MHz, DMSO-d.sub.6, ): 10.3 (br s, 1H), 9.08 (d, J=1.7 Hz, 1H), 8.75 (dd, J=1.6 Hz, 4.9 Hz, 1H), 8.26 (td, J=1.9 Hz, 8.1 Hz, 1H), 7.44 (dd, J=4.7 Hz, 7.9 Hz, 1H), 7.43 (d, J=2.0 Hz, 1H), 7.18 (dd, J=2.0 Hz, 8.4 Hz, 1H), 6.91 (d, J=8.4 Hz, 1H), 6.02 (s, 2H).

(148) .sup.13C NMR (100 MHz, DMSO-d.sub.6, ): 163.7, 152.0, 148.6, 147.0, 143.5, 135.3, 133.1, 130.6, 123.5, 113.4, 108.0, 102.5, 101.1.

(149) Anal. Calcd. for C.sub.13H.sub.10N.sub.2O.sub.3: C, 64.46; H, 4.16; N, 11.56. Found: C, 64.60; H, 4.37; N, 11.16.

(150) General Procedure for the Arylation Reactions of Cyclic Amide/Oxazolidinones

(151) An oven dried Schlenk tube equipped with a Teflon-coated magnetic stir bar is charged with [(-allyl)Pd(tBuBrettPhos)]OTf (11.7 mg, 0.015 mmol, 1.5 mol %), aryl chloride (1.00 mmol, if solid), amide/oxazolidinone (1.20 mmol, if solid), and K.sub.3PO.sub.4 (297 mg, 1.40 mmol). The tube is capped with a rubber septum and is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. The amide (1.20 mmol, if liquid) aryl chloride (1.00 mmol, if liquid), and anhydrous tBuOH (2 mL) are added sequentially via syringe. The tube is placed in a preheated oil bath (110 C.), sealed, and stirred for 3 hours. The tube is then removed from the oil bath and allowed to cool to room temperature. H.sub.2O (5 mL) was added, and the aqueous phase is extracted with EtOAc (35 mL). The organic extracts are combined, dried over anhydrous MgSO.sub.4, filtered, and concentrated in vacuo. The residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf.

1-(4-methoxyphenyl)pyrrolidin-2-one

(152) ##STR00093##

(153) According to the general procedure, a mixture of 4-chloroanisole (123 mL, 1.00 mmol), 2-pyrrolidinone (91 mL, 1.20 mmol), K.sub.3PO.sub.4 (297 mg, 1.40 mmol), [(-allyl)Pd(tBuBrettPhos)]OTf (11.7 mg, 0.015 mmol), and 2 mL of anhydrous tBuOH are stirred at 110 C. for 3 hours. The crude material is chromatographed on silica gel with a gradient of 40-100% EtOAc/hexanes as the eluent to give 183 mg (0.96 mmol, 96%) of 1-(4-methoxyphenyl)pyrrolidin-2-one as a white solid. The spectroscopic properties match those previously reported (Easton, C. J.; Pitt, M. J.; Ward, C. M. Tetrahedron 1995, 51, 12781).

3-(4-(trifluoromethoxy)phenyl)oxazolidin-2-one

(154) ##STR00094##

(155) According to the general procedure, a mixture of 1-chloro-4-trifluoromethoxybenzene (144 mL, 1.00 mmol), 2-oxazolidinone (105 mg, 1.20 mmol), K.sub.3PO.sub.4 (297 mg, 1.40 mmol), [(-allyl)Pd(tBuBrettPhos)]OTf (11.7 mg, 0.015 mmol), and 2 mL of anhydrous tBuOH are stirred at 110 C. for 3 hours. The crude material is chromatographed on silica gel with a gradient of 0-40% EtOAc/hexanes as the eluent to give 247 mg (1.00 mmol, 100%) of 3-(4-(trifluoromethoxy)phenyl)oxazolidin-2-one as a white solid.

(156) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 7.55 (app d, J=9.5 Hz, 2H), 7.20 (app d, J=8.8 Hz, 2H), 4.51-4.40 (m, 2H), 4.07-3.98 (m, 2H).

(157) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 155.3, 145.2, 137.1, 121.8, 120.6 (q, J.sub.C-F=256 Hz), 119.4, 61.4, 45.2.

(158) HRMS (ESI) m/z [M+H].sup.+ Calcd. for C.sub.10H.sub.9F.sub.3NO.sub.3: 248.0535. Found: 248.0537.

(S)-4-(4-benzyl-2-oxooxazolidin-3-yl)benzonitrile

(159) ##STR00095##

(160) According to the general procedure, a mixture of 4-chlorobenzonitrile (138 mg, 1.00 mmol), (S)-()-4-benzyl-2-oxazolidinone (186 mg, 1.20 mmol), K.sub.3PO.sub.4 (297 mg, 1.40 mmol), [(-allyl)Pd(tBuBrettPhos)]OTf (11.7 mg, 0.015 mmol), and 2 mL of anhydrous tBuOH are stirred at 110 C. for 3 hours. The crude material is chromatographed on silica gel with a gradient of 0-40% EtOAc/hexanes as the eluent to give 265 mg (0.95 mmol, 95%) of (S)-4-(4-benzyl-2-oxooxazolidin-3-yl)benzonitrile as a brown solid. The spectroscopic properties match those previously reported (Ghosh, A.; Sieser, J. E.; Riou, M.; Cai, W.; Rivera-Ruiz, L. Org. Lett. 2003, 5, 2207).

N-(4-methoxyphenyl)thiazol-2-amine

(161) ##STR00096##

(162) An oven dried Schlenk tube equipped with a Teflon-coated magnetic stir bar is charged with [(-allyl)Pd(tBuBrettPhos)]OTf (11.7 mg, 0.015 mmol, 1.5 mol %), 2-aminothiazole (100 mg, 1.00 mmol), and K.sub.2CO.sub.3 (194 mg, 1.40 mmol). The tube is capped with a rubber septum and is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. 4-Bromoanisole (125 mL, 1.00 mmol) and anhydrous tBuOH (4 mL) are added sequentially via syringe. The tube is placed in a preheated oil bath (110 C.), sealed, and stirred for 3 hours. The tube is then removed from the oil bath and diluted with 10 mL of EtOAc and H.sub.2O (5 mL). The aqueous phase is extracted (35 mL of EtOAc). The combined extracts are washed with brine (5 mL), dried over anhydrous MgSO.sub.4, filtered, and concentrated in vacuo. The residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf with a gradient of 0-3% MeOH/CH.sub.2Cl.sub.2 as the eluent to give 176 mg (0.85 mmol, 85%) of N-(4-methoxyphenyl)thiazol-2-amine as a tan solid. The spectroscopic properties match those previously reported (McGowan, M. A.; Henderson, J. L.; Buchwald, S. L. Org. Lett. 2012, 14, 1432).

Example 9 (According to the Invention)

(163) Coupling Reactions Using Allylpalladium Precatalysts

(164) Several cationic complexes of the present invention are evaluated to assess their efficiency in a wider scope of cross-coupling reactions. These include cross-coupling reactions involving sulphonamides, alcohols and indoles.

(165) ##STR00097##
General Procedure for the Sulfonamidation Reactions

(166) An oven dried threaded 2 dram, 1760 mm reaction vial equipped with a Teflon-coated magnetic stir bar is charged with [(-allyl)Pd(tBuXPhos)]OTf (7.2 mg, 0.01 mmol, 1 mol %), aryl halide (1.20 mmol, if solid), sulfonamide (1.00 mmol), and K.sub.3PO.sub.4 (318 mg, 1.50 mmol). The vial is capped with a polypropylene cap with PTFE-faced silicone septum and is evacuated and backfilled with nitrogen through a needle. This evacuation/backfill cycle is repeated two additional times. Anhydrous 2-methyl-2-butanol (4 mL) and the aryl halide (1.20 mmol, if liquid) are added sequentially via syringe. The nitrogen needle is removed and the vial is placed on a preheated aluminum block (110 C.) and stirred for 3 hours. The vial is then removed from the heating block and allowed to cool to room temperature. Saturated ammonium chloride (10 mL) is added, and the aqueous phase is extracted with EtOAc (310 mL). The organic extracts are combined, dried over anhydrous MgSO.sub.4, filtered, and concentrated in vacuo. The residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf.

4-methyl-N-(pyrazin-2-yl)benzenesulfonamide

(167) ##STR00098##

(168) According to the general procedure, a mixture of 2-chloropyrazine (107 L, 1.20 mmol), p-toluenesulfonamide (171 mg, 1.00 mmol), K.sub.3PO.sub.4 (318 mg, 1.50 mmol), [(-allyl)Pd(tBuXPhos)]OTf (7.2 mg, 0.01 mmol), and 4 mL of anhydrous 2-methyl-2-butanol are stirred at 110 C. for 3 hours. The crude material is chromatographed on silica gel with a gradient of 0-100% EtOAc/hexanes as the eluent to give 152 mg (0.61 mmol, 61%) of 4-methyl-N-(pyrazin-2-yl)benzenesulfonamide as a white solid. The spectroscopic properties match those previously reported (Baffoe, J.; Hoe, M. Y.; Tour, B. B. Org. Lett. 2010, 12, 1532).

N-(isoquinolin-5-yl)methanesulfonamide

(169) ##STR00099##

(170) According to the general procedure, a mixture of 5-bromoisoquinoline (250 mg, 1.20 mmol), methanesulfonamide (95 mg, 1.00 mmol), K.sub.3PO.sub.4 (318 mg, 1.50 mmol), [(-allyl)Pd(tBuXPhos)]OTf (7.2 mg, 0.01 mmol), and 4 mL of anhydrous 2-methyl-2-butanol are stirred at 110 C. for 3 hours. The crude material is chromatographed on silica gel with a gradient of 0-5% MeOH/CH.sub.2Cl.sub.2 as the eluent to give 194 mg (0.87 mmol, 87%) of N-(isoquinolin-5-yl)methanesulfonamide as an off-white solid.

(171) .sup.1H NMR (400 MHz, DMSO-d.sub.6, ): 9.92 (s, 1H), 9.34 (s, 1H), 8.58 (app d, J=5.9 Hz, 1H), 8.12 (app d, J=5.9 Hz, 1H), 8.03 (app d, J=8.1 Hz, 1H), 7.78 (app d, J=7.4 Hz, 1H), 7.69 (app t, J=7.9 Hz, 1H), 3.06 (s, 3H).

(172) .sup.13C NMR (100 MHz, DMSO-d.sub.6, ): 152.4, 143.1, 132.3, 131.7, 129.0, 127.4, 126.6, 125.9, 116.0, 39.92.

(173) Anal. Calcd. for C.sub.10H.sub.10N.sub.2O.sub.2S: C, 54.04; H, 4.54; N, 12.60. Found: C, 54.05; H, 4.26; N, 12.38.

N-(6-methoxypyridin-2-yl)cyclopropanesulfonamide

(174) ##STR00100##

(175) According to the general procedure, a mixture of 2-chloro-6-methoxypyridine (143 L, 1.20 mmol), cyclopropanesulfonamide (121 mg, 1.00 mmol), K.sub.3PO.sub.4 (318 mg, 1.50 mmol), [(-allyl)Pd(tBuXPhos)]OTf (7.2 mg, 0.01 mmol), and 4 mL of anhydrous 2-methyl-2-butanol are stirred at 110 C. for 3 hours. The crude material is chromatographed on silica gel with a gradient of 0-40% EtOAc/hexanes as the eluent to give 207 mg (0.90 mmol, 90%) of N-(6-methoxypyridin-2-yl)cyclopropanesulfonamide as a white solid.

(176) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 7.52 (t, J=7.9 Hz, 1H), 7.00 (bs, 1H), 6.79 (d, J=7.8 Hz, 1H), 6.45 (d, J=8.1 Hz, 1H), 3.86 (s, 3H), 2.79-2.73 (m, 1H), 1.30-1.26 (m, 2H), 1.03-0.98 (m, 2H).

(177) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 163.7, 149.1, 141.0, 105.8, 103.6, 53.9, 31.3, 6.1.

(178) Anal. Calcd. for C.sub.9H.sub.12N.sub.2O.sub.3S: C, 47.36; H, 5.30; N, 12.27. Found: C, 47.42; H, 5.27; N, 12.19.

(179) General Procedure for the CO Coupling Reactions

(180) An oven dried threaded 2 dram, 1760 mm reaction vial equipped with a Teflon-coated magnetic stir bar is charged with [(-allyl)Pd(RockPhos)]OTf (7.7 mg, 0.01 mmol, 1 mol %), aryl halide (1.00 mmol, if solid), and K.sub.3PO.sub.4 (318 mg, 1.50 mmol). The vial is capped with a polypropylene cap with PTFE-faced silicone septum and is evacuated and backfilled with nitrogen through a needle. This evacuation/backfill cycle is repeated two additional times. Anhydrous toluene (1 mL), the aryl halide (1.00 mmol, if liquid), and alcohol (1.50 mmol) are added sequentially via syringe. The nitrogen needle is removed and the vial is placed on a preheated aluminum block (100 C.) and stirred for 16 hours. The vial is then removed from the heating block and allowed to cool to room temperature. The reaction mixture is diluted with 10 mL of EtOAc, filtered through a pad of Celite, and concentrated in vacuo. The residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf.

5-(furan-2-ylmethoxy)pyrimidine

(181) ##STR00101##

(182) According to the general procedure, a mixture of 5-bromopyrimidine (159 mg, 1.00 mmol), furfuryl alcohol (130 L, 1.50 mmol), K.sub.3PO.sub.4 (318 mg, 1.50 mmol), [(-allyl)Pd(RockPhos)]OTf (7.7 mg, 0.01 mmol), and 1 mL of anhydrous toluene are stirred at 100 C. for 16 hours. The crude material is chromatographed on silica gel with a gradient of 0-50% EtOAc/hexanes as the eluent to give 141 mg (0.80 mmol, 80%) of 5-(furan-2-ylmethoxy)pyrimidine as a yellow oil.

(183) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 8.83 (s, 1H), 8.46 (s, 2H), 7.43 (s, 1H), 6.45 (app d, J=2.9 Hz, 1H), 6.37-6.36 (m, 1H), 5.08 (s, 2H).

(184) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 152.6, 152.1, 148.8, 144.4, 143.9, 111.4, 110.9, 63.0.

(185) HRMS (ESI) m/z: [M+H].sup.+ Calcd. for C.sub.9H.sub.9N.sub.2O.sub.2: 177.0664. Found: 177.0661.

3-(2-(thiophen-2-yl)ethoxy)pyridine

(186) ##STR00102##

(187) According to the general procedure, a mixture of 3-chloropyridine (94 L, 1.00 mmol), 2-thiopheneethanol (167 L, 1.50 mmol), K.sub.3PO.sub.4 (318 mg, 1.50 mmol), [(-allyl)Pd(RockPhos)]OTf (7.7 mg, 0.01 mmol), and 1 mL of anhydrous toluene are stirred at 100 C. for 16 hours. The crude material is chromatographed on silica gel with a gradient of 0-100% EtOAc/hexanes as the eluent to give 170 mg (0.83 mmol, 83%) of 3-(2-(thiophen-2-yl)ethoxy)pyridine as a colorless oil.

(188) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 8.31 (s, 1H), 8.20 (s, 1H), 7.18-7.15 (m, 3H), 6.95-6.90 (m, 2H), 4.21 (t, J=6.7 Hz, 2H), 3.31 (t, J=6.7 Hz, 2H).

(189) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 155.0, 142.6, 140.0, 138.3, 127.1, 125.9, 124.3, 124.0, 121.4, 68.9, 30.1.

(190) Anal. Calcd. for C.sub.11H.sub.11NOS: C, 64.36; H, 5.40; N, 6.82. Found: C, 64.31; H, 5.64; N, 6.91.

(191) Indole Arylation Reactions

1-(naphthalen-1-yl)-1H-indole

(192) ##STR00103##

(193) An oven dried threaded 2 dram, 1760 mm reaction vial equipped with a Teflon-coated magnetic stir bar is charged with [(-allyl)Pd(Bippyphos)]OTf (8.0 mg, 0.01 mmol, 2 mol %), BippyPhos (5.1 mg, 0.01 mmol, 2 mol %), indole (58.6 mg, 0.50 mmol), and NaOt-Bu (67.3 mg, 0.70 mmol). The vial is capped with a polypropylene cap with PTFE-faced silicone septa and is evacuated and backfilled with nitrogen through a needle. This evacuation/backfill cycle is repeated two additional times. Anhydrous toluene (2 mL) and 1-bromonaphthalene (70.0 L, 0.50 mmol) are added sequentially via syringe. The nitrogen needle is removed and the vial is placed on a preheated aluminum block (110 C.) and stirred for 16 hours. The tube is then removed from the heating block and allowed to cool to room temperature. The reaction mixture is diluted with 5 mL of EtOAc, filtered through a pad of Celite, and concentrated in vacuo. The residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf with a gradient of 0-5% EtOAc/hexanes as the eluent to give 109 mg (0.45 mmol, 89%) of 1-(naphthalen-1-yl)-1H-indole as a white solid. The spectroscopic properties match those previously reported (Diness, F.; Fairlie, D. P. Angew. Chem. Int. Ed. 2012, 51, 8012).

1-(6-methoxypyridin-2-yl)-2-phenyl-1H-indole

(194) ##STR00104##

(195) An oven dried threaded 2 dram, 1760 mm reaction vial equipped with a Teflon-coated magnetic stir bar is charged with [(-allyl)Pd(Bippyphos)]OTf (16 mg, 0.02 mmol, 2 mol %), BippyPhos (10 mg, 0.02 mmol, 2 mol %), 2-phenylindole (193 mg, 1.00 mmol), and NaOt-Bu (135 mg, 1.40 mmol). The vial is capped with a polypropylene cap with PTFE-faced silicone septum and is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. Anhydrous toluene (4 mL) and 2-chloro-6-methoxypyridine (119 L, 1.00 mmol) are added sequentially via syringe. The nitrogen needle is removed and the vial is placed on a preheated aluminum block (110 C.) and stirred for 16 hours. The tube is then removed from the heating block and allowed to cool to room temperature. The reaction mixture is diluted with 10 mL of EtOAc, filtered through a pad of Celite, and concentrated in vacuo. The residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf with a gradient of 0-5% EtOAc/hexanes as the eluent to give 293 mg (0.98 mmol, 98%) of 1-(6-methoxypyridin-2-yl)-2-phenyl-1H-indole as a colorless oil.

(196) .sup.1H NMR (400 MHz, CDCl.sub.3, ): 7.75 (d, J=7.8 Hz, 1H), 7.69 (d, J=7.8 Hz, 1H), 7.55 (t, J=7.8 Hz, 1H), 7.31-7.20 (m, 7H), 6.80 (s, 1H), 6.67-6.62 (m, 2H), 3.76 (s, 3H).

(197) .sup.13C NMR (100 MHz, CDCl.sub.3, ): 163.7, 149.6, 140.6, 140.1, 138.4, 133.5, 129.0, 128.9, 128.3, 127.5, 123.0, 121.5, 120.8, 113.6, 111.7, 108.6, 105.6, 53.8.