AIR-STABLE Ni(0)-OLEFIN COMPLEXES AND THEIR USE AS CATALYSTS OR PRECATALYSTS

Abstract

The present invention relates to air stable, binary Ni(0)-olefin complexes and their use in organic synthesis.

Claims

1. An air-stable Ni(R).sub.3—complex wherein Ni represents Ni(0) and R is the same or different and represents a trans-stilbene of the Formula (I): ##STR00027## wherein R.sup.1 to R.sup.10 are the same or different and are selected from H, Cl, Br, F, CN, C.sub.1 to C.sub.6 alkyl,. or C.sub.3 to C.sub.6 cycloalkyl, which alkyl or cycloalkyl are optionally substituted by one or more halogens, wherein R.sup.11 to R.sup.12 are the same or different and are selected from H, C.sub.1 to C.sub.6 alkyl, C.sub.3 to C.sub.6 cycloalkyl, —O—C.sub.1 to C.sub.6 alkyl, or —O—C.sub.3 to C.sub.6 cycloalkyl, with the proviso that at least one of R.sup.1 to R.sup.12 is not hydrogen.

2. An air-stable Ni(R).sub.3—complex according to claim 1, wherein Ni represents Ni(0), wherein R is the same or different and represents a trans-stilbene of the Formula (I); wherein in Formula (I), at least one of R.sup.1 to R.sup.5 and at least one of R.sup.6 to R.sup.10 are the same or different and are selected from Cl, Br, F, CN, C.sub.1 to C.sub.8 alkyl, or C.sub.3 to C.sub.6 cycloalkyl, which alkyl or cycloalkyl is optionally substituted by one or more halogens, and the others of R.sup.1 to R.sup.10 are hydrogen, and R.sup.11 to R.sup.12 are the same or different and are selected from H, C.sub.1 to C.sub.8 alkyl, C.sub.3 to C.sub.6 cycloalkyl, —O—C.sub.1 to C.sub.8 alkyl, or —O—C.sub.3 to C.sub.6 cycloalkyl.

3. An air-stable Ni(R).sub.3—complex according to claim 1, wherein Ni represents Ni(0), wherein R is the same or different and represents a trans-stilbene of the Formula (I); wherein in Formula (I), R.sup.3 and R.sup.8 are the same or different and are selected from C.sub.1 to C.sub.8 alkyl which is optionally substituted by one or more halogens, and the others of R.sup.1 to R.sup.10 are hydrogen, and R.sup.11 to R.sup.12 are the same or different and are selected from H, C.sub.1 to C.sub.6 alkyl, —O—C.sub.1 to C.sub.6 alkyl, C.sub.3 to C.sub.6 cycloalkyl or —O—C.sub.3 to C.sub.6 cycloalkyl.

4. An air-stable Ni(R).sub.3—complex according to claim 1, wherein Ni represents Ni(0), wherein R is the same or different and represents a trans-stilbene of the Formula (I); wherein in Formula (I), R.sup.3 and R.sup.8 are the same or different and are selected from C.sub.1 to C.sub.8 perfluoro alkyl and the others of R.sup.1 to R.sup.10 are hydrogen, and R.sup.11 to R.sup.12 may be the same or different and are selected from H, C.sub.1 to C.sub.6 alkyl, O—C.sub.1 to C.sub.6 alkyl, C.sub.3 to C.sub.6 cyclolkyl or —O—C.sub.3 to C.sub.6 cycloalkyl.

5. An air-stable Ni(R).sub.3—complex according to claim 1, wherein Ni represents Ni(0), wherein R is the same and represents a trans-stilbene of the Formula (I); wherein in Formula (I), R.sup.3 and R.sup.8 are each C.sub.1 to C.sub.8 perfluoro alkyl and the others of R.sup.1 to R.sup.10 and R.sup.11 to R.sup.12 are hydrogen.

6. An air-stable Ni(R).sub.3—complex according to claim 1, wherein Ni represents Ni(0), wherein R is the same and represents a trans-stilbene of the Formula (I); wherein in Formula (I), R.sup.3 and R.sup.8 are each —CF.sub.3, and the others of R.sup.1 to R.sup.10 and R.sup.H to R.sup.12 are hydrogen.

7. Process for preparing an air-stable Ni(R).sub.3—complex wherein Ni represents Ni(0) and R are the same or different and represents a trans-stilbene of the Formula (I): ##STR00028## wherein R.sup.1 to R.sup.10 are the same or different and are selected from H, Cl, Br, F, CN, C.sub.1 to C.sub.6 alkyl, or C.sub.3 to C.sub.6 cycloalkyl, which alkyl or cycloalkyl is optionally substituted by one or more halogens, wherein R.sup.11 to R.sup.12 are the same or different and are selected from H, C.sub.1 to C.sub.6 alkyl, C.sub.3 to C.sub.6 cycloalkyl, —O—C.sub.1 to C.sub.6 alkyl, or —O—C.sub.3 to C.sub.6 cycloalkyl, said process comprising reacting a Nickel (II) compound, selected from NiF.sub.2, NiCl.sub.2, NiBr.sub.2, NiI.sub.2, Ni(OTf).sub.2, Ni(BF.sub.4).sub.2, Ni(OTs).sub.2, Ni(glyme)Cl.sub.2, Ni(glyme)Br.sub.2, Ni(diglyme)Cl.sub.2, Ni(diglyme)Br.sub.2, Ni(NO.sub.3).sub.2, Ni(OR.sup.13).sub.2 (where R.sup.13 represents —C(O)—C.sub.1—C.sub.6-alkyl which is optionally substituted with one of more halogen), preferably Cl or F, Ni(acetyl acetonate).sub.2, Ni(Ac).sub.2, or mixtures thereof, is reacted with the trans-stilbene of Formula (I), preferably at least three equivalents, in the presence of an aluminum alkyl of the Formula Al(R.sup.14).sub.3, preferably at least two equivalents, wherein R.sup.14 may be the same or different and is selected from C.sub.1 to C.sub.6 alkyl or C.sub.3 to C.sub.6 cycloalkyl.

8. Process for preparing an air-stable Ni(R).sub.3—complex according to claim 7 wherein the aluminum alkyl of the Formula Al(R.sup.14).sub.3 is selected from Al(CH.sub.3).sub.3 or Al(C.sub.2H.sub.5).sub.3.

9. Process for preparing an air-stable Ni(R).sub.3—complex according to claim 7, wherein R represents a trans-stilbene of the Formula (I), wherein in Formula (I), at least one of R.sup.1 to R.sup.5 and at least one of R.sup.6 to R.sup.10 are the same or different and are selected from Cl, Br, F, CN, C.sub.1 to C.sub.8 alkyl, or C.sub.3 to C.sub.6 cycloalkyl, which alkyl or cycloalkyl is optionally substituted by one or more halogens, and the others of R.sup.1 to R.sup.10 are hydrogen, and R.sup.11 to R.sup.12 are the same or different and are selected from H, C.sub.1 to C.sub.8 alkyl, C.sub.3 to C.sub.6 cycloalkyl, —O—C.sub.1 to C.sub.8 alkyl, or —O—C.sub.3 to C.sub.6 cycloalkyl.

10. Method of using an air-stable Ni(R).sub.3 —complex according to claims 1 as catalyst or precatalyst in organic synthesis, wherein: Ni represents Ni(0) and R are the same or different and represents a trans-stilbene of the Formula (I): ##STR00029## R.sup.1 to R.sup.10 are the same or different and are selected from H, Cl, Br, F, CN, C.sub.1 to C.sub.6 alkyl, or C.sub.3 to C.sub.6 cycloalkyl, which may optionally be substituted by one or more halogens, R.sup.11 to R.sup.12 are the same or different and are selected from H, —O—C.sub.1 to C.sub.6 alkyl, C.sub.1 to C.sub.6 alkyl, or C.sub.3 to C.sub.6 cycloalkyl, optionally with the proviso that at least one of R.sup.1 to R.sup.12 is not hydrogen.

11. Method of using an air-stable Ni(R).sub.3—complex according to claim 1 as catalyst in organic synthesis.

12. An air-stable Ni(R).sub.3—complex according to claim 2, wherein at least one of R.sup.1 to R.sup.5 and at least one of R.sup.6 to R.sup.10 are the same or different and are selected from C.sub.1 to C.sub.8 alkyl which may optionally be branched and/or substituted by one or more halogens.

13. Process for preparing an air-stable Ni(R).sub.3 —complex according to claim 7, wherein the Nickel (II) compound is reacted with at least three equivalents of the trans-stilbene of Formula (I) in the presence of at least two equivalents of the aluminum alkyl of the Formula Al(R.sup.14).sub.3.

Description

THE FIGURES ILLUSTRATE

[0043] FIG. 1. a: State-of-the-art binary Ni(0) olefin complexes for Ni catalysis. [0044] b: Current strategies to circumvent the air-sensitivity issues related to Ni(0) species; [0045] c: The present Invention as exemplified by Ni(.sup.Fstb).sub.3: an air-stable 16-electron Ni(0)-olefin complex [0046] d: Six different inventive Ni(.sup.Xstb).sub.3complexes (1-6), each having a different aryl substituent(s) on each aryl core and their preparation and stability

[0047] FIG. 2 Synthesis of complexes 1 and 2: [0048] Reaction conditions: all-trans-Ni(CDT) (1.0 equiv.), trans-stilbene or trans-(4-trifluoromethylphenyl)stilbene (3.30 and 3.15 equiv. respectively) at −5° C. in THF or Et2O.

[0049] FIG. 3 Ligand exchange of complex 2 with different common ligands in catalysis: [0050] a) 2 (1.0 equiv.), dppf (1.0 equiv.) in THF at 25° C., quantitative; [0051] b) 2 (1.0 equiv.), bipy (1.0 equiv.) in THF at 25° C., quantitative; [0052] c) 2 (1.0 equiv.), PPh.sub.3 (2.0 equiv.) in THF at 25° C., quantitative; [0053] d) Slow crystallization of 2 in THF at −78° C. Ar=p-CF.sub.3-C.sub.6H.sub.4.

[0054] FIG. 4 Catalytic properties of 2 in a variety of Ni-catalyzed transformations. a. Suzuki cross-coupling; [0055] b. Cycloisomerization reaction; [0056] c. C-H activation; [0057] d. Buchwald-Hartwig C—N bond formation with alkylamines; [0058] e. Buchwald-Hartwig C—N bond formation with arylamines; [0059] f. C—O arylation of acetals; [0060] g. Ester formation through C—N bond activation of amides; [0061] h. Alkyl-alkyl cross-coupling; [0062] i. Negishi cross-coupling; [0063] j. C—SMe reduction with silanes.

[0064] FIG. 5 Complex 2 avoids traditional COD side-reactions.

[0065] FIG. 6 Illustrations of two industrially relevant transformations and coordination of catalyst 6.

[0066] As shown in FIG. 6A, the stability and facility of ligand exchange with other olefins is also demonstrated in two industrially relevant transformations which require Ni(COD).sub.2 in the state of art. As for example shown in FIG. 6A, the Ni-catalyzed isomerization of 2M3BN (2-methyl-3-butenenitrile (44)—in the presence of Ni(.sup.4-tBuStb).sub.3 (6) - to 3PN (3-pentenenitrile, (45), which is crucial in the efficient synthesis of adiponitrile from butadiene, this transformation proceeds under neat conditions with the aid of PPh.sub.3, and affords comparable levels of reactivity towards 45 (67%). Another process is the Ni-catalyzed SHOP (Shell Higher Olefin Process) (FIG. 6B), which enables the oligomerization of ethylene to obtain higher molecular weight α-olefins. Under un-optimized conditions and without pre-catalyst isolation, complex 6 together with the ligand mixture depicted in FIG. 6B, successfully catalyzed the formation of a mixture of a-olefins in high efficiency. These results highlight the potential of 6 in industrially relevant settings, thus providing an air- and temperature-stable alternative to current Ni(0) catalysts.

[0067] Although Ni(.sup.4-tBustb).sub.3 (6) might be regarded as an air-stable Ni(COD).sub.2 surrogate, the fundamental coordination chemistry of both complexes differ significantly. For example, when Ni(COD).sub.2 is mixed with 4.0 equiv. of PPh.sub.3, an inseparable mixture of Ni(PPh.sub.3).sub.4 and (PPh.sub.3).sub.2Ni(COD) is commonly obtained (FIG. 6C, top). On the other hand, when 6 is used instead, clean conversion to the 16-electron compound 45 is formed (FIG. 6C, bottom). These differences in coordination chemistry provide an orthogonal tool to existing strategies for the synthesis of well-defined L—Ni(0)-olefin complexes.

[0068] General Experimental Notes

[0069] Unless otherwise stated, all manipulations were performed using Schlenk techniques under dry argon in heatgun-dried glassware. Ni(.sup.Xstb).sub.3 were stored in a screw cap vial under air in the freezer (−18° C.) except for Ni(.sup.4-tBustb).sub.3, which was stored on the bench. All complexes were weight out in air. Anhydrous solvents were distilled from appropriate drying agents and were transferred under Argon: THF, Et.sub.2O (Mg/anthracene), CH.sub.2Cl.sub.2, CH.sub.3CN (CaH.sub.2), hexanes, toluene (Na/K), Et.sub.3N, DMA, 1,4-dioxane (MS), CPME, NMP and tAmOH were purchased in anhydrous grade and were stored over MS. Anhydrous K.sub.3PO.sub.4, NaOtBu and NaHMDS were stored in a Schlenk or in a glovebox. Flash column chromatography: Merck silica gel 60 (40-63 μm). MS (El): Finnigan MAT 8200 (70 eV). Accurate mass determinations: MAT 95 (Finnigan). NMR spectra were recorded using a Bruker Avance VIII-300 or Bruker Avance Ill HD 400 MHz spectrometer. .sup.1H NMR spectra were referenced to the residual protons of the deuterated solvent used. .sup.13C NMR spectra were referenced internally to the D-coupled .sup.13C resonances of the NMR solvent. Chemical shifts (δ) are given in ppm, relative to TMS (tetramethylsilane), and coupling constants (J) are provided in Hz. .sup.19F NMR spectra were referenced externally to the .sup.19F resonances of CFCl.sub.3. .sup.31P

[0070] NMR spectra were referenced externally to the .sup.31P resonances of H.sub.3PO.sub.4.

[0071] General procedure for the preparation of (E)-stilbenes

##STR00004##

[0072] The substituted benzaldehyde (1 equiv.) was added to THF (0.3 M) in a three necked round bottom flask equipped with a large stirring bar and a reflux condenser. The solution was cooled to −78° C. and TiCl.sub.4 (1.25 equiv.) was added dropwise. The reaction was allowed to warm to rt and stirred for 10 min. Zn powder (2.5 equiv.) was added in several portions over 2 min. The reaction was refluxed for 3 h and then allowed to cool to rt. Water (1.5×THF amount) was added, followed by HCl (0.1×THF amount, 3.sub.M). The reaction was stirred for 5 min. and transferred to a separation funnel. The aqueous layer was extracted with MTBE (2×double THF amount), the combined organic layers were washed with sat. aq. NaCl solution and dried over MgSO.sub.4. The solvent was evaporated under reduced pressure and the residue was subjected to column chromatography. The purified product was dried under high vacuum.

(E)-1,2-Bis(4-(trifluoromethyl)phenyl)ethane

[0073] ##STR00005##

[0074] Prepared according to the general procedure from 4-trifluormethylbenzaldehyde (11.0 mL, 14.0 g, 80.5 mmol), TiCl.sub.4 (11.0 mL, 19.0 g, 100.3 mmol, 1.25 equiv.) and Zn powder (13.0 g, 198 mmol, 2.5 equiv.). Column chromatography: gradient hexanes:MTBE (100:0 to 99:1).

[0075] Yield: 8.44 g, 26.7 mmol, 66%; colorless solid

(E)-1,2-Bis(4-(tert-butyl)phenyl)ethene

[0076] ##STR00006##

[0077] Prepared according to the general procedure from 4-(tert-butyl)benzaldehyde (10.20 ml, 9.86 g, 60.8 mmol, 1 equiv.), TiCl.sub.4 (20.0 mL, 34.6 g, 182.4 mmol, 3 equiv.) and Zn powder (29.8 g, 456 mmol, 7.5 equiv.). Column chromatography: gradient hexanes:MTBE (50:1 to 20:1). Spectroscopic data are in accordance with the literature.

[0078] Yield: 3.98 g, 13.6 mmol, 45%; colorless solid

(E)-1,2-Bis(4-fluorophenyl)ethane

[0079] ##STR00007##

[0080] Prepared according to the general procedure from 4-fluorbenzaldehyde (1.30 ml, 1.50 g, 12.09 mmol, 1 equiv.), TiCl.sub.4 (1.60 mL, 2.75 g, 14.50 mmol, 1.2 equiv.) and Zn powder (1.98 g, 30.22 mmol, 2.5 equiv.). Column chromatography: 99:1 (hexanes:MTBE). Spectroscopic data are in accordance with the literature.

[0081] Yield: 1.28 g, 5.91 mmol, 49%; colorless solid

(E)-1,2-Bis(3,5-dimethylphenyl)ethane

[0082] ##STR00008##

[0083] Prepared according to the general procedure from 3,5-Dimethylbenzaldehyde (5.01 ml, 5.00 g, 37.27 mmol, 1 equiv.), TiCl.sub.4 (4.90 mL, 8.48 g, 44.72 mmol, 1.2 equiv.) and Zn powder (6.10 g, 93.28 mmol, 2.5 equiv.). Column chromatography: 50:1 (hexanes:MTBE). Spectroscopic data are in accordance with the literature.

[0084] Yield: 2960 mg, 18.63 mmol, 67%; colorless solid

Synthesis of (E)-1,2-Di-p-tolylethene

[0085] ##STR00009##

[0086] 4-Methylstyrene (1.98 mL, 1.77 g, 15 mmol, 1 equiv.) and Grubbs generation II (9.4 mg, 0.015 mmol, 0.1 mol %) were dissolved in DCM (3 mL). The reaction was refluxed for 3 h, the solvent was evaporated under reduced pressure and the solids were purified by column chromatography (pure hexanes). Spectroscopic data are in accordance with the literature.

[0087] Yield: 1.1212 g, 5.38 mmol, 72%; colorless solid

[0088] Preparation of Ni(stb).sub.3 (1)

##STR00010##

[0089] A Schlenk tube was charged with Ni(CDT) (CDT=1,5,9-trans,trans,trans-cyclododecatriene) (794 mg, 3.60 mmol) via argon trousers and dissolved in THF (7 mL). The solution was filtered under argon into a Schlenk tube held at −78° C. The filter cake was washed with 3 mL of THF. A separate Schlenk tube was charged with trans-stilbene (2.13 g, 11.87 mmol, 3.30 equiv.) and subjected to one cycle of vacuum/argon. The ligand was suspended in THF (10 mL) and transferred as a suspension to the first Schlenk tube, followed by one wash (2 mL THF) to ensure quantitative transfer. The reaction was stirred at −78° C. for 10 min and was then placed in a cooling bath at −5° C. and stirred at that temperature for 12 h. An argon frit was cooled to −30° C. and the reaction was transferred into the frit. The mixture was allowed to cool down for 1 min and was then filtered with positive pressure of argon. The solid on the frit was dried by passing a flow of argon through the frit. The solid was then transferred to a Schlenk tube and dried further under high vacuum at room temperature to give 1 as an air stable brown-red solid (1.07 g, 1.66 mmol, 46%).

[0090] Preparation of Ni(.sup.4-CF3stb).sub.3 (2)

##STR00011##

[0091] A Schlenk tube was charged with Ni(CDT) (CDT=1,5,9-trans,trans,trans-cyclododecatriene) (610 mg, 2.76 mmol) via argon trousers and fresh Et2O (10 mL) was added at −78° C. to suspend the starting material. A separate Schlenk tube was charged with trans-pCF.sub.3-stilbene (2.28 g, 9.12 mmol, 3.15 equiv.) and subjected to one cycle of vacuum/argon. The ligand was suspended in Et.sub.2O (10 mL) and transferred as a suspension to the first Schlenk tube, followed by several washings (3+2+2 mL) to ensure quantitative transfer. The reaction was placed in a cooling bath at −5° C. and stirred at that temperature for 3 h. An argon frit was cooled to −30° C. and the reaction was transferred onto the frit. The reaction was allowed to cool down for 1 min and was then filtered with positive pressure of argon. The solid on the frit was washed with Et.sub.2O (3×2 mL) and dried by passing a flow of argon through the frit. The solid was then transferred to a Schlenk tube and dried further under high vacuum at room temperature to give 2 as an air stable red solid (1.93 g, 1.92 mmol, 70%). The catalyst was stored under air in a freezer.

[0092] Preparation of Ni(.sup.4-CF3stb).sub.3 from Ni(acac).sub.2

##STR00012##

[0093] A 100 mL Schlenk tube was charged with anhydrous Ni(acac).sub.2 (904.4 mg, 3.52 mmol) via argon trousers and (E)-1,2-bis(4-(trifluoromethyl)phenyl)ethane (3.50 g, 11.1 mmol, 3.14 equiv.). Diethyl ether (20 mL) was added and the solution was cooled to −20° C. AlEt3 (neat) (1.10 mL, 7.5 mmol, 2.1 equiv.) was dissolved in diethyl ether (5 mL). Then, this solution was added dropwise over 10 min to the Schlenk containing Ni(acac).sub.2 and stilbene ligand. The reaction was stirred at −20° C. for 1 hour and then cooled down in a dry-ice bath (−78° C.) for 10 minutes. The suspension was filtered over a cooled (−78° C.) argon frit, leaving the product on the frit. The solid was washed with diethyl ether (2×2 mL) and dried under high vacuum. Ni(.sup.Fstb).sub.3 was isolated in pure form as a red solid (2.17 g, 2.16 mmol, 61%). The other Ni(0)-complexes were prepared in line with the above process.

[0094] Catalytic Reactions

5-(Thiophen-3-yl)pyrimidine (13)

[0095] ##STR00013##

[0096] Ni(.sup.4-CF3stb).sub.3(2.0 mg, 0.002 mmol, 0.005 equiv.), 5-bromopyrimidine (64.5 mg, 0.406 mmol), thiophen-3-ylboronic acid (102.3 mg, 0.800 mmol, 2 equiv.), dppf (1.1 mg, 0.002 mmol, 0.005 equiv.) and anhydrous K.sub.3PO.sub.4 (135 mg, 0.64 mmol, 1.5 equiv.) were placed in a screw cap vial which was subsequently subjected to one cycle of vaccum/argon. 1,4-dioxane (1 mL) was added and the reaction was heated to 80° C. for 8 h. Water was added and the aqueous layer was extracted 3 times with 10 mL Et.sub.2O. The combined organic layers were dried with MgSO.sub.4 and evaporated under reduced pressure. The crude product was subjected to column chromatography (3:1 to 1:1; Hexanes:EtOAc) to yield 13 in analytically pure form as an white solid (66.7 mg, >99%). The same yield was obtained when a sample of complex 2 was used as precatalyst after storing it for >100 days in the freezer.

4,5-Dimethyl-2-phenylpyridine (16)

[0097] ##STR00014##

[0098] Ni(.sup.4-CF3stb).sub.3 (50.4 mg, 0.05 mmol, 0.1 equiv.) was placed in a pressure tight Schlenk tube which was sealed and subjected to one cycle of vacuum/argon. The Schlenk tube was transferred to the glovebox PCy.sub.3 (56.1 mg, 0.2 mmol, 0.4 equiv.) was added and the Schlenk was taken out of the glovebox again. Toluene (3 mL) was added followed by 2,3-dimethylbuta-1,3-diene (226.3 μL, 164.3 mg, 2 mmol, 4 equiv.) and benzonitrile (51.1 μL, 51.6 mg, 0.5 mmol). The Schlenk tube was sealed pressure tight and heated to 130° C. for 48 h. The solvent was removed under reduced pressure and the crude product was purified by column chromatography (9:1 to 5:1; Hexanes:EtOAc) to yield 16 as an yellow oil (76.7 mg, 0.419 mmol, 84%).

3,4-Dipropyl-2-(pyridin-2-ylmethyl)isoquinolin-1(2H)-one (19)

[0099] ##STR00015##

[0100] A 10-mL pressure-tight Schlenk tube was charged with N-(pyridin-2-ylmethyl)benzamide (106.1 mg, 0.50 mmol), PPh.sub.3 (52.5 mg, 0.20 mmol, 0.4 equiv.), 4-octyne (0.22 mL, 1.50 mmol, 3.0 equiv.) and Ni(.sup.4-CF3stb).sub.3 (50.4 mg, 0.05 mmol, 0.1 equiv.). Dry toluene (2 mL) was added and the reaction mixture was placed into a preheated oil bath at 170° C. and stirred for 20 h. After cooling to room temperature, the solvent was removed under reduced pressure. Purification of the crude residue via column chromatography (1:1; Hexanes:EtOAc) afforded pure 19 (151 mg, 0.47 mmol, 94%) as a yellowish oil.

4-(4-(Trifluoromethyl)phenyl)morpholine (22)

[0101] ##STR00016##

[0102] A 12 mL screw-cap vial was charged with Ni(.sup.4-CF3stb).sub.3 (27.2 mg, 0.027 mmol, 0.05 equiv.), SIPr.HCl (26.8 mg, 0.063 mmol, 0.116 equiv.) and dry CPME (1.5 mL). 4-chlorobenzotrifluoride (72 μL, 0.540 mmol, 1.00 equiv.) and morpholine (57 μL, 0.648 mmol, 1.20 equiv.) were added to the solution. While stirring the solution for 15 min at room temperature the mixture became orange-yellowish. NaOtBu (2 M in THF, 543 μL, 1.080 mmol, 2.00 equiv.) was then added and the brown reaction mixture was stirred for 4 h in a preheated oil bath at 100° C. After cooling to room temperature the solvent was removed under reduced pressure. Column chromatography of the crude residue (9:1; Hexanes:EtOAc) afforded 22 (114 mg, 0.493 mmol, 91% yield) as a colorless solid.

N-(4-Methoxyphenyl)-2,5-dimethylaniline (825)

[0103] ##STR00017##

[0104] A 12 mL screw-cap vial was charged with Ni(.sup.4-CF3stb).sub.3 (20.1 mg, 0.02 mmol, 0.02 equiv.), dppf (22.2 mg, 0.04 mmol, 0.04 equiv.) and anhydrous sodium t-butoxide (134.5 mg, 1.40 mmol, 1.40 equiv.). Toluene (2 mL) was added followed by 2-chloro-p-xylol (0.134 mL, 1.00 mmol, 1.00 equiv.) and p-anisidine (147.8 mg, 1.20 mmol, 1.20 equiv.). Additional toluene (2 mL) was added and the vial was set into a preheated oil bath at 130° C. and stirred for 48 h. After cooling to room temperature the reaction mixture was diluted with EtOAc and water was added and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over MgSO4. The solvent was removed under reduced pressure, and the crude residue was purified via column chromatography (gradient: 50:1 to 20:1; Hexanes:EtOAc) to afford 25 as an orange oil (205.1 mg, 0.90 mmol, 90% yield).

2-(2-(Trifluoromethyl)phenyl)-2H-chromene (28)

[0105] ##STR00018##

[0106] A 12 mL screw cap vial was charged with Ni(.sup.4-CF3stb).sub.3 (58.6 mg, 0.05 mmol, 0.09 equiv.) and PPh.sub.3 (39.3 mg, 0.15 mmol, 0.27 equiv.). 1,4 dioxane (1 ml) was added and the solution was stirred for 5 min. A 50 mL Schlenk tube was charged with 2-ethoxy-2H-chromene (98.9 mg, 0.56 mmol), (2-(trifluoromethyl)phenyl)boronic acid (189.9 mg, 1.00 mmol, 1.78 equiv.), dioxane (23 mL) and t-AmOH (2 mL). The catalyst+ligand solution was transferred two the second Schlenk tube and the reaction was placed in a preheated oil bath at 100° C. for 40 min. The reaction as allowed to cool down and the solvents were evaporated under reduced pressure. The residue was subjected to column chromatography (pure hexanes) to give pure 28 as a colorless oil (131.9 mg, 0.56 mmol, 85%).

2-(1H-Indo1-3-yl)ethyl 3-phenylpropanoate (31)

[0107] ##STR00019##

[0108] A 12 mL screw-cap vial was charged with Ni(.sup.4-CF3stb).sub.3 (20.1 mg, 0.02 mmol, 0.1 equiv.), terpyridine (4.7 mg, 0.02 mmol, 0.1 equiv.), tert-butyl benzyl(3-phenylpropanoyl)carbamate (67.9 mg, 0.20 mmol, 1.00 equiv.) and tryptophol (40.3 mg, 0.25 mmol, 1.25 equiv.). Toluene (0.2 mL) was added and the vial was set into a preheated oil bath at 130° C. After stirring for 23 h the solution was allowed to cool to room temperature and the contents were transferred with EtOAc and hexanes into a round-bottomed flask. The solvent was removed under reduced pressure and the crude residue was purified via column chromatography (7:1; Hexanes/EtOAc) to afford 31 as an orange oil (38.5 mg, 0.13 mmol, 65% yield).

[0109] 2-Methylundecane (34)

##STR00020##

[0110] A 12 mL screw-cap vial was charged with Ni(.sup.4-CF3stb).sub.3 (10.0 mg, 0.010 mmol, 0.04 equiv.) and 2,6-bis((R)-4-phenyl-4,5-dihydrooxazol-2-yl)pyridine (7.4 mg, 0.020 mmol, 0.08 equiv.). DMA (0.4 mL) was added under argon, the deep-blue solution was stirred for 10 min at room temperature and tetradecane (internal standard for GC analysis, 20 μL, 0.077 mmol) was added. The mixture was stirred for further 10 min. at room temperature and a solution of n-nonylzinc bromide (0.85 M in DMA, 0.47 mL, 0.400 mmol, 1.57 equiv.) and i-propyl bromide (24 μL, 0.256 mmol, 1.00 equiv.) were added. After stirring the reaction mixture for 20 hours at 60° C. a 58% yield of 34 was determined by GC-FID analysis.

[0111] 1-Vinylnaphthalene (37)

##STR00021##

[0112] A screw cap vial was charged with Ni(.sup.4-CF3stb).sub.3 (10.1 mg, 0.01 mmol, 0.05 equiv.) once cycle of vacuum/ argon was performed and the vial was transferred to a glovebox. Xantphos (5.8 mg, 0.01 mmol, 0.05 equiv.) was added and the vial was removed from the glovebox. THF (150 μL), 1-bromonaphthalene (28.0 μL, 41.4 mg, 0.2 mmol) and vinylzincbromide (1M in THF/NMP, 350 μL, 1.75 equiv.) were added. The reaction was heated to 50° C. for 5 h and was subsequently diluted with EtOAc. Mesitylene (25 μL 21.6 mg) was added as internal standard and a 92% yield of 37 was determined via GC-FID analysis.

[0113] Naphtalene (40)

##STR00022##

[0114] A 12 mL screw-cap vial was charged with 2-(methylthio)naphthalene (87.2 mg, 0.50 mmol, 1.0 equiv.) and Ni(.sup.4-CF3stb).sub.3 (50.4 mg, 0.05 mmol, 0.1 equiv.). n-Dodecane (internal standard for GC analysis, 20 μL, 0.09 mmol), EtMe.sub.2SiH (0.13 mL, 0.98 mmol, 2.0 equiv.) and toluene (2 mL) were added. The vial was set into a preheated oil bath at 90° C. and kept stirring for 14 hours. After cooling to room temperature the mixture was diluted with EtOAc (4 mL) and a 91% yield of 40 was determined via GC-FID analysis.

1,2,3,4,5-Pentafluoro-6-(oct-4-en-4-yl)benzene (43)

[0115] ##STR00023##

[0116] A screw cap vial was charged with Ni(.sup.4-CF3stb).sub.3 (20.1 mg, 0.02 mmol, 0.1 equiv.) IMes HCl (6.8 mg, 0.02 mmol, 0.1 equiv.) and anhydrous NaHMDS (3.6 mg, 0.02 mmol, 0.1 equiv.). Toluene (1.5 mL) was added and the mixture was stirred for 5 min. 1,2,3,4,5-pentafluorobenzene (22.2 μL, 33.6 mg, 0.2 mmol) and 4-octin (44.0 μL, 33.1 mg, 0.3 mmol, 1.5 equiv.) were added and toluene (0.5 mL) was used to wash the substrates down. The reaction as stirred at rt for 3h and was quenched by addition of CH.sub.2Cl.sub.2. The mixture was filtered over a plug of silica and evaporated to dryness. α,α,α-Trifluortoluol (24.6 μL, 29.2 mg, 0.2 mmol, 1.0 equiv.) was added as internal standard and the yield (90%) was determined by .sup.19F NMR. As stated above, a long-standing problem in the area of Ni catalysis has been solved by providing the inventive complex as a Ni(0) precatalyst which mimics the remarkable reactivity of Ni(COD).sub.2 but has the advantages of being robust, air-stable and easy to handle in open-flask conditions. Herein, the inventors reported the synthesis and characterization of a binary Ni(0)-olefin complex that fulfills all these requirements and permits Ni catalysis without the use of complex Schlenk techniques or gloveboxes. The inventive Ni(0)-olefin complex Ni(R).sub.3 is a unique example of a modular Ni(0)-olefin complex which has remarkable stability under air and benefits from a high reactivity in solution due to its 16-electron configuration. Its catalytic abilities have been benchmarked with those of Ni(COD).sub.2 and the inventors have shown that Ni(R).sub.3 is an excellent precatalyst in a range of Ni-catalyzed transformations. Differently than the common air-stable precursors based on Ni(II) complexes, Ni(R).sub.3 is characterized by its intrinsic ability to deliver Ni(0) species in solution and afford discrete and well-defined Ni(0)—Ligand complexes. The great performance of Ni(R).sub.3 as Ni(0) precatalyst is envisaged to rapidly expand to all areas of Ni catalysis thus permitting facile setups and accelerating the discovery of new reactivity.

[0117] (E)-Pent-3-enenitrile (45

##STR00024##

[0118] This compound was prepared following a literature procedure but replacing Ni(COD).sub.2 by complex 6. A Schlenk tube was charged with Ni(.sup.4-tBustb).sub.3 (1.04 g, 1.11 mmol, 0.9 mol %) and PPh.sub.3 (2.91 g, 11.1 mmol, 9 mol %). 2-methylbut-3-enenitrile (12.5 ml, 10.0 g, 123.3 mmol, 1 equiv.) was added and the reaction was heated to 100° C. for 3 h. After allowing the reaction to cool to room temperature, the solution was opened to air and transferred to a round-bottom flask with non-dry toluene. A distillation was attempted, but failed due to the close boiling points of the product and three if it's isomers. All fractions were combined with the residue of the distillation and CH.sub.2Br.sub.2 (8.65 mL, 21.43 g, 123.3 mmol, 1 equiv.) was added as internal standard. The yield was determined by NMR: 67% (6.70g, 82.6 mmol).

[0119] α-Olefins C.sub.6 to C.sub.22

##STR00025##

[0120] These compounds were prepared adopting a literature procedure but replacing Ni(COD).sub.2 by complex 6. A 50 mL steel autoclave with a glass inlet was set under argon. A Schlenk tube was charged with Ni(.sup.4-tBustb).sub.3 (12.2 mg, 0.013 mmol, 1 equiv.), 1-phenyl-2-(triphenyl-A.sup.5-phosphanylidene)ethan-1-one (4.9 mg, 0.013 mmol, 1 equiv.) and PPh.sub.3 (3.4 mg, 0.013 mmol, 1 equiv.). The solids were dissolved in toluene (20 mL) and transferred to the autoclave with a syringe. The autoclave was pressured with 5 bars of ethylene gas and stirred for 15 h at 25° C.

[0121] The autoclave was then pressurized with 60 bars of ethylene and heated to 60° C. for 45 min. The reaction exhibited exothermic properties, leading to rising pressure and temperature with a peak at 80 bars and 75° C. internal temperature. The autoclave was allowed to reach room temperature and the pressure was released. 1-Undecene (200 μL, 150 mg) was added as internal standard and a GC sample was prepared (filtration over plug of silica, eluting with pentane).

[0122] Result of GC analysis:

TABLE-US-00001 #carbons mass mmol turnovers needed mmol ethylene 6 72.0 0.856 3 2.57 8 125.1 1.115 4 4.46 10 97.1 0.692 5 3.46 12 83.4 0.495 6 2.97 14 70.8 0.361 7 2.53 16 65.5 0.292 8 2.34 18 68.1 0.270 9 2.43 20 55.0 0.196 10 1.96 22 52.9 0.171 11 1.88 SUM 689.9 24.59

[0123] Ni(PPh.sub.3).sub.2(.sup.4-tBustb) (48)

##STR00026##

[0124] Ni(.sup.4-tBustb).sub.3 (46.8 mg, 0.05 mmol, 1 equiv.) and PPh.sub.3 (52.4 mg, 0.2 mmol, 4 equiv.) were dissolved in d.sub.8-toluene (1 mL) and transferred to an NMR tube. Analysis by .sup.31P NMR shows a 1:1 mixture of and complex 48 and 2 equiv. of free PPh.sub.3. Following the same procedure Ni(COD).sub.2 (13.8 mg, 0.05 mmol, 1 equiv.) and PPh.sub.3 (52.4 mg, 0.2 mmol, 4 equiv.) were dissolved in d8-toluene (1 mL) and analyzed by .sup.31P NMR. A 1:3 mixture of Ni(COD)(PPh.sub.3).sub.2 and Ni(PPh.sub.3).sub.4

[0125] Summarizing the above, the present invention presents the synthesis of a family of air-stable 16-electron tris-olefin-Ni(0) complexes which differ on their substitution in the aryl rings of the supporting stilbenes, and their use in various catalytic applications. A systematic study of these substituents enabled the inventors to establish that the origin of the high stability towards oxidation is the result of a steric demand inferred by the substituents preferably at the para position of the stilbene ligands. This fundamental observation proved to be a superior Ni(0) source with remarkable physical properties. The inventive complexes, depending on their actual substitution on the aryl residue, provide faster kinetic profiles, broader catalytic performance and have been shown to perform, in most of the applications, at the same level than Ni(COD).sub.2 in challenging catalytic transformations. The high resemblance in reactivity to Ni(COD).sub.2, the broad applicability, high practicality and robustness of the inventive complexes will find rapid application in the field of Ni catalysis.