Process for the catalytic reversible alkene-nitrile interconversion

Abstract

The present invention refers to processes for catalytic reversible alkene-nitrile interconversion through controllable HCN-free transfer hydrocyanation.

Claims

1. A process for effecting a catalytic reversible alkene-nitrile interconversion, said process comprising reacting an unsaturated hydrocarbon (I) with an alkylnitrile (II) in the presence of a transition metal coordinated to a ligand and a Lewis acid co-catalyst, optionally in a solvent, to yield an alkylnitrile (III) and an unsaturated hydrocarbon (IV), alkylnitrile (III) and unsaturated hydrocarbon (IV) being different from alkylnitrile (II) and unsaturated hydrocarbon (I), respectively, as represented in the following reaction scheme: ##STR00031## wherein: R.sup.1, R.sup.2, R.sup.3 and R.sup.4 can be the same or different and each independently represents H, straight chain or branched chain alkyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, each being optionally substituted by one or more groups selected from straight chain or branched chain alkyl, cycloalkyl, heterocycloalkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heteroaralkyl or a heterosubstituent; or a heterosubstituent, or at least two of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 may each form a cyclic 3 to 20 membered ring structure which may further be substituted by one or more groups selected from straight chain or branched chain alkyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl or a heterosubstituent, and optionally including any of O, S, N in the straight chain, branched chain or cyclic structure; or R.sup.2 and R.sup.4 form a bond; wherein at least one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is not hydrogen; R.sup.5, R.sup.6, R.sup.7 and R.sup.8 can be the same or different and each independently represents H, straight chain or branched chain alkyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, each being optionally substituted by one or more groups selected from straight chain or branched chain alkyl, cycloalkyl, heterocycloalkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heteroaralkyl, or a heterosubstituent, or a heterosubstituent; or at least two of R.sup.5, R.sup.6, R.sup.7 and R.sup.8 may each form a cyclic 3 to 20 membered hydrocarbon ring structure which may further be substituted by one or more groups selected from straight chain or branched chain alkyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl or a heterosubstituent, and optionally including any of O, S, N in the straight chain, branched chain or cyclic structure; wherein optionally at least one of R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is not hydrogen; the metal of the coordinated transition metal catalyst is selected from a metal of the Iron-group, Cobalt-group, Nickel-group or Copper group; the ligand of the coordinated transition metal catalyst is selected from compounds having the ability to coordinate to said transition metal, optionally phosphorous-, nitrogen-, As-, Sb- or N-heterocyclic based ligands; and the Lewis acid co-catalyst is selected from compounds of aluminum, boron, zinc, titanium, scandium.

2. Process according to claim 1, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 can be the same or different and each independently represents H, aryl, aralkyl, heteroaryl, heteroaralkyl, each being optionally substituted by one or more groups selected from straight chain or branched chain alkyl, cycloalkyl, heterocycloalkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heteroaralkyl or a heterosubstituent, or a heterosubstituent, or R.sup.2 and R.sup.4 form a bond; wherein at least one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is not hydrogen.

3. Process according to claim 1, wherein R.sup.5, R.sup.6, R.sup.7 and R.sup.8 can be the same or different and each independently represents H, straight chain or branched chain alkyl, cycloalkyl, heterocycloalkyl, each being optionally substituted by one or more groups selected from straight chain or branched chain alkyl, cycloalkyl, heterocycloalkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, heteroaralkyl or a heterosubstituent, or a heterosubstituent, or at least two of R.sup.5, R.sup.6, R.sup.7 and R.sup.8 may each form a cyclic 3 to 20 membered hydrocarbon ring structure which may further be substituted by one or more groups selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl or heterosubstituent, and optionally having any of O, S, N in the straight chain, branched chain or cyclic structure, wherein optionally at least one of R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is not hydrogen.

4. Process according to claim 3, wherein R.sup.5, R.sup.6, R.sup.7 and R.sup.8 can be the same or different and each independently represents H, straight chain or branched chain alkyl, or cycloalkyl, or at least two of R.sup.5, R.sup.6, R.sup.7 and R.sup.8 may each form a cyclic 3 to 20 membered aliphatic hydrocarbon ring structure which may further be substituted by one or more groups selected from alkyl, cycloalkyl, heterocycloalkyl, or heterosubstituent, and optionally having any of O, S, N in the straight chain, branched chain or cyclic structure, wherein at least one of R.sup.5, R.sup.6, R.sup.7 and R.sup.8 is not hydrogen.

5. Process according to claim 3, wherein the compound of formula (II) is a lower alkyl nitrile having 1 to 6 carbon atoms, optionally substituted by one or more heterosubstituents.

6. Process according to claim 1, wherein the compound of formula (I) is a cyclic unsaturated hydrocarbon having 4 to 20 optionally substituted by one or more heterosubstituents.

7. Process according to claim 1, wherein the coordinated transition metal catalyst is obtained from a transition metal catalyst precursor selected from Ni(COD).sub.2, Ni(acac).sub.2, Ni(CO).sub.4, Pd(dba).sub.2, Pd(OAc).sub.2, Co.sub.2(CO).sub.8.

8. Process according to claim 1, wherein the Lewis acid co-catalyst is selected from AlMe.sub.3, AlMe.sub.2Cl, AlMeCl.sub.2, AlCl.sub.3, BPh.sub.3, B(C.sub.6F.sub.5).sub.3, Zn(OTf).sub.2, ZnCl.sub.2, TiCl.sub.4, and Sc(OTf).sub.3.

9. Process according to claim 1, wherein the ligand is selected from the group consisting of phosphine ligands, and mixtures thereof.

10. Method of using a reaction pair of a coordinated transition metal catalyst and a Lewis acid co-catalyst for a nitrile transfer reaction from an hydrocarbon nitrile to an unsaturated hydrocarbon, wherein the metal of the coordinated transition metal catalyst is selected from a metal of the Iron-group, Cobalt-group, Nickel-group or Copper group; the ligand of the coordinated transition metal catalyst is selected from compounds having the ability to coordinate to said transition metal, including phosphorous-, nitrogen-, As-, Sb- or N-heterocyclic based ligands; and the Lewis acid co-catalyst is selected from compounds of aluminum, boron, zinc, titanium, scandium.

11. Process according to claim 9, wherein the ligand is selected from the group consisting of PPh.sub.3, PCy.sub.3, P(OPh).sub.3, PEt.sub.3, BINAP, Xanthphos, DuPhos, DPEPhos, dppf, dppe, and mixtures thereof.

Description

(1) The invention is further illustrated in the attached drawings and the following experimental section below.

(2) In the attached drawings:

(3) FIG. 1 shows the: (A) Traditional approach to hydrocyanation using HCN. (B) Proposed HCN-free transfer hydrocyanation reaction and mechanism. (C) The process of the present invention

(4) FIG. 2 shows the: (A) Model reaction. (B) Reagent optimization for hydrocyanation 1.fwdarw.2. (C) Reagent optimization for retro-hydrocyanation 2.fwdarw.1.

(5) FIG. 3 shows the: A. Scope of the hydrocyanation. B. Scale-up experiment

EXPERIMENTAL SECTION

(6) After successfully finding initial reactivity using a Nickel catalyst and an Al co-catalyst, the inventors developed the ideas for efficiently manipulating the reaction equilibrium and they have found suitable alkene and alkyl nitrile reagents that allow to selectively drive the forward reaction from 1.fwdarw.2 and the reverse reaction from 2.fwdarw.1 under appropriate conditions (FIG. 2). Considering other metal catalyzed reversible reactions, such as the alkene metathesis reaction, the inventors reasoned that the use of simple driving forces, such as the extrusion of a gaseous side product or the release of ring strain, would efficiently shift the thermodynamic equilibrium to afford the desired product.

(7) In the case of the forward reaction (FIG. 2B), hydrocyanation, the inventors evaluated a range of simple aliphatic nitriles (3-6) as potential hydrocyanating reagents and they found that (1) the degree of substitution of the alkene by-product correlates with the efficiency of the reaction in the order isobutylene>propene>ethylene, and (2) the formation of gaseous alkenes further improves the system, particularly when conducted in an open system. Thus, isovaleronitrile (5), which releases isobutylene as a gaseous byproduct, was identified as the best reagent for the hydrocyanation reaction of 1 and gave 86% yield of product 2 in toluene at 100 C. in the presence of catalytic Ni and Al.

(8) Alternatively, alkyl nitrile product 2, formed in the forward reaction, can be used as test substrate to evaluate the efficiency of diverse alkene traps to drive the retro-hydrocyanation reaction to completion (FIG. 2C). A control reaction using no acceptor alkene did not lead to any significant formation of product 1. This result clearly shows that the formation of HCN and an alkene from an alkyl nitrile is thermodynamically disfavored, emphasizing the need to use an acceptor alkene to drive the process. Both norbornene (NBE, 7) and norbornadiene (NBD, 8) were then evaluated since they possess significant ring strain that should help to drive the retro-hydrocyanation reaction. Gratifyingly, NBD proved extremely efficient as a trapping reagent due to its high ring strain, affording good yields of the desired alkene product 1 at room temperature (RT).

(9) Having demonstrated the ability of the inventors' reaction to be tuned on demand towards either side of the reaction, the inventors studied the scope of the hydrocyanation process (FIG. 3A). The transfer hydrocyanation of styrene derivatives gave the products in high yields and good linear to branched ratios (up to 85% for mono-substituted and full linear selectivity in the case of disubstituted styrenes 1 and 19), a selectivity complementary to previous protocols giving mostly the branched isomer. Non-activated, terminal aliphatic alkenes were also very active substrates in the transformation and gave the linear product as the major product (up to 100% I/b selectivity in the case of sterically congested tBu (30)). Next, the inventors investigated 1,2-disubstituted substrates. Cycloalkenes (33, 35 and 37) and strained norbornenes (7 and 43) were well tolerated and afforded the cyanated products in high yields. Two renewable feedstocks, methyl oleate (45) and camphene (47), were subjected to the reaction conditions and high yields of the products were obtained. Remarkably, the inventors' catalytic reaction could also be extended to the efficient hydrocyanation of both conjugated (23) and aliphatic alkynes (21) in good yields. Finally, the reaction of styrene (9) could be performed on a preparative scale (5 g) using inexpensive butyronitrile (4) as a reagent and solvent and 2 mol % of Ni catalyst to give the product in 94% yield after distillation (FIG. 3B).

(10) The invention is further illustrated by the following non limiting examples.

Examples

Preparation Examples

(11) General Procedure for the Preparation of Nitriles

(12) A: General Procedure for the Preparation of Alkyl Nitriles

(13) To a 0 C. solution of corresponding alkyl alcohol (5 mmol) in CH.sub.2Cl.sub.2 (5 mL) were added pyridine (2 mL), and 4-toluenesulfonyl chloride (1.06 g, 5.56 mmol). The resultant reaction mixture was stirred at room temperature for overnight. After that time, water was added and the resultant mixture extracted with CH.sub.2Cl.sub.2. The combined organic layers were subsequently washed with a 2M aqueous solution of HCl, a saturated aqueous solution of NaHCO.sub.3, and brine and dried over anhydrous Na.sub.2SO.sub.4. After the desiccant was removed, the solvent was distilled off under vacuum to give the corresponding alkyl p-toluenesulfonate in quantitative yield and was used without any further purification.

(14) To a solution of alkyl p-toluenesulfonate (ca. 5 mmol) in DMSO (10 mL) was added powdered NaCN (0.49 g, 10 mmol), and the mixture was stirred at 100 C. for 5 hours. After completion of the reaction, the reaction was cooled down to room temperature and quenched with saturated aqueous solution of Na.sub.2CO.sub.3. The aqueous phase was extracted with methyl tert-butyl ether (3*20 mL), the combined organic layers were washed several times with brine and dried over anhydrous Na.sub.2SO.sub.4. The solution was concentrated in vacuo, and purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give the corresponding alkyl nitrile in high yield.

(15) B: General Procedure for the Preparation of -alkyl Benzyl Nitriles

(16) Lithium bis(trimethylsilyl)amide (5.5 mL, 5.50 mmol; 1M solution in tetrahydrofuran) was added dropwise to a stirred solution of 2-phenylacetonitrile derivative (5.0 mmol) in anhydrous tetrahydrofuran (20 mL) at 78 C. under an atmosphere of argon. The anion was allowed to form over ca. 30 minutes, then corresponding bromide (5.25 mmol) was added dropwise and the reaction allowed to stir for ca. 1 hour before being slowly warmed to room temperature and stirred until completion (t.l.c. control). The reaction mixture was then quenched by addition of saturated aqueous ammonium chloride solution and extracted with methyl tert-butyl ether. The organic layers were combined, dried (anhyd. Na.sub.2SO.sub.4), filtered and concentrated in vacuo to afford the crude product. Purification by flash column chromatography (silica gel, eluting with hexane/ethyl acetate) afforded the corresponding -alkyl benzyl nitrile.

Example 1

(17) ##STR00002##

(18) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), -methylstyrene 1 (65 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube with a reflux condenser was taken out of the glove box, and was then connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at 130 C. for 16 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 2 (66.1 mg, yield: 91%). .sup.1H NMR (500 MHz, CDCl.sub.3) 7.34-7.30 (m, 2H), 7.26-7.21 (m, 3H), 3.13 (h, J=7.0 Hz, 1H), 2.59 (dd, J=16.7, 6.5 Hz, 1H), 2.53 (dd, J=16.7, 7.6 Hz, 1H), 1.43 (d, J=7.0 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 143.26, 128.99, 127.46, 126.67, 118.72, 36.65, 26.49, 20.80. The spectral data are consistent with those reported in the literature.

Example 2

(19) ##STR00003##

(20) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), 1,1-diphenylethylene 19 (88 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube with a reflux condenser was taken out of the glove box, and was then connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at 130 C. for 16 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 20 (54.9 mg, yield: 53%). .sup.1H NMR (500 MHz, CDCl.sub.3) 7.39-7.36 (m, 4H), 7.32-7.26 (m, 6H), 4.42 (t, J=7.7 Hz, 1H), 3.07 (d, J=7.7 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 141.34, 129.03, 127.66, 127.54, 118.55, 47.26, 24.36.

Example 3

(21) ##STR00004##

(22) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), cyclopentene 33 (44 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 25 mL pressure tube under an argon atmosphere in a glove box. The pressure tube was taken out of the glove box and heated at 100 C. for 16 hours. After that time, the reaction was cooled down to room temperature, and n-dodecane (100 L) as internal standard was added to the solution. The reaction mixture was analyzed by GC and the yield of 34 determined by comparing their peak areas to that of the internal standard. (Retention time: 6.38 min, GC yield: 83%)

Example 4

(23) ##STR00005##

(24) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), cyclohexene 35 (51 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 25 mL pressure tube under an argon atmosphere in a glove box. The pressure tube was taken out of the glove box and heated at 100 C. for 16 hours. After that time, the reaction was cooled down to room temperature, and n-dodecane (100 L) as internal standard was added to the solution. The reaction mixture was analyzed by GC and the yield of 36 determined by comparing their peak areas to that of the internal standard. (Retention time: 7.62 min, GC yield: 91%)

Example 5

(25) ##STR00006##

(26) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), cyclooctene 37 (65 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube with a reflux condenser was taken out of the glove box, and was then connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at 130 C. for 16 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 38 (59.7 mg, yield: 87%). .sup.1H NMR (500 MHz, CDCl.sub.3): 2.78-2.73 (m, 1H), 1.98-1.92 (m, 2H), 1.87-1.72 (m, 4H), 1.60-1.47 (m, 8H); .sup.13C NMR (125 MHz, CDCl.sub.3) 123.69, 29.58, 28.87, 26.96, 25.26, 24.39. The spectral data are consistent with those reported in the literature.

Example 6

(27) ##STR00007##

(28) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), norbornene 7 (47.1 mg, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 25 mL pressure tube under an argon atmosphere in a glove box. The pressure tube was taken out of the glove box and heated at 100 C. for 16 hours. After cooling to room temperature, the reaction mixture directly purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 42 (51.5 mg, yield: 85%). .sup.1H NMR (500 MHz, CDCl.sub.3) 2.59 (d, J=3.5 Hz, 1H), 2.39 (d, J=3.6 Hz, 1H), 2.35 (ddd, J=9.1, 4.8, 1.6 Hz, 1H), 1.85-1.76 (m, 1H), 1.73-1.66 (m, 1H), 1.64-1.50 (m, 3H), 1.41-1.34 (m, 1H), 1.27-1.14 (m, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 123.71, 41.90, 37.30, 36.20, 36.13, 31.18, 28.63, 28.50. HRMS-ESI (m/z): [M+Na].sup.+ calcd for C.sub.8H.sub.11NNa, 144.078368; found, 144.078550.

Example 7

(29) ##STR00008##

(30) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), 43 (126.7 mg, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 25 mL pressure tube under an argon atmosphere in a glove box. The pressure tube was taken out of the glove box and heated at 100 C. for 16 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/ethyl acetate=2/1) to give 44 (128.9 mg, yield: 92%). .sup.1H NMR (500 MHz, CDCl.sub.3) 7.30-7.17 (m, 5H), 4.53 (s, 2H), 2.93 (s, 1H), 2.76 (d, J=3.3 Hz, 1H), 2.55 (q, J=7.1 Hz, 2H), 2.44 (ddd, J=9.1, 4.8, 1.6 Hz, 1H), 1.96-1.84 (m, 1H), 1.82-1.73 (m, 1H), 1.57-1.42 (m, 1H), 1.05 (d, J=11.9 Hz, 1H), .sup.13C NMR (125 MHz, CDCl.sub.3) 176.97, 176.36, 135.57, 128.79, 128.76, 128.17, 121.57, 47.49, 47.26, 44.22, 42.68, 39.35, 34.70, 32.24, 29.84. HRMS-ESI (m/z): [M+Na].sup.+ calcd for C.sub.17H.sub.16N.sub.2O.sub.2Na, 303.110396; found, 303.110200.

Example 8

(31) ##STR00009##

(32) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), styrene 9 (57.5 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube was taken out of the glove box, and was then connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at heated at 100 C. for 16 hours. After cooling to room temperature, the reaction mixture was analyzed by GC and the regioselectivity of 10 determined by comparing their peak areas (I/b: 81/19). The reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 10 (linear product: 45.9 mg, yield: 70%; branched product: 10.5 mg, yield: 16%).

(33) Linear product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.29-7.23 (m, 2H), 7.22-7.17 (m, 1H), 7.17-7.12 (m, 2H), 2.86 (t, J=7.4 Hz, 2H), 2.52 (t, J=7.4 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 138.13, 128.93, 128.34, 127.29, 119.24, 31.60, 19.41. Branched product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.42-7.31 (m, 5H), 3.90 (q, J=7.3 Hz, 1H), 1.65 (d, J=7.4 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 137.19, 129.30, 128.19, 126.85, 121.74, 31.41, 21.63.

Example 9

(34) ##STR00010##

(35) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), 2-vinylnaphthalene 11 (77.1 mg, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube was taken out of the glove box, and was then connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at heated at 100 C. for 16 hours. After cooling to room temperature, the reaction mixture was analyzed by GC and the regioselectivity of 12 determined by comparing their peak areas (I/b: 82/18). The reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 12 (linear product: 66.1 mg, yield: 73%; branched product: 14.5 mg, yield: 16%).

(36) Linear product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.88-7.78 (m, 3H), 7.69 (s, 1H), 7.54-7.43 (m, 2H), 7.35 (dd, J=8.3, 1.8 Hz, 1H), 3.12 (t, J=7.4 Hz, 2H), 2.70 (t, J=7.5 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 135.56, 133.59, 132.59, 128.77, 127.80, 127.75, 127.00, 126.48, 126.43, 126.04, 119.26, 31.82, 19.38. The spectral data are consistent with those reported in the literature.

(37) Branched product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.92-7.79 (m, 4H), 7.56-7.48 (m, 2H), 7.43 (dd, J=8.5, 1.9 Hz, 1H), 4.07 (q, J=7.4 Hz, 1H), 1.73 (d, J=7.3 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 134.44, 133.44, 132.90, 129.27, 127.98, 127.85, 126.87, 126.62, 125.71, 124.54, 121.72, 31.55, 21.57. The spectral data are consistent with those reported in the literature.

Example 10

(38) ##STR00011##

(39) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), 2-methylstyrene 13 (65 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube was taken out of the glove box, and was then connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at heated at 100 C. for 16 hours. After cooling to room temperature, the reaction mixture was analyzed by GC and the regioselectivity of 14 determined by comparing their peak areas (I/b: 86/14). The reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 14 (linear product: 57.3 mg, yield: 79%; branched product: 9.4 mg, yield: 13%).

(40) Linear product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.23-7.14 (m, 4H), 2.98 (t, J=7.7 Hz, 2H), 2.59 (t, J=7.7 Hz, 2H), 2.34 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 136.34, 135.91, 130.78, 128.84, 127.50, 126.62, 119.35, 29.01, 19.30, 18.14. The spectral data are consistent with those reported in the literature.

(41) Branched product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.45 (dd, J=7.3, 1.7 Hz, 1H), 7.29-7.17 (m, 3H), 4.05 (q, J=7.2 Hz, 1H), 2.37 (s, 3H), 1.61 (d, J=7.2 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 135.38, 134.90, 131.12, 128.26, 127.13, 126.84, 121.94, 28.30, 20.18, 19.15. The spectral data are consistent with those reported in the literature.

Example 11

(42) ##STR00012##

(43) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), 4-vinylanisole 15 (66.5 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube was taken out of the glove box, and was then connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at heated at 100 C. for 16 hours. After cooling to room temperature, the reaction mixture was analyzed by GC and the regioselectivity of 16 determined by comparing their peak areas (I/b: 79/21). The reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=5/1) to give 16 (linear product: 59.6 mg, yield: 74%; branched product: 15.3 mg, yield: 19%).

(44) Linear product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.18-7.12 (m, 2H), 6.90-6.83 (m, 2H), 3.80 (s, 3H), 2.90 (t, J=7.3 Hz, 2H), 2.58 (t, J=7.4 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 158.85, 130.24, 129.44, 119.38, 114.35, 55.40, 30.87, 19.82. The spectral data are consistent with those reported in the literature.

(45) Branched product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.32-7.21 (m, 2H), 6.95-6.85 (m, 2H), 3.85 (q, J=7.3 Hz, 1H), 3.81 (s, 3H), 1.62 (d, J=7.3 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 159.43, 129.21, 127.98, 122.01, 114.60, 55.50, 30.61, 21.68.

(46) The spectral data are consistent with those reported in the literature.

Example 12

(47) ##STR00013##

(48) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), 4-fluorostyrene 17 (60 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube was taken out of the glove box, and was then connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at heated at 100 C. for 16 hours. After cooling to room temperature, the reaction mixture was analyzed by GC and the regioselectivity of 18 determined by comparing their peak areas (I/b: 83/17). The reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 18 (linear product: 56.7 mg, yield: 76%; branched product: 11.2 mg, yield: 15%).

(49) Linear product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.23-7.17 (m, 2H), 7.06-6.98 (m, 2H), 2.93 (t, J=7.3 Hz, 2H), 2.60 (t, J=7.3 Hz, 2H); .sup.13C NMR (126 MHz, CDCl.sub.3) 162.11 (d, J.sub.C-F=243.75 Hz), 133.81, 129.98 (d, J.sub.C-F=7.50 Hz), 119.06, 115.84 (d, J.sub.C-F=21.25 Hz), 30.86, 19.67. The spectral data are consistent with those reported in the literature.

(50) Branched product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.36-7.29 (m, 2H), 7.10-7.04 (m, 2H), 3.89 (q, J=7.3 Hz, 1H), 1.63 (d, J=7.3 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 162.47 (d, J.sub.C-F=245.12 Hz), 132.97, 128.56 (d, J.sub.C-F=8.25 Hz), 121.53, 116.23 (d, J.sub.C-F=22.12 Hz), 30.71, 21.65. The spectral data are consistent with those reported in the literature.

Example 13

(51) ##STR00014##

(52) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), allyltriphenylsilane 27 (150.2 mg, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube connected with a reflux condenser was taken out of the glove box, and was subsequently connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at 130 C. for 16 hours. After cooling to room temperature, the reaction mixture was analyzed by GC (Temperature program: 15 C./min to 180 C., 15 C./min to 300 C., 300 C. (15 min)) and the regioselectivity of 28 determined by comparing their peak areas (I/b: 84/16). The reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 28 (linear product: 127.7 mg, yield: 78%; branched product: 24.5 mg, yield: 15%).

(53) Linear product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.54-7.49 (m, 6H), 7.46-7.35 (m, 9H), 2.37 (t, J=6.9 Hz, 2H), 1.88-1.78 (m, 2H), 1.57-1.49 (m, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 135.66, 134.18, 129.90, 128.22, 119.75, 20.94, 20.82, 13.13. HRMS-EI (m/z): [M].sup.+ calcd for C.sub.22H.sub.21NSi, 327.144327; found, 327.144175.

(54) Branched product: .sup.1H NMR (500 MHz, CDCl.sub.3) 7.60-7.53 (m, 6H), 7.49-7.37 (m, 9H), 2.73 (sext, J=7.0 Hz, 1H), 1.97 (dd, J=15.2, 7.0 Hz, 1H), 1.68 (dd, J=15.2, 7.8 Hz, 1H), 1.27 (d, J=7.0 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 135.73, 133.45, 130.15, 128.31, 124.07, 21.67, 21.47, 19.19. HRMS-EI (m/z): [M].sup.+ calcd for C.sub.22H.sub.21NSi, 327.144327; found, 327.144029.

Example 14

(55) ##STR00015##

(56) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), allylbenzene 25 (66 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube connected with a reflux condenser was taken out of the glove box, and was subsequently connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at 130 C. for 16 hours. After that time, the reaction was cooled down to room temperature, and n-dodecane (100 L) as internal standard was added to the solution. The reaction mixture was analyzed by GC and the yield of 26 determined by comparing their peak areas to that of the internal standard. (GC yield: 88%, ratio of regioisomers: 58/29/13, retention time: 11.48, 10.77, 10.56 min respectively).

Example 15

(57) ##STR00016##

(58) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), 3,3-dimethyl-1-butene 29 (65 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 25 mL pressure tube under an argon atmosphere in a glove box. The pressure tube was taken out of the glove box and heated at 100 C. for 16 hours. After cooling to room temperature, the reaction mixture directly purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 30 (38.4 mg, yield: 69%). .sup.1H NMR (500 MHz, CDCl.sub.3) 2.31-2.25 (m, 2H), 1.64-1.59 (m, 2H), 0.93 (s, 9H); .sup.13C NMR (125 MHz, CDCl.sub.3) 120.74, 39.33, 30.48, 28.80, 12.87. The spectral data are consistent with those reported in the literature.

Example 16

(59) ##STR00017##

(60) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), 1-octene 31 (78.5 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube with a reflux condenser was taken out of the glove box, and was subsequently connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at 130 C. for 16 hours. After that time, the reaction was cooled down to room temperature, and n-dodecane (100 L) as internal standard was added to the solution. The reaction mixture was analyzed by GC and the yield of desired product determined by comparing their peak areas to that of the internal standard. (GC yield: 90%, ratio of regioisomers: 48/32/11/9, retention time: 9.70, 8.95, 8.81, 8.71 min respectively).

Example 17

(61) ##STR00018##

(62) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), trans-4-octene 39 (78.5 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube connected with a reflux condenser was taken out of the glove box, and was subsequently connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at 130 C. for 16 hours. After that time, the reaction was cooled down to room temperature, and n-dodecane (100 L) as internal standard was added to the solution. The reaction mixture was analyzed by GC and the yield of desired product determined by comparing their peak areas to that of the internal standard. (GC yield: 98%, ratio of regioisomers: 46/30/12/12, retention time: 9.70, 8.95, 8.81, 8.71 min respectively).

Example 18

(63) ##STR00019##

(64) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), N-vinylcarbazole 40 (96.6 mg, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube connected with a reflux condenser was taken out of the glove box, and was subsequently connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at 130 C. for 16 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/ethyl acetate=2/1) to give 41 (71.6 mg, yield: 65%). .sup.1H NMR (500 MHz, CDCl.sub.3) 8.11 (d, J=8.1 Hz, 2H), 7.54-7.48 (m, 2H), 7.41 (d, J=8.1 Hz, 2H), 7.33-7.27 (m, 2H), 4.65 (t, J=7.2 Hz, 2H), 2.84 (t, J=7.2 Hz, 2H); .sup.13C NMR (125 MHz, CDCl.sub.3) 139.62, 126.33, 123.48, 120.85, 120.09, 117.46, 108.26, 39.02, 17.39. HRMS-ESI (m/z): [M+Na].sup.+ calcd for C.sub.15H.sub.12N.sub.2Na, 243.089266; found, 243.089470.

Example 19

(65) ##STR00020##

(66) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), camphene 47 (68 mg, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube connected with a reflux condenser was taken out of the glove box, and was subsequently connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at 130 C. for 16 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 48 (62.8 mg, yield: 77%, diastereoselectivity based on .sup.1H NMR: 7/3). .sup.1H NMR (500 MHz, CDCl.sub.3) 2.35-2.18 (m, 3.42H), 2.15-2.09 (m, 0.84H), 1.84-1.79 (m, 2H), 1.76-1.74 (m, 0.42H), 1.69-1.64 (m, 1.42H), 1.63-1.61 (m, 0.42H), 1.59-1.54 (m, 1H), 1.44 (ddd, J=8.9, 6.7, 1.7 Hz, 0.42H), 1.37-1.30 (m, 2H), 1.25-1.23 (m, 3.26H), 1.16 (dt, J=10.2, 1.6 Hz, 0.42H), 1.04 (s, 1.28H), 1.02 (s, 3H), 0.94 (s, 1.28H), 0.87 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 120.36, 50.74, 49.54, 49.02, 47.36, 43.84, 42.13, 37.11, 36.92, 35.61, 32.04, 29.86, 29.49, 27.71, 24.56, 24.47, 23.94, 21.07, 20.11, 19.04, 15.36. HRMS-ESI (m/z): [M+Na].sup.+ calcd for C.sub.11H.sub.17NNa, 186.125318; found, 186.125480.

Example 20

(67) ##STR00021##

(68) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), 99% purity of methyl oleate 45 (170 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 10 mL Schlenk tube under an argon atmosphere in a glove box. The Schlenk tube connected with a reflux condenser was taken out of the glove box, and was subsequently connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at 130 C. for 16 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=5/1) to give 46 (137.5 mg, yield: 85%). .sup.1H NMR (500 MHz, CDCl.sub.3) 3.77-3.60 (m, 3H), 2.57-2.41 (m, 1H), 2.36-2.24 (m, 2H), 1.65-1.50 (m, 7H), 1.46-1.37 (m, 2H), 1.31-1.24 (m, 19H), 0.98-0.84 (m, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 174.49 (CO.sub.2), 122.63 (CN). HRMS-ESI (m/z): [M+Na].sup.+ calcd for C.sub.20H.sub.37NO.sub.2Na, 346.271648; found, 346.271560. It should be noted that the isolated product 46 containing 9 regioisomers which were observed by GC analysis (Temperature program: 15 C./min to 180 C.; 15 C./min to 300 C.; 300 C. (15 min)).

Example 21

(69) ##STR00022##

(70) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), 4-octyne 21 (73 L, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 4 mL Screw-cap vial under an argon atmosphere in a glove box. The vial was taken out of the glove box, the temperature of which was fixed at 28 C. The reaction mixture was stirred for 16 hours at 28 C. After that time, the reaction mixture directly purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 22 (51.5 mg, yield: 89%, the ratio of Z/E based on .sup.1H NMR: 8/1). Z-product: .sup.1H NMR (500 MHz, CDCl.sub.3) 6.35 (tt, J=7.6, 1.2 Hz, 1H), 2.20-2.13 (m, 4H), 1.57 (sext, J=7.4 Hz, 2H), 1.45 (sext, J=7.4 Hz, 2H), 0.96-0.91 (m, 6H); .sup.13C NMR (125 MHz, CDCl.sub.3) 148.32, 120.37, 115.03, 30.54, 30.51, 21.92, 21.43, 13.85, 13.50. The spectral data are consistent with those reported in the literature.

(71) HRMS-ESI (m/z): [M+Na].sup.+ calcd for C.sub.9H.sub.15NNa, 160.109668; found, 160.109800.

Example 22

(72) ##STR00023##

(73) Isovaleronitrile 5 (0.26 mL, 2.50 mmol), diphenylacetylene 23 (89 mg, 0.50 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (0.10 mL, 0.10 mmol) were added sequentially to a solution of Ni(COD).sub.2 (6.9 mg, 5 mol %) and DPEphos (13.5 mg, 5 mol %) in toluene (1.0 mL) prepared in a 25 mL pressure tube under an argon atmosphere in a glove box. The pressure tube was taken out of the glove box and heated at 100 C. for 16 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (pentane/methyl tert-butyl ether=10/1) to give 24 (75.9 mg, yield: 74%). .sup.1H NMR (500 MHz, CDCl.sub.3) 7.92-7.88 (m, 2H), 7.71-7.67 (m, 2H), 7.55 (s, 1H), 7.51-7.39 (m, 6H); .sup.13C NMR (125 MHz, CDCl.sub.3) 142.39, 134.58, 133.83, 130.67, 129.39, 129.33, 129.19, 129.09, 126.12, 118.13, 111.80. The spectral data are consistent with those reported in the literature.

Example 23

(74) ##STR00024##

(75) Example 23 refers to a Scale-up experiment as illustrated in FIG. 3B. Styrene 9 (4.58 mL, 40 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (3.2 mL, 3.2 mmol, 8 mol %) were added sequentially to a solution of Ni(COD).sub.2 (220.0 mg, 2 mol %) and DPEphos (430.8 mg, 2 mol %) in butyronitrile 4 (80 mL) prepared in a 250 mL round bottle flask under an argon atmosphere in a glove box. The flask with a reflux condenser was taken out of the glove box, and was then connected to a continuous flow of argon (positive pressure: 0.4 bar) and heated at 130 C. for 16 hours. After cooling to room temperature, the reaction was quenched with methanol and the mixture was filtered through celite to remove the solid. The reaction mixture was analyzed by GC and the regioselectivity of 10 determined by comparing their peak areas (I/b: 82/18). The methanol and butyronitrile were distilled off under vacuum. The residue was directly purified by bulb-to-bulb distillation (Buchi Glass oven B-585) to give the desired product in 94% yield (4.95 g).

Example 24

(76) ##STR00025##

(77) 69 (82.6 mg, 0.50 mmol), norbornadiene 8 (51 L, 0.5 mmol) and 1.0M solution of AlMe.sub.2Cl in hexane (50 L, 10.0 mol %, 0.05 mmol) were added sequentially to a solution of Ni(COD).sub.2 (3.45 mg, 2.5 mol %, 12.5 mol) and DPEphos (6.75 mg, 2.5 mol %, 12.5 mol) in benzene (1.0 mL) prepared in a 4 mL Screw-cap vial under an argon atmosphere in a glove box. The vial was taken out of the glove box, the temperature of which was fixed at 28 C. The reaction mixture was stirred for 16 hours at 28 C. After that time, the reaction mixture was concentrated under reduced pressure and the residue purified by flash column chromatography on silica gel (100% pentane) to 70 (49.0 mg, yield: 71%). .sup.1H NMR (500 MHz, CDCl.sub.3) 5.74-5.64 (m, 1H), 5.13-5.06 (m, 1H), 4.99-4.88 (m, 2H), 2.12 (p, J=7.0 Hz, 1H), 2.01-1.89 (m, 2H), 1.68 (s, 3H), 1.60 (s, 3H), 1.35-1.26 (m, 2H), 0.99 (d, J=6.9 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) 144.91, 131.44, 124.80, 112.61, 37.51, 36.89, 25.88, 20.30, 17.83.

(78) Further experimental work of the inventors evidenced that other reaction systems with different ligands, Lewis acids and/or different metals also lead to satisfying conversion results as illustrated in the following Schemes.

(79) ##STR00026## ##STR00027##

(80) ##STR00028##

(81) ##STR00029## ##STR00030##

(82) TABLE-US-00001 Entry Catalyst Ligand Lewis acid Conversion Yield 1 Ni(COD).sub.2 PPh.sub.3 AlMe.sub.2Cl 73% 58% 2 Ni(COD).sub.2 L1 AlMe.sub.2Cl 71% 59% 3 Ni(COD).sub.2 L2 AlMe.sub.2Cl 69% 46% 4 Ni(COD).sub.2 P(Et).sub.3 AlMe.sub.2Cl 41% 25% 5 Ni(COD).sub.2 L3 AlMe.sub.2Cl 67% 56% 6 Ni(COD).sub.2 L4 AlMe.sub.2Cl 75% 69% 7 Ni(COD).sub.2 L4 AlCl.sub.3 49% 41% 8 Ni(COD).sub.2 L4 AlMe3 70% 65% 9 Ni(COD).sub.2 L5 AlMe.sub.2Cl 65% 49% 10 Ni(COD).sub.2 L6 AlMe.sub.2Cl 76% 55% 11 Ni(COD).sub.2 L7 AlMe.sub.2Cl 65% 41% 12 Ni(COD).sub.2 L8 AlMe.sub.2Cl 80% 52% 13 Ni(COD).sub.2 L9 AlMe.sub.2Cl 37% 30% 14 Ni(COD).sub.2 L10 AlMe.sub.2Cl 36% 29%

(83) The inventors have shown in the above experimental results that a metal-catalyzed, in particular, Ni-catalyzed transfer hydrocyanation reaction between alkyl nitriles and alkenes can be fully manipulated to produce either product selectively using simple driving forces. This exceptionally powerful synthetic tool could be applied to the catalytic hydrocyanation and retro-hydrocyanation of a wide range of structurally different molecules (>40 examples) without relying on the use of highly toxic HCN. In a broader context, the functional group metathesis strategy delineated in this invention will likely be a milestone in the development of reversible hydrofunctionalization reactions of alkenes that do not rely on the use of hazardous gases.