METHOD FOR SELECTIVE PALLADIUM-CATALYZED TELOMERIZATION OF SUBSTITUTED DIENES

Abstract

A method for the selective synthesis of a tail-to-head, or a head-to-head, or a tail-to-tail telomer from an unsymmetrical diene by polymerizing the diene in the presence of [Pd(C.sub.3H.sub.5)COD]BF.sub.4 and dicyclohexyl-[1-(2,4,6-trimethylphenyl)imidazol-2-yl]phosphane, Pd(OAc).sub.2 and triphenylphosphine, or [Pd(C.sub.3H.sub.5)COD]BF.sub.4 and tris(2,4-di-tert-butylphenyl)phosphite in combination with a polar protic alcohol, an acidic polar protic alcohol, a polar aprotic ether, or a non-polar aprotic hydrocarbon is provided.

Claims

1. A method for regioselective synthesis of a telomer from a diene comprising the step of polymerizing the diene in the presence of an active catalytic system containing: (a) an active catalyst precursor and a ligand, wherein (i) the active catalyst precursor is selected from the group consisting of [Pd(C.sub.3H.sub.5)COD]BF.sub.4 and Pd(OAc).sub.2; and (ii) the ligand is selected from the group consisting of dicyclohexyl-[1-(2,4,6-trimethylphenyl) imidazol-2-yl]phosphane, triphenylphosphine and tris(2,4-di-tert-butylphenyl)phosphite; and (b) a solvent comprising methanol, ethanol, propanol, iso-propanol, toluene, acetone, acetonitrile, trifluoroethanol, diethyl ether or tetrahydrofuran.

2. The method of claim 1, wherein the active catalyst precursor and the ligand have a molar ratio between 1:3 and 1:0.1.

3. The method of claim 1, wherein the active catalyst precursor is [Pd(C.sub.3H.sub.5)COD]BF.sub.4; the ligand is dicyclohexyl-[1-(2,4,6-trimethylphenyl)imidazol-2-yl]phosphane; and the solvent comprises methanol, ethanol, propanol, iso-propanol, toluene, acetone, or acetonitrile and wherein the telomer comprises a tail-to-head telomer.

4. The method of claim 3, wherein the tail-to-head telomer has a yield of greater than 60% by weight.

5. The method of claim 1, wherein the active catalyst precursor is [Pd(C.sub.3H.sub.5)COD]BF.sub.4; the ligand is triphenylphosphine; and the solvent comprises trifluoroethanol, and wherein the telomer comprises a head-to-head telomer.

6. The method of claim 5, wherein the head-to-head telomere has a yield of greater than 60% by weight.

7. The method of claim 1, wherein the active catalyst precursor is Pd(OAc).sub.2; the ligand is triphenylphosphine; and the solvent comprises trifluoroethanol, and wherein the telomer comprises a head-to-head telomer.

8. The method of claim 7, wherein the head-to-head telomere has a yield of greater than 60% by weight.

9. The method of claim 1, wherein the active catalyst precursor is [Pd(C.sub.3H.sub.5)COD]BF.sub.4; the ligand is tris(2,4-di-tert-butylphenyl)phosphite; and the solvent comprises diethyl ether, tetrahydrofuran or toluene, and wherein the telomer comprises a tail-to-tail telomer.

10. The method of claim 9, wherein the tail-to-tail telomere has a yield of greater than 60% by weight.

11. The method of claim 1, wherein the diene is a conjugated diene.

12. The method of claim 1, wherein the active catalytic system further contains a nucleophile.

13. The method of claim 12, wherein the nucleophile comprises an amine.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0011] By screening Pd precursors, phosphines, solvents and reaction conditions, a new catalytic system, i.e., [Pd(C.sub.3H.sub.5)COD]BF.sub.4/22 in the presence of MeOH, was found to provide excellent yields and selectivities of the tail-to-head telomer (1)

##STR00004##

[0012] Moreover, two catalytic systems, i.e., (a) [Pd(C.sub.3H.sub.5)COD]BF.sub.4/22 in the presence of TFE and (b) Pd(OAc).sub.2/PPh.sub.3 in TFE, were key in providing excellent yields and selectivities of the head-to-head telomer (2). In addition, [Pd(C.sub.3H.sub.5)COD]BF.sub.4/27 in the presence of ethereal solvents like Et.sub.2O and THF, or toluene were found to provide excellent yields and selectivities of the tail-to-tail telomer (3). Furthermore, telomerization of dimethylbutadiene, a symmetric diene, was successfully performed using the catalytic system Pd(OAc).sub.2/PPh.sub.3 (triphenylphosphine). Accordingly, the present invention provides a method for regioselective synthesis of tail-to-head, head-to-head, and tail-to-tail telomers from dienes by polymerizing a diene in the presence of specific combinations of [Pd(C.sub.3H.sub.5)COD]BF.sub.4/22, Pd(OAc).sub.2/PPh.sub.3, or [Pd(C.sub.3H.sub.5)COD]BF.sub.4/27 and polar protic solvents like MeOH (methanol), polar aprotic solvents like Et.sub.2O (diethyl ether), or acidic polar protic solvents like TFE (trifluoroethanol). As used herein, “regioselective synthesis” refers to the selective production of a particular telomer.

[0013] As used herein, a diene is a hydrocarbon containing two carbon double bonds that may or may not be adjacent to each other. In some embodiments, the diene used in the accordance with this invention is a conjugated diene, i.e., a molecule having double bonds separated by one single bond. In other embodiment, the diene is an unconjugated diene, i.e., a compound having double bonds separated by two or more single bonds. Conjugated and unconjugated dienes of this invention can contain from 4 to 15 carbon atoms per molecule. Conjugated dienes containing between 4 to 15 carbon atoms per molecule include, but are not limited to, isoprene, chloroprene, 2-methoxy-1,3-butadiene, 1,3-butadiene, 1,3-pentadiene, 2,3-dimethyl-1,3-butadiene, 1,3-hexadiene, 7-methyl-3-methylene-1,6-octadiene (myrcene), farnesene, and the like. If desired, mixtures of two or more dienes can be employed in the instant methods.

[0014] In a certain embodiment, the conjugated diene has the structure of Formula I:

##STR00005##

wherein R.sup.1 is a hydrogen, halo or C.sub.1-C.sub.11 alkyl, alkoxy, alkylene, aryl, cycloalkane or alkenyl group. As used herein, “halo” refers to F, Cl, Br, or I.

[0015] “Alkyl” means a linear saturated monovalent hydrocarbon radical of one to six carbon atoms or a branched saturated monovalent hydrocarbon radical of three to six carbon atoms, e.g., methyl, ethyl, propyl, 2-propyl, butyl (including all isomeric forms), or pentyl (including all isomeric forms), and the like.

[0016] “Alkoxy” means a radical —OR where R is alkyl as defined herein, e.g., methoxy, ethoxy, propoxy, or 2-propoxy, n-, iso-, or tert-butoxy, and the like.

[0017] “Alkylene” means a linear saturated divalent hydrocarbon radical of one to six carbon atoms or as otherwise indicated or a branched saturated divalent hydrocarbon radical of two to six carbon atoms or as otherwise indicated, e.g., methylene, prop-2,2-diyl, eth-1,2-diyl, prop-1,3-diyl, 1-methylprop-1,3-diyl, 2-methylprop-1,3-diyl, but-1,4-diyl (including all isomeric forms), or pent-1,5-diyl (including all isomeric forms), and the like.

[0018] “Aryl” means a monovalent, monocyclic or fused bicyclic hydrocarbon radical of 6 to 12 ring atoms, wherein the ring comprising a monocyclic radical ring is aromatic and wherein at least one of the fused rings comprising a bicyclic radical is aromatic. Unless otherwise stated, the valency of the group may be located on any atom of any ring within the radical, valency rules permitting. More specifically the term aryl includes, but is not limited to, phenyl, naphthyl, indanyl (including, for example, indan-5-yl, or indan-2-yl, and the like) or tetrahydronaphthyl (including, for example, tetrahydronaphth-1-yl, tetrahydronaphth-2-yl, and the like), and the like.

[0019] “Cycloalkane” refers to saturated cyclic hydrocarbons having from 3 to about 10 carbon atoms, more usually from about 5 to about 8 carbon atoms. Non-limiting examples of cycloalkanes include cyclopentane, cyclohexane, cycloheptane, and cyclooctane.

[0020] “Alkenyl” means a linear monovalent hydrocarbon radical of two to six carbon atoms or a branched monovalent hydrocarbon radical of three to six carbon atoms containing one or two double bonds, e.g., ethenyl, propenyl (including all isomeric forms), 1-methylpropenyl, butenyl (including all isomeric forms), or pentenyl (including all isomeric forms) and the like.

[0021] Generally, the active catalytic system and method of this invention includes the use of an active catalyst precursor, a ligand, a nucleophile, a solvent and other optional additives. The active catalytic system of the present invention provides effective production of a particular telomer. As used herein, “ligand” refers to a component required to promote the formation of the active catalyst from the active catalyst precursor, in-situ. As used herein, an “active catalyst precursor” refers to an organometallic complex of Palladium and a stabilizing or coordinating ligand. An active catalyst precursor can be used in combination with an additional additive or ligand to generate an active catalyst in-situ. As used herein, “active catalyst” refers to the resulting combination of an active catalyst precursor, an additive and/or a ligand, required for making the reaction greater in effectiveness towards the production of a particular telomer.

[0022] As indicated, the catalytic system of this invention uses either [Pd(C.sub.3H.sub.5) (COD)]BF.sub.4/22, Pd(OAc).sub.2/PPh.sub.3, or [Pd(C.sub.3H.sub.5) (COD)]BF.sub.4/27 as the precursor and ligand combination. In one embodiment, [Pd(C.sub.3H.sub.5) (COD)]BF.sub.4/22 is used in the synthesis of a tail-to-head or head-to-head telomer. In another embodiment, Pd(OAc).sub.2/PPh.sub.3 is used in the synthesis of a head-to-head telomer. In another embodiment, [Pd(C.sub.3H.sub.5) (COD)]BF.sub.4/27 is used in the synthesis of the tail-to-tail telomer. Selectivity for a particular telomer can be achieved when the molar ratio of precursor to ligand is between 1:3 and 1:0.1, or more preferably between 1:2 and 1:0.5, or most preferably 1:1.5 to 1:1. Similarly, precursor loading in the present method can be in the range of 0.5 to 5 mol %, or more preferably in the range of 0.5 to 3 mol %, or most preferably in the range of 0.5 to 1 mol %.

[0023] In certain embodiments, solvents like TFE, MeOH, Et.sub.2O or a combination thereof are used in the present method. In particular embodiments, the combination of [Pd(C.sub.3H.sub.5)COD]BF.sub.4/22 and MeOH is selective for a tail-to-head telomer, whereas the combination of [Pd(C.sub.3H.sub.5)COD]BF.sub.4/22 and TFE or Pd(OAc).sub.2/PPh.sub.3 in TFE is selective for a head-to-head telomer, and the combination of [Pd(C.sub.3H.sub.5) (COD)]BF.sub.4/27 and Et.sub.2O is selective for a tail-to-tail telomer.

[0024] The method of the invention can be carried out in the presence of a compound having at least one active hydrogen atom, i.e., a nucleophile such as an amine, alcohol, water or carbanion precursor. In particular embodiments, the nucleophile is a primary or secondary amine. Examples of amines of use in the method of the invention include, but are not limited to, n-butylamine, dimethyl amine, and diethyl amine as well as the amines presented in Table 12. In certain embodiments the molar ratio of diene to nucleophile is in the range of about between 1:3 and 1:0.1, or more preferably between 1:2 and 1:0.5, or most preferably 1:1.5 to 1:0.5.

[0025] The telomerization reaction of this invention can be carried out continuously, semi-batch or batch-wise. Moreover, depending on the nature of the starting material, the reaction can be carried out at a temperature between −20 and 180° C. Preferably, the temperature is in the range from 20 to 150° C. More particularly, the temperature is in the range from 20 to 70° C.

[0026] As is known in the art, telomerization is a chemical reaction that creates short chain polymers, called oligomers, composed of between two to ten repeating units. In some embodiments, the method of the invention results in production of a dimer, trimer, tetramer, pentamer, hexamer, heptamer or octamer. In one embodiment, the monomeric units of the oligomer are arranged in a tail-to-head orientation. In another embodiment, the monomeric units of the oligomer are arranged in a head-to-head orientation. In another embodiment, the monomeric units of the oligomer are arranged in a tail-to-tail orientation. In certain embodiments, greater than 60%, 70%, 80%, or 90% regioselectivity is achieved using the method of this invention. Furthermore, yields using the method of the invention can be in the range of 50-100%, 60-100%, 70-100%, 80-100% or 90-100%.

[0027] Telomers synthesized in accordance with the method of the invention can be linear, branched or trienes. By way of illustration, the products presented in Table 1 can be obtained by telomerization of a compound of Formula I in accordance with the method of this invention.

TABLE-US-00001 TABLE 1 [00006] Linkage Telomer Tail-To-Head Head-To-Head Tail-to-tail Linear [00007] [00008] [00009] Branched [00010] [00011] [00012] Triene [00013] [00014] [00015] R—H is a compound containing an active hydrogen. Pd = precursor, L = ligand.

[0028] The telomerization products prepared can be recovered via fractionation, distillation and/or crystallization, and may advantageously be employed as such or used for example for the synthesis of polymers, synthetic resins, surface-active agents, or non-naturally occurring terpene derivatives. Further, the diene adducts of the invention can serve as inexpensive intermediates and captive products for use in home and personal care products. Uses of these telomer terpene-like materials could also be envisioned as intermediates or captive products in markets related to uses of, or adjacent to, natural terpenes such as citronellal, citronellol, geraniol, menthol, myrcene, and other related products.

[0029] Additionally, diene adducts of this invention could be useful in mint oil, confectionary, cough and cold, tobacco, oral care, and nasal care.

Example 1: Experimental

[0030] Commercially available reagents were used as received without further purification. MeOH, NHEt.sub.2, and isoprene were freshly distilled under N.sub.2 according to reported procedures (Armarego & Chan (2009) Purification of Laboratory Chemicals, Elsevier). 1H, .sup.13C{H}, COSY, HSQC, HMBC and .sup.31P{1H} NMR spectra were recorded on VARIAN MERCURY-400 and VARIAN-400-MR spectrometers. .sup.1H and .sup.13C NMR chemical shifts were reported in parts per million (ppm) relative to CDCl.sub.3. The GC/MS analysis was carried out on an Agilent 7890A with a MS 5975C detector using a Column HP5-MS (30 m, 0.25 mm, 0.25 μm). Product ratios were obtained by direct analysis of isolated product by GC/MS using the following conditions: 50° C. for 1 minute, 50-100° C., 3° C./minute, 100-240° C., 20° C./minute.

[0031] General Procedure for Isoprene Telomerization with Diethylamine.

[0032] In a 5 ml flask, the palladium precursor, phosphine ligand, isoprene, diethylamine and solvent, were stirred for 24 hours at room temperature. The resulting solution was evaporated under vacuum, and then distilled in vacuo providing the telomer products. Selectivity was determined by GC/MS.

[0033] Synthesis of Telomer 1.

[0034] [Pd(C.sub.3H.sub.5) (COD)]BF.sub.4 (0.05 mmol), 22 (0.05 mmol), isoprene (10 mmol), diethylamine (9.6 mmol) and MeOH (2 ml), were stirred for 24 hours at room temperature. The resulting solution was handled in accordance with the general procedure providing telomer 1 as a colorless liquid in 85% yield and a 92/0/4/4 (1/2/3/4) ratio. .sup.1H NMR (CDCl.sub.3, 400 MHz) δ=5.678 (ddd, 1H, .sup.3J.sub.2, 1=17.6 Hz, .sup.3J.sub.2, 1′=10.4 Hz, .sup.3J.sub.2, 3=7.6 Hz, H-2); 5.254 (tq, 1H, .sup.3J.sub.6, 5=7.2 Hz, .sup.3J.sub.6, 9=1.2 Hz, H-6); 4.930 (br d, 1H, .sup.3J.sub.1, 2=17.2 Hz, H-1); 4.896 (br d, 1H, .sup.3J.sub.1′,2=10.4 Hz, H-1′); 2.855 (s, 2H, H-8); 2.431 (q, 4H, .sup.3J.sub.11, 12=7.2 Hz, H-11); 2.103 (m, 1H, H-3); 1.995 (m, 2H, H-5); 1.606 (s, 3H, Me.sub.(9)); 1.319 (m, 2H, H-4); 0.981 (t, 6H, .sup.3J.sub.12, 11=7.2 Hz, H-12); 0.959 (d, 3H, .sup.3J.sub.Mel0, 3=6.8 Hz, Me.sub.{10}). .sup.13C NMR (CDCl.sub.3, 400 MHz) δ=144.880 (C-2); 133.744 (C-7); 127.524 (C-6); 112.743 (C-1); 62.366 (C-8); 46.840 (C-11); 37.635 (C-3); 36.759 (C-4); 25.747 (C-5); 20.349 (C-10); 15.262 (C-9); 11.888 (C-12).

[0035] Synthesis of Telomer 2.

[0036] Pd(OAc).sub.2 (0.05 mmol), PPh.sub.3 (0.075 mmol), isoprene (10 mmol), diethylamine (9.6 mmol) and TFE (2 ml), were stirred for 24 hours at room temperature. The resulting solution was handled in accordance with the general procedure providing telomer 2 as a colorless liquid in an 86% yield and a 9/91/0/0 (1/2/3/4) ratio. 1H NMR (CDCl.sub.3, 400 MHz) δ=5.662 (ddd, 1H, .sup.3J.sub.2, 1=17.2 Hz, .sup.3J.sub.2, 1′=10 Hz, .sup.3J.sub.2, 3=7.6 Hz, H-2); 5.233 (br t, 1H, .sup.3J.sub.7, 8=6.8 Hz, H-7); 4.926 (br d, 1H, .sup.3J.sub.1, 2=17.0 Hz, H-1); 4.885 (br d, 1H, .sup.3J.sub.1′,2=10.4 Hz, H-1′); 3.038 (d, 2H, .sup.3J.sub.8, 7=6.8 Hz, H-8); 2.482 (q, 4H, .sup.3J.sub.11, 12=7.2 Hz, H-11); 2.055 (m, 1H, H-3); 1.959 (m, 2H, H-5); 1.604 (s, 3H, H-9); 1.364 (m, 2H, H-4); 0.995 (t, 6H, .sup.3J.sub.12, 11=7.2 Hz, H-12); 0.953 (d, 3H, .sup.3J.sub.10, 3=6.8 Hz, H-10). .sup.13C NMR (CDCl.sub.3, 400 MHz) δ=144.828 (C-2); 138.128 (C-6); 121.687 (C-7); 112.753 (C-1); 50.689 (C-8); 46.858 (C-11); 37.591 (C-3); 37.568 (C-5); 34.954 (C-4); 20.313 (C-10); 16.544 (C-9); 11.999 (C-12).

[0037] Synthesis of Telomer 3.

[0038] [Pd(C.sub.3H.sub.5)COD]BF.sub.4 (0.05 mmol), 27 (0.075 mmol), isoprene (10 mmol), diethylamine (9.6 mmol), Et.sub.2O (2 ml), were stirred for 24 h at 40° C. The resulting solution handled in accordance with the general procedure providing telomer 3 as a colorless liquid in 90% yield and a 4/0/90/6 (1/2/3/4) ratio. .sup.1H NMR (CDCl.sub.3, 400 MHz) 5=5.299 (tq, 1H, .sup.3J.sub.6,5=7.2 Hz, .sup.4J.sub.6,9=1.2 Hz, H-6); 4.702 (br s, 1H, H-1/H-1′); 4.673 (br s, 1H, H-1/H-1′); 2.884 (s, 2H, H-8); 2.453 (q, 4H, .sup.3J.sub.11,12=7.2 Hz, H-1); 2,020 (m, 4H, H-5 and H-4/H-3); 1.717 (s, 3H, Me(10)); 1.634 (s, 3H, Me(9)); 1.514 (m, 2H, H-3/H-4); 0.995 (t, 6H, .sup.3J.sub.12,11=7.2 Hz, H-11). .sup.13C NMR (CDCl.sub.3, 400 MHz) δ=146.218 (C-2); 133.988 (C-7); 127.367 (C-6); 109.931 (C-1); 62.363 (C-8); 46.640 (C-11); 37.603 (C-3/C-4); 27.864 and 27.598 (C-5 and C4/C3); 22.597 (C-10); 15.275 (C-9); 11.677 (C-12).

Example 2: Telomerization of Isoprene

[0039] A screening of various Pd precursors and ligands was first performed to evaluate their influence on the catalytic output of isoprene telomerization. The results using monophosphine ligands are summarized in Table 2.

[0040] The telomerization of isoprene with Pd/PPh.sub.3 and Pd/10 has been previously reported. Aiming to know the effect of the precursor under similar reaction conditions, Pd(OAc).sub.2, PdCl.sub.2 or [Pd(C.sub.3H.sub.5)COD]BF.sub.4 (COD=cyclooctadiene) were tested in the presence of PPh.sub.3 obtaining in all cases full conversion and a similar mixture of linear telomers (Table 2, Entries 1-2), with a slight increase in selectivity for telomer 1 when [Pd(C.sub.3H.sub.5) COD]BF.sub.4 was used (entry 3).

TABLE-US-00002 TABLE 2 1 [00016] 2 [00017] 3 [00018] 4 [00019] Yield Selectivity Entry.sup.a Ligand Telomers (%) (1/2/3/4)  1.sup.  PPh.sub.3 >99 51/29/19/1  2.sup.b PPh.sub.3 >99 55/12/25/8  3.sup.c PPh.sub.3 >99 70/8/22/0  4.sup.d PPh.sub.3 53 51/27/20/2  5.sup.  P[2,4,6(OMe).sub.3—C.sub.6H.sub.2].sub.3 2 6/94/0/0  6.sup.e P[2,4,6(OMe).sub.3—C.sub.6H.sub.2].sub.3 19 5/90/5/0  7.sup.c P[2,4,6(OMe).sub.3—C.sub.6H.sub.2].sub.3 83 5/94/1/0  8 P(2-OMe—C.sub.6H.sub.4).sub.3 73 52/38/10/0  9 P(3,5-CF.sub.3—C.sub.6H.sub.3).sub.3 0 — 10.sup.  P(4-CF.sub.3—C.sub.6H.sub.4).sub.3 4 55/0/45/0 11.sup.  P(C.sub.6F.sub.5).sub.3 7 70/11/15/4 .sup.aReaction conditions: Pd(OAc).sub.2 (0.05 mmol), Ligand (0.075 mmol), isoprene (10 mmol), NHEt.sub.2 (9.6 mmol), MeOH (2 ml), room temperature, 24 hours. .sup.bPdCl.sub.2 (0.05 mmol) used instead of Pd(OAc).sub.2. .sup.c[Pd(C.sub.3H.sub.5)COD]BF.sub.4 (0.05 mmol) used instead of Pd(OAc).sub.2. .sup.d50 μl of H.sub.2O used as additive. .sup.e48 hours.

[0041] As PdCl.sub.2 was poorly soluble in MeOH, Pd(OAc).sub.2 was selected as precursor for subsequent experiments. Upon addition of water to the reaction mixture, the yield decreased, but the selectivity remained unchanged (Entry 4, compared with Entry 1).

[0042] The catalytic systems bearing the electron rich phosphine P[2,4,6(OMe).sub.3-C.sub.6H.sub.2].sub.3 (10) afforded high selectivity toward telomer 2. However, the yields strongly depended on the palladium precursor used, achieving up to 83% yield and 94% selectivity when [Pd(C.sub.3H.sub.5)COD]BF.sub.4 was used (Entries 5-7). The tris(di-o-methoxyphenyl)phosphine ligand, which is a basic phosphine with less steric hindrance than ligand 10, was also tested (Entry 8) but provided lower selectivity. The use of fluorinated ligands provided very low conversion with no relevant selectivities (Entries 9-11).

[0043] The following monophosphines and diphosphines were also tested and the results are summarized in Tables 3-4, and 10.

##STR00020## ##STR00021##

TABLE-US-00003 TABLE 3 1 [00022] 2 [00023] 3 [00024] 4 [00025] Yield Selectivity Entry.sup.a Ligand Telomers (%) (1/2/3/4)  1.sup.b 17  78.sup.  70/7/20/3  2.sup.  18  93.sup.  75/8/15/2  3.sup.  19  90.sup.  76/9/14/1  4.sup.b 20  92.sup.  73/6/21/0  5.sup.  21   0.sup.c —  6.sup.  22  11.sup.  83/3/10/4  7.sup.d 22  88.sup.  90/0/6/4  8.sup.d 23 100.sup.  67/33/0/0  9.sup.d 23 100.sup.  60/40/0/0 10.sup.d 25  80.sup.  75/25/0/0 .sup.aReaction conditions: Pd(OAc).sub.2 (0.05 mmol), L (0.075 mmol), isoprene (10 mmol), NHEt.sub.2 (9.6 mmol), MeOH (2 ml), room temperature, 24 hours. .sup.bPd/L ratio = 1/1. .sup.cHydroamination products were only formed (29% yield monomers). .sup.d[Pd(C.sub.3H.sub.5)COD]BF.sub.4 (0.05 mmol) used instead of Pd(OAc).sub.2.

[0044] Phosphines bearing a biphenyl or phenyl-azol moiety are very successful ligands in various transition metal catalyzed processes. Phosphines 17, 18, 19 and 20 provided close to 90% yield with moderate selectivity to telomer 1 (Entries 1-4). However, the more sterically hindered phosphine 21 did not provide telomerization products and only hydroamination products were recovered (Entry 5). Phosphorus ligands bearing pyrrole, imidazole or indole moieties were also tested (Entries 6-10). The catalytic system bearing ligand 22 afforded low yield and high selectivity to telomer 1 (Entry 6). Both yield and selectivity were improved when [Pd(C.sub.3H.sub.5)COD]BF.sub.4 was used as precursor, achieving 88% yield and 90% selectivity (Entry 7). The catalysts bearing phosphines bearing a pyrrole group (23-25) provided excellent conversions, but selectivity for telomer 1 decreased (Entries 8-10).

[0045] The influence of diphosphine ligands with different bite angles was also evaluated in this reaction. The results are summarized in Table 4.

TABLE-US-00004 TABLE 4 1 [00026] 2 [00027] 3 [00028] 4 [00029] Yield Selectivity Entry.sup.a Ligand Telomers (%) (1/2/3/4) 1 dppm 26.sup.  71/14/14/1 2 dppe 59.sup.  76/5/19/0 3 dppb 69.sup.  71/10/19/0 4 dppp 69.sup.  69/12/19/0 5 BINAP  0.sup.  — 6 DPEphos  0.sup.b — 7 XANTphos  5.sup.  52/24/24/0 8 XANTphos(NEt).sub.2 25.sup.  66/13/18/3 .sup.aReaction conditions: [Pd(C.sub.3H.sub.5)COD]BF.sub.4 (0.05 mmol), ligand (0.05 mmol), isoprene (10 mmol), NHEt.sub.2 (9.6 mmol), MeOH (2 ml), room temperature, 24 hours. .sup.bHydroamination products were only formed (45% yield monomers).

[0046] Initial tests with diphosphines dppm, dppe, dppb and dppp showed that the most relevant results were obtained using [Pd(C.sub.3H.sub.5)COD]BF.sub.4 as precursor, rather than Pd(OAc).sub.2 or PdCl.sub.2. These ligands provided similar results in terms of selectivity, despite their difference in bite angles (Table 4, Entries 1-4). The systems bearing diphosphines BINAP, DPEphos or XANTphos were not active in the telomerization of isoprene (Entries 5-7), and only the bis-diethylamino derivative of XANTphos provide an active system, although low yield was obtained (Entry 8). Similar to the results obtained with the bulky monophosphine 21 the products of hydroamination were formed using DPEphos. It could be concluded that the use of bulky ligands did not favour the coordination of two molecules of isoprene, and consequently favoured the hydroamination of the substrate under these conditions.

[0047] From this analysis, it was concluded that [Pd(C.sub.3H.sub.5)COD]BF.sub.4/22 was an excellent catalytic system for the telomerization of isoprene providing high yields and selectivities for the telomer 1. In this context, the Pd/L ratio, Pd loading, solvent, and temperature (Tables 5-7) were analyzed.

TABLE-US-00005 TABLE 5 1 [00030] 2 [00031] 3 [00032] 4 [00033] Pd/L Yield Selectivity Entry.sup.a ratio Pd loading Telomers (%) (1/2/3/4) 1 1/2   0.5 69 90/0/6/4 2 1/1.5 0.5 88 90/0/6/4 3 1/1   0.5 85 90/0/6/4 4 1/0.5 0.5 77 90/0/7/3 5 1/1   1 89 67/20/13/0 6 1/1   3 95 60/25/15/0 .sup.aReaction conditions: [Pd(C.sub.3H.sub.5)COD]BF.sub.4, 22, isoprene (10 mmol), NHEt.sub.2 (9.6 mmol), MeOH (2 ml), 24 hours, room temperature.

[0048] This analysis indicated that when the Pd/L ratio was varied, yield was slightly altered but the selectivity remained practically unchanged (Entries 1-4). Noteworthy, the use of a 1/1 ratio provided 85% yield and 90% selectivity to telomer 1 (Entry 3). When 1 or 3 mol % of Pd were used (Entries 5 and 6), the yield reached 95% but the selectivity to 1 decreased to ca. 60% under these conditions. Different palladium species could be formed at different concentrations.

[0049] The effect of various protic and aprotic solvents was also evaluated (Table 6).

TABLE-US-00006 TABLE 6 1 [00034] 2 [00035] 3 [00036] 4 [00037] Yield Selectivity Entry.sup.a Solvent Telomers (%) (1/2/3/4) 1 EtOH 81 90/0/7/3 2 PrOH 94 88/0/9/3 3 .sup.iPrOH 79 87/0/10/3 4 Toluene 65 90/0/9/1 5 Acetone 65 85/0/11/4 6 THF 58 85/0/14/1 7 ACN 67 69/15/13/3 8 Hexane 5 36/11/52/1 9 TFE 86 9/91/0/0 .sup.aReaction conditions: [Pd(C.sub.3H.sub.5)COD]BF.sub.4 (0.05 mmol), 22 (0.05 mmol), isoprene (10 mmol), NHEt.sub.2 (9.6 mmol), solvent (2 ml), 24 hours, room temperature. .sup.bPd(OAc).sub.2 (0.05 mmol) used instead of [Pd(C.sub.3H.sub.5)COD]BF.sub.4

[0050] The use of EtOH, PrOH and .sup.1PrOH provided high yields (>79%) and selectivities to 1 (>87%) (Entries 1-3). When toluene, acetone and THF were tested, high selectivities to 1 were also obtained, but yields slightly decrease (Entries 4-6). While acetonitrile provided moderate yield and selectivities to telomer 1 (Entry 7), low yield and moderate selectivity to telomer 3 were obtained by hexane (Entry 8). Furthermore, the use of TFE provided a striking selectivity to telomer 2 (91%) in high yield (Entry 9) This latter system was further analyzed and the results are described in Tables 8 and 9.

[0051] The influence of the isoprene/NHEt.sub.2 molar ratio on the catalytic performance of this system was studied (Table 7).

TABLE-US-00007 TABLE 7 1 [00038] 2 [00039] 3 [00040] 4 [00041] Isoprene/NHEt.sub.2 Temperature Yield Selectivity Entry.sup.a Molar Ratio (°C.) Telomers (%) (1/2/3/4) 1.sup.  1/1.37 r.t. 34 78/12/10/0 2.sup.  1/2.74 r.t. 25 77/10/13/0 3.sup.b 1/0.96 −10 19 94/0/4/2 4.sup.  1/0.96   40 91 68/16/16/0 .sup.aReaction conditions: [Pd(C.sub.3H.sub.5)COD]BF.sub.4 (0.05 mmol), 22 (0.05 mmol), isoprene (10 mmol), NHEt.sub.2, MeOH (2 ml), 24 hours. .sup.b72 hours

[0052] Increasing the concentration of NHEt.sub.2 resulted in a drop in both yield and selectivity of telomer 1 (Entries 1 and 2). Further, when the reaction was carried out at −10° C., low yield (19%) and high selectivity (94%) were achieved (Entry 3). However, at 40° C., the selectivity for telomer 1 decreased to 68% (Entry 4).

[0053] In the previous screening of solvents it was found that when the reaction was driven in trifluoroethanol, telomer 2 was obtained in excellent yields and selectivities. Thus, other parameters of the reaction were studied. Initially, the effect of the Pd loading was evaluated, the results of which are presented in Table 8.

TABLE-US-00008 TABLE 8 1 [00042] 2 [00043] 3 [00044] 4 [00045] Pd loading Yield Selectivity Entry.sup.a (mol %) Telomers (%) (1/2/3/4) 1 0.5 46 7/93/0/0 2 1 66 9/91/0/0 3 3 86 3/97/0/0 .sup.aReaction conditions: [Pd(C.sub.3H.sub.5)COD]BF.sub.4 (0.1 mmol), 22 (0.1 mmol), isoprene (10 mmol), NHEt.sub.2 (9.6 mmol), TFE (2 ml), 24 hours, room temperature.

[0054] The increase in Pd precursor loading revealed a significant influence on both yield and selectivity (Entries 1-3). Increasing catalyst precursor from 0.5% to 3% significantly increased yields of telomer products to 86% (Entry 3). Selectivity also increased, providing 97% of telomer 2 (Entry 3).

[0055] When the amount of NHEt.sub.2 was increased (Table 9), the selectivity toward telomer 2 decreased, favoring the formation of telomer 1 up to 67% when 2.74 eq. of NHEt.sub.2 were used (Entries 1 and 2).

TABLE-US-00009 TABLE 9 Isoprene/NHEt.sub.2 Yield Selectivity Entry.sup.a Molar Ratio Telomers (%) (1/2/3/4) 1 1/1.37 59 26/74/0/0 2 1/2.74 91 67/29/4/0 .sup.aReaction conditions: [Pd(C.sub.3H.sub.5)COD]BF.sub.4 (0.1 mmol), 22 (0.1 mmol), isoprene (10 mmol), NHEt.sub.2, TFE (2 ml), 24 hours, room temperature.

[0056] The behavior of other catalytic systems such as Pd(OAc).sub.2/PPh.sub.3 in TFE was also determined. Using this catalytic system, 86% yield and 91% selectivity toward telomer 2 was achieved. Interestingly, conversion and selectivity were similar to that obtained with Pd/22 as the catalytic system, which indicated that under these reaction conditions, the selectivity was determined by the solvent.

[0057] The first selective system affording telomer 3 that was identified was Pd(OAc).sub.2/PPh.sub.3 in the presence of DMF and different amounts of NEt.sub.3, which provided good yields (63%-74%) and selectivity (81%-87%) (Table 10, Entries 1 and 2). Using the conditions that provided highest selectivity to 3, that is using 20 mmols of NEt.sub.3 as additive, different ligands were tested. The use of 26, provided low yield (29%) and high selectivity to 3 (84%) (Entry 3). Moderate yields (36%-58%) and high selectivity to 3 was obtained using dppp (88%) and dppb (91%) (Entries 4 and 5). The catalytic system [Pd(C.sub.3H.sub.5)COD]BF.sub.4/27 in presence of DMF provided moderate yield (61%) and high selectivity to 3 (89%) (Entry 6). Yield was increased to 81% using THF instead of DMF with a selectivity up to 87% to 3 (Entry 7), and improved further using the same catalyst by replacing THF with Et.sub.2O at slightly higher reaction temperature (Entry 10).

TABLE-US-00010 TABLE 10 Yield Selec- Telomers tivity Entry.sup.a Pd/L system Solvent (%) (1/2/3/4)  1.sup.b,e Pd(OAc).sub.2/PPh.sub.3 DMF/NEt.sub.3 74 3/10/81/6  2.sup.e Pd(OAc).sub.2/PPh.sub.3 DMF 63 2/8/87/3  3.sup.e Pd(OAc).sub.2/26 DMF 29 7/9/84/0  4.sup.f Pd(OAc).sub.2/dppp DMF 36 3/5/88/4  5.sup.f Pd(OAc).sub.2/dppb DMF 58 2/5/91/2  6.sup.e [Pd(C.sub.3H.sub.5)COD]BF.sub.4/27 DMF 61 4/2/89/5  7.sup.c,e [Pd(C.sub.3H.sub.5)COD]BF.sub.4/27 THF 81 6/0/87/7  8.sup.d,e [Pd(C.sub.3H.sub.5)COD]BF.sub.4/27 Hexane 41 2/2/94/2  9.sup.d,e [Pd(C.sub.3H.sub.5)COD]BF.sub.4/27 Toluene 75 4/0/94/2 10.sup.d,e [Pd(C.sub.3H.sub.5)COD]BF.sub.4/27 Et.sub.2O 90 4/0/90/6 .sup.aConditions: [Pd] (0.05 mmol), L, isoprene (10 mmol), NHEt.sub.2 (9.6 mmol), solvent (2 ml), 80° C., 24 h, sealed tube. .sup.bNEt.sub.3 (10 mmols). .sup.cRoom temperature. .sup.dReaction temperature: 40° C. .sup.ePd/L ratio: 1/1.5. .sup.fPd/L ratio: 1/1.

[0058] Efforts to improve upon the highest yield/selectivity ratio using [Pd(C.sub.3H.sub.5)COD]BF.sub.4/27 was further explored by evaluating the effect of the [Pd]precursor, [Pd] loading, the use of Et.sub.3N as additive, temperatures and different solvents (Table 11). The best results remained to be [Pd(C.sub.3H.sub.5)COD]BF.sub.4/27 in the presence of Et.sub.2O. Therefore, it has been found that Et.sub.3N is not a necessary additive when [Pd(C.sub.3H.sub.5)COD]BF.sub.4 is used in combination with ligand 27 and ethereal solvents like THF or Et.sub.2O.

TABLE-US-00011 TABLE 11 Pd Yield Selectivity Entry.sup.a mol % Solvents Telomeres (1/2/3/4)  1.sup.d 0.5 THF 81 6/0/87/7  2.sup.b,d 0.5 THF 0 —  3.sup.b,e 0.5 THF 0 —  4.sup.d 1 THF 82 13/0/72/15  5.sup.d 3 THF 72 23/1/53/23  6.sup.c,d 0.5 THF 22 5/0/90/5  7.sup.f 0.5 THF 91 7/0/85/8  8.sup.f 0.5 DMF 25 6/0/89/5  9.sup.f 0.5 DCM 85 32/6/27/35 10.sup.f 0.5 Hexane 41 2/2/94/2 11.sup.f 0.5 Toluene 75 4/0/94/2 12.sup.f 0.5 Et.sub.2O 90 4/0/90/6 .sup.aConditions: [Pd(C.sub.3H.sub.5)COD]BF.sub.4, 27 (1.5 eq.), isoprene (10 mmol), NHEt.sub.2 (9.6 mmol), solvent (2 ml). .sup.bPd(OAc).sub.2 (0.05 mmol) used as precursor. .sup.cNEt.sub.3 (15 mmols) used as additive. .sup.dReaction temperature: room temperature. .sup.eReaction temperature: 70° C. .sup.fReaction temperature: 40° C. All reactions were carried out for 24 hours.

[0059] In order to know the influence of the nucleophile, the following amines were tested under the catalytic system that provided the best yield and selectivity towards telomer 2 using diethylamine: diisopropylamine (iPr.sub.2NH), dibenzylamine (Bn.sub.2NH), morpholine, and cyclopentylamine. The results of this analysis are presented in Table 12.

##STR00046##

TABLE-US-00012 TABLE 12 Amine Yield (%) Selectivity (%) 2 86 91 28  5 <90 29 Trace 82 30 67 89 31 34 91

[0060] High selectivity toward the telomers head-to-head (28-31) was obtained in all cases, although yield strongly depended on the hindrance of the secondary amine. Thus, Compounds 28 and 29 were obtained in very low yield using the bulky amines i-Pr.sub.2NH and Bn.sub.2NH.

[0061] Based upon the above-referenced analyses, optimal yield and selectivity of telomer 1 is achieved using [Pd(C.sub.3H.sub.5) COD]BF.sub.4/22 and HNEt.sub.2 in combination with a variety of solvents under the conditions listed in Table 13. Similarly, optimal yield and selectivity of telomer 2 is achieved using [Pd(C.sub.3H.sub.5)COD]BF.sub.4/22 (or Pd(OAc).sub.2, PPh.sub.3) and HNEt.sub.2 in combination with TFE under the conditions listed in Table 13. Further, optimal yield and selectivity of telomer 3 is achieved using [Pd(C.sub.3H.sub.5) COD] BF.sub.4/27 and HNEt.sub.2 in combination with ethers such as Et.sub.2O or THF under the conditions listed in Table 13.

TABLE-US-00013 TABLE 13 Telomer Condition 1.sup.a 2.sup.b 3.sup.c Pd/L ratio 1:0.5* to 1:0.5* to 1:0.5* to 1:2.sup.# 1:2.sup.# 1:2.sup.# Pd loading 0.5 mol %* to 0.5 mol %* to 0.5 mol %* to 0.9 mol %.sup.# 3 mol %* 0.9 mol %.sup.# Isoprene/HNEt.sub.2 1:0.51* to 1:0.50* to 1:0.51.sup.# to ratio 1:1.36.sup.# 1:1.36.sup.# 1:1.36.sup.# Temperature −10° C.* to −10° C.* to 28° C.*.sup.# to 49° C..sup.# 28° C..sup.# 40° C.* .sup.a[Pd(C.sub.3H.sub.5)COD]BF.sub.4/22/MeOH. .sup.b[Pd(C.sub.3H.sub.5)COD]BF.sub.4/22/TFE. .sup.c[Pd(C.sub.3H.sub.5)COD]BF.sub.4/27/Et.sub.2O. *Yield lower. .sup.#Selectivity lower.

Example 3: Telomerization of Other Dienes

[0062] There are very few examples of telomerization of dienes other than butadiene and isoprene (Consiglio & Waymouth (1989) supra; Clement, et al. (2008) supra; van Leeuwen, et al. (2011) supra; Grotevendt, et al. (2007) supra; Tschan, et al. (2010) supra). Accordingly, the instant analysis was extended to assess the telomerization of dimethylbutadiene (Scheme 3).

##STR00047##

[0063] The results obtained in the telomerization of this substrate using Pd(OAc).sub.2/PPh.sub.3 as a catalytic system are presented in Table 14.

TABLE-US-00014 TABLE 14 Isoprene/ Conver- Yield NHEt.sub.2 Temp. sion Telomers Selectivity Entry.sup.a Molar Ratio (° C.) (%) (%) (32/33/34/35/36) 1 1/0.96 r.t. 0 0 — 2 1/0.96 70 72 53 84/0/0/0/16 3 1/1.94 70 64 51 76/0/0/0/24 4.sup.b 1/0.96 70 0 0 — 5.sup.c 1/0.96 70 65 57 88/0/4/1/7 .sup.aReaction conditions: Pd(OAc).sub.2 (0.05 mmol), PPh.sub.3 (0.075 mmol), dimethylbutadiene (10 mmol), NHEt.sub.2 MeOH (2 ml), 24 hours. .sup.bTFE (2 ml) was used instead of MeOH. .sup.cdppe (0.05 mmol).

[0064] When the reaction was carried at room temperature, telomerization products were not detected (Entry 1). However, upon increasing the temperature to 70° C., a mixture of telomer 32 and the monomer 36 was obtained (Entry 2). Both products were easily separated by distillation in vacuo. It is noteworthy that the branched product 33 was not observed either by NMR or by GC/MS techniques. When the amount of diethylamine was increased, conversion was similar, but the amount of 36 increased (Entry 3). Unexpectedly, using TFE as the solvent, no conversion was observed (Entry 4). However, the replacement of triphenylphosphine by a diphosphine (dppe) provided a similar conversion (57%) and the selectivity increased to 88%, decreasing significantly the monomer 36 (Entry 5).