Aryl phosphines with fused ring ortho-alkoxy substitution

Abstract

An aryl phosphine with fused ring ortho-alkoxy substitution that includes an aryl monophosphine and an aryl bi-sphosphme.

Claims

1. An aryl phosphine of Formula (I): ##STR00033## where n is an integer in a range from 1 to 3, where R.sup.1 and R.sup.3 are independently selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, and a substituted or unsubstituted phenyl ring, where each R.sup.2 and R.sup.2 is independently selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, and a substituted or unsubstituted phenyl ring, where R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are independently selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, a substituted or unsubstituted cycloalkyl having 3 to 18 carbons, a halogen, and a substituted or unsubstituted phenyl ring, where permissible substituents on R.sup.1, R.sup.2, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are functional groups that include heteroatoms selected from the group consisting of oxygen, nitrogen, halogens, sulfur, boron, phosphorus, and silicon.

2. The aryl phosphine of claim 1, wherein R.sup.4 and R.sup.5 are independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, adamantyl, phenyl, biphenyl, and cyclohexyl.

3. The aryl phosphine of claim 1, where R.sup.4 and R.sup.5 together with the phosphorus atom form a 5- , 6-, or 7- membered ring.

4. The aryl phosphine of claim 1, where R.sup.4 and R.sup.5 are independently selected from the group consisting of Formula (II) to (X): ##STR00034## ##STR00035## where m is 1 or 2, where Q.sup.1, Q.sup.2, and Q.sup.5 are independently selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, a substituted or unsubstituted cycloalkyl having 3 to 18 carbons, a halogen, and a substituted or unsubstituted phenyl ring, Q.sup.3 is selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, and a substituted or unsubstituted phenyl ring, each Q.sup.4 and Q.sup.4 is independently selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, and a substituted or unsubstituted phenyl ring, where u is an integer in a range from 0 to 2, where v is an integer in a range from 0 to 2, and where when R.sup.4 and R.sup.5 are both Formula (X), R.sup.4 and R.sup.5 are optionally covalently bound together at the ortho position to the respective C atoms in Formula (X).

5. The aryl phosphine of claim 1, where the aryl phosphine is selected from the group consisting of: ##STR00036##

6. An aryl phosphine of Formula (I): ##STR00037## where n is an integer in a range from 1 to 3, where R.sup.1 and R.sup.3 are independently selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, and a substituted or unsubstituted phenyl ring, where each R.sup.2 and R.sup.2 is independently selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, and a substituted or unsubstituted phenyl ring, where R.sup.4 is selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, a halogen, a substituted or unsubstituted cycloalkyl having 3 to 18 carbons, and a substituted or unsubstituted phenyl ring, where permissible substituents on R.sup.1, R.sup.2, R.sup.2, R.sup.3 R.sup.4, R.sup.6, and R.sup.7 are functional groups that include heteroatoms selected from the group consisting of oxygen, nitrogen, halogen, sulfur, boron, phosphorus, and silicon, and where R.sup.5 is a bridging group that includes an aromatic ring and connects the aryl phosphine of Formula (I) to a second phosphine.

7. The aryl phosphine of claim 6, where R.sup.5 and the second phosphine together form a structure selected from the group consisting of Formulae (II) to (IV): ##STR00038##

8. An aryl phosphine of Formula (I): ##STR00039## where n is an integer in a range from 1 to 3, where R.sup.1 and R.sup.3 are independently selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, and a substituted or unsubstituted phenyl ring, where each R.sup.2 and R.sup.2 is independently selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, and a substituted or unsubstituted phenyl ring, where R.sup.4 is selected from the group consisting of H, a substituted or unsubstituted alkyl having 1 to 18 carbons, a halogen, a substituted or unsubstituted cycloalkyl having 3 to 18 carbons, and a substituted or unsubstituted phenyl ring, where permissible substituents on R.sup.1, R.sup.2, R.sup.2, R.sup.4, R.sup.6, and R.sup.7 are functional groups that include heteroatoms selected from the group consisting of oxygen, nitrogen, halogen, sulfur, boron, phosphorus, fluorine, and silicon, and where R.sup.5 is a bridging group selected from the group consisting of Formulae (II) to (XVII): ##STR00040## ##STR00041## where Z is the aryl phosphine of Formula (I), where R.sup.8 and R.sup.9 are independently selected from H and an alkyl having 4 carbons, where R.sup.10 is selected from the group consisting of C and S, where R.sup.11 is selected from the group consisting of O and S, where R.sup.12, R.sup.13, R.sup.14 and R.sup.15 are each independently selected from the group consisting of C and O, where R.sup.16 is selected from the group consisting of N and C, with the proviso that when R.sup.16 is N then R.sup.14 and R.sup.15 are C.

9. The aryl phosphine of claim 8, where the aryl phosphine has the formula: ##STR00042##

10. The aryl phosphine of claim 1, where the aryl phosphine is a ligand for a transition metal selected from the group consisting of titanium (Ti), copper (Cu), palladium (Pd), cobalt (Co), rhodium (Rh), ruthenium (Ru), chromium (Cr) and platinum (Pt).

Description

EXAMPLES

(1) Unless otherwise noted, perform all reactions under a nitrogen atmosphere. Obtain all reactants and reagents for use in the examples, unless noted otherwise, from Sigma-Aldrich. Use degassed reverse osmosis water (water) in all reactions, unless otherwise noted. 7-bromo-2,3-dihydrobenzofuran (synthesize according to Kerrigan, F.; Martin, C.; Thomas, G. H. Tetrahedron Lett. 1998, 39, 2219 (Kerrigan)); di-tert-butylchlorophosphine (Strem), dicyclohexylchlorophosphine (Strem), 8-bromochroman (synthesize according to Kerrigan); 9-bromo-2,3,4,5-tetrahydrobenzo[b]oxepine (synthesize according to Kerrigan); chlorobis(2-methoxyphenyl)phosphine (Alfa Aesar); allylpalladium(II) chloride dimer (Strem); toluene (Fisher).

(2) Obtain proton, carbon-13, phosphorus-31 NMR, and .sup.19F spectra with on one of four spectrometers: (1) Varian Mercury VXR-300, (2) Varian Mercury VX-400, (3) Varian MR-400, or (4) Varian VNMRS-500. Chemical shifts are in parts per million (ppm) relative to solvent peaks: .sup.1H=7.25 for CHCl.sub.3 in CDCl.sub.3 and 7.16 for C.sub.6HD.sub.5 in C.sub.6D.sub.6, .sup.13C=77.23 for CDCl.sub.3 and 128.39 for C.sub.6D.sub.6.

Aryl Phosphine Including Fused Ring Ortho-Alkoxy Substitution Example (AP Ex) 1

di-tert-butyl(2,3-dihydrobenzofuran-7-yl)phosphine

(3) ##STR00020##

(4) Prepare AP Ex 1 as follows. Add dihydrobenzofuran (2.6 grams (g), 8.3 millimoles (mmol)) to a glass jar with a PTFE-coated stirbar. Stir the contents of the glass jar and add diethyl ether (40 milliliters (mL)) to dissolve the dihydrobenzofuran. Add n-Butyllithium (n-BuLi) (9.1 mL, 2.5 molar (M) in hexanes) dropwise to the stirred contents of the glass jar. Stir the contents of the glass jar for 22 hours (hr)s at 23 C. Remove all but 10 mL of solvent from the contents of the glass jar in vacuo. Isolate an orange oil by decanting the remaining solvent from the orange oil. Dry the orange oil under vacuum to yield aryllithium (1.47 g, 11.4 mmol).

(5) Add the aryllithium (1.47 g) and diethyl ether (40 mL) to a second glass jar to dissolve the aryllithium. Place the contents of the second glass jar in a freezer at 40 C. for 10 minutes. Remove the second glass jar from the freezer and add di-tert-butylchlorophosphine (2.2 mL, 11.4 mmol) dropwise to the contents of the second glass jar. Stir the contents of the second glass jar for 20 hrs. Add 40 mL of water to the contents of the second glass jar to quench the reaction. Isolate the organic layer and rinse with 20 mL of water. Dry the organic layer over MgSO.sub.4, filter, and place under vacuum to remove solvent. Suspend the oily white solid in 10 mL of methanol (MeOH) and place in a freezer at 40 C. for 30 minutes. Isolate the solid and dry under vacuum to yield AP Ex 1 (0.79 g) in a white solid form.

(6) Analyze AP Ex 1 by .sup.1H, .sup.13C, and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, CD.sub.2Cl.sub.2) 7.40 (b, 1H), 7.19 (d, J=6.9 Hz, 1H)), 6.80 (t, J=6.5 Hz, 1H), 4.49 (t, J=8.4 Hz, 2H), 3.20 (t, J=8.7 Hz, 2H), 1.19 (d, J.sub.P-H=11.8 Hz, 18H); .sup.13C NMR (101 MHz, CD.sub.2Cl.sub.2) 165.8 (b, 1C), 134.1 (s, 1CH), 127.3 (s, C), 126.1 (b, 1CH), 120.0 (s, 1CH), 117.9 (d, J=28 Hz, 1C), 70.8 (s, 1CH.sub.2), 32.6 (d, J=22 Hz, 2C), 30.9 (d, J=15 Hz, 6CH.sub.3), 30.4 (s, 1CH.sub.2); .sup.31P NMR (162 MHz, CD.sub.2Cl.sub.2) 51.1 (37% conformer A), 11.5 (63% conformer B). The coexistence of two conformers at 23 C. has been identified for a related structure (Organometallics 2007, 26, 3585-3596).

AP Ex 2

bis(3,5-bis(trifluoromethyl)phenyl)(2,3-dihydrobenzofuran-7-yl)phosphine

(7) ##STR00021##

(8) Prepare AP Ex 2 as follows. Add dihydrobenzofuran (2.65 g) to a glass jar with a PTFE-coated stirbar. Stir the contents of the glass jar and add diethyl ether (40 mL) to dissolve the dihydrobenzofuran. Add n-BuLi (8.8 mL, 2.5 M in hexanes) dropwise to the stirred contents of the glass jar. Stir the contents of the glass jar for 22 hrs at 23 C. Remove 90% of the solvent from the contents of the jar in vacuo. Add hexane to the contents of the glass jar. Isolate resultant oily solid by decanting the remaining solvent from the oily solid. Rinse the oily solid with hexanes twice. Dry the oily solid under vacuum to yield a solid (1.11 g).

(9) Suspend the solid (0.80 g) in diethyl ether (40 mL) in a second glass jar. Place the contents of the second glass jar in a freezer at 40 C. for 10 minutes. Add a solution of ether (10 mL) and bis(3,5-di(trifluoromethyl)phenyl)chlorophosphine (2.0 g) that has been previously stored in the freezer at 40 C. dropwise to the contents of the second glass jar. Maintain a reaction temperature that is cold to the touch by stopping addition of the reagents occasionally and placing the reagents back in the freezer for 5 to 10 minutes. Add a PTFE-coated stirbar to the contents of the second glass jar and stir overnight. Add 20 mL of water to the contents of the jar. Rinse the organic layer with another 20 mL of water. Isolate the organic layer, dry over MgSO.sub.4, filter, and remove remaining solvent in vacuo. Isolate an orange precipitate from MeOH. Dry the orange precipitate under vacuum for 3 hours to form AP Ex 2 (0.74 g).

(10) Analyze AP Ex 2 by .sup.1H, .sup.13C, .sup.31P, and .sup.19F NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, CD.sub.2Cl.sub.2) 7.92 (s, 2H), 7.88 (s, 2H), 7.86 (s, 2H), 7.37 (d, J=7.4 Hz, 1H), 7.00 (t, J=7.5 Hz, 1H), 6.92 (t, J=7.4 Hz, 1H), 4.47 (t, J=8.7 Hz, 2H), 3.24 (t, J=8.7 Hz, 2H); .sup.13C{.sup.1H}NMR (101 MHz, CD.sub.2Cl.sub.2) 163.2 (d, J=7 Hz, C), 140.0 (d, J=17 Hz, C), 134.4 (s, CH), 134.2 (s, CH), 134.0 (d, J=22 Hz, CH), 132.2 (qd, J=33, 6 Hz, CCF.sub.3), 128.8 (s, CH), 128.8 (s, C), 123.9 (q, J=273 Hz, CF.sub.3), 123.7 (m, CH), 122.1 (d, J=8 Hz, CH), 119.9 (s, C), 113.0 (d, J=13 Hz, C), 72.2 (s, CH.sub.2), 30.1 (s, CH.sub.2); .sup.31P{.sup.1H}NMR (162 MHz, CD.sub.2Cl.sub.2) 9.9 (s); .sup.19F NMR (376 MHz, CD.sub.2Cl.sub.2) 63.8 (s).

AP Ex 3

Dicyclohexyl(2,3-dihydrobenzofuran-7-yl)phosphine

(11) ##STR00022##

(12) Prepare AP Ex 3 as follows to yield aryllithium (1.79 g). Repeat AP Ex 1, but with changes, add dihydrobenzofuran (2.65 g) to a glass jar. Stir the contents of the glass jar for 20 hrs at 23 C.

(13) Add the aryllithium (1.79 g) and diethyl ether (40 mL) to a second glass jar to dissolve the aryllithium. Place the contents of the second glass jar in a freezer at 40 C. for 10 minutes. Add a PTFE-coated stirbar to the contents of the second glass jar and add dicyclohexylchlorophosphine (2.6 mL, 11.9 mmol) while stirring. Stir the contents of the second glass jar overnight at 23 C. Add 30 mL of water to the contents of the second glass jar to quench the reaction. Isolate the organic layer and rinse with 20 mL of water. Dry the organic layer over MgSO.sub.4, filter, and place under vacuum to remove solvent. Add hot (50 C.) MeOH to the contents of the second glass jar to suspend oil. Decant the hot MeOH from the oil. Add hot (50 C.) MeOH again to the contents of the second glass jar to suspend the oil. Decant the hot MeOH from the oil and cool the contents of the second glass jar in a freezer at 40 C. to produce AP Ex 3 (0.69 g) in a solid form.

(14) Analyze AP Ex 3 by .sup.1H, .sup.13C, and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, CD.sub.2Cl.sub.2) 7.18 (m, 2H), 6.82 (t, J=7.4 Hz, 1H), 4.52 (t, J=8.8 Hz, 2H), 3.19 (t, J=8.7 Hz, 2H), 2.11 (m, 2H), 1.55-1.95 (m, 10H), 0.95-1.4 (m, 10H); .sup.13C{.sup.1H}NMR (101 MHz, CD.sub.2Cl.sub.2) peaks not identified 164.44, 164.37, 134.80, 134.62, 127.12, 125.97, 120.40, 120.34, 116.31, 116.09, 71.13, 33.34, 33.22, 31.35, 31.17, 30.30, 30.12, 30.04, 27.87, 27.74, 27.67, 27.12; .sup.31P{.sup.1H}NMR (162 MHz, CD.sub.2Cl.sub.2) 6-5.3 (s).

AP Ex 4

chroman-8-ylbis(2-methoxyphenyl)phosphine

(15) ##STR00023##

(16) Prepare AP Ex 4 as follows. Add 8-bromochroman (407 mg, 1.91 mmol) in dry tetrahydrofuran (THF, 10 mL) cooled in a dry ice/acetone bath to a glass jar with a PTFE-coated stirbar. Stir the contents of the glass jar and add n-BuLi (2.5M in hexanes, 0.76 mL, 1.9 mmol) dropwise. Stir the contents of the glass jar at 78 C. for 1.5 hrs. Add a suspension of chlorobis(2-methoxyphenyl)phosphine (482 mg, 1.72 mmol) in dry THF (15 mL) over the course of 10 minutes (min). Allow the contents of the glass jar to warm to 23 C. Stir the contents of the glass jar for 2 hrs at 23 C. and remove volatiles with a rotary evaporator. Quench the reaction with water (10 mL) and wash with dichloromethane (DCM). Dry the organic layer over MgSO.sub.4, filter, and remove volatiles with a rotary evaporator. Add the organic layer, warm ethanol (55 mL, 50 C.), and DCM (8 mL) to a second glass jar to recrystallize the organic layer. Collect 2 crops of crystals from mother layer to yield AP Ex 4 (359 mg, 55% yield) in crystalline form.

(17) Analyze AP Ex 4 by .sup.1H, .sup.13C, and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.32 (t, J=7.7 Hz, 2H), 7.03 (d, J=7.5 Hz, 1H), 6.94-6.77 (m, 4H), 6.71 (t, J=5.6 Hz, 3H), 6.53-6.42 (m, 1H), 4.10 (apparent t, J=5.0 Hz, 2H), 3.75 (s, 6H), 2.81 (t, J=6.4 Hz, 2H), 1.95 (dt, J=11.4, 5.7 Hz, 2H); .sup.13C NMR (101 MHz, CDCl.sub.3) 161.61 (d, J=16.8 Hz), 133.84 (s), 131.54 (s), 130.38 (s), 129.80 (s), 124.93 (d, J=13.5 Hz), 123.63 (d, J=12.8 Hz), 120.81 (s), 119.98 (s), 110.18 (s), 66.59 (s), 55.76 (s), 25.07 (d, J=1.7 Hz), 22.31 (s); .sup.31P NMR (162 MHz, CDCl.sub.3) 38.86 (s).

AP Ex 5

2,3-dihydrobenzofuran-7-yl)diphenylphosphine

(18) ##STR00024##

(19) Repeat AP Ex 4, but with changes: add 7-bromo-2,3-dihydrobenzofuran (200 mg, 1.0 mmol), rather than 8-bromochroman and add chlorodiphenylphosphine (0.19 mL, 1.0 mmol), neat, rather than chlorobis(2-methoxyphenyl)phosphine to produce AP Ex 5 in white powder form (129 mg, 45% yield).

(20) Analyze AP Ex 5 by .sup.1H, .sup.13C, and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.49-7.34 (m, 10H), 7.26 (dd, J=7.2, 0.8 Hz, 1H), 6.84 (t, J=7.5 Hz, 1H), 6.69 (dd, 1H), 4.59 (t, J=8.7 Hz, 2H), 3.26 (t, J=8.7 Hz, 2H); .sup.13C NMR (101 MHz, CDCl.sub.3) 162.44 (d, J=16.7 Hz), 136.06 (d, J=10.0 Hz), 133.58 (d, J=19.8 Hz), 131.84 (s), 128.49 (s), 128.26 (d, J=7.0 Hz), 126.26 (d, J=2.8 Hz), 125.62 (s), 120.66 (s), 116.93 (d, J=13.4 Hz), 71.12 (s), 29.48 (s); .sup.31P NMR (162 MHz, CDCl.sub.3) 18.50 (s).

AP Ex 6

2,3-dihydrobenzofuran-7-yl)bis(2-methoxyphenyl)phosphine

(21) ##STR00025##

(22) Repeat AP Ex 4, but with changes: add 7-bromo-2,3-dihydrobenzofuran (350 mg, 1.76 mmol), rather than 8-bromochroman, and add chlorobis(2-methoxyphenyl)phosphine (444 mg, 1.76 mmol) as a suspension in THF (12 mL) to produce AP Ex 6 in white crystalline form (192 mg, 33% yield).

(23) Analyze AP Ex 6 by .sup.1H, .sup.13C, and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.33 (t, J=7.7 Hz, 1H), 7.18 (d, J=7.2 Hz, 1H), 6.92-6.81 (m, 2H), 6.77-6.69 (m, 1H), 6.56-6.48 (m, 1H), 4.52 (t, J=8.7 Hz, 1H), 3.74 (s, 3H), 3.21 (t, J=8.7 Hz, 1H). .sup.13C NMR (101 MHz, CDCl.sub.3) 162.76 (d, J=18.1 Hz), 161.52 (d, J=16.5 Hz), 133.72 (s), 132.12 (s), 130.04 (s), 126.08 (d, J=2.8 Hz), 125.28 (s), 124.02 (d, J=12.6 Hz), 120.88 (s), 120.53 (s), 116.39 (d, J=14.2 Hz), 110.23 (s), 71.11 (s), 55.72 (s), 29.74 (s). .sup.31P NMR (162 MHz, CDCl.sub.3) 40.23 (s).

AP Ex 7

chroman-8-yldiphenylphosphine

(24) ##STR00026##

(25) Repeat AP Ex 4, but with changes: add 8-bromochroman (500 mg, 2.35 mmol) and add chlorodiphenylphosphine (0.434 mL, 2.35 mmol), neat, rather than chlorobis(2-methoxyphenyl)phosphine to produce AP Ex 7 in white crystalline form (429 mg, 57% yield).

(26) Analyze AP Ex 7 by .sup.1H, .sup.13C, and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.40-7.24 (m, 10H), 7.06 (d, J=7.4 Hz, 1H), 6.75 (t, J=7.5 Hz, 1H), 6.52-6.41 (m, 1H), 4.13 (apparent t, J=5.1 Hz, 1H), 2.82 (t, J=6.5 Hz, 1H), 2.06-1.87 (m, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) 156.64 (d, J=15.5 Hz), 136.96 (d, J=10.3 Hz), 133.92 (d, J=20.0 Hz), 131.47 (s), 130.83 (s), 128.53 (s), 128.35 (d, J=7.0 Hz), 124.55 (d, J=11.5 Hz), 121.75 (s), 120.28 (s), 66.80 (s), 24.97 (s), 22.27 (s); .sup.31P NMR (162 MHz, CDCl.sub.3) 15.91 (s).

AP Ex 8

bis(2-methoxyphenyl)(2,3,4,5-tetrahydrobenzo[b]oxepin-9-yl)phosphine

(27) ##STR00027##

(28) Repeat AP Ex 4, but with changes: add: 9-bromo-2,3,4,5-tetrahydrobenzo[b]oxepine (200 mg, 0.88 mmol), rather than 8-bromochroman and add chlorodiphenylphosphine (0.19 mL, 1.01 mmol), neat, rather than chlorobis(2-methoxyphenyl)phosphine to produce AP Ex 8.

(29) Analyze AP Ex 8 by .sup.1H, .sup.13C, and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.53-7.44 (m, 10H), 7.28 (d, J=7.3 Hz, 1H), 7.03 (t, J=7.5 Hz, 1H), 6.71 (ddd, J=7.5, 3.9, 1.6 Hz, 1H), 3.77 (apparent t, J=5.0 Hz, 2H), 2.97 (dd, J=13.8, 8.3 Hz, 2H), 2.05-1.95 (m, 2H), 1.86-1.76 (m, 2H); .sup.13C NMR (101 MHz, CDCl.sub.3) 162.39 (d, J=16.6 Hz), 137.50 (d, J=11.0 Hz), 136.76-136.42 (m), 135.79 (d, J=1.0 Hz), 134.47 (d, J=20.4 Hz), 131.75 (s), 131.36 (s), 130.77 (d, J=9.2 Hz), 129.00 (s), 128.73 (d, J=7.1 Hz), 123.87 (s), 73.29 (s), 34.68 (d, J=1.2 Hz), 32.48 (s), 26.48 (s); .sup.31P NMR (162 MHz, CDCl.sub.3) 17.65 (s).

AP Ex 9

tris(2,3-dihydrobenzofuran-7-yl)phosphine

(30) ##STR00028##

(31) Repeat AP Ex 4, but with changes: add 7-bromo-2,3-dihydrobenzofuran (1.09 g, 5.49 mmol), rather than 8-bromochroman and add phosphorus trichloride (0.48 mL, 5.49 mmol), neat, rather than chlorobis(2-methoxyphenyl)phosphine to produce AP Ex 9 in white crystalline form (356 mg, 53% yield).

(32) Analyze AP Ex 9 by .sup.1H and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, CDCl.sub.3) 7.18 (dd, J=7.2, 1.2 Hz, 1H), 6.75 (t, J=7.4 Hz, 1H), 6.65-6.57 (m, 1H), 4.53 (t, J=8.7 Hz, 3H), 3.20 (t, J=8.7 Hz, 3H); .sup.31P NMR (162 MHz, CDCl.sub.3) 45.71 (d, J=34.6 Hz).

AP Ex 10

P,P-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis[bis(2,3-dihydrobenzofuran-7-yl)phosphine)

(33) ##STR00029##

(34) In a N.sub.2-purged dry box, add P,P-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis[N,N,N,N-tetraethyl-phosphonous diamide] (0.944 g, 1.69 mmol) to a glass jar. Dissolve the contents of the glass jar by adding toluene (60 mL). Place the glass jar in a N2-purged dry box freezer at 35 C. for 30 min to cool the pale yellow solution. Remove the glass jar from the dry box freezer and add hydrogen chloride (2.0 M solution in diethyl ether, 9.0 mL) to the contents of the glass jar and stir for one hr at 23 C. to form a white precipitate. Remove an aliquot of the contents of the glass jar, filter, and analyze by .sup.31P NMR spectroscopy. A single peak at 156 ppm confirmed formation of the desired P,P-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(dichlorophosphine). Filter the contents of the glass jar through Celite and pump down to dryness to produce a sticky white residue. Triturate the sticky white residue with hexanes (40 mL) to produce a white solid. Suspend the white solid in hexanes (40 mL) and filter. Dry the white solid under vacuum for 30 min at 23 C. to produce P,P-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(dichlorophosphine) (0.455 g, 1.10 mmol, 65% yield).

(35) Add dihydrobenzofuran (2.60 g) to a second glass jar with a PTFE-coated stirbar. Stir the contents of the second glass jar and add diethyl ether (40 mL) to dissolve the dihydrobenzofuran. Add n-BuLi (9.0 mL of a 2.5 M solution in hexanes) to the contents of the second glass jar and stir for 48 hrs at 23 C. to produce an orange solution and light orange precipitate. Pump the contents of the glass jar down to dryness to produce a red oil. Add hexanes (20 mL) to the red oil in the second glass jar and stir to produce a light orange solid precipitate. Decant the hexanes from the light orange solid and wash the light orange solid in hexanes (20 mL). Collect the light orange solid by filtration and dry under vacuum for 1 hr at 23 C. to produce impure aryllithium salt (0.99 g).

(36) Add a portion of the light orange solid (0.55 g) and THF (30 mL) to a third glass jar to dissolve the light orange solid and cool the contents of the third glass jar in a dry box freezer at 35 C. for 1 hr. Add P,P-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(dichlorophosphine) from the previous step (0.455 g, 1.10 mL) and THF (40 mL) to a fourth glass jar and cool in the dry box freezer at 35 C. for 1 hr. Remove the third and fourth glass jars from the freezer. Add the contents of the third glass jar dropwise to the contents of the fourth glass jar, while stirring. Allow the contents of the fourth glass jar to warm to 23 C. while stirring for 1 hr. Remove an aliquot of the contents of the fourth glass jar and analyze by .sup.31P NMR spectroscopy. The spectrum revealed incomplete conversion to the desired AP Ex 10. Add an additional portion of the light orange solid (0.30 g) to the contents of the fourth jar, while stirring. Remove an aliquot of the contents of the fourth jar and analyze by .sup.31P NMR spectroscopy. A single peak at 39 ppm confirmed formation of the desired AP Ex 10.

(37) Quench the reaction mixture with MeOH (2 mL) and pump down to dryness to produce off-white residue. Suspend off-white residue in MeOH (20 mL) for 1 hr at 60 C., filter, and dry under vacuum for 1 hr at 23 C. to produce sticky solids. Dissolve the sticky solids in toluene (40 mL) and filter through fritted glass funnel Pump filtrate down to dryness to form off-white residue. Triturate off-white residue with hexanes (40 mL) to produce off-white powder. Suspend off-white powder in hexanes (40 mL), filter, and dry under vacuum for 1 hr at 23 C. to yield AP Ex 10 (0.327 g, 0.438 mmol, 40% yield). Analyze AP Ex 10 by .sup.1H, .sup.13C, and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, C.sub.6D.sub.6) 7.22-7.17 (m, 4H), 7.16 (brs, 2H), 7.09 (dd, J=7.6 Hz, J=1.6 Hz, 2H), 6.91 (dd, J=7.2 Hz, J=1.2 Hz, 4H), 6.85 (t, J=7.6 Hz, 2H), 6.71 (t, J=7.6 Hz, 4H), 4.06-3.89 (m, 8H), 2.58-2.49 (m, 8H), 1.34 (s, 6H); .sup.13C{.sup.1H}NMR (101 MHz, C.sub.6D.sub.6) 163.7 (t, J=8.0 Hz, Ar), 153.7 (t, J=10.2 Hz, Ar) 133.5 (t, J=4.3 Hz, ArH), 133.2 (s, ArH), 130.2 (m, Ar), 126.8 (s, ArH), 126.7 (m, Ar), 125.5 (s, ArH), 123.6 (s, ArH), 121.1 (s, ArH), 118.1 (d, J=18.3 Hz), 118.1 (d, J=3.4 Hz), 71.0 (s, CH.sub.2), 34.8 (s, C), 32.5 (s, CH.sub.2), 30.1 (s, CH.sub.3); .sup.31P{.sup.1H}NMR (162 MHz, C.sub.6D.sub.6) 38.5 (s) ppm.

AP Ex 11

bis(2,3-dihydrobenzofuran-7-yl))chlorophosphine

(38) ##STR00030##

(39) Add dihydrobenzofuran (2.60 g) and a PTFE-coated stirbar to a glass jar in an N.sub.2-purged dry box. Stir the contents of the glass jar and add diethyl ether (40 mL) to dissolve the dihydrobenzofuran. Add n-BuLi (9.0 mL of a 2.5 M solution in hexanes) to the contents of the glass jar and stir for 48 hrs at 23 C. to form a light orange precipitate. Filter the contents of the glass jar and pump to dryness to produce a red oil. Add hexanes (20 mL) to the red oil and stir to produce a light orange solid precipitate. Decant the hexanes from the light orange solid and wash with hexanes (20 mL), filter, and dry under vacuum for 1 hr at 23 C. to produce impure aryllithium salt (0.75 g). Dissolve a portion of the impure aryllithium salt (0.69 g) with THF (50 mL) in a second glass jar and cool in dry box freezer at 35 C. for 1 hr. Add dimethylphosphoramidous dichloride (0.30 mL, 2.6 mmol) dropwise to the contents of the second glass jar. Allow the contents of the second glass jar to warm to 23 C. and stir for one hr. Remove an aliquot of the contents of the second glass jar and analyze by .sup.31P NMR spectroscopy. The spectrum showed conversion to the desired bis(2,3-dihydrobenzofuran-2-yl)dimethylaminophosphine (46.8 ppm, 82% yield). The (2,3-dihydrobenzofuran-7-71)(dimethylamino)chlorophosphine was also present as an impurity (125.5 ppm, 14%).

(40) Pump down the reaction mixture to dryness and triturate with hexanes (40 mL) to produce white residue. Slurry white residue in toluene (60 mL) with stirring and filter through Celite to remove LiCl. Place toluene filtrate in a third glass jar in a dry box freezer at 35 C. for 30 min. Add hydrogen chloride (2.0 M solution in diethyl ether, 2.8 mL) to the contents of the third glass jar while stirring. Allow the contents of the third glass jar to warm to 23 C. and stir for one hr to form white precipitate. Remove an aliquot of the reaction mixture, filter, and analyze by .sup.31P NMR spectroscopy. The spectrum showed conversion to the desired AP Ex 11 (66 ppm). Filter the reaction mixture through Celite and pump down to dryness. Triturate resultant yellow oil in hexanes (40 mL) to produce an off-white solid. Slurry off-white solid in hexanes (40 mL) with stirring, collect by filtration and dry under vacuum for 1 hr at 23 C. to produce AP Ex 11 (0.171 g, 0.561 mmol, yield 22%).

(41) Analyze AP Ex 11 by .sup.1H, .sup.13C, and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, C.sub.6D.sub.6) 7.61-7.57 (m, 2H), 6.84 (dq, J=7.6 Hz, J=1.2 Hz, 2H), 6.73 (t, J=8.0 Hz, 2H), 3.87 (t, J=8.8 Hz, 4H), 2.35 (t, J=8.8 Hz, 4H); .sup.13C{.sup.1H}NMR (101 MHz, C.sub.6D.sub.6) 163.0 (d, J=20.0 Hz, Ar), 131.5 (d, J=7.3 Hz, ArH), 127.7 (d, J=1.7 Hz, Ar), 127.6 (s, ArH) 121.3 (s, ArH), 118.6 (d, J=38.0 Hz, Ar), 71.8 (s, CH.sub.2), 29.5 (s, CH.sub.2); .sup.31P{.sup.1H} NMR (162 MHz, C.sub.6D.sub.6) 66.6 (s) ppm.

(42) Transition Metal Complexes (TMC)

TMC Ex 1

Acetylacetonato[dicyclohexyl(2,3-dihydrobenzofuran-7-yl)phosphine]rhodium(I)

(43) ##STR00031##

(44) Prepare TMC Ex 1 as follows: Add AP Ex 3 (0.039 g, 0.12 mmol) to a glass vial in a N.sub.2-purged dry box. Add C.sub.6D.sub.6 (1 mL) to the glass vial to completely dissolve AP Ex 3. In a second glass vial, add acetylacetonatodicarbonylrhodium(I) (0.032 g, 0.12 mmol). Add the contents of the first glass vial to the second glass vial to produce a yellow solution. Note evolution of CO gas from solution, indicating formation of a phosphine-rhodium complex. Transfer solution in glass vial to NMR tube and analyze by .sup.1H and .sup.31P NMR spectroscopy. .sup.31P NMR indicates near quantitative conversion (>97%) to TMC Ex 1. Return NMR sample to N.sub.2-purged dry box and transfer to a third glass vial. Use 3 mL of THF to wash out NMR tube and transfer washings to vial. Remove solvent under vacuum. Add 2 mL of hexanes to vial and remove solvent under vacuum. Repeat. Slurry resultant pale yellow powder in 1 mL of hexanes and place in dry box freezer at 35 C. for 1 hour. Collect pale yellow powder by filtration and dry under vacuum for 1 hour to yield TMC Ex1 (0.020 g, 0.039 mmol, 31%).

(45) Analyze TMC Ex 1 by .sup.1H, .sup.13C, and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, C.sub.6D.sub.6) 8.25 (dd, J=7.2 Hz, J=12.0 Hz, 1H), 6.86 (m, 1H), 6.76 (td, J=0.8 Hz, J=7.6 Hz, 1H), 5.38 (s, 1H), 3.91 (t, J=8.8 Hz, 2H), 2.92 (m, 2H), 2.42 (t, J=8.8 Hz, 2H), 2.24 (m, 2H), 1.97 (s, 3H), 1.95 (m, 2H), 1.78 (s, 3H), 1.74-1.55 (m, 10H), 1.42-1.23 (m, 4H), 1.08 (m, 2H); .sup.13C{.sup.1H}NMR (101 MHz, C.sub.6D.sub.6) 191.5 (dd, J=23.5 Hz, J=77.0 Hz), 188.5 (s), 184.7(s), 161.9 (s), 140.1 (d, J=17.9 Hz), 127.7 (d, J=2.2 Hz), 127.3 (d, J=4.1 Hz), 120.6 (d, J=11.3 Hz), 111.2 (d, J=43.0 Hz), 101.0 (d, J=2.3 Hz), 71.3 (s), 33.7 (s), 33.4 (s), 30.3 (d, J=3.7 Hz), 29.6 (s), 29.2 (d, J=1.9 Hz), 28.1 (dd, J=1.0 Hz, J=5.2 Hz), 27.9 (d, J=4.3 Hz), 27.8 (d, J=7.8 Hz), 27.5 (m), 27.0 (d, J=1.3 Hz); .sup.31P{.sup.1H}NMR (162 MHz, C.sub.6D.sub.6) 64.3 (d, J=174.6 Hz) ppm.

TMC Ex 2

allyl[di-tert-butyl(2,3-dihydrobenzofuran-7-yl)phosphine]palladium(II) chloride

(46) ##STR00032##

(47) Prepare TMC Ex 2 as follows: Add AP Ex 1 (0.051 g, 0.19 mmol) to a glass vial in a N.sub.2-purged dry box. Add C.sub.6D.sub.6 (1 mL) to the glass vial to completely dissolve AP Ex 1. In a second glass vial, add allylpalladium(II) chloride dimer (0.035 g, 0.096 mmol). Add the contents of the first glass vial to the second glass vial to produce a yellow solution. Transfer solution in glass vial to NMR tube and analyze by .sup.1H and .sup.31P NMR spectroscopy. .sup.31P NMR indicates quantitative conversion to TMC Ex 2. Return NMR sample to N.sub.2-purged dry box and transfer to a third glass vial. Use 5 mL of THF to wash out NMR tube and transfer washings to vial. Remove solvent under vacuum. Add 2 mL of hexanes to vial and remove solvent under vacuum. Slurry resultant yellow powder in 1 mL of hexanes and collect powder by filtration. Dry yellow powder under vacuum for 1 hour to yield TMC Ex 2 (0.039 g, 0.087 mmol, 91%).

(48) Analyze TMC Ex 1 by .sup.1H, .sup.13C, and .sup.31P NMR spectroscopy to confirm formation. .sup.1H NMR (400 MHz, CD.sub.2Cl.sub.2) 7.48 (m, 1H), 7.28 (m, 1H), 6.85 (t, J=7.2 Hz, 1H), 5.48 (m, 1H), 4.51 (m, 3H), 3.60 (dd, J=9.2 Hz, J=13.6 Hz, 1H), 3.34 (br s, 1H), 3.22 (t, J=8.4 Hz, 2H), 2.67 (br s, 1H), 1.42 (br s, 18H); .sup.13C{.sup.1H}NMR (101 MHz, CD.sub.2Cl.sub.2) 161.1 (s), 137.1 (br s), 127.8 (d, J=2.9 Hz), 127.1 (d, J=1.8 Hz), 119.3 (d, J=10.2 Hz), 115.0 (d, J=4.7 Hz), 112.9 (d, J=24.5 Hz), 78.8 (d, J=29.7 Hz), 70.7 (s), 58.3 (s), 36.4 (br s), 29.7 (br d, J=94.8 Hz), 29.4 (s); .sup.31P{.sup.1H} NMR (162 MHz, CD.sub.2Cl.sub.2) 77.7 (br s) ppm.

(49) Butadiene Telomerization (BT)

(50) BT Ex 1 with AP Ex 5

(51) In a glovebox, dissolve degassed glacial acetic acid (AcOH) (55.3 L) in degassed MeOH to a volume of 5 mL (0.1932 M AcOH in MeOH) to form AcOH solution. Dissolve palladium(II) acetylacetonate (Pd(acac).sub.2) (0.0147 g, 0.0000483 moles), AP Ex 5 and 0.25 mL of the AcOH solution in MeOH to a total volume of 25 mL to form precatalyst stock solution. Add dibutyl ether (Bu.sub.2O, 5 mL), MeOH (10.96 mL), anhydrous degassed methylcyclohexane (MeCy, 1.6 mL), the precatalyst stock solution (1 mL), and a portion of a solution of sodium methoxide (NaOMe) (1.0 mL) in MeOH (0.01932 M) to a Fisher-Porter bottle. In general, the reactions were conducted with MeOH (12.8M). Seal the Fisher-Porter bottle with a valve equipped with a septum port. Distill butadiene (5 mL) outside of the glovebox into a gas-tight syringe. Determine the mass of butadiene by weighing the syringe before and after addition to the Fisher-Porter bottle. Inject the butadiene into the Fisher-Porter bottle with the needle placed below the surface of the solution (5 mL, with the precise weight for each run being calculated by weighing the syringe before and after injection and taking the difference of the two). Place the reactor in an oil bath heated to 60 C. with stirring and react for a 4 hrs. Remove aliquots through a 24 needle equipped with a gas-tight valve and perform GC analysis.

(52) BT Ex 2 with AP Ex 5

(53) Repeat BT Ex 1, but with changes: heat the oil bath to 90 C.

(54) BT Ex 3 with AP Ex 5

(55) Repeat BT Ex 1, but with changes: heat the oil bath to 40 C.

(56) BT Ex 4 with AP Ex 4

(57) Repeat BT Ex 3, but with changes: use AP Ex 4 rather than AP Ex 5.

(58) BT Ex 5 with AP Ex 4

(59) Repeat BT Ex 1, but with changes: use AP Ex 4 rather than AP Ex 5.

(60) BT Ex 6 with AP Ex 6

(61) Repeat BT Ex 1, but with changes: use AP Ex 6 rather than AP Ex 5.

(62) BT Ex 7 with AP Ex 6

(63) Repeat BT Ex 2, but with changes: use AP Ex 6 rather than AP Ex 5.

(64) BT Ex 8 with AP Ex 7

(65) Repeat BT Ex 1, but with changes: use AP Ex 7 rather than AP Ex 5.

(66) BT Ex 9 with AP Ex 7

(67) Repeat BT Ex 2, but with changes: use AP Ex 7 rather than AP Ex 5.

(68) BT Ex 10 with AP Ex 9

(69) Repeat BT Ex 3, but with changes: use AP Ex 9 rather than AP Ex 5.

(70) BT Ex 11 with AP Ex 9

(71) Repeat BT Ex 1, but with changes: use AP Ex 9 rather than AP Ex 5.

(72) BT Ex 12 with AP Ex 6

(73) Repeat BT Ex 3, but with changes: use AP Ex 6 rather than AP Ex 5.

(74) Comp Ex 1 with tris(2-methoxyphenyl)phosphine

(75) Repeat BT Ex 2, but with changes: use tris(2-methoxyphenyl)phosphine rather than AP Ex 5.

(76) Comp Ex 2 with (2-methoxyphenyl)diphenylphosphine

(77) Repeat BT Ex 2, but with changes: use (2-methoxyphenyl)diphenylphosphine rather than AP Ex 5.

(78) The conversion (Cony) is the moles of butadiene converted divided by the moles of butadiene fed into the reactor. MOD-1 (1-methoxy-2,7-octadiene) is the moles of MOD-1 divided by the moles of all products produced. MOD-3 (3-methoxy-1,7-octadiene) is the moles of MOD-3 divided by the moles of all products. The L/B ratio is the moles of MOD-1 divided by the moles of MOD-3. Catalyst efficiency is the grams of MOD-1 divided by the grams of Pd divided by the hrs of reaction time. Data for tris(2-methoxyphenyl)phosphine (Comp Ex 1) and (2-methoxylphenyl)diphenylphosphine (Comp Ex 2) are from WO2010/019360(A2) and are included as comparative examples.

(79) TABLE-US-00001 TABLE 1 Temper- ature Conv MOD-1 MOD-3 L/B Catalyst Example ( C.) (mol %) (mol %) (mol %) ratio Efficiency BT Ex 1 60 89.3 95.1 4.0 23.8 4845 BT Ex 2 90 77.2 92.3 5.1 18.1 4357 BT Ex 3 40 60.4 96.4 3.1 31.1 3061 BT Ex 4 40 8.1 97.7 2.3 42.5 303 BT Ex 5 60 7.0 96.9 3.1 31.3 394 BT Ex 6 60 17.0 97.3 2.7 36.0 860 BT Ex 7 90 8.4 96.5 3.5 27 490 BT Ex 8 60 47.6 95.1 4.0 23.8 2656 BT Ex 9 90 65.3 92.6 5.2 18.0 3602 BT Ex 10 40 22.3 98.0 2.0 49.0 1429 BT Ex 11 60 32.3 97.3 2.7 36.037 1890 BT Ex 12 40 11.3 97.7 2.3 42.5 599 Comp 90 4.1 86.1 2.6 33 194 Ex 1 Comp 90 65.6 93.6 3.9 24 3363 Ex 2

(80) The data in Table 1 shows the telomerization of butadiene with AP Ex 4, 5, 6, 7 and 9. The table also includes data for tris(2-methoxyphenyl)phosphine as Comp Ex 1 and (2-methoxyphenyl)diphenylphosphine as Comp Ex 2. It is demonstrated that replacing an ortho-methoxyphenyl with a fused ring ortho-alkoxy substitution in some cases can increase the catalyst efficiency. For example, BT Ex 2 demonstrates an increase in catalyst efficiency compared to Comp Ex 2; BT Ex 11 demonstrates an increase in catalyst efficiency compared to Comp Ex 1, and BT Ex 10 demonstrates an increase in catalyst efficiency compared to BT Ex 12.