Synlett 2007(4): 0599-0602  
DOI: 10.1055/s-2007-967974
LETTER
© Georg Thieme Verlag Stuttgart · New York

Chiral P-Chlorophospholane: A Versatile Building Block for the Synthesis of Ligands

Jens Holz*a, Axel Monseesb, Renat Kadyrovc, Armin Börner*a,d
a Leibniz-Institut für Katalyse an der Universität Rostock e. V., Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Fax: +49(381)128151202; e-Mail: jens.holz@catalysis.de; e-Mail: armin.boerner@catalysis.de;
b Degussa AG, Röhm Methacrylate, Kirschenallee, 64293 Darmstadt, Germany
c Degussa AG, Rodenbacher Chaussee 4, Building 097, 63457 Hanau-Wolfgang, Germany
d Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Further Information

Publication History

Received 19 December 2006
Publication Date:
21 February 2007 (online)

Abstract

The synthesis of enantiomerically pure (R,R)-1-chloro-2,5-dimethylphospholane is described, which can be used for the synthesis of a wide range of phosphine ligands bearing a phospholane moiety.

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Other approaches are based on the cleavage of the P-phenyl bond by lithium or by deprotonation of the P-H bond in relevant phospholanes. The latter methods are frequently accompanied by the epimerization of the adjacent chiral C-atoms or the formation of side products and therefore are not suitable for the construction of optically pure ligands.10c,f

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Solvents were dried and freshly distilled under argon before use. All reactions were performed under an argon atmosphere by using standard Schlenk techniques. 1H, 13C and 31P NMR spectra were recorded on a Bruker ARX 400 spectrometer at the following frequencies: 400.13 MHz (1H), 100.63 MHz (13C), 161.98 MHz (31P), 235 MHz (19F) with CDCl3 as solvent.
( R,R )-1-Chloro-2,5-dimethylphospholane (2) A solution of 1-trimethylsilyl-2,5-dimethyl-phospholane (1) (10.0 g, 53.1 mmol) in CH2Cl2 (60 mL) was added via cannula to a solution of hexachloroethane (12.6 g, 53.1 mmol) in CH2Cl2 (80 mL) under stirring at ambient temperature. Then the mixture was stirred under reflux for 30 min. After cooling, the solvent and tetrachlorethene was removed in vacuo (500 mbar) and the residue was distilled to give chlorophospholane 2 (7.40 g, 93%) as a colorless liquid (bp 100-105 °C/100 mbar).
Verification of the optical purity of chlorophospholane 2 was carried out by reaction with (R)-(+)-N-benzyl-α-methyl-benzylamine. Only the expected (R,R,R)-diastereomer was visible [31P NMR (THF-d 8): δ = 66.5]. The (R,S,S)-diastereomer (δ = 61.5) was not observed.
[α]D 20 = +96.8 (c = 1.1; CH2Cl2). 1H NMR: δ = 1.22 (d, J = 7.1 Hz, 3 H, CH3), 1.28 (d, J = 7.1 Hz, 3 H, CH3), 1.50 (m, 2 H, Ha-CH2), 2.08-2.36 (m, 4 H, Hb-CH2, CH-P). 13C NMR: δ = 16.2, 35.5, 43.1. 31P NMR: δ = 143.3.
Preparation of Phospholane Amides 3a-d To a solution of the monoamine (1 mmol) or diamine (0.5 mmol) in Et2O (5 mL) was added n-BuLi (1.05 equiv., 1.6 M in hexane, 0.65 mL) at -10 °C. The solution was stirred for 1 h. After the addition of 2 (0.151 g, 1 mmol) in Et2O (2 mL) the solution was stirred at -10 °C for 1 h and warmed to ambient temperature. After 4 h the solution was filtered and the solvent and byproduct were removed in vacuo to give the phospholanes, which were used without further purification.
( R , R )-1-( N,N -Diethylamino)-2,5-dimethylphospholane (3a) 1H NMR: δ = 0.94 (t, J = 7.0 Hz, 6 H, CH3), 1.05 (dd, J = 7.0, 10.0 Hz, 3 H, CH3), 1.18 (dd, J = 7.1, 18.5 Hz, 3 H, CH3), 1.10-2.15 (m, 6 H, CH-P, CH2), 2.91 (m, 4 H, NCH2). 13C NMR: δ = 14.5, 15.2, 18.5, 34.8, 36.2, 37.3, 37.7, 45.2. 31P NMR: δ = 86.2.
( R , R )-1-( N,N -Diphenylamino)-2,5-dimethylphospholane (3b) 1H NMR: δ = 1.13 (dd, J = 7.2, 19.9 Hz, 3 H, CH3), 1.18 (dd, J = 7.1, 10.4 Hz, 3 H, CH3), 1.10-2.16 (m, 5 H, CH-P, CH2), 2.32 (m, 1 H, CH-P), 7.03-7.18 (m, 6 H, arom. H), 7.26-7.35 (m, 4 H, arom. H). 13C NMR: δ = 14.7, 19.0, 34.9, 36.1, 36.5, 39.5, 122.6, 124.7, 128.9, 148.8. 31P NMR: δ = 78.4.
( R , R )-1-( N,N -Dibenzylamino)-2,5-dimethylphospholane (3c)
1H NMR (CDCl3): δ = 1.06 (dd, J = 7.1, 9.9 Hz, 3 H, CH3), 1.47 (dd, J = 7.0, 18.4 Hz, 3 H, CH3), 1.12-2.14 (m, 5 H, CH-P, CH2), 2.29 (m, 1 H, CH-P), 4.06 (dd, J = 9.2 Hz, 15.3 Hz, 2 H, Ha-NCH2), 4.22 (dd, J = 7.6 Hz, 15.3 Hz, 2 H, Hb-NCH2), 7.26-7.44 (m, 10 H, arom. H). 13C NMR: δ = 15.0, 18.8, 34.7, 37.6, 37.9, 38.6, 55.4, 126.8, 128.1, 128.2, 139.4. 31P NMR: δ = 91.5.
N,N-Bis[( R , R )-2,5-dimethylphospholan-1-yl]- N,N-dimethylethane-1,2-diamine (3d)
1H NMR: δ = 1.08 (dd, J = 7.2, 10.2 Hz, 6 H, CH3), 1.18 (dd, J = 7.2, 18.8 Hz, 6 H, CH3), 1.02-2.25 (m, 12 H, CH-P, CH2), 2.58 (d, J = 4.8 Hz, 6 H, NCH3), 2.95 (m, 4 H, NCH2). 13C NMR: δ = 14.0, 18.8, 35.2, 36.7, 37.5, 38.3, 38.8, 56.6. 31P NMR: δ = 88.4.
(2 R ,2" R )-1,1"-Bis[(2′′ R ,5′′ R )-2,5-dimethylphospholan-1-yl]-2,2"-bipyrrolidine (3e)
1H NMR: δ = 1.09 (dd, J = 7.1, 10.3 Hz, 6 H, CH3), 1.19 (dd, J = 7.2 Hz, 18.5, 6 H, CH3), 1.04-2.32 (m, 20 H, CH-P, CH2), 2.85-3.10 (m, 4 H, NCH2), 3.74 (m, 2 H, NCH). 13C NMR: δ = 14.6, 19.9, 26.4, 27.0, 33.1, 35.7, 37.1, 37.8, 50.6, 67.1. 31P NMR: δ = 67.7.
Preparation of Oxazolinephospholanes 5a-d To a solution of oxazoline derivative 4 (2 mmol) and TMEDA (0.29 g, 2.5 mmol) in Et2O (10 mL) was added n-BuLi (1.6 M in hexane, 1.31 mL) at 0 °C. After stirring for 1 h, the chlorophospholane 2 (0.316 g, 2.1 mmol) dissolved in Et2O (3 mL) was added. Stirring was continued for 3 h at ambient temperature and degassed H2O (4 mL) was added. The aqueous phase was extracted with Et2O (5 mL). The combined organic phases together with traces of n-butyl-phospholane formed were evaporated in vacuo to give oxazoline derivatives 5a-d in yields of 60-75% with a purity of more than 95%. These derivatives were used without further purifications for the preparation of metal complexes.
2-{2-[( R , R )-2,5-Dimethylphospholan-1-yl]phenyl}-4,5-dihydrooxazole (5a)
1H NMR: δ = 0.72 (dd, J = 7.1, 8.6 Hz, 3 H, CH3), 1.26 (dd, J = 7.0, 17.6 Hz, 3 H, CH3), 1.30-1.56 (m, 2 H, CH2), 2.10 (m, 2 H, CH2), 2.52 (m, 2 H, CH-P), 4.10 (m, 2 H, NCH2). 4.37 (m, 2 H, OCH2), 7.26-7.42 (m, 2 H, arom. H), 7.51 (m, 1 H, arom. H), 7.78 (m, 1 H, arom. H). 13C NMR: δ = 17.9, 19.8, 32.4, 33.4, 35.0, 35.4, 55.4, 67.1, 127.5, 129.6, 129.7, 131.6, 133.2, 138.7, 164.7. 31P NMR: δ = 10.9. 2-{2-[( R , R )-2,5-Dimethylphospholan-1-yl]phenyl}-4,4-dimethyl-4,5-dihydrooxazole (5b) 1H NMR: δ = 0.73 (dd, J = 7.1, 8.8 Hz, 3 H, CH3), 1.25 (dd, J = 7.1, 17.4 Hz, 3 H, CH3), 1.32-1.51 (m, 2 H, CH2), 1.37. (s, 6 H, CH3), 2.09 (m, 2 H, CH2), 2.47 (m, 2 H, CH-P), 4.07 (AB-system, 2 H, OCH2), 7.22-7.35 (m, 2 H, arom. H), 7.46 (m, 1 H, arom. H), 7.72 (m, 1 H, arom. H). 13C NMR: δ = 17.7, 19.8, 28.1, 28.4, 32.9, 33.6, 35.1, 35.5, 68.0, 78.7, 127.4,, 129.5, 129.5, 131.5, 133.8, 138.6, 162.7. 31P NMR: δ = 10.2.( R ) -2-{2-[( R , R )-2,5-Dimethylphospholan-1-yl]phenyl}-4-isopropyl-4,5-dihydrooxazole (5c) 1H NMR: δ = 0.68 (dd, J = 7.3, 8.4 Hz, 3 H, CH3), 0.89 (d, J = 7.80 Hz, 3 H, CH3), 1.01 (d, J = 6.7 Hz, 3 H, CH3), 1.19 (dd, J = 7.0, 17.2 Hz, 3 H, CH3), 1.25-1.48 (m, 2 H, CH2), 1.79 (m, 1 H, CH), 1.94-2.13 (m, 2 H, CH2), 2.33-2.54 (m, 2 H, CH-P), 3.97-4.05 (m, 2 H, OCH2), 4.33 (m, 1 H, NCH), 7.19-7.45 (m, 2 H, arom. H), 7.58 (m, 1 H, arom. H), 7.88 (m, 1 H, arom. H). 13C NMR: δ = 17.9, 18.6, 19.1, 19.7, 32.6, 33.1, 33.5, 35.0, 35.4, 70.2, 73.5, 127.4, 129.5, 129.5, 131.5, 133.8, 138.6, 163.5. 31P NMR: δ = 10.2.
(S) -2-{2-[( R , R )-2,5-Dimethylphospholan-1-yl]phenyl}-4-isopropyl-4,5-dihydrooxazole (5d) 1H NMR: δ = 0.72 (dd, J = 7.1, 8.5 Hz, 3 H, CH3), 0.93 (d, J = 6.8 Hz, 3 H, CH3), 1.02 (d, J = 6.7 Hz, 3 H, CH3), 1.24 (dd, J = 7.1, 17.3 Hz, 3 H, CH3), 1.22-1.51 (m, 2 H, CH2), 1.84 (m, 1 H, CH), 2.01-2.15 (m, 2 H, CH2), 2.44-2.64 (m, 2 H, CH-P), 4.05-4.19 (m, 2 H, OCH2), 4.34 (dd, J = 8.0, 9.5 Hz, 1 H, NCH), 7.26-7.39 (m, 2 H, arom. H), 7.51 (m, 1 H, arom. H), 7.80 (m, 1 H, arom. H). 13C NMR: δ = 18.2, 18.5, 19.0, 19.4, 32.2, 33.0, 33.0, 34.9, 35.3, 69.9, 73.1, 127.4, 129.5, 129.6, 131.4, 133.1, 138.8, 163.1. 31P NMR: δ = +11.1.
Preparation of Phospholane-Substituted Pyridines 7a-e To a solution of pyridine derivative 6a-e (1 mmol) and TMEDA (0.145 g, 1.25 mmol) in Et2O (5 mL) was added n-BuLi solution (1.6 M in hexane, 0.66 mL, 1.05 mmol) at -78 °C. After stirring for 1 h, chlorophospholane 2 (0.158 g, 1.05 mmol) dissolved in Et2O (2 mL) was added and the stirring was continued for further 3 h. The reaction mixture was warmed to r.t. and degassed H2O (3 mL) was added to remove the salts and TMEDA. After extraction of the aqueous phase with Et2O (3 mL) the solvent from the combined phases was evaporated. Pyridine derivatives 7a-e (80-90% yield) were used without further purifications for the preparation of metal complexes.
2-[( R , R )-2,5-dimethylphospholan-1-yl]pyridine (7a)
As an example, this compound was further purified by column chromatography; R f = 0.45 heptane : EtOAc, 9:1). 1H NMR: δ = 0.77 (dd, J = 7.0, 10.7 Hz, 3 H, CH3), 1.25 (m, 1 H, Ha-CH2), 1.27 (dd, J = 7.4, 18.6 Hz, 3 H, CH3), 1.42 (m, 1 H, Hb-CH2), 1.85 (m, 1 H, Ha-CH2), 2.10-2.28 (m, 2 H, Hb-CH2, CH-P), 3.20 (m, 1 H, CH-P), 7.09 (m, 1 H, arom. H), 7.42-7.57 (m, 2 H, arom. H), 8.61 (m, 1 H, arom. H). 13C NMR: δ = 15.2, 20.2, 32.6, 36.2, 36.9, 37.0, 122.1, 130.6, 134.3, 149.5, 162.2. 31P NMR: δ = 11.8.
2-[( R , R )-2,5-Dimethylphospholan-1-yl]-6-methyl-pyridine (7b)
1H NMR: δ = 0.75 (dd, J = 7.1, 10.5 Hz, 3 H, CH3), 1.23 (m, 1 H, Ha-CH2), 1.24 (dd, J = 7.3, 18.5 Hz, 3 H, CH3), 1.43 (m, 1 H, Hb-CH2), 1.82 (m, 1 H, Ha-CH2), 2.11-2.27 (m, 2 H, Hb-CH2, CH-P), 2.46 (s, 3 H, CH3), 3.12 (m, 1 H, CH-P), 6.91 (m, 1 H, arom. H), 7.22 (m, 1 H, arom. H), 7.36 (m, 1 H, arom. H). 13C NMR: δ = 15.3, 20.2, 24.7, 32.9, 36.1, 36.8, 37.0, 121.5, 127.0, 134.4, 158.0, 161.3. 31P NMR: δ = 10.9.
2-[( R , R )-2,5-Dimethylphospholan-1-yl]-6-methoxy-pyridine (7c)
1H NMR: δ = 0.78 (dd, J = 7.1, 10.8 Hz, 3 H, CH3), 1.22 (dd, J = 7.3, 18.7 Hz, 3 H, CH3), 1.23 (m, 1 H, Ha-CH2), 1.55 (m, 1 H, Hb-CH2), 1.82 (m, 1 H, Ha-CH2), 2.08-2.26 (m, 2 H, Hb-CH2, CH-P), 3.09 (m, 1 H, CH-P), 3.84 (s, 3 H, OCH3), 6.51 (m, 1 H, arom. H), 7.04 (m, 1 H, arom. H), 7.34 (m, 1 H, arom. H). 13C NMR: δ = 14.8, 20.0, 33.4, 36.2, 36.9, 37.1, 52.8, 109.6, 124.1, 136.9, 159.1, 162.7. 31P NMR: δ = 11.8.
8-[( R , R )-2,5-Dimethylphospholan-1-yl]quinoline (7d) 1H NMR: δ = 0.50 (dd, J = 7.1, 9.2 Hz, 3 H, CH3), 1.18-1.46 (m, 2 H, CH2), 1.24 (dd, J = 7.3, 18.5 Hz, 3 H, CH3), 1.91 (m, 1 H, Ha-CH2), 2.11 (m, 1 H, Hb-CH2), 2.46 (m, 1 H, CH-P), 2.64 (m, 1 H, CH-P), 7.20 (m, 1 H, arom. H), 7.34 (m, 1 H, arom. H), 7.55-7.63 (m, 2 H, arom. H), 7.93 (m, 1 H, arom. H), 8.83 (m, 1 H, arom. H). 13C NMR: δ = 16.7, 20.4, 30.6, 33.8, 34.8, 35.7, 120.6, 125.6, 127.4, 127.4, 131.3, 135.7, 137.6, 148.7, 150.1. 31P NMR: δ = 1.7.
2-{[(2 R ,5 R )-2,5-Dimethylphospholan-1-yl]meth-yl}pyridine (7e) 1H NMR: δ = 0.90 (dd, J = 7.0, 18.0 Hz, 3 H, CH3), 1.16 (m, 1 H, Ha-CH2), 1.12 (dd, J = 7.2, 10.0 Hz, 3 H, CH3), 1.50 (m, 1 H, Hb-CH2), 1.90-2.18 (m, 4 H, CH2, CH-P), 2.86 (doublet of AB-system, 2 H, CH2P), 7.00 (m, 1 H, arom. H), 7.19 (m, 1 H, arom. H), 7.50 (m, 1 H, arom. H), 8.41 (m, 1 H, arom. H). 13C NMR: δ = 14.3, 20.4, 32.8, 34.4, 36.1, 36.5, 36.8, 120.5, 123.4, 136.1, 149.0, 159.5. 31P NMR: δ = 8.3.
( S Fc )-2-[(1 S )-(1- N,N -Dimethylamino)ethyl]-1-[(2′ R ,5′ R )-dimethylphospholan-1-yl]ferrocene (9)
To a solution of (S)-Ugi’s amine (S)-8 (0.28 g, 1.09 mmol) in Et2O (5 mL) was added t-BuLi (1.7 M solution, 0.70 mL) at -78 °C. The solution was stirred for 1.5 hour at ambient temperature and after cooling to -78 °C the chlorophos-pholane 2 (0.18 g, 1.20 mmol) was added. After 30 min. the solution was allowed to warm and stirred for 1.5 hours. After filtration the solvent was removed and the residue was treated with MeOH (1 mL) to give a yellow precipitate (63%).
1H NMR: δ = 0.69 (dd, J = 7.1, 10.1 Hz, 3 H, CH3), 1.22 (m, 1 H, Ha-CH2), 1.22 (d, J = 6.9 Hz, 3 H, CH3), 1.12 (dd, J = 7.3 Hz, 18.9 Hz, 3 H, CH3), 1.38 (m, 1 H, Hb-CH2), 1.00-2.25 (m, 3 H, CH2, CH-P), 2.05 (s, 6 H, NCH3), 2.61 (m, 1 H, CH-P), 3.99 (m, 1 H, HCp), 4.05 (m, 1 H, CH-N), 4.09 (s, 5 H, Cp-ring), 4.21 (m, 1 HCp), 4.26 (m, 1 H, HCp). 13C NMR: δ = 8.0, 15.2, 20.3, 34.9, 36.1, 36.4, 37.0, 39.4, 56.1, 67.8, 68.9, 69.0, 71.0, 98.4. 31P NMR: δ = 6.8.