Download PDF
Synlett 2005(8): 1331-1333  
DOI: 10.1055/s-2005-868475
LETTER
© Georg Thieme Verlag Stuttgart · New York

New Simple Chiral Phosphine Oxazolidine Ligands: Easy Synthesis and ­Application in the Palladium-Catalyzed Asymmetric Allylic Alkylation

Antonio L. Braga*, Jasquer A. Sehnem, Diogo S. Lüdtke, Gilson Zeni, Claudio C. Silveira, Miriam I. Marchi
Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil
Fax: +55(55)2208998; e-Mail: albraga@quimica.ufsm.br;
Further Information

Publication History

Received 9 March 2005
Publication Date:
21 April 2005 (online)

    Permissions and Reprints All articles of this category

Abstract

New types of chiral phosphine-oxazolidines have been easily synthesized in a straightforward one-pot process starting from optically active aminoalcohols. They were screened in the Pd-catalyzed asymmetric allylic alkylations of 1,3-diphenyl-2-propenyl acetate with dimethylmalonate. The reaction proceeds smoothly in good to excellent yields and excellent stereoselectivity was obtained (up to 97%).

Key words

phosphines - oxazolidines - allylic alkylations

8

Typical procedure for the preparation of phosphine oxazolidines 1: To a 50 mL round-bottomed flask equipped with Dean-Stark apparatus, benzene (30 mL), l-phenyl-alaninol (0.302 g, 2.0 mmol), paraformaldehyde (0.03 g, 3.0 mmol) and p-toluenesulfonic acid (cat.) were added. The mixture was heated under reflux for 4 h. After this time, a second portion of paraformaldehyde (0.03 g, 3.0 mmol) and diphenylphosphine (0.446 g, 2.4 mmol) were added. This mixture was heated under reflux for an additional 4 h and then cooled to room temperature. The benzene was removed under vaccum, the residue was dissolved in of CH2Cl2 (30 mL), and washed with 0.1 M NaOH solution. After drying over magnesium sulfate and filtration, the solvent was removed in vacuo yielding a yellow solid, which was purified by flash chromatography (hexane-EtOAc, 9:1). The product was dried in vacuo to afford 0.596 g (1.65 mmol, 82%) of the phosphine-oxazolidine 1a.
( S )-4-Benzyl-1,3-oxazolan-3-ylmethyl(diphenyl)phos-phane ( 1a) Mp 71-72 °C; [α]D 20 +30 (c 0.7, CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 7.51-7.04 (m, 15 H), 4.47 (dd, 2 H, J 1 = 7.76 Hz, J 2 = 5.76 Hz), 3.85-3.82 (m, 1 H), 3.48 (d, 2 H, J = 7.00 Hz), 3.43-3.40 (m, 2 H), 2.79 (dd, 1 H, J 1 = 13.70 Hz, J 2 = 5.88 Hz), 2.51 (dd, 1 H J 1 = 13.70 Hz, J 2 = 5.88 Hz); 13C NMR (CDCl3, 100 MHz): δ = 131.87-126.25 (m), 87.35 (d, J = 6.30 Hz), 68.60, 61.08 (d, J = 9.60 Hz), 55.58 (d, J = 87.80 Hz), 39.40; 31P NMR (CDCl3, 161.98 MHz): δ = 29.21; LRMS: m/z (%) = 361 (2, M+), 162 (100), 91 (50), 77 (67); Anal. Calcd for C23H24NOP: C, 76.43; H, 6.69; N, 3.88. Found: C, 76.19, H, 6.81; N 3.77.
( S )-4-Isopropyl-1,3-oxazolan-3-ylethyl(diphenyl)phos-phane ( 1b) Yield: 0.439 g (1.40 mmol, 70%); mp 60-62 °C; [α]D 20 +14 (c 0.7, CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 7.81-7.44 (m, 10 H), 4.58 (d, 1 H, J = 6.08 Hz), 4.39 (d, 1 H, J = 6.08 Hz), 3.88 (dd, 1 H, J 1 = 8.24 Hz, J 2 = 7.16 Hz), 3.57 (dd, 1 H, J 1 = 16.00 Hz, J 2 = 5.16 Hz), 3.45-3.37 (m, 2 H), 2.77-2.72 (m, 1 H), 1.53-1.45 (m, 1 H), 0.71 (d, 3 H, J = 6.07 Hz), 0.69 (d, 3 H, J = 6.07 Hz); 13C NMR (CDCl3, 100 MHz): δ = 132.30-127.20 (m), 86.55 (d, J = 8.10 Hz), 72.45 (d, J = 22.30 Hz), 66.06, 55.57 (d, J = 176.30 Hz), 30.04, 19.36, 17.56. 31P NMR (CDCl3, 161.98 MHz): δ = 28.59; LRMS: m/z (%) = 313 (2, M+), 128 (100), 84 (19), 77 (14), 69 (14), 55 (13), 42 (51); Anal. Calcd for C19H24NOP: C, 72.82; H, 7.72; N, 4.47. Found: C, 72.57; H, 7.85; N 4.22.
( S )-4-Methyl-1,3-oxazolan-3-ylmethyl(diphenyl)phos-phane ( 1c) Yield: 0.325 g (1.14 mmol, 57%); bp 63-65 °C (0.30 mmHg); [α]D 20 +9 (c 0.7, CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 7.47-6.94 (m, 10 H), 4.11 (d, 1 H, J = 5.04 Hz), 3.91 (d, 1 H, J = 5.04 Hz), 3.59-3.52 (m, 1 H), 3.18 (dd, 1 H, J 1 = 15.04 Hz, J 2 = 7.42 Hz), 3.00 (dd, 1 H, J 1 = 15.04 Hz, J 2 = 6.22 Hz), 3.05-2.71 (m, 2 H), 0.93 (d, 3 H, J = 6.22 Hz); 13C NMR (CDCl3, 100 MHz): δ = 136.81-127.85 (m), 86.72 (d, J = 5.76 Hz), 70.11, 60.54 (d, J = 10.16 Hz), 53.82 (d, J = 89.16 Hz), 15.05. 31P NMR (CDCl3, 161.98 MHz): δ = 29.32; LRMS: m/z (%) = 285 (2, M+), 100 (100), 77 (11), 70 (30), 42 (27), 28 (11); Anal. Calcd for C17H20NOP: C, 71.56; H, 7.06; N, 4.91. Found: C, 71.63, H, 6.90; N 4.77.
( S )-4-Phenyl-1,3-oxazolan-3-ylmethyl(diphenyl)phos-phane ( 1d) Yield: 0.493 g (1.42 mmol, 71%); mp 108-109 °C; [α]D 20 +90 (c 0.7, CH2Cl2); 1H NMR (CDCl3, 400 MHz): δ = 7.64-7.11 (m, 15 H), 5.02 (d, 1 H, J = 3.84 Hz), 4.41 (d, 1 H, J = 3.84 Hz), 4.17 (dd, 1 H, J 1 = 7.82 Hz, J 2 = 7.30 Hz), 3.83 (dd, 1 H, J 1 = 7.82 Hz, J 2 = 7.30 Hz), 3.58-3.50 (m, 2 H). 3.25 (dd, 1 H, J 1 = 14.76 Hz, J 2 = 5.48 Hz); 13C NMR (CDCl3, 100 MHz): δ = 137.95-127.64 (m), 87.71, 72.66, 69.72 (d, J = 13.80 Hz), 52.26 (d, J = 87.20 Hz); 31P NMR (CDCl3, 161.98 MHz): δ = 29.95, LRMS: m/z (%) = 347 (2)(M+), 176 (100), 91 (62), 77 (33), 42 (89); Anal. Calcd for C22H22NOP: C, 76.06; H, 6.38; N, 4.03. Found: C, 76.30; H, 6.31; N, 3.88.
( R )-4-Phenyl-1,3-oxazolan-3-ylethyl(diphenyl)phos-phane ( ent- 1d) Yield: 0.507 g (1.46 mmol, 73%); mp 108-109 ºC; [α]D 20 -90 (c 0.7, CH2Cl2); for the other spectral and analytical data see 1d.

11

General Procedure for the Asymmetric Allylic Alkylation: A THF (1 mL) solution of [Pd(η3-C3H5)Cl]2 (1 mg, 0.025 mmol, 2.5 mol%), catalyst 1a-d (10 mol%) was stirred for 30 min under an argon atmosphere and then 1,3-diphenyl-2-propenyl acetate (0.252 g, 1.0 mmol) was added. The mixture was stirred for 10 min and a solution of sodium dimethyl malonate, prepared from dimethyl malonate (0.264 g, 2.0 mmol) and sodium hydride (0.036 g, 1.5 mmol) in THF (3 mL), was added at room temperature. The reaction mixture was then stirred for the time specified in Table [1] , at room temperature. After this time, saturated NH4Cl was added and it was extracted with CH2Cl2 (3 × 15 mL) and the combined organic layers were dried with MgSO4. The solvent was evaporated and the crude product was purified by flash chromatography eluting with hexane-EtOAc (98:2). The enantiomeric excess of 4 was determined by 1H NMR (CDCl3) analysis with chiral shift reagent Eu(hfc)3 and the absolute configuration was determined by comparison of the optical rotation.