Synthesis of Novel Highly Active Thiophene and Benzothiophene Containing Diphosphine Ligands and their Use in the Asymmetric Allylation of Catechol

Abstract

Novel thiophene and benzothiophene containing diphosphine ligands 5-8 with a chiral cyclohexyl diamine backbone have been prepared and used in the asymmetric allylation of catechol. The advantage of these new ligands is their high reactivity and excellent selectivity. The best results were obtained using ligand 7 to give the allylated catechol 24b from 23b in 90% ee and 91% yield within 4 hours.

Key words

allylation - asymmetric catalysis - catechol - palladium - phosphines - thiophenes

References

• Reviews:
• 1a Tietze LF. Ila H. Bell HP. Chem. Rev.  2004,  in press
• 1b Overman LE. Dounay AB. Chem. Rev.  2003,  103:  2945 
• 1c Shibasaki M. Boden CDJ. Kojima A. Tetrahedron  1997,  53:  7371 
• 2a Graening T. Schmalz H.-G. Angew. Chem. Int. Ed.  2003,  42:  2580 ; Angew. Chem. 2003, 115, 2684
• 2b Trost BM. Chem. Pharm. Bull.  2003,  50:  1 
• 2c Trost BM. Crawley ML. Chem. Rev.  2003,  103:  2921 
• 3a Trost BM. Van Vranken DL. Angew. Chem., Int. Ed. Engl.  1992,  31:  228 ; Angew. Chem. 1992, 104, 194
• 3b Knuehl G. Sennhenn P. Helmchen G. J. Chem. Soc., Chem. Commun.  1995,  18:  1845 
• 3c Pfaltz A. von Matt P. Angew. Chem., Int. Ed. Engl.  1993,  32:  566 ; Angew. Chem. 1993, 105, 614
• 3d Helmchen G. Sprinz J. Tetrahedron Lett.  1993,  34:  1769 
• 4a Tietze LF. Thede K. Synlett  2000,  1470 
• 4b Tietze LF. Thede K. Sannicolò F. Chem. Commun.  2000,  583 
• 4c Tietze LF. Thede K. Chem. Commun.  1999,  18:  1811 
• 5 Tietze LF. Lohmann JK. Synlett  2002,  2083 
• 6a Shilai M. Kondo YT. J. Chem. Soc., Perkin Trans. 1  2001,  442 
• 6b Kristensen J. Lysen M. Vedsø P. Begtrup M. Org. Lett.  2001,  3:  1435 
• 7 Persigehl P. Jordan R. Nuyken O. Macromolecules  2000,  33:  6977 

8

Synthesis of Ligand 7: A mixture of 3-bromo-thiophene-2-carboxylic acid (16, 9.44 g, 46 mmol) and Me₃SiCl (92 mmol, 2.0 equiv) in MeOH was refluxed for 24 h. After cooling, the crude product was adsorbed on silica gel (20 g) and purified by column chromatography (n-pentane/EtOAc, 10:1). The methyl ester 17 (9.50 g, 43.0 mmol, 93%) was obtained as a white solid. A solution of this ester (7.1 g, 32.1 mmol), dry NaOAc (5.47 g, 66.7 mmol, 2.1 equiv) and catalyst 19 (620 mg, 2 mol%) was degassed and diphenylphosphine (7.5 mL, 8.03 g, 43.1 mmol, 1.3 equiv) was added via syringe. The solution was heated under argon to 100 °C for 5 h. After cooling, H₂O (200 mL) was added. Extraction with EtOAc (3 × 200 mL) gave the crude product, which was purified via column chromatography (n-pentane: EtOAc, 10:1). The ester (6.90 g, 21.1 mmol) was dissolved in THF/MeOH/H₂O (5:5:1, 100 mL) and LiOH·H₂O (105 mmol, 5.0 equiv) was added. After 24 h 1 N HCl (200 mL) was added and the solution was extracted with EtOAc (3 × 150 mL). The product was purified by chromatography (n-pentane:EtOAc, 10:1, 1% HOAc) and the acid 18 (6.25 g, 20.0 mmol, 95%) was obtained as a white solid. The acid (1.12 g, 3.6 mmol) was dissolved in DMF (50 mL) and HOBt (3.6 mmol) and EDC·HCl (3.6 mmol) were added at r.t. After 30 min, cyclohexanediamine (1.8 mmol) was added and the reaction mixture was stirred for 24 h. 1 N HCl (100 mL) was added add the resulting mixture was extracted thrice with EtOAc (100 mL). After purification by column chromatography ligand 7 was obtained as a white foam.
[α]_D ²⁰ -110.8 (c 0.3, CHCl₃); R_f (n-pentane:EtOAc = 4:1, 1% Et₃N) = 0.41. IR (KBr): ν = 3281, 3014, 2932, 2051, 1638, 1526 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.26 (m_c, 2 H, 3′-H), 1.68 (m_c, 1 H, 2′-H_a), 2.04 (m_c, 1 H, 2′-H_b), 3.87 (m_c, 1 H, 1′-H), 6.52 (dd, J = 5.0, 1.0 Hz, 1 H, 5-H), 7.23-7.33 (m, 11 H, Ph-H, N-H), 7.64 (dd, J = 8.0, 5.0 Hz, 1 H, 4-H). ¹³C NMR (125 MHz, CDCl₃): δ = 24.44 (C-3′), 31.99 (C-2′), 54.12 (C-1′), 128.21 (d, J = 2.5 Hz, C-5), 128.61 (d, J = 7.0 Hz, Ph-C-3), 128.88 (d, J = 6.5 Hz, C-4), 133.23, 133.27 (d, J = 19.5 Hz, Ph-C-2), 133.34, 133.37 (Ph-C-4), 136.21, 136.43 (d, J = 8.0 Hz, Ph-C-1), 137.87 (d, J = 21.0 Hz, C-2), 142.73 (d, J = 24.5 Hz, C-3), 162.30 (d, J = 2.5 Hz, C=O). ³¹P NMR (80 MHz, CDCl₃): δ = -22.70. MS (EI): m/z = 702 (M⁺), 310. Anal. Calcd for C₄₀H₃₆N₂O₂P₂S₂: 702.1694. Found: 702.1694 (HRMS).