Asymmetric Synthesis of Ferrocenyl-2-thiazoline Ligands with C ₂ -Symmetry

Abstract

The synthesis of previously unreported chiral ferrocene-thiazoline ligands is described. (S)-2-Azido-1-ferrocenylethanol, available by enantioselective reduction of α-azidoacetyl ferrocene was converted into the corresponding 5-ferrocenyl thiazoline by the three-step sequence: catalytic hydrogenation, acylation and cyclization promoted by Lawesson’s reagent. New chiral ferrocene-thiazolines with C₂ symmetry were obtained when diacyl chlorides were used as acylating reagents.

ferrocene - thiazoline - asymmetric reduction - acylation - azides

References

1 For a recent review see: Braunstein P. Naud F. Angew. Chem. Int. Ed.  2001,  40:  680 

2a Sammakia T. Latham HA. Schaad DR. J. Org. Chem.  1995,  60:  10 

2b Zhang W. Kida T. Nakatsuji Y. Ikeda I. Tetrahedron Lett.  1996,  37:  7995 

2c Zhang W. Adachi Y. Hirao T. Ikeda I. Tetrahedron: Asymmetry  1996,  7:  451 

2d Stangeland EL. Sammakia T. Tetrahedron  1997,  53:  16503 

2e Sammakia T. Stangeland L. J. Org. Chem.  1997,  62:  6104 

2f Ahn KH. Cho CW. Park J. Lee S. Tetrahedron: Asymmetry  1997,  8:  1179 

2g Nishibayashi Y. Segawa K. Arikawa Y. Ohe K. Hidai M. Uermura S. J. Organomet. Chem.  1997,  545:  381 

2h Zhang W. Yoneda Y. Kida T. Nakatsuji Y. Ikeda I. Tetrahedron: Asymmetry  1998,  9:  3371 

2i Bolm C. Muñiz-Fernández K. Seger A. Raabe G. Günther K. J. Org. Chem.  1998,  63:  7860 

2j Zhang W. Yoneda Y. Kida T. Nakatsuji Y. Ikeda I. J. Organomet. Chem.  1999,  574:  19 

2k Zhang W. Shimanuki T. Kida T. Nakatsuji Y. Ikeda I. J. Org. Chem.  1999,  64:  6247 

3 Tárraga A. Molina P. Curiel D. López JL. Velasco MD. Tetrahedron  1999,  55:  14701 

4 Tárraga A. Molina P. Curiel D. Velasco MD. Tetrahedron  2001,  57:  14701 

5 Leffler JE. Temple RD. J. Am. Chem. Soc.  1967,  89:  5235 

6a Ojima I. Catalytic Asymmetric Synthesis   Wiley; New York: 2000. 

6b Ager DJ. Prakash I. Schaad DR. Chem. Rev.  1996,  96:  835 

7 Corey EJ. Bakshi RK. Shibata S. J. Am. Chem. Soc.  1987,  109:  5551 

8

( S )-2-Azido-1-ferrocenylethanol(3): To a solution of (S)-CBS-oxazaborolidine (1.69 mmol, 1 M in toluene, 1.69 mL) in anhyd THF (5 mL), cooled at 0 °C and under nitrogen, a solution of BH₃THF (1.13 mmol; 1 M in THF, 1.13 mL) was added. Then, a solution of α-azidoacetylferrocene
(1.52 g, 5.65 mmol), in dry THF (5 mL) and BH₃-SMe₂
(6.21 mmol; 2 M in THF, 3.1 mL), in the same solvent
(2 mL) were slowly added over a period of 20 min. After
the addition, the reaction mixture was stirred for 10 min, quenched cautiously with methanol (10 mL) and later with a sat. solution of NH₄Cl (20 mL), and then extracted with CH₂Cl₂ (4 × 15 mL). The organic layers were dried over Na₂SO₄ and the solvent evaporated under reduced pressure. The chemically pure compound 3 was obtained by crystallization from ether/pentane (5/1) (95%) [α]_D = -77 (c 1.35, CHCl₃). Ee (94%) of the product was determined by HPLC fitted with a Cyclobond I 2000 column and using n-hexane/i-PrOH (97/3) as eluent; mp 37-39 °C; IR (Nujol): 3435, 2102, 1448, 1415, 1401, 1312, 1259, 1070, 2033, 822 cm^-1; ¹H NMR (CDCl₃): δ = 2.23 (s, 1 H), 3.39 (d, 2 H, J = 4.0 Hz), 4.21 (s, 8 H), 4.27 (s, 1 H), 4.54 (bs, 1 H); ¹³C NMR (CDCl₃): δ = 57.27 (CH₂), 65.69 (CH, Cp), 67.28 (CH, Cp), 68.51 (2 × CH, Cp), 68.61 (5 × CH, Cp), 69.52 (CH-OH), 89.88 (q, Cp); MS (EI): m/z (rel. intensity) = 271(51) [M⁺], 225(24), 214(97), 186(92), 121(100). Anal. Calcd for C₁₂H₁₃FeN₃O: C, 53.17; H, 4.83; N, 15.50. Found: C, 53.03; H, 4.78; N, 15.62.

9a Wright J. Frambes L. Reeves P. J. Organomet. Chem.  1994,  476:  215 

9b Schwink L. Knochel P. Chem.-Eur. J.  1998,  4:  950 

9c Dübner F. Knochel P. Angew. Chem. Int. Ed.  1999,  38:  379 

10 Schwik L. Knochel P. Eberle T. Okuda J. Organometallics  1998,  17:  7 

11 The (S)-2-amino-1-ferrocenyl ethanol was obtained in an overall yield of 35% via a lipase catalyzed acylation of ferrocene cyanohydrin followed by reduction with AlLiH₄: Patai A. Nicolosi G. Howell JAS. Humpries K. Tetrahedron: Asymmetry  1998,  9:  4381 

12a Saxon E. Bertozzi CR. Science  2000,  287:  2007 

12b Saxon E. Amstrong JI. Bertozzi CR. Organic Lett.  2000,  2:  2146 

13

General Procedure for the Preparation of 2,5-disubstituted Thiazolines: To a suspension of the appropriate β-hydroxyamide (1 equiv) in dry THF (20 mL) Lawesson’s reagent (2 equiv) was added and the mixture was heated under reflux under nitrogen, for 3 h. Then, the solvent was removed under reduced pressure and the residue was directly chromatographed on a silica gel column using CH₂Cl₂/EtOAc (20/1) and then using CH₂Cl₂/MeOH (15/1) to give the corresponding thiazoline. Representative spectroscopic data are given for 2,5-bis(ferrocenyl)thiazoline(8b): IR (Nujol): 1607, 1457, 1414, 1377, 1308, 1289, 1109, 1057, 1003, 742 cm^-1; ¹H NMR (CDCl₃): δ = 4.14 (t, 2 H, J = 1.8 Hz), 4.16-4.25 (m, 12 H), 4.35 (t, 2 H, J =& nbsp;1.8 Hz), 4.28 (dd, 1 H, J = 15.45 Hz, J = 7.80 Hz), 4.45 (dd, 1 H, J = 15.45 Hz, J = 5.40 Hz), 4.67 (m, 1 H), 4.72 (m, 1 H), 4.85 (dd, 1 H, J = 7.80 Hz, J = 5.40 Hz); ¹³C NMR (CDCl₃): δ = 51.01 (CH, thiaz.), 66.70 (CH, Cp), 67.32 (CH, Cp), 68.33 (2 × CH, Cp), 68.86 (5 × CH, Cp), 69.20 (CH, Cp), 69.27 (CH, Cp), 69.96 (5 × CH, Cp), 70.38 (2 × CH, Cp), 71.34 (CH₂, thiaz.), 77.28 (q, Cp), 89.59 (q, Cp), 167.64 (q, thiaz.); MS (EI): m/z (rel. intensity) = 455(100) [M⁺], 244(85), 211(41), 178(19), 121(44). Anal. Calcd for C₂₃H₂₁Fe₂NS: C, 60.69; H, 4.65; N, 3.08. Found: C, 60.58; H, 4.79; N, 3.21.

14 Lafargue P. Guenot P. Lellouche J.-P. Synlett  1995,  171 

15

Tárraga, A.; Molina, P.; Curiel, D., unpublished work.

16a Gokel GW. Marquarding D. Ugi I. J. Org. Chem.  1972,  37:  3052 

16b Gokel G. Hoffmann P. Klusacek M. Marquarding D. Rush E. Ugi I. Angew. Chem., Int. Ed. Engl.  1970,  9:  64 

17 Togni A. Angew. Chem., Int. Ed. Engl.  1996,  108:  1581 ; and references cited therein

18

Spectroscopic data for compound 9: IR (CH₂Cl₂): 1613, 1463, 1289, 1106, 1028, 1001, 820 cm^-1; ¹H NMR (CDCl₃): δ = 1.55 (s, 6 H), 4.10-4.17 (m, 18 H), 4.38-4.45 (m, 4 H), 4.78-4.84 (m, 2 H); ¹³C NMR (CDCl₃). δ = 26.64 (2 × CH₃), 47.61 (q), 51.66 (2 × CH, thiaz.), 67.00 (2 × CH, Cp), 67.37 (2 × CH, Cp), 68.28 (4 × CH, Cp), 68.86 (10 × CH, Cp), 71.51 (2 × CH₂, thiaz.), 89.38 (2 × q, Cp), 174.57 (2 × q, thiaz.); MS (EI): m/z (rel. intensity)= 582(100) [M⁺], 566(24), 518(6), 517(19), 515(10), 395(20), 313(48), 253(37), 212(36), 212(27). Anal. Calcd for C₂₉H₃₀Fe₂N₂S₂: C, 59.81; H, 5.19; N, 4.81. Found: C, 59.97; H, 5.00; N, 4.69. Spectroscopic data for compound 10: IR (CH₂Cl₂): 1612, 1458, 1104, 1059, 1004, 819 cm^-1; ¹H NMR (CDCl₃): δ = 4.14-4.23 (m, 18 H), 4.36-4.43 (m, 8 H), 4.67-4.76 (m, 4 H), 4.84-4.91 (m, 2 H); ¹³C NMR (CDCl₃): δ = 51.47 (2 × CH, thiaz.), 66.87 (2 × CH, Cp), 67.46 (2 × CH, Cp), 68.48 (2 × CH, Cp), 68.51 (2 × CH, Cp), 68.99 (10 × CH, Cp), 70.79 (2 × CH, Cp), 70.96 (2 × CH, Cp), 71.51 (2 × CH₂, thiaz.), 72.76 (4 × CH, Cp), 78.77 (2 × q, Cp), 9.51 (2 × q, Cp), 167.62 (2 × q, thiaz.); MS (EI): m/z (rel. intensity) = 724(100) [M⁺], 659(14), 481(33), 480(24), 335(55), 244(64), 212(70), 186(26), 121(31). Anal. Calcd for C₃₆H₃₂Fe₃N₂S₂: C, 59.70; H, 4.45; N, 3.87. Found: C, 59.82; H, 4.38; N, 3.71.