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Synlett 2002(1): 0158-0160
DOI: 10.1055/s-2002-19343
LETTER
© Georg Thieme Verlag Stuttgart · New York

One-pot Preparation of 1,2-Aminoalcohols or Pyrroles by CeCl 3 ·7 H2O-mediated Barbier Reactions of N,N’-Bis[(S)-1-phenylethyl]ethanediimine

Gianluca Martelli, Stefano Morri, Diego Savoia*
Dipartimento di Chimica ”G. Ciamician", via Selmi 2, 40126 Bologna, Italy
Fax: +39(051)2099456; e-Mail: savoia@ciam.unibo.it;
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Publication History

Received 31 October 2001
Publication Date:
01 February 2007 (online)

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Abstract

1,2-Aminoalcohols or pyrroles were obtained from N,N’-bis[(S)-1-phenylethyl]ethanediimine by a one-pot procedure involving two Barbier additions of allylic and/or propargyl zinc reagents alternated with the hydrolysis of the unreacted imine function, followed by a cyclisation/dehydration sequence when a 1-amino-5-pentyne moiety was involved, all these steps being promoted by CeCl3·7 H2O.

Key words

1,2-aminoalcohols - cerium trichloride - 1,2-diamines - pyrroles - stereoselective synthesis

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Representative Procedure for the Preparation of 1,2-Aminoalcohols and Pyrroles: Zn powder (1.40 g, 20 mmol) was heated at 150 °C for 5 min in a 50 mL two-neck flask under magnetic stirring in a flow of Ar, then was covered with anhyd THF (20 mL) at r.t. To the stirred mixture were added, in the order, the diimine 1 (1.32 g, 5 mmol), CeCl3·7 H2O (1.86 g, 5 mmol) and then, slowly, a solution of prenyl bromide (1.12 g, 7.5 mmol) in THF (7 mL). After that the heterogeneous mixture had become greenish (ca 0.5 h), CeCl3·7 H2O (3.72 g, 10 mmol) was then added and the mixture was heated at reflux temperature for 1 h, a yellowish colour being observed after that time. Then neat prenyl bromide (1.12 g, 7.5 mmol) was added and the mixture was stirred for 1 h at r.t. The reaction mixture was quenched by addition of sat. NaHCO3 solution (10 mL) and the organic materials were extracted with Et2O (3 × 20 mL). The collected ethereal layers were dried over Na2SO4 and concentrated to leave a solid residue, which was chromatographed through a short column of SiO2 to give 4(R),5(R)-N-[1(S)-phenylethyl]-5-amino-3,3,6,6-tetramethyl-1,7-octadien-4-ol 7 as a white solid: 1.00 g (66%). Crystallisation from n-pentane gave pure 7: 0.81 g (54%); mp 65 °C; [α]D 25 -10.7 (c 0.68, CHCl3); 1H NMR (300 MHz, CDCl3): δ = 7.38-7.20 (m, 5 H), 5.84 (dd, J = 10.8 and 17.4 Hz, 1 H), 5.78 (dd, J = 10.8 and 17.4 Hz, 1 H), 5.09 (dd, J = 0.9 and 10.8 Hz, 1 H), 5.03 (dd, J = 0.9 and 17.4 Hz, 1 H), 4.90 (dd, J = 0.9 and 17.4 Hz, 1 H), 4.89 (dd, J = 0.9 and 10.8 Hz, 1 H), 3.88 (q, J = 6.6 Hz, 1 H), 3.24 (d, J = 1.8 Hz, 1 H), 2.51 (d, J = 1.8 Hz,1 H), 1.32 (d, J = 6.6 Hz, 3 H), 1.05 (s, 3 H), 1.0 (s, 3 H), 0.92 (s, 3 H), 0.84 (s, 3 H); IR(nujol): 3317, 3300(broad), 1639 cm-1; MS: m/z = 105(100), 232(20), 128(16), 69(13), 106(13), 98(12), 60(11), 79(10), 77(6), 202(5). Anal. Calcd for C20H31NO: C, 79.67; H, 10.37; N, 4.65. Found: C, 79.65; H, 10.39; N, 4.63. Spectroscopic data of selected products are reported in the following; all products gave satisfactory elemental analyses. 4(R),5(R)-N-[1(S)-Phenylethyl]-5-amino-6,6-dimethyl-3-vinyl-1,7-octadien-4-ol 10: dr 90:10; [α]D 25 -16.2 (c 1.10, CHCl3); 1H NMR (200 MHz, CDCl3-D2O): δ = 5.85 (dd, J = 10.8 and 17.4 Hz, 1 H), 5.81-5.61 (m, 1 H), 5.50-5.28 (m, 1 H), 5.17-4.80 (m, 4 H), 4.72 (d, J = 17.2 Hz, 1 H), 4.42 (dd, J = 1.8 and 18.0 Hz, 1 H), 3.81 (q, J = 6.6 Hz, 1 H), 3.24 (dd, J = 1.4 and 9.2 Hz, 1 H), 2.46 (d, J = 1.4 Hz, 1 H), 1.67 (m, 1 H), 1.37 (d, J = 6.6 Hz, 3 H), 1.04 (s, 3 H), 1.01 (s, 3 H); IR: 3332, 3320(broad) cm-1; MS: m/z = 105(100), 230(36), 126(15), 79(11), 106(10), 202(7). 5-Methyl-1-[1(S)-phenylethyl]-2-propynylpyrrole 14: 1H NMR (200 MHz, CDCl3): δ = 7.4-7.2 (m, 3 H), 7.03 (m, 2 H), 6.025 (d, J = 3.2 Hz, 1 H), 5.83 (d, J = 3.2 Hz, 1 H), 5.59 (q, J = 6.7 Hz, 1 H), 3.41 (dd, J = 2.6 and 7.0 Hz, 2 H), 2.08 (t, J = 2.6 Hz, 1 H), 2.0 (s, 3 H), 1.89 (d, J = 6.7 Hz, 3 H); IR: 3292, 3069, 3056, 3020, 2140, 1680, 1662, 1592 cm-1; MS: m/z = 105(100), 119(54), 223(49), 118(24), 77(23), 104(23), 79(18), 103(17)

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4(R), 5(R)-Di-(2-methyl-2-butyl)-1,3-oxazolidin-2-one 8: In a Parr apparatus a mixture of MeOH (50 mL), 7 (0.62 g, 2 mmol), 10% Pd/C (60 mg) was submitted to H2 pressure (45 psi) for 6 h. The mixture was filtered through a Celite pad and the filtered solution was concentrated to leave 5(R)-amino-3,3,6,6-tetramethyloctan-4(R)-ol as an oil: 0.35 g (87%). [α]D 25 +12.6 (c 0.88, CHCl3); 1H NMR (300 MHz, CDCl3): δ = 3.26 (s, 1 H), 2.73 (s, 1 H), 1.50-1.10 (m, 4 H), 0.85 (m, 12 H), 0.73 (2 s, 6 H); MS: m/z = 100(100), 130(79), 60(38), 71(22), 55(17), 59(16). A solution of this compound (0.35 g, 1.7 mmol) and 1,1-carbonyldiimidazole (0.324 g, 2 mmol) in CH2Cl2 (8 mL) was stirred for 2 h, then H2O (5 mL) was added and the mixture was stirred for further 0.5 h. The organic phase was separated and the aq phase was extracted with CH2Cl2 (2 × 5 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated to leave 8 as a white solid: 0.33 g (86%); mp 85 °C; crystallisation from Et2O gave an analytical sample: mp 89 °C; [α]D 25 +71.8 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3): δ = 6.24 (broad, 1 H), 4.06 (d, J = 2.1 Hz, 1 H), 3.27 (d, J = 2.1 Hz, 1 H), 1.50-1.15 (m, 4 H), 0.92-0.80 (m, 18 H); IR(nujol): 3265, 1751 cm-1; irradiating the absorption at either δ = 4.06 (d) or δ = 3.27 (d) only a response (8%) at 0.81 (m) was observed; MS: m/z = 128(100), 86(58), 71(29), 156(13), 55(12), 129(10), 142(7). Anal. Calcd for C13H25NO2: C, 68.68; H, 11.08; N, 6.16. Found C, 68.65; H, 11.10; N, 6.15.