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

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.

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

References

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3 Basile T. Bocoum A. Savoia D. Umani-Ronchi A. J. Org. Chem.  1994,  59:  7766 

4 The deprotection of O-MEM ethers by CeCl₃·7 H₂O in refluxing acetonitrile was reported when we had already obtained this results: (a) Sabitha G. Babu RS. Rajkumar M. Srividya R. Yadav JS. Org. Lett.  2001,  3:  1149 

4 Similarly, FeCl₃·6 H₂O has been used to deprotect acetals and thioacetals in CH₂Cl₂: (b) Sen SE. Roach SL. Boggs JK. Ewing GJ. Magrath J. J. Org. Chem.  1997,  62:  6684 

4 See also: (c) Khamal A. Laxman E. Reddy PSM. Synlett  2000,  1476 

4 Carbonyl compounds have been obtained from N,N-dimethylhydrazones by employing Ni, Hg and Mn complexes and 1 drop of water in CHCl₃: (d) Khamal A. Arifuddin M. Rao MV. Synlett  2000,  1482 

5a Poisson J.-F. Normant JF. J. Org. Chem.  2000,  65:  6553 

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For a review of metal-initiated amination of alkenes and alkynes: (f) Müller TE. Beller M. Chem. Rev.  1998,  98:  675 

8 The pyrrole should be also obtained by the analogous cyclisation of the partially formed aminoallene: Arredondo VM. McDonald FE. Marks TJ. J. Am. Chem. Soc.  1998,  120:  4871 

9 It should be observed that even heating CeCl₃·7 H₂O at 150 °C and 0.03 Torr for 12 h forms a material containing approximately 1 equiv of water, which reacts with MeLi to form methane: Evans WJ. Feldman JD. Ziller JW. J. Am. Chem. Soc.  1996,  118:  4581 

10

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)

11

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.

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