Zinc-Mediated Stereoselective Barbier Allylation of N-Carbethoxy-α-amino Ketones in Aqueous Solution

Gabriel O. Resende; Lucia C. S. Aguiar; O. A. C. Antunes

doi:10.1055/s-2004-836039

LETTER

Zinc-Mediated Stereoselective Barbier Allylation of N-Carbethoxy-α-amino Ketones in Aqueous Solution

Gabriel O. Resende^a, Lucia C. S. Aguiar*^a, O. A. C. Antunes^b
^a Núcleo de Pesquisas de Produtos Naturais, UFRJ, Cidade Universitária, CCS Bloco H, Rio de Janeiro, RJ 21941-590, Brazil
e-Mail: lcsequeira@nppn.ufrj.br;
^b Instituto de Química, UFRJ, Cidade Universitária, CT Bloco A, Lab 641, Rio de Janeiro, RJ 21941-590, Brazil

Abstract

Alle Artikel dieser Rubrik

Abstract

Zinc-mediated aqueous allylic Barbier reaction of N-carbethoxy-α-amino phenylketones was carried out with good diastereoselectivity (up to 95% de), leading to vicinal amino alcohols. The corresponding reaction using N-carbethoxy-α-amino methylketones did not present good facial diastereoselectivity.

Key words

diastereoselectivity - zinc - allylations - amino ketones - Barbier reaction

Volltext

Referenzen

References

1 Li C.-J. Tetrahedron 1996, 52: 5643

2a Hanessian S. Park H. Yang R.-Y. Synlett 1997, 353

2b Hanessian S. Park H. Yang R.-Y. Synlett 1997, 351

2c Jurczak J. Krasinski A. Tetrahedron Lett. 2001, 42: 2019

2d Giannis A. Seck S. Rubsam F. Tetrahedron 1997, 53: 2823

3a Kabalka GW. Pace RD. J. Org. Chem. 1995, 60: 4838 ; and references therein

3b Loh T.-P. Huang J.-M. Xu K.-C. Go S.-H. Vittal JJ. Tetrahedron Lett. 2000, 41: 6511

4 Rapoport H. Buckley TF. J. Am. Chem. Soc. 1981, 103: 6157

5 Gordon EM. Godfrey JD. Von Langen DJ. Tetrahedron Lett. 1987, 28: 1603

6 Rich DH. Bernatowicz MS. Boparai AS. Kawai M. J. Org. Chem. 1983, 48: 1876

7 Mullen G. Napier J. Balestra M. DeCory T. Hale G. Macor J. Mack R. Loch J. Wu E. Kover A. Verhoest P. Sampognaro A. Phillips E. Zhu Y. Murray R. Griffith R. Blosser J. Gurley D. Machulskis A. Zongrone J. Rosen A. Gordon J. J. Med. Chem. 2000, 43: 4045

8a Azzolina O. Collina S. Brusotti G. Rossi D. Linati L. Lanza E. Ghislandi V. Tetrahedron Lett. 2004, 45: 1355

8b Collina S. Azzolina O. Vercesi D. Benevelli F. Callegari A. Tadini C. Lanza E. Barbieri A. Ghislandi V. Bioorg. Med. Chem. 2000, 8: 769

9 Yao Z.-J. Zha H.-Y. Qin D.-G. J. Org. Chem. 2002, 67: 1038

10 Liotta DC. Crane HM. Lagu BR. J. Org. Chem. 1993, 58: 4191

11

General Procedure for the Allylation of Amino Ketones 2a-f:
Zinc dust (6 mmol) was added to a solution of the N-protected α-amino ketones (1 mmol) and allyl bromide (3 mmol) in sat. aq NH₄Cl-THF (5 mL:1 mL) at 0 °C (ca. 1 h). Filtration, extraction (EtOAc), and evaporation gave the desired products after column chromatography (10-15% EtOAc in hexane).

12

Analytical data for amino alcohols obtained:
Compound 1a: [α]_D +45.8 (c 0.9, CH₂Cl₂). ¹H NMR (200 MHz, CDCl₃): δ = 7.40-7.20 (m, 5 H), 5.50-5.28 (m, 1 H), 5.20-5.02 (m, 3 H), 4.16 (q, J = 6.96 Hz, 2 H), 4.16-3.94 (m, 1 H), 2.81 (dd, J = 13.92 and 5.43 Hz, 1 H), 2.62 (dd, J = 13.55 and 8.79 Hz, 1 H), 1.27 (t, J = 7.14, 3 H), 0.87 (d, J = 6.59, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 14.50, 16.03, 44.10, 54.01, 60.75, 77.71, 119.92, 125.29, 126.69, 128.10, 132.94, 143.33, 156.57.
Compound 1b: [α]_D +7.5 (c 2, CH₂Cl₂). ¹H NMR (200 MHz, CDCl₃): δ = 5.46-5.22 (m, 1 H), 5.20-5.02 (m, 2 H), 4.84 (br d, 1 H), 4.17 (q, J = 7.08 Hz, 2 H), 4.12-3.80 (m, 1 H), 2.80 (dd, J = 13.67 and 4.96 Hz, 1 H), 2.57 (dd, J = 13.73 and 9.09 Hz, 1 H), 1.62-1.42 (m, 2 H), 1.28 (t, J = 7.14, 3 H), 1.32-1.22 (m, 1 H), 0.76 (d, J = 6.72, 3 H), 0.75 (d, J = 6.47, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 14.53, 21.01, 23.68, 24.51, 38.84, 44.39, 56.58, 60.83, 78.36, 119.97, 125.29, 126.64, 128.14, 132.97, 143.58, 157.16.
Compound 1c: [α]_D +25.2 (c 1,5, CH₂Cl₂). ¹H NMR (200 MHz, CDCl₃): δ = 7.64-6.80 (m, 10 H), 5.50-5.20 (m, 1 H), 5.20-5.00 (m, 3 H), 4.26 (td, J = 9.46 and 5.37 Hz, 1 H), 4.00 (q, J = 7.08 Hz, 2 H), 2.85 (dd, J = 13.92 and 8.79 Hz, 1 H), 2.64 (dd, J = 13.92 and 9.04 Hz, 1 H), 2.54-2.46 (m, 2 H), 1.12 (t, J = 7.08 Hz, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 14.43, 35.90, 44.51, 59.95, 60.70, 78.20, 119.91, 125.30, 125.89, 126.84, 127.98, 128.31, 128.85, 132.90, 138.61, 143.55, 156.81.
Compound 1d: ¹H NMR (200 MHz, CDCl₃): δ = 6.00-5.75 (m, 1 H), 5.20-5.05 (m, 3 H), 4.11 (q, J = 7.11 Hz, 2 H), 3.75-3.55 (m, 1 H), 2.27 (d, J = 7.44 Hz, 2 H), 1.24 (t, J = 7.08 Hz, 3 H), 1.17 (d, J = 6.82 Hz, 3 H), 1.13 (s, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 14.41, 15.54 (15.76), 22.97 (24.00), 43.39 (44.02), 53.15 (53.61), 60.73, 73.84 (73.95), 118.64, 133.36, 156.58 (156.73).
Compound 1e: ¹H NMR (200 MHz, CDCl₃): δ = 6.00-5.80 (m, 1 H), 5.20-5.05 (m, 2 H), 4.70 (br d, 1 H), 4.10 (q, J = 6.90 Hz), 3.72-3.50 (m, 1 H), 2.40-2.08 (m, 2 H), 1.65-1.58 (m, 2 H), 1.41-1.30 (m, 1 H), 1.24 (t, J = 7.14 Hz, 3 H), 0.93 (d, J = 6.59 Hz, 3 H), 0.90 (d, J = 6.32 Hz, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 14.33, 21.18, 22.81, 23.82, 24.69, 38.36 (38.68), 43.39 (44.00), 55.98 (56.17), 60.65 (60.74), 74.33 (74.49), 118.36, 133.46, 157.10 (157.34). Compound 1f: ¹H NMR (200 MHz, CDCl₃): δ = 7.32-7.12 (m, 5 H), 6.06-5.80 (m, 1 H), 5.26-5.08 (m, 2 H), 4.84 (m, 1 H), 3.94 (q, J = 6.96 Hz, 2 H), 3.86-3.64 (m, 1 H), 3.20-2.98 (m, 1 H), 2.70-2.22 (m, 3 H), 1.25 (s, 3 H), 1.10 (t, J = 7.13, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 14.35, 23.62 (24.27), 35.39 (35.64), 43.92 (44.37), 59.30 (59.41), 60.75, 74.16 (74.28), 118.76 (118.95), 126.08, 128.17, 128.97, 138.50 (138.64), 156.80 (157.05).