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Synlett 2005(1): 119-120  
DOI: 10.1055/s-2004-836039
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Gabriel O. Resendea, Lucia C. S. Aguiar*a, O. A. C. Antunesb
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
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Publication History

Received 3 September 2004
Publication Date:
29 November 2004 (online)

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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

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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).