InCl3-Mediated Cascade Reactions for the Construction of Highly Functionalized 1-Oxadecalins

Weiguo Peng; Chi-Sing Lee

doi:10.1055/s-2007-990953

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Synlett 2008(1): 142-146
DOI: 10.1055/s-2007-990953

LETTER

InCl₃-Mediated Cascade Reactions for the Construction of Highly Functionalized 1-Oxadecalins

Weiguo Peng, Chi-Sing Lee*
Laboratory of Chemical Genomics, Shenzhen Graduate School, Peking University, Shenzhen University Town, Xili, Shenzhen 518055, P. R. of China
Fax: +86(755)26035326; e-Mail: lizc@szpku.edu.cn;

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Publication History

Received 23 October 2007
Publication Date:
11 December 2007 (online)

Abstract
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Abstract

A one-pot, two-component InCl₃-mediated cascade reaction has been developed. Starting from readily available β-keto ester and alkynal substrates, this cascade reaction provided highly functionalized 1-oxadecalins in good yields and excellent diastereoselectivities.

Key words

1-oxadecalin - indium - cascade cyclizations - Prins - Conia-ene reactions

References and Notes

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14

General ProceduresTo a stirred solution of a β-keto ester (1.5 equiv) and an alkynal (1 equiv) in the appropriate solvent (alkynal concentration = 0.1 mol/L) at 0 °C or r.t. was added a Lewis acid (1 equiv or the amount indicated). The resulting mixture was stirred at the indicated reaction temperature and the reaction was monitored by TLC analysis. After the substrates and intermediates were consumed, the mixture was cooled to r.t., treated with sat. aq NaHCO₃, and extracted with EtOAc (3×). The combined extracts were washed with brine and H₂O, dried over anhyd MgSO₄, filtered, and concentrated. The residue was purified by silica gel flash column chromatography (hexane-EtOAc = 100:1 to 70:1).

15

Tetrahydropyran 3: colorless oil. ¹H NMR (300 MHz, CDCl₃): δ = 12.21 (s, 0.1 H), 7.30-7.42 (m, 5 H), 4.74 (dd, J = 3, 12 Hz, 0.9 H), 4.63-4.68 (m, 0.1 H), 4.57 (dd, J = 4, 10 Hz, 0.1 H), 4.22-4.34 (m, 2 H), 4.07-4.15 (m, 2 H), 3.38 (d, J = 11 Hz, 1 H), 2.75 (dd, J = 3, 14 Hz, 1 H), 2.57 (dd, J = 12, 14 Hz, 1 H), 2.22-2.26 (m, 2 H), 1.95 (t, J = 3 Hz, 1 H), 1.68-1.90 (m, 4 H), 1.32 (t, J = 7 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 201.7, 168.0, 140.2, 128.7, 128.2, 125.5, 83.9, 78.4, 78.3, 68.7, 62.9, 61.3, 48.8, 33.9, 24.3, 18.2, 14.2. HRMS (+ESI): m/z calcd for C₁₉H₂₂O₄Na⁺ [M + Na⁺]: 337.1416; found: 337.1433. The NOE (%)of 3 are consistent with the boat conformation of a similar compound (E = CO₂Me, R = i-Pr) that reported in the literature (Figure [3] ).^10a

20

Oxadecalin 4a: colorless oil (73%). ¹H NMR (500 MHz, CDCl₃): δ = 7.29-7.38 (m, 5 H, Ph), 5.22 (d, J = 2 Hz, 1 H, H_f), 4.82 (dd, J = 3, 12 Hz, 1 H, H_a), 4.57 (d, J = 2 Hz, 1 H, H_e), 4.55 (t, J = 3 Hz, 1 H, H_d), 4.25-4.32 (m, 2 H, ethyl ester), 2.92 (dd, J = 12, 15 Hz, 1 H, H_c), 2.62 (dd, J = 3, 15 Hz, 1 H, H_b), 2.48 (d, J = 15 Hz, 1 H, H_g), 2.21-2.28 (m, 1 H, H_h), 2.17-2.14 (m, 1 H), 1.95-2.05 (m, 1 H), 1.57-1.66 (m, 2 H), 1.31 (t, J = 7 Hz, 3 H, ethyl ester). ¹³C NMR (125 MHz, CDCl₃): δ = 204.8, 169.3, 143.0, 140.8, 128.7, 128.2, 125.6, 115.8, 79.1, 78.0, 69.0, 61.7, 47.1, 33.5, 28.6, 20.2, 14.1. HRMS (+ESI): m/z calcd for C₁₉H₂₂O₄Na⁺ [M + Na⁺]: 337.1416: found_ 337.1406.

21

Characterizations of Selected Products in Table 2Oxadecalin 4e: colorless oil (52%). ¹H NMR (500 MHz, CDCl₃): δ = 5.16 (d, J = 2 Hz, 1 H), 4.62 (t, J = 3 Hz, 1 H), 4.53 (d, J = 2 Hz, 1 H), 4.21-4.28 (m, 2 H), 2.79 (d, J = 14 Hz, 1 H), 2.39-2.42 (m, 1 H), 2.24 (d, J = 14 Hz, 1 H), 2.13-2.19 (m, 1 H), 1.93-1.98 (m, 1 H), 1.83-1.92 (m, 1 H), 1.48-1.59 (m, 2 H), 1.33 (s, 3 H), 1.28 (t, J = 7 Hz, 3 H), 1.26 (s, 3 H). ¹³C NMR(125 MHz, CDCl₃): δ = 206.0, 169.4, 142.9, 115.7, 75.1, 71.3, 68.2, 61.5, 50.3, 33.6, 30.9, 28.8, 24.3, 19.9, 14.0. HRMS (+ESI): m/z calcd for C₁₅H₂₂O₄Na⁺ [M + Na⁺]: 289.1416; found: 289.1411.Oxadecalin 4f (major): colorless oil (53%). ¹H NMR (500 MHz, CDCl₃): δ = 7.31-7.37 (m, 5 H), 5.27 (d, J = 2 Hz, 1 H), 4.59 (d, J = 2 Hz, 1 H), 4.55 (t, J = 3 Hz, 1 H), 4.33 (d, J = 11 Hz, 1 H), 3.81 (3 H, s). 2.99-3.06 (m, 1 H), 2.50 (d, J = 15 Hz, 1 H), 2.18-2.24 (m, 1 H), 2.08-2.11 (m, 1 H), 1.95-2.04 (m, 1 H), 1.52-1.63 (m, 2 H) 0.84 (d, J = 7 Hz, 3 H). ¹³C NMR(125 MHz, CDCl₃): δ = 206.4, 169.9, 143.8, 140.0, 128.6, 128.5, 127.0, 115.8, 86.2, 78.2, 69.4, 52.6, 48.8, 33.6, 28.7, 20.2, 9.5. HRMS (+ESI): m/z calcd for C₁₉H₂₂O₄Na⁺ [M + Na⁺]: 337.1416; found: 337.1433.Compound 4g: colorless oil (70%). ¹H NMR (300 MHz, CDCl₃): δ = 7.28-7.41 (m, 5 H), 5.34 (t, J = 2 Hz, 1 H), 5.06 (t, J = 2 Hz, 1 H), 4.79-4.84 (m, 2 H), 4.25 (q, J = 7 Hz, 2 H), 2.74-2.88 (m, 1 H), 2.72 (dd, J = 12, 16 Hz, 1 H), 2.62-2.68 (m, 1 H), 2.56 (dd, J = 3, 16 Hz, 1 H), 2.16 (q, J = 7 Hz, 1 H), 1.71-1.85 (m, 1 H), 1.30 (t, J = 7 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 202.7, 168.9, 146.7, 140.2, 128.7, 128.3, 125.7, 113.6, 85.6, 77.7, 72.7, 62.0, 45.0, 31.1, 29.6, 14.1. HRMS (+ESI): m/z calcd for C₁₈H₂₀O₄Na⁺ [M + Na⁺]: 323.1259; found: 323.1255.