Download PDF
Synlett 2008(1): 142-146  
DOI: 10.1055/s-2007-990953
LETTER
© Georg Thieme Verlag Stuttgart · New York

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;
Further Information

Publication History

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

    Permissions and Reprints All articles of this category

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

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

Figure 3

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, Hf), 4.82 (dd, J = 3, 12 Hz, 1 H, Ha), 4.57 (d, J = 2 Hz, 1 H, He), 4.55 (t, J = 3 Hz, 1 H, Hd), 4.25-4.32 (m, 2 H, ethyl ester), 2.92 (dd, J = 12, 15 Hz, 1 H, Hc), 2.62 (dd, J = 3, 15 Hz, 1 H, Hb), 2.48 (d, J = 15 Hz, 1 H, Hg), 2.21-2.28 (m, 1 H, Hh), 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.