Association of Intramolecular Furan Diels-Alder Reaction and N-Acylim­­i­n­ium Alkylation for the Synthesis of Pentacyclic Precursor of Aromathecins

Abstract

A new approach for the synthesis of isoindoloquinoline and aromathecin templates is presented. These were obtained in a few steps starting from inexpensive reagents by two different strategies. The key step for both sequences was the IMFDA reaction, leading diastereoselectively to the formation of the unsaturated DE ring system of the expected alkaloid skeletons.

benzoindolizino[1,2-b]quinolinone - heterocycle - N-acyl­iminium - α-amidoalkylation - Diels-Alder

References and Notes

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<A NAME="RD14109ST-15">15</A>

Data for 2A
Mp 123 ˚C (white solid); R _f = 0.27 (cyclohexane-EtOAc = 1:1). IR: ν = 1729 (C=O), 1684 (C=O), 1645 (C=C), 1444 (CH), 1426 (CH), 1290 (CO) cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 1.12-1.24 (m, 1 H, H_{6 α}), 1.20 (t, 3 H, CH₃CH₂, J = 7.0 Hz), 2.37-2.47 (m, 1 H, H₇), 2.63-2.75 (m, 1 H, H_{6 β}), 2.68-2.75 (m, 1 H, H₈), 3.70 (d, 1 H, H_{4 α}, J = 15.6 Hz), 4.10 (q, 2 H, CH₃CH₂, J = 7.0 Hz), 4.41 (dd, 1 H, H₅, J = 12.5, 3.1 Hz), 4.90 (d, 1 H, H_{4 β}, J = 15.6 Hz), 5.10 (dd, 1 H, H₁, J = 4.7, 1.6 Hz), 6.28 (d, 1 H, H₃, J = 5.5 Hz), 6.42 (dd, 1 H, H₂, J = 5.5, 1.6 Hz), 7.38-7.55 (m, 3 H, H_ar), 7.83 (d, 1 H, H_ar, J = 7.0 Hz). ^¹³C NMR (50 MHz, CDCl₃): δ = 14.4 (CH₃), 36.6 (C₆), 39.6 (C₇), 41.1 (C₄), 53.7 (C₈), 57.5 (C₅), 61.1 (CH_{2 ester}), 80.1 (C₁), 85.7 (C_q), 122.0 (CH_ar), 124.2 (CH_ar), 128.6 (CH_ar), 131.6 (CH_ar), 132.5 (C_q), 136.7 (C₃), 137.7 (C₂), 145.2 (C_q), 166.7 (C=O), 171.5 (C=O). Anal. Calcd for C₁₉H₁₉NO₄ (325.13): C, 70.14; H, 5.89; N, 4.31. Found: C, 69.98; H, 5.66; N, 4.21.

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<A NAME="RD14109ST-17">17</A> Roma G. di Braccio M. Balbi A. Mazzei M. Ermili A. J. Heterocycl. Chem.  1987,  24:  329 

<A NAME="RD14109ST-18">18</A>

Only traces of product 24 were detected by ^¹H NMR.

<A NAME="RD14109ST-19">19</A> See, for example: Mentink G. Van Maarseveen JH. Hiemstra H. Org. Lett.  2002,  4:  3497 

<A NAME="RD14109ST-20">20</A>

Data for 3A
Mp 159 ˚C (white solid); R _f = 0.23 (cyclohexane-EtOAc = 2:3). IR: ν = 2903 (CH), 1731 (C=O), 1692 (C=O), 1636 (C=N), 1508 (C=C) cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 1.21-1.31 (m, 1 H, H_{11 α}), 1.24 (t, 3 H, CH₃CH₂, J = 7.0 Hz), 2.42-2.53 (m, 1 H, H₁₂), 2.77 (dd, 1 H, H₁₃, J = 4.7, 3.9 Hz), 2.96-3.08 (m, 1 H, H_{11 β}), 3.77 (d, 1 H, H_{4 α}, J = 14.9 Hz), 4.10 (q, 2 H, CH₃CH₂, J = 7.0 Hz), 4.60 (dd, 1 H, H₅, J = 12.1, 2.7 Hz), 5.02 (d, 1 H, H_{4 β}, J = 14.9 Hz), 5.13 (dd, 1 H, H₁, J = 3.9, 1.6 Hz), 6.30 (d, 1 H, H₃, J = 6.3 Hz), 6.47 (dd, 1 H, H₂, J = 6.3, 1.6 Hz), 7.62 (dd, 1 H, H₈, J = 7.8, 7.0 Hz), 7.78-7.86 (m, 1 H, H₇), 7.98 (d, 1 H, H₉, J = 7.8 Hz), 8.14 (d, 1 H, H₆, J = 8.6 Hz), 8.62 (s, 1 H, H₁₀). ^¹³C NMR (50 MHz, CDCl₃): δ 14.4 (CH₃), 35.3 (C₁₁), 39.6 (C₁₂), 41.2 (C₄), 53.7 (C₁₃), 58.9 (C₅), 61.1 (CH_{2 ester}), 80.2 (C₁), 85.5 (C_q), 123,8 (C_q), 127.3 (C₈), 127.9 (C_q), 129.4 (C₆), 129.8 (C₉), 131.7 (C₇), 133.2 (C₁₀), 137.1 (C₃), 137.4 (C₂), 149.8 (C_q), 163.2 (C=N), 164.9 (C=O), 171.3 (C=O). Anal. Calcd for C₂₂H₂₀N₂O₄ (376.41): C, 70.20; H, 5.36; N, 7.44. Found: C, 70.05; H, 5.16; N, 7.28.