Sc(OTf)₃-Catalyzed [3+3] Annulation of Cyclopropane 1,1-Diesters with β-(Indol-2-yl)-α,β-unsaturated Ketones: Synthesis of Polysubstituted Tetrahydrocarbazoles

Abstract

A Sc(OTf)₃-catalyzed cascade reaction consisting of a Friedel–Crafts alkylation followed by a Michael addition between cyclopropane 1,1-diesters and β-(indol-2-yl)-α,β-unsaturated ketones allows for the efficient synthesis of polysubstituted tetrahydrocarbazoles under very mild reaction conditions.

Key words

Lewis acids - scandium - catalysis - annulation - heterocycles

• References and Notes

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• 11 General Procedure for the Friedel–Crafts Alkylation–Michael Addition Cascade Reactions The cyclopropanes 2 (0.3 mmol) and alkenylindoles 3 (0.3 mmol) were dissolved in CH₂Cl₂ or DCE (3 mL). Sc(OTf)₃ (2 mol%) was then added, and a reflux condenser was attached. Then the reaction was brought to reflux. Upon completion by TLC analysis, the reaction mixture was concentrated and purified by flash chromatography (acetone–PE = 1:10) to yield the desired tetrahydrocarbazoles. Compound cis -4aa: white solid; mp 172–174 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.70 (s, 1 H), 7.95 (d, J = 7.6 Hz, 2 H), 7.59–7.55 (m, 1 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.31–7.22 (m, 6 H), 7.04–7.00 (m, 1 H), 6.79–6.75 (m, 1 H), 6.65 (d, J = 8.0 Hz, 1 H), 4.67 (d, J = 8.8 Hz, 1 H), 4.07 (dd, J = 11.2, 6.0 Hz, 1 H), 3.72 (s, 6 H), 3.46 (dd, J = 18.4, 10.4 Hz, 1 H), 3.18 (dd, J = 18.4, 2.4 Hz, 1 H), 2.94 (dd, J = 14.0, 6.0 Hz, 1 H), 2.29 (dd, J = 14.0, 11.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 199.1, 170.7, 170.0, 144.6, 137.0, 136.4, 136.1, 133.8, 128.8, 128.5, 128.1, 127.9, 126.6, 126.1, 121.5, 119.8, 118.9, 110.8, 109.6, 58.9, 53.1, 53.0, 42.7, 38.2, 36.3, 32.6. IR (KBr): ν_max = 3439, 2953, 1734, 1682, 1452, 1245, 1194, 1178, 1056, 732, 648 cm^–1. ESI-HRMS: m/z calcd for C₃₀H₂₈NO₅ [M + H]⁺: 482.1962; found: 482.1964.
• 12 Crystal data for trans-4aa and cis- 4aa have been deposited in CCDC with the deposition number 1038619 and 1055500, respectively. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.com.
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