Visible-Light Photolysis of Allyl Zirconocenes: A Photoinduced Three-Component Radical (4+2)-Cyclization–Allylation Reaction

Abstract

A photoinduced, three-component radical (4+2)-cyclization–allylation reaction between 3-(2-iodoethyl)indoles, acceptor-substituted alkenes, and allyl zirconocenes of the structure Cp₂ZrCl(σ-allyl) was developed. The protocol leads to highly functionalized hexahydrocarbazoles in a single step, establishing three C–C bonds and three contiguous stereocenters at once. The radical reaction is initiated by direct photolysis of allyl zirconocenes to generate free allyl radicals.

Key words

radical reactions - multicomponent reactions - photochemistry - indolines - allylation

• References and Notes


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• 14 Typical Experimental Procedure In a 10 mL crimp cap vial, Cp₂ZrCl₂ (88 mg, 0.30 mmol) was dissolved in THF (1.0 mL) under N₂, and the solution was cooled to –78 °C. Allylmagnesium chloride (0.15 mL of a 2.0 M solution in THF, 0.30 mmol) was added dropwise, and the resulting yellow solution was stirred for 30 min. A solution of substrate 1a (43 mg, 0.10 mmol), methyl acrylate (2a, 27 μL, 0.30 mmol), and Ir(ppy)₃ (0.7 mg, 1 mol%) in THF (1.0 mL) was added via syringe, and the resulting mixture was rapidly warmed to r.t., then again degassed (3× freeze-pump-thaw). The vial was placed inside a blue LED reactor (10.1 W, 294 lm, 460 ± 15 nm) and irradiated with stirring at r.t. for 5 h. Then 5 M HCl (aq, 2 mL) was added to the mixture and stirring was continued for 2 h. The mixture was diluted with H₂O and extracted with Et₂O (3×). The combined organic layers were dried with MgSO₄, filtered, and evaporated. Column chromatography (silica gel; EtOAc–PE, 1:15 to 1:9) gave the byproducts 8a and 7a, and 13 mg (31%) of hexahydrocarbazole 5a (R_f = 0.27; EtOAc–PE, 1:9) as a single diastereomer. Analytical Data for Compound 5a ¹H NMR (400 MHz, CDCl₃): δ = 1.03–1.16 (m, 1 H, 3-H^a), 1.23–1.30 (m, 1 H, 1′’-H^a), 1.45–1.65 (m, 4 H, 2-H^a, 3-H^b, 4-H^a, 1′-H^b), 1.66–1.75 (m, 1 H, 2-H^b), 1.98 (m_c, 1 H, 4-H^b), 2.34 (s, 3 H, Me), 2.64 (ddd, J = 4.5, 7.6, 10.3 Hz, 1 H, 1-H), 3.78 (s, 3 H, OMe), 4.30 (d, J = 7.6 Hz, 9a-H), 4.53 (dd, J = 2.1, 17.0 Hz, 1 H, 3′-H^a), 4.83 (dd, J = 2.1, 10.1 Hz, 1 H, 3′-H^b), 5.34 (m_c, 1 H, 2′-H), 6.91 (d, J = 7.5 Hz, 1 H, 5-H), 7.03 (t, J = 7.5 Hz, 1 H, 6-H), 7.18–7.26 (m, 3 H, 7-H, Ts), 7.68–7.73 (m, 3 H, 8-H, Ts) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 19.3 (t, C-3), 21.5 (q, Me), 24.7 (t, C-2), 29.0 (t, C-4), 46.8 (d, C-1′), 47.5 (d, C-1), 47.6 (s, C-4a), 52.1 (q, OMe), 68.8 (d, C-9a), 116.5 (d, C-8), 118.5 (t, C-3′), 123.2 (d, C-5), 123.8 (d, C-6), 127.0 (d, Ts), 128.2 (d, C-7), 129.6 (d, Ts), 132.4 (d, C-2′), 136.2 (s, Ts), 136.7 (s, C-4b), 140.4 (s, C-8a), 143.9 (s, Ts), 175.0 (s, CO) ppm. IR: ν = 2945 (C–H), 1735 (C=O), 1360, 1170 cm^–1. ESI-HRMS: m/z calc. for C₂₄H₂₇NNaO₄S⁺ [M + Na]⁺: 448.1553; found: 448.1477.