Synthesis of Coumarins via [4+2] Cyclization of Siloxy Alkynes and Salicylaldehydes

Abstract

A new approach for the synthesis of coumarins from siloxy alkynes and salicylaldehydes is disclosed. Unlike the previous benzannulation reactions of siloxy alkynes that all proceed by electron-inversed Diels–Alder mechanism, this process represents a new [4+2] cyclization. In the presence of the superior HNTf₂ catalyst, a wide range of coumarins were efficiently synthesized. This process was also extended to the synthesis of 2-quinolones. The polarized electron-rich triple bond might react sequentially with the aldehyde and hydroxy group by polarity switching in the stepwise formation of the C–C and C–O bonds. Control experiments provided insights into the mechanistic understanding.

Key words

coumarins - siloxy alkynes - cyclization - heterocycle

Publication History

Received: 11 June 2020

Accepted after revision: 24 July 2020

Article published online:
07 September 2020

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• 9 3-Butyl-6-hydroxy-2H-chromen-2-one (3d) – Typical Procedure In a glovebox, an oven-dried 4 mL vial was charged with the 2,5-dihydroxybenzaldehyde (41.4 mg, 0.3 mmol), (hex-1-yn-1-yloxy)triisopropylsilane (2a, 152.7 mg, 0.6 mmol), and dry acetonitrile (3.0 mL, 0.1 M). The mixture was stirred for 3 min to become homogeneous. Next, HNTf₂ (16.9 mg, 20 mol%) was added. The vial was capped and removed from the glovebox. The reaction mixture was stirred at room temperature for 24 h and then filtered through a short pad of silica gel, which was washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography (eluent: hexanes/ethyl acetate = 10:1) to afford 3d in 86% yield (56.3 mg) as a light yellow solid. ¹H NMR (400 MHz, acetone-d ₆): δ = 8.75 (br s, 1 H), 7.66 (s, 1 H), 7.18 (d, J = 8.8 Hz, 1 H), 7.06–7.02 (m, 2 H), 2.52 (t, J = 8.0 Hz, 2 H), 1.63–1.57 (m, 2 H), 1.43–1.38 (m, 2 H), 0.97 (t, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, acetone-d ₆): δ = 161.9, 154.6, 147.6, 139.1, 130.6, 121.1, 119.2, 117.5, 112.7, 31.1, 30.9, 22.9, 14.0. IR (thin film): 3341, 2958, 1689, 1614, 1510 cm^–1. HRMS (CI+): m/z calcd for C₁₃H₁₄O₃ [M⁺]: 218.0943; found: 218.0953.