Base-Promoted Formal (2+1) Cycloaddition of Benzofuran-Derived Oxadienes with Bromomalonates

Abstract

A base-promoted formal (2+1) cycloaddition of benzofuran-derived oxadienes with bromomalonates was established that afforded benzofuranone-based spirocyclopropanes in generally good yields (up to 98%) and high diastereoselectivities (up to 91:9 dr). This reaction is the first highly diastereoselective formal (2+1) cycloaddition of benzofuran-derived oxadienes, and will contribute to the chemistry of these compounds. In addition, this approach provides an atom-economic and useful protocol for constructing benzofuranone-based spiro skeletons.

Key words

(2+1) cycloaddition - diastereoselectivity - benzofurans - oxadienes - bromomalonates - spiro compounds

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• 15 Spirobenzofurans 3; General Procedure The appropriate benzofuran-derived oxadiene 1 (0.2 mmol), bromomalonate 2 (0.4 mmol), and DBU (0.6 mmol) were added to a reaction tube. EtOH (1 mL) was then added and the mixture was stirred at 0 °C for 12 h. When the reaction was complete (TLC), the mixture was concentrated under a reduced pressure and the residue was purified by flash column chromatography [silica gel, PE–EtOAc (10:1)]. Diethyl 3-Oxo-3′-phenyl-2′H,3H-spiro[1-benzofuran-2,1′-cyclopropane]-2′,2′-dicarboxylate (3aa) White solid; yield: 98% (74.6 mg, 84:16 dr); mp 103.2–104.5 °C. IR (KBr): 3626, 1744, 1717, 1614, 1461, 1292, 1236, 1138, 871, 757 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.76 (d, J = 7.6 Hz, 1 H), 7.71–7.66 (m, 1 H), 7.40–7.29 (m, 6 H), 7.23–7.18 (m, 1 H), 4.37–4.24 (m, 2 H), 4.10 (q, J = 7.2 Hz, 2 H), 3.77 (s, 1 H), 1.30 (t, J = 7.2 Hz, 3 H), 1.10 (t, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 194.1, 171.4, 164.4, 162.8, 137.7, 130.6, 129.6, 128.3, 127.8, 124.2, 123.0, 120.4, 113.9, 76.1, 62.4, 61.9, 47.3, 38.0, 14.0, 13.8. ESI FTMS: m/z [M – H]^– calcd for C₂₂H₁₉O₆: 379.1187; found: 379.1172.
• 16 CCDC 2235785 contains the supplementary crystallographic data for compound 3aa. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures . See also the Supporting Information for details.