Reusable Scandium/Ionic Liquid Catalyst System for Sequential C-C and C-O Bond Formations between Phenols and Dienes with Atom Economy

Abstract

Mild, efficient, and atom economical sequential C-C/C-O bond formations between phenols and dienes using the reusable catalyst system, Sc(OTf)₃-[bmim][PF₆], have been developed to afford in good yields a variety of dihydrobenzopyran and dihydrobenzofuran ring systems, which are important motifs in both naturally occurring and biologically active compounds. In these reactions the ionic liquid acts as not only an efficient additive but also an immobilizing agent for facilitating catalyst recycling.

heterocycles - bicyclic compounds - annulations - scandium - ionic liquids

References and Notes

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7 For one-pot synthesis of dihydrobenzopyrans by the reactions of phenols with dienes using Amberlyst 15 as a reusable catalyst, see: Cichewicz RH. Kenyon VA. Whitman S. Morales NM. Arguello JF. Holman TR. Crews P. J. Am. Chem. Soc.  2004,  126:  14910 ; and references therein

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12b

For effects of the anions, see: refs. 9b and 8c and references therein.

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15

General Procedure for the Sc-IL-Catalyzed Reaction of Phenols and Dienes and Catalyst Recycling: To a solution of phenol and diene (2 equiv) in toluene (0.1 M) and [bmim][PF₆] (0.5 equiv) was added Sc(OTf)₃ (20 mol%). The resulting mixture was stirred at the reported temperature for 18-48 h. The organic(toluene) layer was decanted to leave the ionic liquid phase containing Sc(OTf)₃ which was washed with Et₂O (3 ×) for extraction of the product. The combined organic layer was concentrated and the residue was purified by column chromatography on silica gel (EtOAc-n-hexanes, 1:20-1:100) to give the corresponding product.
The recovered ionic liquid layer remaining in the vessel was reused without any pre-treatment. For the second cycle, more reactants (phenol and diene) and toluene were added to the recovered ionic liquid layer.
5,7-Dimethoxy-2,2-dimethylchroman (5): Colorless oil (EtOAc-n-hexane, 1:20). ¹H NMR (400 MHz, CDCl₃): δ = 1.32 (s, 6 H), 1.75 (t, J = 6.8 Hz, 2 H), 2.57 (t, J = 6.8 Hz, 2 H), 3.75 (s, 3 H), 3.78 (s, 3 H), 6.01 (d, J = 2.4 Hz, 1 H), 6.03 (d, J = 2.4 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 16.6, 26.6, 32.4, 55.2, 55.3, 74.2, 90.8, 93.5, 102.4, 155.0, 158.5, 159.3. HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₈O₃: 222.1256; found: 222.1255.
5,6,7-Trimethoxy-2,2-dimethylchroman (6): Colorless oil (EtOAc-n-hexane, 1:20). ¹H NMR (400 MHz, CDCl₃): δ = 1.31 (s, 6 H), 1.74 (t, J = 6.8 Hz, 2 H), 2.63 (t, J = 6.8 Hz, 2 H), 3.78 (s, 3 H), 3.80 (s, 3 H), 3.88 (s, 3 H), 6.16 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.0, 26.6, 32.3, 55.7, 60.5, 61.0, 74.0, 96.5, 106.6, 135.3, 149.9, 151.3, 152.3. HRMS (EI): m/z [M]⁺ calcd for C₁₄H₂₀O₄: 252.1362; found: 252.1364.
2,2,8,8-Tetramethyl-3,4,9,10-tetrahydro-2 H ,8 H -pyrano[2,3- f ]chromene (8) and 2,2,8,8-Tetramethyl-3,4,7,8-tetrahydro-2 H ,6 H -pyrano[3,2- g ]chromene (9): The mixture of isomers was obtained as a colorless oil (8/9 = 3:2, EtOAc-n-hexane, 1:50). Signals corresponding to 8: ¹H NMR (400 MHz, CDCl₃): δ = 1.32 (s, 3 H), 1.33 (s, 3 H), 1.77 (m, 4 H), 2.62 (t, J = 6.8 Hz, 2 H), 2.70 (t, J = 6.8 Hz, 2 H), 6.34 (d, J = 8.5 Hz, 1 H), 6.80 (d, J = 8.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.1, 22.0, 26.7, 27.1, 32.4, 32.9, 73.5, 73.9, 108.4, 109.5, 111.3, 127.0, 151.7, 152.8. Signals corresponding to 9: ¹H NMR (400 MHz, CDCl₃): δ = 1.32 (s, 6 H), 1.77 (m, 4 H), 2.69 (t, J = 6.8 Hz, 4 H), 6.24 (s, 1 H), 6.74 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 21.8, 26.8, 33.1, 73.8, 104.7, 112.6, 129.3, 153.1. HRMS (EI): m/z [M]⁺ calcd for C₁₆H₂₂O₂: 246.1620; found: 246.1618.
2,2,8,8,10-Pentamethyl-3,4,7,8-tetrahydro-2 H ,6 H -pyrano[3,2- g ]chromene (10): White solid (EtOAc-n-hexane, 1:50). ¹H NMR (400 MHz, CDCl₃): δ = 1.33 (s, 12 H), 1.76 (t, J = 6.8 Hz, 4 H), 2.03 (s, 3 H), 2.70 (t, J = 6.8 Hz, 4 H), 6.62 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 8.0, 22.1, 27.1, 33.1, 73.5, 111.8, 113.0, 125.8, 150.7. HRMS (EI): m/z [M]⁺ calcd for C₁₇H₂₄O₂: 260.1776; found: 260.1776.