A Flow Microreactor Approach to a Highly Efficient Diels–Alder Reaction with an Electrogenerated o-Quinone

Published as part of the Cluster Electrochemical Synthesis and Catalysis

Abstract

We have demonstrated a Diels–Alder reaction of an o-quinone generated in an electrochemical flow microreactor. In the flow microreactor system, 4-tert-butyl-o-benzoquinone was easily electrogenerated from 4-tert-butylpyrocatechol in the absence of chemical oxidants and then rapidly used, without decomposing, in a subsequent Diels–Adler reaction with various fulvenes to give the desired products efficiently.

Key words

quinones - Diels–Alder reaction - microreactor - electrochemical synthesis - flow chemistry - butylcatechol

• References and Notes

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• 10 Electrochemical Reaction in a Batch-Type Reactor The reaction of 4-tert-butylpyrocatechol (1; 10 mM) with 6,6-dimethylfulvene (3; 200 mM) was performed by using a graphite plate anode (working electrode; 2 × 2 cm²) and a Pt plate cathode (counter-electrode, 2 × 2 cm²) in a 100 mM solution of NaClO₄ in MeCN (10 mL). A constant current (1.5 mA cm^–2) was applied during the electrolysis. After the electrolysis was complete, the mixture was analyzed by HPLC to determine the yield of the Diels–Alder cycloadduct 4. Electrochemical Reactions in the Flow Microreactor; General Procedure A 10 mM solution of 4-tert-butylpyrocatechol in a 100 mM solution of NaClO₄ in MeCN was introduced into the reactor from a syringe pump (Model 100; KD Scientific, Holliston, MA: see Figs. S1 and S2 in the Supporting Information). Constant-current electrolysis was performed at 1.5 mA cm^–2 by using the electrochemical flow microreactor. The electrolyzed solution emerging from the microreactor was poured into CH₂Cl₂ containing the appropriate fulvene (200 mM), and the mixture was stirred for 8 h. The mixture was then analyzed by HPLC to determine the yield of the Diels–Alder cycloadduct. (3aR*,4S*,7R*,7aS*)-6-(tert-Butyl)-1-(1-methylethylidene)-3a,4,7,7a-tetrahydro-1H-4,7-ethanoindene-8,9-dione (4) Yellow solid; yield: 75%; mp 97.7 °C. IR (KBr): 2964, 1732, 1508, 1473, 1458, 1363, 1099, 812 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 6.42 (dd, J = 5.7, 1.9 Hz, 1 H), 5.86 (ddd, J = 6.6, 2.2, 0.6 Hz, 1 H), 5.58 (dd, J = 5.7, 2.5 Hz, 1 H), 3.70 (dd, J = 3.0, 2.4 Hz, 1 H), 3.61 (dd, J = 6.8, 2.7 Hz, 1 H), 3.56 (d, J = 7.9 Hz, 1 H), 3.31 (d, J = 7.9 Hz, 1 H), 1.80 (s, 3 H), 1.77 (s, 3 H), 1.00 (s, 9 H). ¹³C NMR (126 MHz, CDCl₃): δ = 191.5, 191.2, 151.8, 139.4, 135.6, 132.2, 125.2, 118.3, 54.1, 50.5, 46.4, 40.6, 35.3, 28.3, 21.7, 21.4. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₈H₂₂NaO₂: 293.1512; found: 293.1498. (3aR*,4S*,7R*,7aS*)-6-tert-Butyl-1-(1-methylhexylidene)-3a,4,7,7a-tetrahydro-1H-4,7-ethanoindene-8,9-dione (6) Yellow solid; yield: 47%; mp 101.1 °C. IR (KBr): 2966, 2870, 1735, 1463, 1365, 1161, 813 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 6.44 (dd, J = 5.7, 1.9 Hz, 1 H), 5.84 (dd, J = 6.5, 2.1, 1 H), 5.60 (dd, J = 5.7, 2.5 Hz, 1 H), 3.69 (m, 1 H), 3.57 (dd, J = 6.8, 2.7 Hz, 1 H), 3.53 (m, 1 H), 3.34 (dd, J = 7.9, 2.5 Hz, 1 H), 2.10 (q, J = 7.04 Hz, 4 H), 1.48–1.55 (m, 1 H), 1.30–1.46 (m, 3 H) 1.00 (s, 9 H), 0.95 (t, J = 7.41 Hz, 3 H), 0.86 (t, J = 7.41 Hz, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 191.2, 191.2, 151.6, 139.9, 135.5, 134.0, 132.3, 118.1, 53.8, 51.1, 46.0, 40.0, 35.0, 34.5, 33.9, 28.1, 22.1, 21.6, 14.2, 13.9. HRMS (ESI) m/z [M + H]⁺ calcd for C₂₂H₃₁O₂; 327.2309; found: 327.2319.
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