Synlett, Table of Contents Synlett 2019; 30(10): 1194-1198DOI: 10.1055/s-0037-1611725 cluster © Georg Thieme Verlag Stuttgart · New YorkA Flow Microreactor Approach to a Highly Efficient Diels–Alder Reaction with an Electrogenerated o-Quinone Authors Author Affiliations Kenta Tanaka Hirona Yoshizawa Mahito Atobe * Department of Environment and System Sciences, Yokohama National University, 79-7 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa 240-8501, Japan Email: atobe@ynu.ac.jp Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) 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 Key wordsquinones - Diels–Alder reaction - microreactor - electrochemical synthesis - flow chemistry - butylcatechol Full Text References References and Notes 1a Diels O, Alder K. Justus Liebigs Ann. Chem. 1928; 460: 98 ; For reviews on Diels–Alder reactions, see for example: 1b Nicolaou KC, Snyder SA, Montagnon T, Vassilikogiannakis G. Angew. Chem. Int. Ed. 2002; 41: 1668 1c Takao K.-i, Munakata R, Tadano K.-i. Chem. Rev. 2005; 105: 4779 1d Nawrat CC, Moody CJ. Angew. Chem. Int. Ed. 2014; 53: 2056 2a Nair V, Menon RS, Bijub AT, Abhilashc KG. Chem. Soc. Rev. 2012; 41: 1050 2b Nair V, Kumar S. Synlett 1996; 1143 2c Nair V, Kumar S, Williard PG. Tetrahedron Lett. 1995; 36: 1605 2d Allmann R, Debaerdemaeker T, Friedrichsen W, Jürgens HJ, Betz M. Tetrahedron 1976; 32: 147 2e Kaicharla T, Bhojgude SS, Biju AT. Org. Lett. 2012; 14: 6238 2f Xu D, Chiaroni A, Largeron M. Org. Lett. 2005; 7: 5273 3a Takata T, Tajima R, Ando W. J. Org. Chem. 1983; 48: 4764 3b Nair V, Sethumadhavan D, Nair SM, Rath NP, Eigendorf GK. J. Org. Chem. 2002; 67: 7533 3c Nair V, Mathew B, Radhakrishnan KV, Rath NP. Tetrahedron 1999; 55: 11017 3d Nair V, Anilkumar G, Radhakrishnan KV, Sheela KC, Rath NP. Tetrahedron 1997; 53: 17361 4a Sagawa Y, Kobayashi S, Mukaiyama T. Chem. Lett. 1988; 17: 1105 4b Chiba K, Tada M. J. Chem. Soc., Chem. Commun. 1994; 0: 2485 5a Jung ME, Perez F. Org. Lett. 2009; 11: 2165 5b Wanzlick HW, Lehmann-Horchler M, Mohrmann S, Gritzky R, Heidepriem H, Pankow B. Angew. Chem. Int. Ed. 1964; 3: 401 5c Zhang N.-T, Gao X.-G, Zeng C.-C, Hu L.-M, Tian H.-Y, She Y.-B. RSC Adv. 2012; 2: 298 5d Gao X.-G, Zhang N.-T, Zenga C.-C, Liu Y.-D, Hu L.-M, Tian H.-Y. Curr. Org. Synth. 2014; 11: 141 6a Atobe M, Tateno H, Matsumura Y. Chem. Rev. 2018; 118: 4541 6b Plutschack MB, Pieber B, Gilmore K, Seeberger PH. Chem. Rev. 2017; 117: 11796 6c Hardwick T, Ahmed N. RSC Adv. 2018; 8: 22233 7a Yoshida J.-i, Takahashi Y, Nagaki A. Chem. Commun. 2013; 49: 9896 7b Yoshida J.-i, Nagaki A, Yamada T. Chem. Eur. J. 2008; 14: 7450 8a Qu Y, Tsuneishi C, Tateno H, Matsumura Y, Atobe M. React. Chem. Eng. 2017; 2: 871 8b Mizuno M, Tateno H, Matsumura Y, Atobe M. React. Chem. Eng. 2017; 2: 642 8c Matsumura Y, Yamaji Y, Tateno H, Kashiwagi T, Atobe M. Chem. Lett. 2016; 45: 816 8d Arai T, Tateno H, Nakabayashi K, Kashiwagi T, Atobe M. Chem. Commun. 2015; 51: 4891 8e Tateno H, Matsumura Y, Nakabayashi K, Senboku H, Atobe M. RSC Adv. 2015; 5: 98721 9a Kashiwagi T, Amemiya F, Fuchigami T, Atobe M. Chem. Commun. 2012; 48: 2806 9b Kashiwagi T, Amemiya F, Fuchigami T, Atobe M. J. Flow Chem. 2012; 3: 17 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. 11 Nair V, Kumar S. Tetrahedron 1996; 52: 4029 Supplementary Material Supplementary Material Supporting Information (PDF) (opens in new window)
