Synlett 2020; 31(19): 1903-1906
DOI: 10.1055/s-0040-1706417
cluster
© Georg Thieme Verlag Stuttgart · New York

Flow Synthesis of Triptycene via Triple Cycloaddition of Ynolate to Benzyne

Takayuki Iwata
a  Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga-koen, Kasuga 816-8580, Japan   Email: shindo@cm.kyushu-u.ac.jp
,
Tatsuro Yoshinaga
b  Interdisciplinary Graduate School of Engineering Sciences, Kyushu University, Kasuga-koen, Kasuga 816-8580, Japan
,
Mitsuru Shindo
a  Institute for Materials Chemistry and Engineering, Kyushu University, Kasuga-koen, Kasuga 816-8580, Japan   Email: shindo@cm.kyushu-u.ac.jp
› Author Affiliations
This work was partially supported by the Japan Society for the Promotion of Science (JSPS KAKENHI, Grant No. JP18H02557, JP18H04418, JP18H04624, JP20H04780, JP17K14449, and JP20K15283), the NAGASE Science Technology Foundation (M.S.), the Asahi Glass Foundation (T.I.), the Qdai-jump Research Program Wakaba Challenge at Kyushu University (T.I.), and the IRCCS Fusion Emergent Research Program (T.I.). This work was performed under the Cooperative Research Program ‘Network Joint Research Center for Materials and Devices’.
Further Information

Publication History

Received: 30 June 2020

Accepted after revision: 17 July 2020

Publication Date:
21 August 2020 (online)


Published as part of the Cluster Integrated Synthesis Using Continuous-Flow Technologies

Abstract

Flow synthesis of triptycene was achieved using triple cycloaddition of ynolate to benzyne. Employing the borate-type benzyne precursor, side reactions triggered by the addition of alkyllithium to benzyne were efficiently suppressed under microflow conditions, thus producing triptycene with a higher yield than that obtained under the corresponding batch conditions. Furthermore, ynolate prepared from α,α-dibromoester under microflow conditions was continuously added to the flow reaction with benzyne, which successfully synthesized triptycene in only one minute.

Supporting Information

 
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  • 13 Representative Procedure for the Synthesis of 9-Hydroxyltriptycene 3 Using Benzyne Precursor 4 Solution A o-(Trifluoromethanesulfonyloxy)arylboronic acid pinacol ester (4, 1.58 g, 4.50 mmol) was dissolved in Et2O (10.0 mL), and the resulting solution was put in a syringe. Solution B s-BuLi (0.97 M in cyclohexane and hexane) was diluted with hexane to be 0.45 M solutions, 10.0 mL of which was put in a syringe. Solution C To a solution of ethyl 2,2-dibromohexanoate (227 mg, 0.750 mmol) in Et2O (3.0 mL), cooled to –78 °C under argon atmosphere, was added dropwise a solution of t-BuLi (1.50 M in pentane, 2.0 mL, 3.0 mmol). The resulting yellow solution was stirred for 30 min at –78 °C and then for another 30 min at 0 °C. The resulting colorless solution of ynolate was diluted with Et2O to make total volume of 10.0 mL and put in a syringe. Reaction A flow microreactor system consisting of two micromixers (M1 and M2, comet X each) and two microtube reactors (R1: ø = 1000 μm, L = 100 cm, V = 0.8 mL and R2: ø = 1000 μm, L = 100 cm, V = 0.8 mL) was used. M1, M2, and R1 were dipped in a cooling bath at –78 °C, and R2 was dipped in a warming bath at 40 °C. Solutions A and B were introduced to M1 using syringe pumps in a flow rate of 1.0 mL/min each. The resulting solution was passed through R1 and was mixed with solution C (flow rate: 1.0 mL/min) in M2. The resulting solution was then poured into 1 M HCl. After a steady state was reached, the product solution was collected for 120 s (corresponding to 0.15 mmol of ynolate solution). The collected mixture was extracted with CHCl3. The combined organic phase was washed with brine, dried over MgSO4, filtered, and concentrated. The crude product (24% NMR yield) was purified by silica gel column chromatography (hexane–EtOAc = 25:1) to afford compound 3 (15.2 mg, 31%) as a white solid. Triptycene 3 1H NMR (600 MHz, CDCl3): δ = 7.54 (d, J = 6.9 Hz, 3 H), 7.39 (d, J = 6.9 Hz, 3 H), 7.03–7.08 (m, 6 H), 3.25 (s, 1 H), 2.93 (t, J = 7.6 Hz, 2 H), 2.12–2.17 (m, 2 H), 1.79–1.85 (m, 2 H), 1.16 (t, J = 7.2 Hz, 3 H). The NMR spectrum was matched with that of our previous report.