Flow Synthesis of Triptycene via Triple Cycloaddition of Ynolate to Benzyne

Takayuki Iwata; Tatsuro Yoshinaga; Mitsuru Shindo

doi:10.1055/s-0040-1706417

Synlett, Table of Contents

Synlett 2020; 31(19): 1903-1906
DOI: 10.1055/s-0040-1706417

cluster

Flow Synthesis of Triptycene via Triple Cycloaddition of Ynolate to Benzyne

Takayuki Iwata

^aInstitute for Materials Chemistry and Engineering, Kyushu University, Kasuga-koen, Kasuga 816-8580, Japan Email: shindo@cm.kyushu-u.ac.jp

,

Tatsuro Yoshinaga

^bInterdisciplinary Graduate School of Engineering Sciences, Kyushu University, Kasuga-koen, Kasuga 816-8580, Japan

,

Mitsuru Shindo∗

^aInstitute for Materials Chemistry and Engineering, Kyushu University, Kasuga-koen, Kasuga 816-8580, Japan Email: shindo@cm.kyushu-u.ac.jp

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Abstract

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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.

Keywords

triptycene - ynolate - benzyne - flow synthesis - cycloadditionborate

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References

References and Notes

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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.

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