Synlett 2021; 32(06): 636-640
DOI: 10.1055/a-1343-5455
letter

Synthesis of Dihydroanthracenes via Palladium-Catalyzed Tandem Mizoroki–Heck/Reductive Heck Reactions Using Cyclic Diaryliodoniums and Alkenes

Xiaopeng Peng
,
Jianfeng Yang
,
Xinhua Qiu
,
Yuansheng Duan
,
Zeqing Bao
,
Jingfeng Chen
This work was supported by the Guangdong Provincial Department of Education Youth Innovation Talents Project (2017GkQNCX099) and the Guangdong Medical Research Foundation (A2018497), P. R. of China.


Abstract

An efficient Pd-catalyzed domino Mizoroki–Heck and reductive Heck reaction of terminal alkenes with six-membered cyclic diaryliodoniums is reported for the facile access to a diverse set of novel dihydroanthracenes. The scope of alkenes is general, leading to concise generation of 30 dihydroanthracenes which are not easily accessed by conventional methods. Furthermore, one of the newly synthesized dihydroanthracene displayed excellent antiproliferative activity against PANC-1 cancer cells (IC50 = 11.74 μM).

Supporting Information



Publication History

Received: 31 October 2020

Accepted after revision: 28 December 2020

Accepted Manuscript online:
28 December 2020

Article published online:
27 January 2021

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  • 12 Procedure to Synthesize Dihydroanthracene 4a To a seal tube was added cyclic diaryliodonium salt 2a (0.1 g, 0.226 mmol, 1.0 equiv), methyl acrylate 3a (0.039 g, 0.45 mmol, 2.0 equiv), Pd(PPh3)4 (0.026 g, 0.022 mmol, 0.1 equiv), Et3N (0.069 g, 0.67 mmol, 3.0 equiv), HCOONa (0.031 g, 0.45 mmol, 2.0 equiv), and DCE (3.0 mL). Then the tube was sealed, degassed, and recharged with argon. The reaction proceeded at 100 °C for 15 h under argon atmosphere. The remained mixture was extracted with DCM (20 mL), the combined organic layers were washed with H2O (3 × 2 mL) and brine, dried over anhydrous Na2SO4, and evaporated in vacuo. The residue was purified by column chromatography on a silica gel (PE/EtOAc = 50:1 to 20:1) to provide compound 4a (0.036 g, 78%). 1H NMR (400 MHz, CDCl3): δ = 7.78 (d, J = 7.6 Hz, 2 H), 7.51 (d, J = 7.6 Hz, 2 H), 7.41 (t, J = 7.2 Hz, 2 H), 7.33–7.29 (m, 2 H), 4.46 (t, J = 7.2 Hz, 1 H), 4.07 (s, 2 H), 3.81 (s, 3 H), 2.80 (d, J = 7.2 Hz, 2 H). 13C NMR (101 MHz, CDCl3): δ = 173.14, 146.39, 140.91, 127.63, 127.33, 124.47, 120.10, 51.99, 43.72, 41.79, 38.63. HRMS (ESI): m/z calcd for C17H17O2 [M + H]+: 253.1150; found: 253.1146. Procedure to Synthesize Dihydroanthracene 5a To a seal tube was added cyclic diaryliodonium salt 2 (0.1 g, 0.213 mmol, 1.0 equiv), acrylonitrile 3 (0.022 g, 0.426 mmol, 2.0 equiv), Pd(PPh3)4 (0.024 g, 0.021 mmol, 0.1 equiv), Et3N (0.065 g, 0.639 mmol, 3.0 equiv), HCOONa (0.029 g, 0.426 mmol, 2.0 equiv), and DCE (3.0 mL). Then the tube was sealed, degassed, and recharged with argon. The reaction proceeded at 100 °C for 15 h under argon atmosphere. The remained mixture was extracted with DCM (20 mL), the combined organic layers were washed with H2O (3 × 2 mL) and brine, dried over anhydrous Na2SO4, and evaporated in vacuo. The residue was purified by column chromatography on a silica gel (PE/EtOAc = 50:1 to 20:1) to provide compound 5a (0.033 g, 67%). 1H NMR (400 MHz, CDCl3): δ = 7.62 (d, J = 7.6 Hz, 2 H), 7.45 (d, J = 0.4 Hz, 2 H), 7.23 (d, J = 8.0 Hz, 2 H), 4.10 (t, J = 7.2 Hz, 1 H), 4.01 (s, 2 H), 2.79 (d, J = 7.2 Hz, 2 H), 2.44 (s, 6 H). 13C NMR (101 MHz, CDCl3): δ = 144.22, 138.37, 137.19, 129.22, 125.09, 119.82, 118.73, 42.79, 41.75, 22.24, 21.78. HRMS (ESI): m/z calcd for C18H18N [M + H]+: 248.1361; found: 248.1375.