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Synlett 2021; 32(14): 1428-1432
DOI: 10.1055/a-1533-1080
DOI: 10.1055/a-1533-1080
letter
Synthesis of 6-Alkynyl-6-hydroxyindoloquinazolinone Scaffolds via Copper-Catalyzed Alkynylation of Tryptanthrins
We are grateful for financial support of the National Natural Science Foundation of China (Grant Number 21571144), the Natural Science Foundation of Zhejiang Province (Grant Numbers LY18B020011 and LQ19B020004), and the Foundation of Zhejiang Educational Committee (Grant Number Y201839490).
Abstract
We report a copper-catalyzed direct alkynylation reaction of tryptanthrins with terminal alkynes under mild reaction conditions. The developed method provides an array of synthetic building blocks of 6-alkynyl-6-hydroxyindoloquinazolinone compounds in moderate to good yields with varied functional group compatibility. Furthermore, the obtained adducts can be smoothly converted into versatile building blocks via hydrogenation, hydration, and further Sonogashira coupling transformations.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1533-1080.
- Supporting Information
Publication History
Received: 03 April 2021
Accepted after revision: 21 June 2021
Accepted Manuscript online:
21 June 2021
Article published online:
06 July 2021
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Copper-Catalyzed Addition Reaction of Tryptanthrins and Alkynes – General Procedure
In air, a clean and dried Schlenk tube was charged with CuCl2·2H2O (0.02 mmol,10 mol%), K2CO3 (0.4 mmol, 2.0 equiv.), tryptanthrin 1a (0.2 mmol, 1.0 equiv.), alkyne 2 (1.0 mmol, 5.0 equiv.), and 1,4-dioxane or THF (2 mL). The resulting mixture was stirred at the 60 °C or 80 °C for 36 h until the reaction completed. The crude mixture was purified through flash column chromatography on a silica gel using DCM/EtOAc (100:1, v/v) as eluent to give the desired products.
6-Hydroxy-6-(phenylethynyl)indolo[2,1-b]quinazolin-12(6H)-one (3a)
This compound was prepared according to the typical procedure, which was purified using DCM/EtOAc (100:1, v/v) as eluent and was obtained (55.3 mg, 79% yield) as a white solid; mp 246.7–247.2 °C. 1H NMR (500 MHz, DMSO): δ = 8.44 (d, J = 8.0 Hz, 1 H), 8.32 (d, J = 7.4 Hz, 1 H), 7.97–7.81 (m, 3 H), 7.69–7.56 (m, 3 H), 7.53–7.33 (m, 6 H). 13C NMR (126 MHz, DMSO): δ = 158.68, 158.19, 146.87, 137.97, 134.96, 132.84, 131.55, 130.66, 129.30, 128.73, 127.93, 127.79, 127.31, 126.54, 124.84, 121.52, 121.05, 116.40, 87.35, 85.20, 70.85. HRMS (ESI): m/z calcd for C23H15N2O2
+ [M + H]+: 351.1128; found: 351.1124.
6-[(2-Bromophenyl)ethynyl]-6-hydroxyindolo[2,1-b]quinazolin-12(6H)-one (3b)
This compound was prepared according to the typical procedure, which was purified using DCM/EtOAc (100:1, v/ v) as eluent and was obtained (57.5 mg, 67% yield) as a yellow solid; mp 239.5–240.9 °C. 1H NMR (500 MHz, DMSO): δ = 8.47 (d, J = 8.0 Hz, 1 H), 8.33 (d, J = 7.2 Hz, 1 H), 7.98–7.87 (m, 3 H), 7.74–7.56 (m, 5 H), 7.52 (t, J = 7.5 Hz, 1 H), 7.44–7.32 (m, 2 H). 13C NMR (126 MHz, DMSO): δ = 158.67, 157.91, 146.86, 137.96, 135.00, 133.73, 132.60, 132.53, 131.03, 130.73, 127.99, 127.83, 127.82, 127.29, 126.56, 125.00, 124.91, 122.99, 121.50, 116.39, 91.55, 83.69, 70.97. HRMS (ESI): m/z calcd for C23H14BrN2O2
+ [M + H]+: 429.0233; found: 429.0239.
For selected examples on chemistry of propargylic alcohols, see:
For selected reviews, see:
For selected examples on catalytic addition of terminal alkynes to ketones, see: