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DOI: 10.1055/a-1755-2061
Synthesis of Quinolino[1,2-c]quinazolin-6-one Derivatives via Formal (4+2)-Cycloaddition of Alkenes to Quinazolinе-Derived N-Acyliminium Cations: An Experimental and Theoretical Study
We gratefully acknowledge financial support provided by the Russian Foundation for Basic Research (Project no. 20-33-90325). This work was supported by the Ministry of Science and Higher Educationof the Russian Federation (0785.00.X6019). V.M.B. is grateful to the Ministry of Education and Science of the Russian Federation (0791-2020-0006) for financial support.
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Abstract
3-Aryl-4-hydroxy-1-methyl-3,4-dihydroquinazolin-2(1H)-ones were synthesized by reduction of 3-aryl-1-methylquinazoline-2,4(1H,3H)-diones with sodium triethylborohydride and studied as precursors of N-acyliminium cations that were expected to be trapped with various alkenes as (4+2)-cycloadducts. Unsubstituted 3-aryl-4-hydroxy-1-methyl-3,4-dihydroquinazolin-2(1H)-ones in the presence of BF3·Et2O failed to produce the desired cycloadducts probably due to a homooligomerization reaction involving N-acyliminium intermediates. To prevent this side reaction, we found it necessary to introduce substituents at both positions C6 and C8 of the quinazoline ring and C4′ of the 3-phenyl substituent. Utilizing bromine atoms as substituents at C6 and C8, N-acyliminium cations generated from 3-aryl-6,8-dibromo-4-hydroxy-1-methyl-3,4-dihydroquinazolin-2(1H)-ones in the presence of BF3·Et2O smoothly reacted with such alkenes as indene, acenaphthylene, styrene, α-methylstyrene to give new quinolino[1,2-c]quinazolin-6-one derivatives with high regio- and stereoselectivity. Density functional theory calculations were performed at the M06-2x/cc-pVDZ level to obtain an insight into the mechanism of the (4+2)-cycloaddition reaction of quinazoline-derived N-acyliminium cations to alkenes.
Key words
stepwise cycloaddition - electrophilic addition - Friedel–Crafts alkylation reaction - N-acyliminium cations - electron-rich alkenes - regioselectivity - diastereoselectivity - DFT calculationsSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1755-2061.
- Supporting Information
- CIF File
Publication History
Received: 29 September 2021
Accepted after revision: 31 January 2022
Accepted Manuscript online:
31 January 2022
Article published online:
16 March 2022
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