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

Alexander S. Filatov; Anna G. Larina; Mikhail L. Petrov; Vitali M. Boitsov; Alexander V. Stepakov

doi:10.1055/a-1755-2061

Synthesis, Table of Contents

Synthesis 2022; 54(10): 2395-2414
DOI: 10.1055/a-1755-2061

paper

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

Alexander S. Filatov

^aSaint Petersburg State University, Universitetskaya nab. 7/9, 199034, St. Petersburg, Russian Federation

,

Anna G. Larina

^aSaint Petersburg State University, Universitetskaya nab. 7/9, 199034, St. Petersburg, Russian Federation

,

Mikhail L. Petrov

^bSaint Petersburg State Institute of Technology, Moskovskii pr. 26, 190013, St. Petersburg, Russian Federation

,

Vitali M. Boitsov

^cSaint Petersburg National Research Academic University of the Russian Academy of Sciences, ul. Khlopina 8/3, 194021, St. Petersburg, Russian Federation

,

Alexander V. Stepakov∗

^aSaint Petersburg State University, Universitetskaya nab. 7/9, 199034, St. Petersburg, Russian Federation

^bSaint Petersburg State Institute of Technology, Moskovskii pr. 26, 190013, St. Petersburg, Russian Federation

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Abstract

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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 calculations

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References

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