Synthesis of Quinolino[1,2-c]quinazolin-6-one Derivatives via Formal (4+2)-Cycloaddition of Alkenes to Quinazoline-Derived N-Acyliminium Cations: An Experimental and Theoretical Study

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. Uns...

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Published inSynthesis (Stuttgart) Vol. 54; no. 10; pp. 2395 - 2414
Main Authors Filatov, Alexander S., Larina, Anna G., Petrov, Mikhail L., Boitsov, Vitali M., Stepakov, Alexander
Format Journal Article
LanguageEnglish
Published STUTTGART Thieme Medical Publishers 17.05.2022
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
regioselectivity
N-acyliminium cations
INTERMOLECULAR ADDITION-REACTIONS
Friedel-Crafts alkylation reaction
electrophilic addition
IONS
electron-rich alkenes
diastereoselectivity
stepwise cycloaddition
DFT calculations
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Summary: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 center dot 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-4hydroxy-1-methyl-3,4-dihydroquinazolin-2(1H)-ones in the presence of BF3 center dot Et2O smoothly reacted with such alkenes as indene, acenaphthylene, styrene, alpha-methyl styrene 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.
ISSN:0039-7881
1437-210X
DOI:10.1055/a-1755-2061