REAL

[1,5]-Hydride Shift-Cyclization versus C(sp2)-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4- and 1,5-Benzoxazepines

Vargáné Szalóki, Dóra and Tóth, László and Buglyó, Balázs and Kiss-Szikszai, Attila and Mándi, Attila and Mátyus, Péter and Antus, Sándor and Chen, Yinghan and Li, Dehai and Tao, Lingxue and Zhang, Haiyan and Kurtán, Tibor (2020) [1,5]-Hydride Shift-Cyclization versus C(sp2)-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4- and 1,5-Benzoxazepines. MOLECULES, 25. p. 1265. ISSN 1420-3049

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Abstract

Domino cyclization reactions of N-aryl-1,4- and 1,5-benzoxazepine derivatives involving [1,5]-hydride shift or C(sp2)-H functionalization were investigated. Neuroprotective and acetylcholinesterase activities of the products were studied. Domino Knoevenagel-[1,5]-hydride shift-cyclization reaction of N-aryl-1,4-benzoxazepine derivatives with 1,3-dicarbonyl reagents having active methylene group afforded the 1,2,8,9-tetrahydro-7bH-quinolino [1,2-d][1,4]benzoxazepine scaffold with different substitution pattern. The C(sp3)-H activation step of the tertiary amine moiety occurred with complete regioselectivity and the 6-endo cyclization took place in a complete diastereoselective manner. In two cases, the enantiomers of the chiral condensed new 1,4-benzoxazepine systems were separated by chiral HPLC, HPLC-ECD spectra were recorded, and absolute configurations were determined by time-dependent density functional theory- electronic circular dichroism (TDDFT-ECD) calculations. In contrast, the analogue reaction of the regioisomeric N-aryl-1,5-benzoxazepine derivative did not follow the above mechanism but instead the Knoevenagel intermediate reacted in an SEAr reaction [C(sp2)-H functionalization] resulting in a condensed acridane derivative. The AChE inhibitory assays of the new derivatives revealed that the acridane derivative had a 6.98 uM IC50 value.

Item Type: Article
Subjects: Q Science / természettudomány > QD Chemistry / kémia > QD01 Analytical chemistry / analitikai kémia
Q Science / természettudomány > QD Chemistry / kémia > QD04 Organic chemistry / szerves kémia
Depositing User: Mándi Attila
Date Deposited: 24 Sep 2020 07:29
Last Modified: 24 Sep 2020 07:29
URI: http://real.mtak.hu/id/eprint/114310

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