Title
Multifaceted Domino Knoevenagel-Cyclization Reactions; Four Movements for 2H-Chromenes and Chromans
Author
Király, Sándor Balázs, László Tóth, Tibor Kovács, Attila Bényei, Erika Lisztes, Balázs István Tóth, Tamás Bíró, Attila Kiss-Szikszai, Katalin E. Kövér, Attila Mandi, and Tibor Kurtan
Year
2023
Journal
Advanced Synthesis & Catalysis
Abstract
Domino Knoevenagel-cyclization reactions of 2H-chromene and chroman derivatives containing o-formylaryl amine or ether side-chain was carried out to produce four series of chiral condensed heterocycles representing four novel skeletons and exhibiting antiproliferative activity. The cyclization step occurred with four different mechanisms: a concerted intramolecular hetero Diels-Alder reaction (IMHDA), a stepwise polar [2+2] cycloaddition, a [1,5]-hydride shift-6-endo cyclization or a multi-step nitro hetero Diels-Alder-ring-opening-Cadogan-type cyclization sequence. The latter reaction provided a new route to hydroxyindoles by an inverse Cadogan-type cyclization, in which the nitro group is deoxygenated by a nitro IMHDA-ring-opening sequence. The cyclization mechanisms and their stereoselectivity were studied by DFT calculations, based on which we proposed a mechanism for the multi-step cyclization to hydroxyindoles and explained the observed diastereoselectivity.
Instrument
FT/IR-4100,J-810,,HPLC
Keywords
Chiral HPLC separation and ECD measurement,Configuration determination, Diastereoselectivity,Domino reactions, Heterocycles