Diversity-Oriented Synthesis of Novel Trihalomethyl-Containing Spirochromeno[3,4- a ](thia)pyrrolizidines and Spirochromeno-[3,4- a ]indolizidines by One-Pot, Three-Component [3+2]-Cyclo addition Reaction

Abstract

Regio- and stereoselective methods for the synthesis of 6′-trifluoro(trichloro)methyl substituted spiro[acenaphthylene-1,11′-chromeno[3,4- a ](thia)pyrrolizidin]-2-ones and spiro[acenaphthylene-1,12′-chromeno[3,4- a ]indolizidin]-2-ones have been developed based on the three-component reaction of 3-nitro-2-trifluoro(trichloro)methyl-2 H -chromenes with azomethine ylides generated in situ from acenaphthenequinone and cyclic α-amino acids. The cycloaddition proceeds under mild conditions in ethanol or DMSO, and only endo -isomers of the products with cis -arrangement of nitro and trifluoromethyl groups are formed. The relative configuration of cycloadducts is reliably confirmed by X-ray diffraction analysis and by 2D NOESY spectroscopy. © 2021 Georg Thieme Verlag. All rights reserved.