Tandem synthesis of functionalized hexaalkyl benzoisoquinolinopyrrolonaphthyridine-hexacarboxylate, via isoquinoline based multi-component reaction (original) (raw)

2013, Chinese Chemical Letters

Tandem CC bond formations are powerful methods for the rapid, elegant and convenient construction of complex organic molecules from relatively simple starting materials in a straightforward way [1-11]. These transformations are usually operated in one-pot reactors without the need for intermediate workups or purifications. In particular, the development of tandem reactions for the efficient construction of complex molecules is an important goal in combinatorial chemistry from the viewpoints of operational simplicity and assembly efficiency. The rich and fascinating chemistry that stems from the addition of nucleophiles to activated acetylenic compounds has evoked considerable interest. N-heterocycles are known to form zwitterions with activated acetylene compounds, such as dimethyl acetylenedicarboxylate [12-14]. These zwitterions can be trapped by a variety of electrophiles and proton donors, which is a novel protocol for the synthesis of heterocyclic compounds [12-16]. Recently, our research group was involved in various multicomponent reactions that can provide easy access to important heterocyclic systems [16,17]. We now report the results of our studies involving the reactions of zwitterions derived from isoquinoline 1 and dialkyl acetylenedicarboxylates 2 in the presence of dialkyl chloromalonate (3), which constitutes a synthesis of hexaalkyl benzoisoquinolinopyrrolonaphthyridinehexacarboxylate 4a-f in good yields (Scheme 1). 2. Experimental The reagents and solvents in this work were obtained from Aldrich and Fluka and were used without further purification. The analytical equipment included: mp, Electrothermal-9100 apparatus. IR spectra (KBr, cm À1), Shimadzu IR-460 spectrometer; in cm À1. 1 H NMR and 13 C NMR spectra, Bruker DRX-300 Avance instrument; in CDCl 3 at 300 and 75 MHz, respectively; d in ppm, J in Hz. MS, Finnigan-MAT-8430 mass spectrometer, at 70 eV; in m/z (rel.%). Elemental analyses (C, H, N), Heraeus CHN-O-Rapid analyzer. General procedure for the preparation of compounds 4: To a stirred solution of 2 (2 mmol) and 3 (2 mmol) in 10 mL of CH 2 Cl 2 was added 0.24 mL of isoquinoline (2 mmol) dropwise at À10 8C over 5 min. The reaction mixture was then allowed to warm to room temperature and stand for 12 h. The solvent was removed under reduced pressure, and the residue was purified by silica gel (Merck 230-240 mesh) column chromatography using n-hexane/ EtOAc (3:1) mixture as eluent to afford the pure product.