Piperidine-mediated [3 + 3] cyclization of 2-amino-4H-chromen-4-ones and substituted 2-benzylidenemalononitriles was developed for the synthesis of 2-amino-4-aryl-5H-chromeno­[2,3-b]­pyridin-5-one derivatives. This novel transformation provides a highly efficient and facile route to functionalized 5H-chromeno­[2,3-b]­pyridines from readily available substrates under mild reaction conditions.

A Yb­(OTf)3-mediated annulation of cyclopropane-1,1-dicarbonitriles and 2-aminobenzaldehydes for the synthesis of polysubstituted quinolines in generally good yields was investigated. In the cascade reaction, the protocol includes ring opening, intermolecular nuclophilic addition, intramolecular nuclophilic addition, and demalononitrile aromatization, in which the malononitrile group serves as a deciduous directing group mediated by Yb­(OTf)3.

A novel approach to the synthesis of substituted 5-amino-4cyanochromeno[4,3,2-de][1,6]naphthyridine-1-carboxylates from a wide range of substituted 2-hydroxybenzaldehydes with alkyl 3-oxo-3-substituted propanoates and malononitrile was investigated via propionic acid-promoted cascade Knoevenagel condensation/Michael addition/intramolecularly nucleophilic addition accompanied by oxidative aromatization. This procedure provided a highly efficient and facile route to functionalized chromenonaphthyridines from readily available substrates under mild reaction conditions.

A formal [3 + 3] cascade annulation strategy for the synthesis of 2-arylchromeno[2,3-b]pyridinones has been developed using 2-aminochromones and substituted cinnamaldehydes or aromatic aldehydes and ethanal as the substrates. The strategy supplies a novel and atom-economical method of accessing a broad range of chromeno[2,3-b]pyridine derivatives in good yields with good functional-group tolerance. The method highlights the inherent practicality of this synthetic transformation.

S2 EXPERIMENTAL SECTIONGeneral. Substituted 2-amino-4H-chromen-4-ones 1a-f were prepared according to reported methods [11] and were purified by recrystallization from ethanol. Common reagents and solvents were purchased from commercial suppliers. Melting points were recorded in a Yanaco melting point apparatus and are uncorrected. TLC was carried out on pre-coated glass plates, and components were monitored by observation under UV light (254 and 365 nm). Flash chromatography was employed on silica gel (230-400 mesh) eluting with ethyl acetate-hexanes mixture. IR spectra were recorded using a Nicolet FT-IR 5DX spectrometer and samples were loaded neat. The 1 H and 13 C NMR spectra were recorded on a Bruker AV-400 spectrometer with TMS as internal reference in CDCl3. Chemical shifts were quoted in ppm. Coupling constants, J, were shown in Hz. HRMS analysis was carried out on a UHR-TOF maXis mass spectrometer in ESI mode. Data collection for the crystal structure was performed using a SMART APEX-II diffractometer with monochromatic Mo KR radiation (λ) 0.71073 Å) and integrated with the SAINT-Plus program. All calculations were performed with programs from the SHELXTL crystallographic software package.The mixture of substituted 2-amino-4H-chromen-4-ones 1a-f (1.0 mmol), aromatic aldehydes 2a-l (2.0 mmol), 1H-indene-1,3(2H)-dione (3a) (292 mg, 2.0 mmol) and potassium carbonate (166 mg, 1.2 mmol) in DMF (8 mL) was stirred at 110 o C in oil bath for 8-11 h. The reaction was monitored by TLC (EtOAc/hexanes, 1/2, silica gel). After complete consumption of 2-amino-4H-chromen-4-ones, most of solvent was removed by reduced pressure distillation. To the cooled residues were added water (15 mL), subsequently the resulting mixture was fully stirred. Then, the resulting mixture was extracted with dichloromethane (10 mL × 2). The combined organic phase was washed with water (10 mL) and brine (10 mL), and dried over anhydrate sodium sulfate. After removal of dichloromethane via vacuum, the crude product was purified by flash chromatography (EtOAc/hexanes, 1/10, silica gel) to give the desirable products 4a-t.