An efficient and practical approach for the synthesis of indoloquinolines and indolo/pyrroloquinoxalines via a Cu-catalyzed Ugi-C/Ugi-N-arylation sequence.

A Cu-catalyzed tandem transformation of Ugi adducts through CH/NH bond functionalization reactions was reported for synthesizing a broad spectrum of indolo/pyrrolo-[1,2-a]quinoxaline-6/4-carboxamide, 7H-indolo[2,3-c]quinoline-6-carboxamide, and 1-(cyclohexylamino)-14H-indolo[2,3-c][1,4]oxazino[4,3-a]quinolin-4(3H)-one derivatives in moderate to excellent yields. In this protocol the Ugi condensation of aromatic aldehydes, anilines, acids, and isocyanides leads to the formation of bis-amides in methanol at room temperature. This approach employed simple reaction conditions, including Ugi product as starting material, CuI, l-proline as a ligand, and cesium carbonate, in DMSO for 8 h. This method demonstrated efficiency in synthesizing fused-nitrogen-containing heterocycles through a convenient pathway.

Two distinct protocols for the synthesis of unsymmetrical 3,4-disubstituted maleimides based on transition-metal catalysts.

Two tandem catalytic systems are described for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts as starting materials. 4-Aryl-3-pyrrolyl- and 4-aryl-3-indolyl-maleimides were successfully obtained via a Pd(OAc)2/PPh3 based protocol. In contrast, maleimide-fused pyrrolo and indolo[1,2-a]quinolines were obtained in a complementary methodology using CuI/L-proline. These strategies involved a combination of benzylic amine oxidation, trans-amidation, intramolecular Knoevenagel condensation, and N-arylation reactions. Computational investigations provide further insights into this reaction sequence.

Cascade synthesis of 2,4-disulfonylpyrroles by the sulfonylation/[2 + 3]-cycloaddition reactions of gem-dibromoalkenes with arylsulfonyl methyl isocyanides.

An efficient cascade reaction involving sulfonylation and [2 + 3]-cycloaddition reactions of gem-dibromoalkenes with arylsulfonyl methyl isocyanides was described for the synthesis of 3-aryl-2,4-disulfonyl-1H-pyrroles. The main highlight of this study is the introduction of a new dual-functional reactivity of arylsulfonyl methyl isocyanides as the sulfonyl source as well as a 1,3-dipolar reagent in the same reaction. This system is facilitated by Cs2CO3 mediation in DMSO and 100 °C conditions.

Isocyanide Reactions Toward the Synthesis of 3-(Oxazol-5-yl)Quinoline-2-Carboxamides and 5-(2-Tosylquinolin-3-yl)Oxazole.

A palladium-catalyzed three-component reaction between 5-(2-chloroquinolin-3-yl) oxazoles, isocyanides, and water to yield 3-(oxazol-5-yl)quinoline-2-carboxamides is described. Interestingly, sulfonylation occurred when the same reaction was performed with toluenesulfonylmethyl isocyanide (TosMIC) as an isocyanide source. The reaction with 5-(2-chloroquinolin-3-yl)oxazoles and TosMIC in the presence of Cs2CO3 in DMSO afforded 5-(2-Tosylquinolin-3-yl)oxazoles. In basic media, TosMIC probably decomposed to generate Ts- species, which were replaced with Cl-. Tandem oxazole formation with subsequent sulfonylation of 2-chloroquinoline-3-carbaldehydes to form directly 5-(2-tosylquinolin-3-yl)oxazoles was also investigated.