Pyrimidine as an Aryl C-H Activating Group.

The Pd-catalyzed regioselective C-H activation/arylation, /iodination, and/acetoxylation reactions of 4-arylpyrimidines using aryl iodides, N-iodosuccinimide, and (diacetoxyiodo)benzene respectively as coupling partners are described. Suzuki-Miyaura coupling and Sonogashira reactions of the resulting aryl iodides are demonstrated. The scalability of the C-H activation/functionalization starting with readily accessible 4-aryl pyrimidines is also reported.

Counter ion effect in Au/Ag-catalyzed chemoselective 6-endo-dig N- and O-cyclizations of enyne-urea system: diversity-oriented synthesis of annulated indoles.

A two-step protocol for the diversity-oriented synthesis of annulated indoles following MCR-post MCR modification concept is described. The reaction initially proceeds through the annulation of 2-(2,2-dibromovinyl)aniline, an isocyanate, and a terminal alkyne in a three-component tandem format via Cu/Pd-catalyzed cross coupling to afford N-1 and C-2 functionalized indole. In the subsequent step, the enyne-urea derivative undergoes chemo- and regioselective 6-endo cyclization to afford O-cyclized product in the presence of Au(I)/AgNO3 and N-cyclized product in the presence of Au(I)/AgOTf under a post-MCR modification step. A mechanistic investigation following a recent pioneering work on the silver effect in gold catalysis (Shi, X. J. Am. Chem. Soc. 2012, 134, 9012) explains the role of counterion on Au/Ag-catalyzed regiodivergent pathways.

Three-component tandem reaction involving acid chlorides, terminal alkynes, and 2-aminoindole hydrochlorides: synthesis of α-carboline derivatives in aqueous conditions via regioselective [3 + 3] cyclocondensation.

An efficient synthesis toward highly diversified α-carboline derivatives via a three-component tandem reaction using acid chlorides, terminal alkynes, and 2-aminoindole hydrochlorides has been described. The salient feature of the one-pot strategy involves regioselective [3 + 3]-cyclocondensation and the presence of water in the reaction medium to facilitate cyclization. Nonaqueous conditions furnished products in poor yields.

Unprecedented Cu-catalyzed coupling of internal 1,3-diynes with azides: one-pot tandem cyclizations involving 1,3-dipolar cycloaddition and carbocyclization furnishing naphthotriazoles.

A one-pot protocol for the synthesis of triazole-annulated polyheterocycles via metal-catalyzed coupling of internal 1,4-disubstituted 1,3-diynes and organic azides has been described. The mechanistic rationale for the reaction suggests tandem cyclizations involving copper-catalyzed cycloaddition and 6-endo carbocyclization reactions. The cascade cyclization leads to an increase in molecular complexity to furnish naphtho[1,2-d]triazoles in satisfactory yields. The generality of the method has been demonstrated by using a series of aromatic/aliphatic azides and symmetrical internal 1,3-diynes.