Copper-Catalyzed Coupling between ortho-Haloanilines and Lactams/Amides: Synthesis of Benzimidazoles and Telmisartan.

An efficient copper-catalyzed synthesis of (annelated) benzimidazoles is reported. This transformation is based on a simple and straightforward one-pot sequence involving a copper-catalyzed cross coupling between o-haloanilines and lactams/amides followed by a subsequent cyclization under acidic conditions. A variety of (annelated) benzimidazoles could be easily obtained in high yields from readily available starting materials, and this procedure could be further applied to the synthesis of the antihypertensive blockbuster drug telmisartan.

Synthesis of 2-amidoindenone derivatives through an ynamide carbosilylation/Houben-Hoesch cyclization 2-step sequence.

Herein we report the efficient and selective two-step synthesis of various 3-silyl-2-amidoindenones from easily accessible ynamides. This sequence involves a regio- and stereo-selective silylcyanation followed by a Houben-Hoesch type cyclization. Thanks to post-transformations, various 3-substituted 2-amidoindenones could be obtained.

Zinc-Catalyzed Hydrocyanation of Ynamides and Photoisomerization, a General and Selective Access to E and Z Trisubstituted α-Enamidonitriles.

The fully regio- and stereoselective Zn-catalyzed hydrocyanation of ynamides is reported and represents a general access to various trisubstituted E-α-enamidonitriles. The catalyst-free photoisomerization selectively yields the energetically comparable Z-stereoisomer. Finally, the synthetic potential of these new α-enamidonitriles was evaluated through the synthesis of original heterocycles.

Direct Access to 2,3-Disubstituted Amido-Indenones through Annulation of 2-Iodobenzaldehydes with Ynamides.

In this paper we report the annulation reaction between 2-iodobenzaldehyde derivatives and various ynamides. This palladium-catalyzed reaction leads to rare polysubstituted amino-indenones in good yields with a regioselectivity up to complete. Remarkably, a regiodivergent selectivity has been identified between aryl and alkyl or silyl ynamides, with the first leading mainly to 2-amido-indenones and the second to 3-amido-indenones.

Palladium-Catalyzed Silylcyanation of Ynamides: Regio- and Stereoselective Access to Tetrasubstituted 3-Silyl-2-Aminoacrylonitriles.

The palladium-catalyzed silylcyanation of ynamides is described. This reaction is fully regioselective, delivering tetrasubstituted 2-aminoacrylonitriles derivatives exclusively. Unexpectedly, the nature (aryl or alkyl) of the substituent located at the ß-position of the ynamide directly controls the stereoselectivity. The reaction tolerates a number of functional groups and can be considered as the first general access to fully substituted 2-aminoacrylonitriles. Given the singular reactivity observed, a computational study was performed to shed light on the mechanism of this intriguing transformation. Relying on the specific reactivity of the newly installed vinylsilane functionality, the scope of 2-aminoacrylonitriles has been enlarged by postfunctionalization.