Ugi–Smiles and Ullmann reactions catalyzed by Schiff base derived from Tröger’s base and BINOL

A Schiff base catalyst (1a) combining a Troger’s base-NH2 and the (R)-BINOL-(CHO)2 was used to promote the Ugi-Smiles reaction. By using isocyanide, malononitrile, aldehydes and low-reactive unfunctionalized 1H-benzo[d]imidazole-2-thiols as substrates, thioimidazolidinone derivatives (6) were obtained with high yields under mild condition. Subsequently, the catalyst was used as the efficient ligand to promote the CuI-catalyzed Ullmann reaction of the products of Ugi-Smiles reaction to give imidazole-containing five-membered fused ring compounds (7). The results indicated that it is an efficient way to develop catalysts to combine TB and BINOL framework. Finally, the antitumor activities of products on human three positive breast cancer cells (MCF-7), human three negative breast cancer cells (MDA-MB-231), human alveolar epithelial cell (A549) and of cytotoxicity on human bronchial epithelial cell (HBE) of all products in vitro were evaluated. Some products showed great inhibition effect on cancer cells (IC50 on MCF-7 and MDA-MB-231 reached nanogram levels) and low toxicity to normal cells, which display their potential in the new drug development.