Synthesis of air-stable mixed bis-carboxylate titanocene complexes and their catalytic behaviors in cross-aldol and Mannich reactions

Tunable organometallic Lewis acid catalysts were developed by combining salicylic acid (H₂-Sal) with benzoic acid (H-Ben), 4-fluorobenzoic acid (H-BenF) and 3-thiophenic acid (H-Th), as coligands for mixed bis-carboxylate titanocene complexes. Three air-stable complexes Cp₂Ti(η¹-HSal)(η¹-Ben)] (1), Cp₂Ti(η¹-HSal)(η¹-BenF)] (2) and Cp₂Tiη¹-HSal](η¹-Th)] (3) were prepared in high yields by the reaction of salicylato titanocene chelate with carboxylate ligands. The mixed bis-carboxylate titanocene complexes were fully characterized by physicochemical and spectroscopic methods. Single-crystal X-ray diffraction studies revealed Ti–O_(H-Sal) bond distances in 1, 2 and 3 of 1.972(3), 1.9245(18) and 1.912(5) Å, respectively, while the bond distances involving the coligands of 1, 2 and 3 are 1.908(3) Å (Ti–O_Ben), 1.9296(19) Å (Ti–O_BenF) and 1.945(5) Å (Ti–O_Th), respectively. These bis-carboxylate titanocene complexes showed satisfactory activities and selectivities in Mannich and cross-aldol reactions. Notably, complex 3 bearing the labile thiophene carboxylate ligand gave high yields with a diastereomer ratio (d.r.) as high as 1:99 for the direct Mannich reactions of benzaldehyde, cyclohexanone and aniline. In cross-aldol reaction of benzaldehyde and cyclohexanone, 1 and 2 successfully catalyzed the formation of double-aldol products in up to 99 % yield.