Titania-supported iridium subnanoclusters as an efficient heterogeneous catalyst for direct synthesis of quinolines from nitroarenes and aliphatic alcohols.

The use of metal nanoparticles (NPs) or nanoclusters (NCs) as versatile catalysts for green and sustainable organic synthesis has attracted tremendous interest in recent years owing to their unique properties, such as a large surface-tovolume ratio and tunable shapes. The control of their size, shape, dispersity, and in particular the combination of metal NPs/NCs with a specific heterogeneous support is essential for enhanced activity and selectivity in a desired application. Although in many classical transformations, reusable supported metal NPs/NCs have exhibited far superior performance than those of conventional metal complex catalysts, the possibilities offered by metal NPs/NCs for sustainable tandem catalysis that allows a rapid increase in molecular complexity through one-pot multistep reactions have scarcely been explored. This situation is somewhat surprising since the integrated use of the reactive sites generated from metal NPs/NCs and a suitable support could be a powerful means for the design of multitask catalysts, thus providing promising candidates to perform sophisticated tandem reactions for synthesis of complex molecular targets from simple and convenient substrates in a domino fashion. Quinolines and their derivatives are an important class of bioactive compounds that are prescribed as antimalarial, antibacterial, antihypertensive, and antiinflammatory drugs. In addition, quinolines are valuable synthons used for the preparation of nanostructures and polymers that combine enhanced electronic, optoelectronic, or nonlinear optical properties with excellent mechanical properties. The most frequent routes to prepare functionalized quinolines include several named reactions, such as Skraup, Doebner–Von Miller, Conrad–Limpach, Friedl nder, and Pfitzinger syntheses based on the reaction of substituted anilines with carbonyl compounds. Despite their utility, these methods often suffer from the requirement of costly aromatic amines and unstable carbonyl compounds, harsh conditions, and the use of large amounts of hazardous acids or bases. More problematic is that the complicated substituted amines must themselves be synthesized first, mostly by multistep procedures. The development of new strategies to obtain quinolines in a fast, clean, and efficient way has been the focus of considerable efforts. In this context, the assembly of the quinolines directly from readily available nitroarenes and aliphatic alcohols through a one-pot tandem reaction is highly attractive. Unfortunately, this straightforward method has proven to be extremely difficult, and effective catalyst systems were severely limited. To date, only two homogeneous transition-metal catalytic systems b] and one UV-irradiated photocatalytic system have been reported. From a synthetic and economic point of view, these systems are not practically useful because of the inherent problems of non-reusability, the necessity of special handling of an external light source, or harsh conditions, as well as low yields and limited substrate scope. Herein, we report for the first time that a new heterogeneous iridium-based multitask catalyst facilitates the rapid direct construction of valuable quinolines from nitroarenes and alcohols under mild conditions through a facile sequential transfer reduction–condensation–dehydrogenation pathway. The combination of sub-nanosized iridium clusters with an oxide support possessing suitable surface acidity, for example, TiO2, provides an optimal catalyst. Iridium was selected because Ir NPs and complexes are well known to catalyze a wide range of organic transformations including dehydrogenation and transfer hydrogenation. The present heterogeneous Ir-catalyzed process shows several fundamental improvements: 1) unprecedented catalytic efficiency; 2) unique functional group tolerance; 3) avoidance of expensive ligands or additives; 4) reusability of the catalyst; and 5) high-quality products without residual heavy-metal contamination. To the best of our knowledge, the reaction is considerably greener than any of the known procedures and involves an easy workup. Initially, the direct transformation of nitrobenzene with npropanol to give 2-ethyl-3-methylquinoline (3a) was inves[*] L. He, Y. Gong, Dr. Y. M. Liu, Prof. Dr. Y. Cao, Prof. Dr. H. Y. He, Prof. Dr. K. N. Fan Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University Shanghai 200433 (P. R. China) E-mail: yongcao@fudan.edu. cn