Mesoporous Silica with Site-Isolated Amine and Phosphotungstic Acid Groups: A Solid Catalyst with Tunable Antagonistic Functions for One-Pot Tandem Reactions**

Scientists engaged in heterogeneous catalysis often cite enzymes as their model catalysts. Enzymes can efficiently catalyze multistep processes that give various types of biomolecules. Remarkably, many enzymes combine two antagonistic catalytic functions, such as acid and base functions. Attracted by this challenge, several groups synthesized homogeneous catalysts that can successfully combine chemically hostile functions. However, the difficulty lies in controlling the separation between these groups and simultaneously working at practical catalyst concentrations. In principle, both of these problems can be solved using heterogeneous catalysis. But synthesizing solid catalysts that combine hostile functions is no easy task. Not surprisingly, examples of solids with both acidic and basic functions are limited. The reported examples combine acids such as sulfonic acids, silanols, ureas, and thiols with amines. However, problems such as low catalytic activity because of weak acidity, complicated preparation, and lack of a continuous range of acidic and basic catalytic sites often significantly limit their application in organic reactions. Here, we present a simple and straightforward route to such bifunctional solids. We combine amine base functions and heteropolyacid functions on periodic mesoporous silica, obtaining an efficient and robust bifunctional acid–base solid catalyst. This new material enables one-pot cooperative catalysis. Moreover, the synthesis permits easy tailoring of the acid/base properties by controlling the number and surface concentration of the acid and base sites, respectively. We demonstrate the catalytic efficiency and robustness of this new system in two cascade reactions: a tandem deprotection– Henry reaction, and a tandem deprotection–aldol reaction. Excellent yields and selectivities are obtained in both cases. Figure 1 shows the synthesis of the catalyst. We started by making a mesoporous silica support S (Figure 1, top; pore diameter of 4.9 nm and surface area of 870 mg , see the Experimental Section). The base functions were then added